A retrospective analysis of ovarian stimulation with letrozole in women undergoing artificial insemination by donor.

PubMed

Sun, X J; Jiang, L; Ji, L C; Nie, R; Chen, H; Jin, L; Zhu, G J; Qian, K

2017-04-01

The aim of this retrospective study was to determine the clinical pregnancy rate in women undergoing letrozole ovarian stimulation and artificial insemination by donor (AID). Between 2012 and 2015, 130 natural cycles, 939 letrozole cycles and 130 letrozole plus gonadotrophin cycles were conducted. Letrozole cycles were divided into three groups according to LH concentration on the day of HCG administration (LH <10 mIU/ml and follicle size ≥18 cm; LH ≤10 to <20 mIU/ml; and LH ≥20 mIU/ml). Pregnancy rates were 17.3%, 22.4% and 26.8%, respectively (P = 0.012). In women given 10 mIU/ml LH or more, logistic regression identified oestradiol (OR 1.002, 95% CI, 1.000 to 1.004, P = 0.029) and leading follicle size (OR 0.861, 95% CI, 0.772 to 0.960, P = 0.007) as significant predictive factors of pregnancy rate; the higher the oestradiol and the smaller the follicles, the better the pregnancy rate. The pregnancy rate was significantly higher in the letrozole plus gonadotrophin group than the letrozole group (P = 0.04). Better pregnancy rates can be achieved if LH surge occurs before HCG administration, especially with higher oestradiol and lower follicle size; treatment with letrozole plus gonadotrophin was significantly more effective than letrozole alone in AID. Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Comparing the Administration of Letrozole and Megestrol Acetate in the Treatment of Women with Simple Endometrial Hyperplasia without Atypia: A Randomized Clinical Trial.

PubMed

Moradan, Sanam; Nikkhah, Niaz; Mirmohammadkhanai, Majid

2017-05-01

The present study was conducted as a pilot to compare the therapeutic effects and the potential side effects of oral Megestrol acetate and Letrozole in the treatment of simple hyperplasia in perimenopausal women. The participants of this randomized clinical trial consisted of two groups of 25 women aged 44-50 presenting with abnormal uterine bleeding diagnosed with simple endometrial hyperplasia without cytologic atypia confirmed by transvaginal ultrasonography and biopsy. The first group received 40-mg doses of Megestrol acetate for 2 weeks per month for a total period of 2 months. The second group received 2.5-mg daily doses of Letrozole for a total period of 2 months. The differences in terms of quantitative measurements were analyzed using the independent two-sample t test and the paired t test. To compare the two groups in terms of the distribution of the categorical variables, Pearson's Chi square and Fisher's Exact tests were used at the significance level of 0.05 by Stata-9.2. Although the intervention led to significant improvements in both groups (P < .001), there was no difference between the groups in terms of accomplishing resolution (P = .74) [seven (28%) patients in the Letrozole group and five (20%) in the Megestrol group], while two patients in the Letrozole group and nine in the Megestrol group suffered from side effects, suggesting significantly lower side effects in the Letrozole group (P = .02). Letrozole and Megestrol acetate seem to have similar effects on the treatment of simple endometrial hyperplasia, the only difference being that Letrozole presents fewer side effects than Megestrol acetate in patients with this condition. Abnormal Uterine Bleeding Research Center of Semnan University of Medical Sciences, Semnan, Iran. IRCT2015031011504N5.

Plasma Letrozole Concentrations in Postmenopausal Women With Breast Cancer Are Associated With CYP2A6 Genetic Variants, Body Mass Index, and Age

PubMed Central

Desta, Z; Kreutz, Y; Nguyen, AT; Li, L; Skaar, T; Kamdem, LK; Henry, NL; Hayes, DF; Storniolo, AM; Stearns, V; Hoffmann, E; Tyndale, RF; Flockhart, DA

2013-01-01

The associations between plasma letrozole concentrations and CYP2A6 and CYP3A5 genetic variants were tested in the Exemestane and Letrozole Pharmacogenomics (ELPH) trial. ELPH is a multicenter, open-label prospective clinical trial in women randomly assigned (n ≈ 250 in each arm) to receive 2 years of treatment with either oral letrozole (2.5 mg/day) or oral exemestane (25 mg/day). CYP2A6 and CYP3A showed effects on letrozole metabolism in vitro. DNA samples were genotyped for variants in the CYP2A6 and CYP3A5 genes. plasma letrozole concentrations showed high interpatient variability (>10-fold) and were associated significantly with CYP2A6 genotypes (P < 0.0001), body mass index (BMI) (P < 0.0001), and age (P = 0.0035). However, CYP3A5 genotypes showed no association with plasma letrozole concentrations. These data suggest that CYP2A6 is the principal clearance mechanism for letrozole in vivo. CYP2A6 metabolic status, along with BMI and age, may serve as a biomarker of the efficacy of letrozole treatment or a predictor of adverse effects. PMID:21975350

Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial.

PubMed

Hassan, AbdelGany; Shehata, Nesreen; Wahba, Amr

2017-04-01

We aimed to compare the cost effectiveness of letrozole versus purified urinary follicle stimulating hormone (FSH) in treating patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). This was a randomized trial conducted in Cairo University and Beni-Suef University Hospitals, Egypt. A cohort of 140 eligible women was randomized to receive either letrozole 2.5 mg twice daily for five days, or FSH using a graduated regimen starting with a dose of 75 IU. Treatment was repeated for three months if pregnancy did not occur. There were no significant differences between the two treatments in the cumulative clinical pregnancy rate (30% vs. 34%; p = 0.578), cumulative ovulation rate (47% vs. 57%; p = 0.236), miscarriage rate (9% vs. 4%, p > 0.999) or multiple pregnancy rate (0% and 8%, p = 0.491) but the FSH cycles were 4.8 times more expensive. Letrozole and FSH were both effective in treating women with CC-resistant PCOS but letrozole was more cost effective.Study registration number: NCT02304107.

Letrozole in the extended adjuvant setting: MA.17

PubMed Central

2007-01-01

Relapse after completing adjuvant tamoxifen therapy is a persistent threat for women with hormone-responsive breast cancer. Third-generation aromatase inhibitors, such as letrozole, provide a new option for extended adjuvant hormonal therapy after 5 years of tamoxifen. MA.17 was conducted to determine whether letrozole improves outcome after discontinuation of tamoxifen. Postmenopausal women with hormone receptor-positive breast cancer (N = 5,187) were randomized to letrozole 2.5 mg or placebo once daily for 5 years. At a median follow-up of 30 months, letrozole significantly improved disease-free survival (DFS; P < 0.001), the primary end point, compared with placebo (hazard ratio [HR] for recurrence or contralateral breast cancer 0.58; 95% confidence interval [CI] 0.45, 0.76] P < 0.001). Furthermore, letrozole significantly improved distant DFS (HR = 0.60; 95% CI 0.43, 0.84; P = 0.002) and, in women with node-positive tumors, overall survival (HR = 0.61; 95% CI 0.38, 0.98; P = 0.04). Clinical benefits, including an overall survival advantage, were also seen in women who crossed over from placebo to letrozole after unblinding, indicating that tumors remain sensitive to hormone therapy despite a prolonged period since discontinuation of tamoxifen. The efficacy and safety of letrozole therapy beyond 5 years is being assessed in a re-randomization study, following the emergence of new data suggesting that clinical benefit correlates with the duration of letrozole. MA.17 showed that letrozole is extremely well-tolerated relative to placebo. Letrozole should be considered for all women completing tamoxifen; new results from the post-unblinding analysis suggest that letrozole treatment should also be considered for all disease-free women for periods up to 5 years following completion of adjuvant tamoxifen. PMID:17912635

Clomiphene Citrate versus Letrozole for Ovarian Stimulation in Therapeutic Donor Sperm Insemination.

PubMed

El Hachem, Hady; Antaki, Roland; Sylvestre, Camille; Kadoch, Isaac-Jacques; Lapensée, Louise; Bouet, Pierre Emmanuel

2017-01-01

To compare clomiphene citrate (CC) and letrozole for ovarian stimulation (OS) in therapeutic donor sperm insemination (TDI) cycles. Retrospective cohort study between January 2011 and June 2014 at a University-affiliated private IVF clinic in Montreal, Canada. 257 normo-ovulatory women ≤40 years of age with no history of infertility undergoing 590 TDI cycles in the absence of a male partner (single women and same-sex couples) or azoospermia were included. Patients received 100 mg CC daily (145 women, 321 cycles) or letrozole 5 mg daily (112 women, 269 cycles), from days 3 to 7. Only the first 3 cycles were included per patient. Our main outcome measure was cumulative live birth rates (LBR). Baseline characteristics were comparable between the 2 groups. There were no differences in LBR per cycle (16.5% (53/321) vs. 11.5% (31/269), p = 0.08) and cumulative LBR (36.6% (53/145) vs. 27.7% (31/112), p = 0.13), between CC and letrozole, respectively. Multiple pregnancy rate (11.6% (8/69) vs. 8.7% (4/46), p = 0.6) and miscarriage rate (21.7 vs. 21.7%, p = 1) were also comparable between CC and letrozole, respectively. In normo-ovulatory women undergoing TDI, OS with CC or letrozole resulted in similar live birth and twin pregnancy rates. © 2016 S. Karger AG, Basel.

The effects of letrozole and clomiphene citrate on ligands expression of Wnt3, Wnt7a, and Wnt8b in proliferative endometrium of women with Polycystic ovarian syndrome.

PubMed

Mehdinejadiani, Shayesteh; Amidi, Fardin; Mehdizadeh, Mehdi; Barati, Mahmood; Safdarian, Leili; Aflatoonian, Reza; Alyasin, Ashraf; Aghahosseini, Marzieh; Pazhohan, Azar; Hayat, Parisa; Mohammadzadeh Kazorgah, Farzaneh; Sobhani, Aligholi

2018-03-06

Polycystic ovarian syndrome (PCOS) is a common endocrinologic disorder in women of reproductive age characterized by polycystic ovaries, oligo/anovulation, and hyperandrogenism. Not only anovulation but also endometrial dysfunction can reduce fertility in PCOS patients. Wnt pathway is responsible for endometrial proliferation which be strongly regulated by estradiol. To determine the effects of clomiphene citrate (CC) and letrozole, we measured the expression of some main ligands of Wnt/β-catenin signaling including Wnt7a, Wnt3, and Wnt8b in the endometrial samples taken from PCOS women on day 12 of the menses who received 100 mg CC or 5 mg letrozole as well as from women without treatment. Significantly, the mean estrogen and progesterone concentration were lower and higher, respectively, in letrozole than CC. The mean endometrial thickness (ET) was significantly greater in letrozole compared to CC. Assessment of the mRNA and protein expression of Wnt7a, Wnt3, and Wnt8b showed significantly lower expression in CC than the letrozole and control groups. Collectively, letrozole provided a better molecular response in the endometrium of PCOS patients during the proliferative phase, similar to natural cycles, compared to CC. CC decreased the ligands expression of Wnt3, Wnt7a, and Wnt8b, resulting in endometrial dysfunction.

Letrozole in advanced breast cancer: the PO25 trial

PubMed Central

2007-01-01

Tamoxifen has been a standard first-line endocrine therapy for post-menopausal women with hormone-responsive advanced breast cancer, but more than half of patients fail to respond and time to progression is less than 12 months in responders. The third-generation aromatase inhibitors were developed to provide more effective alternatives to tamoxifen. In the Femara Study PO25, post-menopausal women with advanced breast cancer were randomized to receive letrozole 2.5 mg (n = 453) or tamoxifen 20 mg (n = 454) given orally daily until progressive disease occurred. Patients were permitted to cross over to the other treatment at progression. In the primary efficacy analysis, median time to progression (TTP) was significantly longer with letrozole than with tamoxifen (9.4 months vs. 6.0 months, respectively; P < 0.0001). The objective response rate (ORR) was significantly higher for letrozole than for tamoxifen (32% vs. 21%; P = 0.0002). Prospectively planned analyses of the intent-to-treat population showed that letrozole significantly improved overall survival (OS) compared with tamoxifen over the first 24 months of the trial. An exploratory analysis of patients, who did not cross over, indicated a median OS benefit of 14 months for letrozole compared with tamoxifen. Letrozole is the only third-generation aromatase inhibitor that has demonstrated significant improvements in ORR, TTP, and early OS. PMID:17333340

A comparison of the efficacy of two doses of letrozole alone or with continuous recombinant follicle-stimulating hormone for ovulation induction in anovulatory women.

PubMed

Wang, Hai-Yan; Zheng, Peng-Sheng

2015-01-01

To determine the efficacy of letrozole alone or with recombinant follicle-stimulating hormone (rFSH) for ovarian induction in anovulatory women. A total of 322 patients undergoing intrauterine insemination (IUI) were included in this retrospective study. Letrozole (2.5 or 5.0 mg) was administered from days 5 to 9 of menses, alone or followed with rFSH started on day 9 until the day of human chorionic gonadotropin administration. A single IUI was performed 24 h after ovulation. The number of follicles, endometrial thickness and serum estradiol levels were significantly higher in the letrozole + rFSH groups than in the letrozole-alone groups (p < 0.05), but no significant difference was found between the two doses of letrozole, whether alone or with rFSH. Women treated with 5.0 mg/day of letrozole + rFSH required a total dose of rFSH similar to women treated with 2.5 mg/day of letrozole + rFSH (230.77 ± 118.29 vs. 258.55 ± 130.13 IU, respectively; p = 0.205). There was no significant difference in pregnancy rates between the two doses of letrozole, whether alone or with rFSH. Treatment with letrozole + rFSH was more efficacious than letrozole alone for pregnancy in the IUI program; however, the effect of 5.0 mg/day of letrozole versus 2.5 mg/day of letrozole on ovulation was equivalent, regardless of whether rFSH was used. © 2014 S. Karger AG, Basel.

Letrozole, Gonadotropin, or Clomiphene for Unexplained Infertility.

PubMed

Diamond, Michael P; Legro, Richard S; Coutifaris, Christos; Alvero, Ruben; Robinson, Randal D; Casson, Peter; Christman, Gregory M; Ager, Joel; Huang, Hao; Hansen, Karl R; Baker, Valerie; Usadi, Rebecca; Seungdamrong, Aimee; Bates, G Wright; Rosen, R Mitchell; Haisenleder, Daniel; Krawetz, Stephen A; Barnhart, Kurt; Trussell, J C; Ohl, Dana; Jin, Yufeng; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping

2015-09-24

The standard therapy for women with unexplained infertility is gonadotropin or clomiphene citrate. Ovarian stimulation with letrozole has been proposed to reduce multiple gestations while maintaining live birth rates. We enrolled couples with unexplained infertility in a multicenter, randomized trial. Ovulatory women 18 to 40 years of age with at least one patent fallopian tube were randomly assigned to ovarian stimulation (up to four cycles) with gonadotropin (301 women), clomiphene (300), or letrozole (299). The primary outcome was the rate of multiple gestations among women with clinical pregnancies. After treatment with gonadotropin, clomiphene, or letrozole, clinical pregnancies occurred in 35.5%, 28.3%, and 22.4% of cycles, and live birth in 32.2%, 23.3%, and 18.7%, respectively; pregnancy rates with letrozole were significantly lower than the rates with standard therapy (gonadotropin or clomiphene) (P=0.003) or gonadotropin alone (P<0.001) but not with clomiphene alone (P=0.10). Among ongoing pregnancies with fetal heart activity, the multiple gestation rate with letrozole (9 of 67 pregnancies, 13%) did not differ significantly from the rate with gonadotropin or clomiphene (42 of 192, 22%; P=0.15) or clomiphene alone (8 of 85, 9%; P=0.44) but was lower than the rate with gonadotropin alone (34 of 107, 32%; P=0.006). All multiple gestations in the clomiphene and letrozole groups were twins, whereas gonadotropin treatment resulted in 24 twin and 10 triplet gestations. There were no significant differences among groups in the frequencies of congenital anomalies or major fetal and neonatal complications. In women with unexplained infertility, ovarian stimulation with letrozole resulted in a significantly lower frequency of multiple gestation but also a lower frequency of live birth, as compared with gonadotropin but not as compared with clomiphene. (Funded by the National Institutes of Health and others; ClinicalTrials.gov number, NCT01044862.).

Clomiphene citrate versus letrozole with gonadotropins in intrauterine insemination cycles: A randomized trial.

PubMed

Pourali, Leila; Ayati, Sedigheh; Tavakolizadeh, Shirin; Soleimani, Hourieh; Teimouri Sani, Fatemeh

2017-01-01

Clomiphene citrate is one of the effective drugs for infertility treatment due to oligo-ovulation or anovulation. Intrauterine insemination (IUI) is one of more adherent methods for treatment of infertile cases which is followed by controlled ovarian hyperstimulation (COH). the aim of this study was to evaluate Clomiphene citrate versus letrozole with gonadotropins in IUI cycles. In this prospective randomized trial, 180 infertile women who were referred to Milad Hospital were selected. The first group received 5 mg/day letrozole on day 3-7 of menstrual cycle. The second group received 100 mg/day Clomiphene in the same way as letrozole. In both groups, human menopausal gonadotropin was administered every day starting on day between 6-8 of cycle. Ovulation was triggered with urinary Human Chorionic Gonadotropin (5000 IU) when have two follicles of ≥16 mm. IUI was performed 36 hr later. The number of matured follicles, cycle cancellation, and abortion were the same in both groups. Endometrial thickness was higher at the time of human menopausal gonadotropin administration in letrozole group. Chemical and clinical pregnancy rates were much higher in letrozole group. Ovarian hyperstimulation was significantly higher in clomiphene group. Letrozole appears to be a good alternative to clomiphene citrate with fewer side effects.

Letrozole and norethisterone acetate versus letrozole and triptorelin in the treatment of endometriosis related pain symptoms: a randomized controlled trial

PubMed Central

2011-01-01

Background When aromatase inhibitors are used to treat premenopausal women with endometriosis, additional drugs should be used to effectively down-regulate gonadal estrogen biosynthesis. This randomized prospective open-label study compared the efficacy in treating pain symptoms and the tolerability of letrozole combined with either norethisterone acetate or triptorelin. Methods Women with pain symptoms caused by rectovaginal endometriosis were treated with letrozole (2.5 mg/day) and were randomized to also receive either oral norethisterone acetate (2.5 mg/day; group N) or intramuscular injection of triptorelin (11.25 mg every 3 months; group T). The scheduled length of treatment was 6 months. A visual analogue scale and a multidimensional categorical rating scale were used to assess the severity of pain symptoms. The volume of the endometriotic nodules was estimated by ultrasonography using virtual organ computer-aided analysis. Adverse effects of treatment were recorded. Results A total of 35 women were randomized between the two treatment protocols. Significantly more patients in group N rated their treatment as satisfactory or very satisfactory (64.7%) as compared to group T (22.2%; p = 0.028). The intensity of both non-menstrual pelvic pain and deep dyspareunia significantly decreased during treatment in both study groups, though no statistically meaningful difference between the two groups was apparent. Reduction in the volume of endometriotic nodules was significantly greater in group T than in group N. Interruption of treatment due to adverse effects significantly differed between the groups, with 8 women in group T (44.4%) and 1 woman in group N (5.9%) interrupting treatment (p = 0.018). Similarly, 14 women included in group T (77.8%) and 6 women included in group N (35.3%) experienced adverse effects of treatment (p = 0.018). During treatment, mineral bone density significantly decreased in group T but not in group N. Conclusions Aromatase inhibitors

Letrozole and norethisterone acetate versus letrozole and triptorelin in the treatment of endometriosis related pain symptoms: a randomized controlled trial.

PubMed

Ferrero, Simone; Venturini, Pier L; Gillott, David J; Remorgida, Valentino

2011-06-21

When aromatase inhibitors are used to treat premenopausal women with endometriosis, additional drugs should be used to effectively down-regulate gonadal estrogen biosynthesis. This randomized prospective open-label study compared the efficacy in treating pain symptoms and the tolerability of letrozole combined with either norethisterone acetate or triptorelin. Women with pain symptoms caused by rectovaginal endometriosis were treated with letrozole (2.5 mg/day) and were randomized to also receive either oral norethisterone acetate (2.5 mg/day; group N) or intramuscular injection of triptorelin (11.25 mg every 3 months; group T). The scheduled length of treatment was 6 months. A visual analogue scale and a multidimensional categorical rating scale were used to assess the severity of pain symptoms. The volume of the endometriotic nodules was estimated by ultrasonography using virtual organ computer-aided analysis. Adverse effects of treatment were recorded. A total of 35 women were randomized between the two treatment protocols. Significantly more patients in group N rated their treatment as satisfactory or very satisfactory (64.7%) as compared to group T (22.2%; p=0.028). The intensity of both non-menstrual pelvic pain and deep dyspareunia significantly decreased during treatment in both study groups, though no statistically meaningful difference between the two groups was apparent. Reduction in the volume of endometriotic nodules was significantly greater in group T than in group N. Interruption of treatment due to adverse effects significantly differed between the groups, with 8 women in group T (44.4%) and 1 woman in group N (5.9%) interrupting treatment (p=0.018). Similarly, 14 women included in group T (77.8%) and 6 women included in group N (35.3%) experienced adverse effects of treatment (p=0.018). During treatment, mineral bone density significantly decreased in group T but not in group N. Aromatase inhibitors reduce the intensity of endometriosis

Investigation of herb-drug interactions with ginkgo biloba in women receiving hormonal treatment for early breast cancer.

PubMed

Vardy, Janette; Dhillon, Haryana M; Clarke, Stephen J; Olesen, Inger; Leslie, Felicity; Warby, Anne; Beith, Jane; Sullivan, Anne; Hamilton, Anne; Beale, Philip; Rittau, Anneliese; McLachlan, Andrew J

2013-12-01

Women receiving treatment for breast cancer commonly ingest herbal medicines. Little is known about the potential for herb-drug interactions in this population. The aim of this study is to investigate the effect of ginkgo biloba co-administration on the pharmacokinetics of tamoxifen, anastrozole and letrozole. This was a prospective open-label cross-over study in 60 women with early stage breast cancer taking either tamoxifen, anastrozole or letrozole (n=20/group). Participants received ginkgo biloba (EGb 761) for 3 weeks (120 mg twice daily). Trough concentrations of drugs were measured before and after ginkgo biloba treatment using LC-MS/MS. Toxicities were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events. Trough concentrations before and after treatment with ginkgo biloba were not significantly different for tamoxifen (93.5 ± 29.0, 86.5 ± 25.3 ng/mL; p=0.16), letrozole (91.1 ± 50.4, 89.6 ± 52.14 ng/mL; p=0.60) or anastrozole (29.1 ± 8.6, 29.1 ± 7.6 ng/mL; p=0.97). Ginkgo biloba was well tolerated, with no difference in toxicity during ginkgo biloba. Co-administration of ginkgo biloba does not significantly affect the pharmacokinetics of tamoxifen, anastrozole or letrozole. There was no difference in the toxicity profile of hormone therapy with ginkgo biloba use in women with early stage breast cancer.

The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause.

PubMed

Chirgwin, Jacquie; Sun, Zhuoxin; Smith, Ian; Price, Karen N; Thürlimann, Beat; Ejlertsen, Bent; Bonnefoi, Hervé; Regan, Meredith M; Goldhirsch, Aron; Coates, Alan S

2012-01-01

Letrozole, an aromatase inhibitor, is ineffective in the presence of ovarian estrogen production. Two subpopulations of apparently postmenopausal women might derive reduced benefit from letrozole due to residual or returning ovarian activity: younger women (who have the potential for residual subclinical ovarian estrogen production), and those with chemotherapy-induced menopause who may experience return of ovarian function. In these situations tamoxifen may be preferable to an aromatase inhibitor. Among 4,922 patients allocated to the monotherapy arms (5 years of letrozole or tamoxifen) in the BIG 1-98 trial we identified two relevant subpopulations: patients with potential residual ovarian function, defined as having natural menopause, treated without adjuvant or neoadjuvant chemotherapy and age ≤ 55 years (n = 641); and those with chemotherapy-induced menopause (n = 105). Neither of the subpopulations examined showed treatment effects differing from the trial population as a whole (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the 641 patients aged ≤ 55 years with natural menopause and no chemotherapy (HR 0.77 [0.51, 1.16]) and among the 105 patients with chemotherapy-induced menopause (HR 0.51 [0.19, 1.39]), the disease-free survival (DFS) point estimate favoring letrozole was marginally more beneficial than in the trial as a whole (HR 0.84 [0.74, 0.95]). Contrary to our initial concern, DFS results for young postmenopausal patients who did not receive chemotherapy and patients with chemotherapy-induced menopause parallel the letrozole benefit seen in the BIG 1-98 population as a whole. These data support the use of letrozole even in such patients.

The advantage of letrozole over tamoxifen in the BIG 1-98 trial is consistent in younger postmenopausal women and in those with chemotherapy-induced menopause

PubMed Central

Sun, Zhuoxin; Smith, Ian; Price, Karen N.; Thürlimann, Beat; Ejlertsen, Bent; Bonnefoi, Hervé; Regan, Meredith M.; Goldhirsch, Aron; Coates, Alan S.

2016-01-01

Letrozole, an aromatase inhibitor, is ineffective in the presence of ovarian estrogen production. Two subpopulations of apparently postmenopausal women might derive reduced benefit from letrozole due to residual or returning ovarian activity: younger women (who have the potential for residual subclinical ovarian estrogen production), and those with chemotherapy-induced menopause who may experience return of ovarian function. In these situations tamoxifen may be preferable to an aromatase inhibitor. Among 4,922 patients allocated to the monotherapy arms (5 years of letrozole or tamoxifen) in the BIG 1-98 trial we identified two relevant subpopulations: patients with potential residual ovarian function, defined as having natural menopause, treated without adjuvant or neoadjuvant chemotherapy and age ≤55 years (n = 641); and those with chemotherapy-induced menopause (n = 105). Neither of the subpopulations examined showed treatment effects differing from the trial population as a whole (interaction P values are 0.23 and 0.62, respectively). Indeed, both among the 641 patients aged ≤55 years with natural menopause and no chemotherapy (HR 0.77 [0.51, 1.16]) and among the 105 patients with chemotherapy-induced menopause (HR 0.51 [0.19, 1.39]), the disease-free survival (DFS) point estimate favoring letrozole was marginally more beneficial than in the trial as a whole (HR 0.84 [0.74, 0.95]). Contrary to our initial concern, DFS results for young postmenopausal patients who did not receive chemotherapy and patients with chemotherapy-induced menopause parallel the letrozole benefit seen in the BIG 1-98 population as a whole. These data support the use of letrozole even in such patients. PMID:21892704

Letrozole pretreatment prior to medical termination of pregnancy: a systematic review.

PubMed

Nash, Christopher M; Philp, Lauren; Shah, Prakesh; Murphy, Kellie E

2018-06-01

The purpose of this systematic review was to evaluate the efficacy of pretreatment with letrozole prior to either a first- or second-trimester medical termination of pregnancy. We searched letrozole, femara, aromatase inhibitors, abortifacient agents, termination of pregnancy and labor induction in MEDLINE, EMBASE, Cochrane Database, Google Scholar and PubMed from inception of each database until September 2015 with no language limitation. A systematic review of all randomized controlled trials (RCTs) was performed where women received either letrozole and misoprostol or placebo and misoprostol for termination of pregnancy. The primary outcome was complete abortion rate, defined as complete evacuation of the products of conception from the uterus. Relative risk with 95% confidence intervals was used to report data. Our systematic review identified 7 studies; 4 RCTs were included in the review. Two RCTs evaluated terminations of pregnancy up to 9 weeks' gestation, while 2 evaluated terminations over 9 weeks' gestation. For each gestational age group, one trial supported an increase in complete abortion rate, while the other showed no difference, with letrozole and misoprostol compared with placebo and misoprostol. Time-to-abortion interval for terminations up to 9 weeks' gestation was not improved with the addition of letrozole to misoprostol. For terminations over 9 weeks' gestation, one trial supported and one trial refuted a decrease in time-to-abortion interval with letrozole and misoprostol. Similarly, for each gestational age group, one study supported a decrease and one study showed no difference in rate of dilation and curettage (D&C) with letrozole and misoprosol. Medication side effects were similar between both treatment groups. There was significant heterogeneity between the trials, and therefore, the results were not meta-analyzed. Some studies and trials report better outcomes (i.e., complete abortion rates, time-to-abortion and D&C rates) in women

Randomized controlled trial of letrozole, berberine, or a combination for infertility in the polycystic ovary syndrome.

PubMed

Wu, Xiao-Ke; Wang, Yong-Yan; Liu, Jian-Ping; Liang, Rui-Ning; Xue, Hui-Ying; Ma, Hong-Xia; Shao, Xiao-Guang; Ng, Ernest H Y

2016-09-01

To study whether a combination of berberine and letrozole results in higher live births than letrozole alone in infertile women with polycystic ovary syndrome (PCOS). A multicenter randomized double-blinded placebo-controlled trial. Reproductive and developmental network sites. Eligible women had PCOS as defined by the Rotterdam criteria. We enrolled 644 participants randomized 1:1:1 among letrozole, berberine, and combination groups. Berberine or berberine placebo were administrated orally at a daily dose of 1.5 g for up to 6 months. Patients received an initial dose of 2.5 mg letrozole or placebo on days 3-7 of the first three treatment cycles. This dose was increased to 5 mg on the last three cycles if not pregnant. Cumulative live births. The cumulative live births were similar between the letrozole and combination groups after treatment (36% and 34%), and were superior to those in the berberine group (22%). Likely, conception, pregnancy, and ovulation rates were similar between the letrozole and combination groups, and these were significantly higher than in the berberine group. There was one twin birth in the letrozole group, three twin births in the combination group, and none in the berberine group. Berberine did not add fecundity in PCOS when used in combination with the new ovulation agent letrozole. ChiCTR-TRC-09000376 (http://apps.who.int/trialsearch/). Copyright © 2016. Published by Elsevier Inc.

Letrozole as upfront endocrine therapy for postmenopausal women with hormone-sensitive breast cancer: BIG 1-98

PubMed Central

Thuerlimann, Beat

2007-01-01

The BIG 1-98 trial is a large, randomized, independently conducted clinical trial designed to compare the efficacy of upfront letrozole versus tamoxifen monotherapy and to compare sequential or up-front use of letrozole and/or tamoxifen as an early adjuvant therapy for patients with early breast cancer. We report on the results from the primary core analysis of the BIG 1-98 trial of 8,010 patients, which compares monotherapy with letrozole versus tamoxifen. This pre-planned core analysis allowed the use of patient data from the monotherapy arms of letrozole and tamoxifen and from the sequential arms prior to the drug switch point. Patients randomized to letrozole had a 19% improved disease-free survival (hazard ratio [HR] = 0.81; P = 0.003), due especially to reduced distant metastases (HR = 0.73; P = 0.001). A 14% risk reduction of fatal events in favor of letrozole was also observed (P = NS). The results from the monotherapy arms alone confirmed the findings from the primary core analysis. Based on the results from this trial, the aromatase inhibitor letrozole (Femara®) is currently recommended as a part of standard adjuvant therapy for postmenopausal women with endocrine-responsive breast cancer and has recently been approved in the early adjuvant setting in both Europe and the United States. A subsequent analysis after additional follow-up will address the question of monotherapy versus sequential therapy. PMID:17912636

Letrozole vs. Placebo Pretreatment in the Medical Management of First Trimester Missed Miscarriage: a Randomized Controlled Trial.

PubMed

Torky, Haitham A; Marie, Heba; ElDesouky, ElSayed; Gebreel, Samy; Raslan, Osama; Moussa, Asem A; Ahmad, Ali M; Zain, Eman; Mohsen, Mohamed N

2018-01-01

Misoprostol is used for the medical management of miscarriage as it is more effective in the early stages of pregnancy. Letrozole has an anti-estrogen effect and is used for the pretreatment of miscarriage with misoprostol. The aim of this study was compare the efficacy and safety of letrozole with placebo pretreatment in the medical management of first trimester missed miscarriage. This was a prospective randomized case-control study. Four hundred and thirty-eight women were randomly divided into two groups of 219; the placebo group received placebo tablets twice daily for 3 days, followed by 800 micrograms of misoprostol vaginally on the fourth day of enrolment, while the letrozole group received letrozole 10 mg twice daily for three days followed by 800 micrograms misoprostol administered vaginally. Symptoms and side effects were recorded, and the women advised to return to hospital if they experienced severe pain or bleeding or intolerable side effects and to report to hospital for a check-up one week after misoprostol administration. Ultrasound was done seven days after misoprostol administration to monitor outcomes. Surgical evacuation was carried out if medical management failed. There were significant differences between the two groups, with better outcomes found for the letrozole group in terms of rates of complete miscarriage, onset of vaginal bleeding, and interval between induction and onset of expulsion (p < 0.001). A higher rate of nausea and vomiting was reported for the letrozole group (p = 0.002). Differences between groups with regard to pre- and post-termination hemoglobin levels, fever, severe pain and severe bleeding needing evacuation were not statistically significant. Adding letrozole to misoprostol improves the success rate and decreases the interval between induction and expulsion in cases of first trimester miscarriage; however, nausea and vomiting is higher with letrozole.

Effect of letrozole on moderate and severe early-onset ovarian hyperstimulation syndrome in high-risk women: a prospective randomized trial.

PubMed

Mai, Qingyun; Hu, Xiaokun; Yang, Gang; Luo, Yingyi; Huang, Kejun; Yuan, Yuan; Zhou, Canquan

2017-01-01

Ovarian hyperstimulation syndrome is an iatrogenic complication of controlled ovarian stimulation. Early ovarian hyperstimulation syndrome occurs during luteal phase of controlled ovarian stimulation within 9 days after human chorionic gonadotropin trigger and reflects an acute consequence of this hormone on the ovaries. Late ovarian hyperstimulation syndrome occurs 10 or more days after human chorionic gonadotropin trigger and reflects increased endogenous human chorionic gonadotropin levels following pregnancy. Human chorionic gonadotropin stimulates granulosa-lutein cells to produce vascular endothelial growth factor messenger RNAs, which in turn raises serum vascular endothelial growth factor concentration and increases vascular permeability in women with ovarian hyperstimulation syndrome. Efforts to reduce the incidence and severity of ovarian hyperstimulation syndrome after oocyte retrieval, and in particular primary prevention efforts, are vital to prevent thrombogenesis and other serious complications. The objective of the study was to compare the efficacy of letrozole, an aromatase inhibitor, with aspirin in primary prevention of early ovarian hyperstimulation syndrome and to compare vascular endothelial growth factor levels between groups. Participants in this prospective randomized trial included 238 participants undergoing cryopreservation of the whole embryos after oocyte retrieval with at least 1 of the following high-risk factors for ovarian hyperstimulation syndrome: oocyte retrieval ≥25; estradiol level ≥5000 pg/mL on the day of human chorionic gonadotropin administration; and clinical or ultrasonographic evidence of ovarian hyperstimulation syndrome on the day of oocyte retrieval, such as ultrasonographic evidence of ascites. After human chorionic gonadotropin triggering, experimental (119 cases) and control (119 cases) groups received letrozole and aspirin, respectively, for 5 days. The 5 categories of ovarian hyperstimulation syndrome

Ribociclib plus letrozole versus letrozole alone in patients with de novo HR+, HER2- advanced breast cancer in the randomized MONALEESA-2 trial.

PubMed

O'Shaughnessy, Joyce; Petrakova, Katarina; Sonke, Gabe S; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Hart, Lowell L; Villanueva, Cristian; Jakobsen, Erik; Beck, Joseph T; Lindquist, Deborah; Souami, Farida; Mondal, Shoubhik; Germa, Caroline; Hortobagyi, Gabriel N

2018-02-01

Determine the efficacy and safety of first-line ribociclib plus letrozole in patients with de novo advanced breast cancer. Postmenopausal women with HR+ , HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021). Patients were randomized to ribociclib (600 mg/day; 3 weeks-on/1 week-off) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was investigator-assessed progression-free survival; predefined subgroup analysis evaluated progression-free survival in patients with de novo advanced breast cancer. Secondary endpoints included safety and overall response rate. Six hundred and sixty-eight patients were enrolled, of whom 227 patients (34%; ribociclib plus letrozole vs placebo plus letrozole arm: n = 114 vs. n = 113) presented with de novo advanced breast cancer. Median progression-free survival was not reached in the ribociclib plus letrozole arm versus 16.4 months in the placebo plus letrozole arm in patients with de novo advanced breast cancer (hazard ratio 0.45, 95% confidence interval 0.27-0.75). The most common Grade 3/4 adverse events were neutropenia and leukopenia; incidence rates were similar to those observed in the full MONALEESA-2 population. Ribociclib dose interruptions and reductions in patients with de novo disease occurred at similar frequencies to the overall study population. Ribociclib plus letrozole improved progression-free survival vs placebo plus letrozole and was well tolerated in postmenopausal women with HR+, HER2- de novo advanced breast cancer.

Comparison of acupuncture pretreatment followed by letrozole versus letrozole alone on live birth in anovulatory infertile women with polycystic ovary syndrome: a study protocol for a randomised controlled trial

PubMed Central

Li, Juan; Ng, Ernest Hung Yu; Stener-Victorin, Elisabet; Hu, Zhenxing; Wu, Wanting; Lai, Maohua; Wu, Taixiang; Ma, Hongxia

2016-01-01

Introduction The high prevalence of insulin resistance in women with polycystic ovary syndrome (PCOS) is considered to be one of the major pathophysiological changes in PCOS that leads to anovulatory infertility. We hypothesise that electroacupuncture pretreatment improves insulin sensitivity and leads to a higher ovulation rate and greater chances of live birth after the induction of ovulation. The effect of electroacupuncture pretreatment followed by ovulation induction in women with anovulatory PCOS has not been investigated before, and we present here a randomised controlled trial to test this hypothesis by comparing electroacupuncture pretreatment followed by letrozole versus letrozole alone in anovulatory women with PCOS. Methods/analysis This is a multicentre, randomised,and controlled trial. A total of 384 patients will be enrolled in this study and will be randomly allocated by a central randomisation system to the treatment group or the control group in a 1:1 ratio. The treatment group will undergo 16 weeks of electroacupuncture pretreatment followed by 4 cycles of letrozole, and the control group will only undergo 4 cycles of letrozole. The primary outcome will be the live birth rate. All statistical analyses will be performed using the SPSS program V.21.0 (SPSS, Chicago, Illinois, USA), and a p value <0.05 will be considered statistically significant. Ethics/dissemination This study has been approved by the ethics committees of each participating centre. Written consent will be obtained from each patient and her husband before any study procedure is performed. Adverse events will be categorised, and the percentage of patients experiencing adverse events or serious adverse events during the treatment period will be documented. The results of this trial will be disseminated in peer-reviewed journals and presented at international meetings. Trial registration number NCT02491333. PMID:27855085

Randomized trial of a telephone-based weight loss intervention in postmenopausal women with breast cancer receiving letrozole: the LISA trial.

PubMed

Goodwin, Pamela J; Segal, Roanne J; Vallis, Michael; Ligibel, Jennifer A; Pond, Gregory R; Robidoux, André; Blackburn, George L; Findlay, Brian; Gralow, Julie R; Mukherjee, Som; Levine, Mark; Pritchard, Kathleen I

2014-07-20

Obesity is associated with poor outcomes in women with operable breast cancer. Lifestyle interventions (LIs) that help women reduce their weight may improve outcomes. We conducted a multicenter randomized trial comparing mail-based delivery of general health information alone or combined with a 24-month standardized, telephone-based LI that included diet (500 to 1,000 kcal per day deficit) and physical activity (150 to 200 minutes of moderate-intensity physical activity per week) goals to achieve weight loss (up to 10%). Women receiving adjuvant letrozole for T1-3N0-3M0 breast cancer with a body mass index (BMI) ≥ 24 kg/m(2) were eligible. Weight was measured in the clinic, and self-report physical activity, quality-of-life (QOL), and diet questionnaires were completed. The primary outcome was disease-free survival. Accrual was terminated at 338 of 2,150 planned patients because of loss of funding. Mean weight loss was significantly (P < .001) greater in the LI arm versus the comparison arm (4.3 v 0.6 kg or 5.3% v 0.7% at 6 months and 3.1 v 0.3 kg or 3.6% v 0.4% at 24 months) and occurred consistently across strata (BMI 24 to < 30 v ≥ 30 kg/m(2); prior v no prior adjuvant chemotherapy). Weight loss was greatest in those with higher baseline levels of moderate-intensity physical activity or improvement in QOL. Hospitalization rates and medical events were similar. A telephone-based LI led to significant weight loss that was still evident at 24 months, without adverse effects on QOL, hospitalizations, or medical events. Adequately powered randomized trials with cancer end points are needed. © 2014 by American Society of Clinical Oncology.

Combined letrozole and clomiphene versus letrozole and clomiphene alone in infertile patients with polycystic ovary syndrome.

PubMed

Hajishafiha, Masomeh; Dehghan, Meisam; Kiarang, Nazila; Sadegh-Asadi, Nahideh; Shayegh, Seyed Navid; Ghasemi-Rad, Mohammad

2013-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age (6.8%-18%), is among the most common causes of infertility due to ovulation factors, and accounts for 55%-70% of infertility cases caused by chronic anovulation. In this study, we used a combination of letrozole and clomiphene in patients resistant to both drugs individually, and studied the effects of this combination in ovulation and pregnancy in resistant PCOS patients. The study population included infertile couples diagnosed as PCOS in the wife. The women used clomiphene for at least six cycles in order to ovulate after failure to form the dominant follicle, and were then put on letrozole for four cycles. Patients who were unable to form the dominant follicle were enrolled on letrozole and clomiphene combination therapy. One hundred enrolled patients underwent 257 cycles of a combination of letrozole and clomiphene, in which 213 were able to form the dominant follicle (82.9%) and 44 were unable to do so (17.1%). The number of mature follicles was 2.3±1.1. The mean endometrial thickness in patients on the day of human chorionic gonadotropin administration was 8.17±1.3 mm. The pregnancy rate was 42%. According to the results of this study, it can be proposed that in PCOS patients resistant to clomiphene and letrozole used as single agents, a combination of the two drugs can be administered before using more aggressive treatment that may have severe complications or surgery. This combination may also be used as a first-line therapy to induce ovulation in severe cases of PCOS in order to save time and expense.

Comparison of the pregnancy outcomes and the incidence of fetal congenital abnormalities in infertile women treated with letrozole and clomiphene citrate.

PubMed

Akbari Sene, Azadeh; Ghorbani, Selma; Ashrafi, Mahnaz

2018-06-01

The aim of the study was to evaluate the incidence of congenital fetal anomalies reported among infertile Iranian women treated with letrozole compared to those treated with Clomiphene Citrate (CC). This retrospective case-control study was performed based on information available from infertile patients referred to the Akbar-Abadi Hospital IVF Center, Tehran, Iran, undergoing ovulation induction (OI) or intrauterine insemination (IUI) cycles from 2007 to 2014.We compared sonographic findings, fertility results, pregnancy complications and congenital anomalies in two groups of women treated with letrozole and CC. Overall, the results of the 2009 cycles including 1237 CC cycles and 772 letrozole cycles were evaluated. In spite of a higher chance of ovulation following CC treatment, overall fertility rates were similar in the two treatment groups. The frequency of adverse outcomes of pregnancy was similar in the two groups, except for the incidence of first trimester abortion, which was significantly higher in the CC-treated group. The frequency of fetal anomalies and major chromosomal abnormalities in the Letrozole group was 4.76% (five cases), and in the CC group, it was 2.12% (three cases). This difference was not statistically significant. Based on the findings of this study, it seems that the incidence of congenital anomalies in offspring after OI with letrozole is not increased compared to the CC group. © 2018 Japan Society of Obstetrics and Gynecology.

Letrozole versus clomiphene citrate for unexplained infertility: a systematic review and meta-analysis.

PubMed

Liu, Aihai; Zheng, Chao; Lang, Junzhe; Chen, Wenbing

2014-05-01

The objective of this study is to investigate and compare the effectiveness of letrozole and clomiphene citrate for improving fertility outcomes, including pregnancy rate, miscarriage rate, multiple pregnancy rate, and incidence rate of adverse events, number of dominant follicles, endometrial thickness at hCG day and serum E2 on hCG day. MEDLINE, EMBASE, CENTRAL, CNKI and CBMdisc databases were searched up to March 2013. Randomized controlled trials comparing letrozole with clomiphene in women with unexplained infertility were included. Pooled relative risk, mean difference and 95% confidence intervals were calculated. We found that there are no differences in pregnancy, miscarriage and multiple pregnancy rates, incidence rate of adverse events, number of dominant follicles (>18 mm) and endometrial thickness at hCG day in women with unexplained infertility between letrozole and clomiphene regimens. The mean (±standard deviation) concentration of serum E2 on hCG day was lower in those treated with letrozole than those with clomiphene. The subgroup of 2.5 mg letrozole displayed a statistically significant higher rate of clinical pregnancy as compared with 100 mg of clomiphene. The results of this study conclude that letrozole is as effective as clomiphene in women with unexplained infertility. Letrozole at a dose of 2.5 mg seems more effective. Further high-quality studies assessing the possible effectiveness of letrozole in selected groups of patients are warranted. © 2014 The Authors. Journal of Obstetrics and Gynaecology Research © 2014 Japan Society of Obstetrics and Gynecology.

Letrozole in the neoadjuvant setting: the P024 trial

PubMed Central

Ma, Cynthia

2007-01-01

Neoadjuvant chemotherapy trials have consistently reported lower response rates in hormone receptor-positive (HR+) breast cancer when compared with HR− cases. Preoperative endocrine therapy has therefore become a logical alternative and has gained considerable momentum from the finding that aromatase inhibitors (AIs) are more effective than tamoxifen for HR+ breast cancer in both the neoadjuvant and adjuvant settings. The most convincing neoadjuvant trial to demonstrate the superiority of an AI versus tamoxifen was the P024 study, a large multinational double-blind trial in postmenopausal women with HR+ breast cancer ineligible for breast-conserving surgery. The overall response rate (ORR) was 55% for letrozole and 36% for tamoxifen (P < 0.001). Significantly more letrozole-treated patients underwent breast-conserving surgery (45 vs. 35%, respectively; P = 0.022). In addition, ORR was significantly higher with letrozole than tamoxifen in the human epidermal growth factor receptor HER1/HER2+ subgroup (P = 0.0004). The clinical efficacy of letrozole in HER2+ breast cancer was confirmed by fluorescent in situ hybridization analysis and was found to be comparable to that of HER2− cases (ORR 71% in both subsets). Biomarker studies confirmed the superiority of letrozole in centrally assessed estrogen receptor-positive (ER+) tumors and found a strong relationship with the degree of ER positivity for both agents. Interestingly, letrozole was effective even in marginally ER+ tumors and, unlike tamoxifen, consistently reduced the expression from estrogen-regulated genes (progesterone receptor and trefoil factor 1). Furthermore, when analyzed by Ki67 immunohistochemistry, letrozole was significantly more effective than tamoxifen in reducing tumor proliferation (P = 0.0009). Thus, neoadjuvant letrozole is safe and superior to tamoxifen in the treatment of postmenopausal women with HR+ locally advanced breast cancer. PMID:17912634

The efficacy and safety of neoadjuvant chemotherapy +/- letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial.

PubMed

Mohammadianpanah, Mohammad; Ashouri, Yaghoub; Hoseini, Sare; Amadloo, Niloofar; Talei, Abdolrasoul; Tahmasebi, Sedigheh; Nasrolahi, Hamid; Mosalaei, Ahmad; Omidvari, Shapour; Ansari, Mansour; Mosleh-Shirazi, Mohammad Amin

2012-04-01

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.

SPE-UPLC-MS/MS assay for determination of letrozole in human plasma and its application to bioequivalence study in healthy postmenopausal Indian women.

PubMed

Vanol, Pravin G; Singhal, Puran; Shah, Priyanka A; Shah, Jaivik V; Shrivastav, Pranav S; Sanyal, Mallika

2016-08-01

A rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method is described for determination of letrozole in human plasma. Following solid phase extraction (SPE) of letrozole and letrozole-d4 on Orochem DVB-LP cartridges, chromatography was performed on Acquity UPLC BEH C 18 (50 mm×2.1 mm, 1.7 µm) column using methanol-0.1% formic acid in water (85:15, v/v) as the mobile phase. Detection was carried out on a triple quadrupole mass spectrometer with an electrospray source, operated under positive ionization mode. Quantitation of letrozole and letrozole-d4 was done using multiple reaction monitoring (MRM) following the transitions at m/z 286.2→217.0 and m/z 290.2→221.0, respectively. The calibration plots were linear through the concentration range of 0.10-100 ng/mL ( r 2 ≥0.9990) using 100 µL human plasma. The extraction recovery of letrozole ranged from 94.3% to 96.2% and the intra-batch and inter-batch precision was ≤5.2%. The method was successfully applied to a bioequivalence study of letrozole after oral administration of 2.5 mg tablet formulation to 16 healthy postmenopausal Indian women. The assay reproducibility was also established through incurred sample reanalysis (ISR) of 74 subject samples.

Combined letrozole and clomiphene versus letrozole and clomiphene alone in infertile patients with polycystic ovary syndrome

PubMed Central

Hajishafiha, Masomeh; Dehghan, Meisam; Kiarang, Nazila; Sadegh-Asadi, Nahideh; Shayegh, Seyed Navid; Ghasemi-Rad, Mohammad

2013-01-01

Background Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of childbearing age (6.8%–18%), is among the most common causes of infertility due to ovulation factors, and accounts for 55%–70% of infertility cases caused by chronic anovulation. In this study, we used a combination of letrozole and clomiphene in patients resistant to both drugs individually, and studied the effects of this combination in ovulation and pregnancy in resistant PCOS patients. Methods The study population included infertile couples diagnosed as PCOS in the wife. The women used clomiphene for at least six cycles in order to ovulate after failure to form the dominant follicle, and were then put on letrozole for four cycles. Patients who were unable to form the dominant follicle were enrolled on letrozole and clomiphene combination therapy. Results One hundred enrolled patients underwent 257 cycles of a combination of letrozole and clomiphene, in which 213 were able to form the dominant follicle (82.9%) and 44 were unable to do so (17.1%). The number of mature follicles was 2.3±1.1. The mean endometrial thickness in patients on the day of human chorionic gonadotropin administration was 8.17±1.3 mm. The pregnancy rate was 42%. Conclusion According to the results of this study, it can be proposed that in PCOS patients resistant to clomiphene and letrozole used as single agents, a combination of the two drugs can be administered before using more aggressive treatment that may have severe complications or surgery. This combination may also be used as a first-line therapy to induce ovulation in severe cases of PCOS in order to save time and expense. PMID:24348019

Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial.

PubMed

Rabaglio, M; Sun, Z; Price, K N; Castiglione-Gertsch, M; Hawle, H; Thürlimann, B; Mouridsen, H; Campone, M; Forbes, J F; Paridaens, R J; Colleoni, M; Pienkowski, T; Nogaret, J-M; Láng, I; Smith, I; Gelber, R D; Goldhirsch, A; Coates, A S

2009-09-01

To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients.

Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial

PubMed Central

Rabaglio, M.; Sun, Z.; Castiglione-Gertsch, M.; Hawle, H.; Thürlimann, B.; Mouridsen, H.; Campone, M.; Forbes, J. F.; Paridaens, R. J.; Colleoni, M.; Pienkowski, T.; Nogaret, J.-M.; Láng, I.; Smith, I.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

2009-01-01

Background: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. Methods: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. Results: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. Conclusions: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients. PMID:19474112

Comparison of acupuncture pretreatment followed by letrozole versus letrozole alone on live birth in anovulatory infertile women with polycystic ovary syndrome: a study protocol for a randomised controlled trial.

PubMed

Li, Juan; Ng, Ernest Hung Yu; Stener-Victorin, Elisabet; Hu, Zhenxing; Wu, Wanting; Lai, Maohua; Wu, Taixiang; Ma, Hongxia

2016-10-07

The high prevalence of insulin resistance in women with polycystic ovary syndrome (PCOS) is considered to be one of the major pathophysiological changes in PCOS that leads to anovulatory infertility. We hypothesise that electroacupuncture pretreatment improves insulin sensitivity and leads to a higher ovulation rate and greater chances of live birth after the induction of ovulation. The effect of electroacupuncture pretreatment followed by ovulation induction in women with anovulatory PCOS has not been investigated before, and we present here a randomised controlled trial to test this hypothesis by comparing electroacupuncture pretreatment followed by letrozole versus letrozole alone in anovulatory women with PCOS. This is a multicentre, randomised,and controlled trial. A total of 384 patients will be enrolled in this study and will be randomly allocated by a central randomisation system to the treatment group or the control group in a 1:1 ratio. The treatment group will undergo 16 weeks of electroacupuncture pretreatment followed by 4 cycles of letrozole, and the control group will only undergo 4 cycles of letrozole. The primary outcome will be the live birth rate. All statistical analyses will be performed using the SPSS program V.21.0 (SPSS, Chicago, Illinois, USA), and a p value <0.05 will be considered statistically significant. This study has been approved by the ethics committees of each participating centre. Written consent will be obtained from each patient and her husband before any study procedure is performed. Adverse events will be categorised, and the percentage of patients experiencing adverse events or serious adverse events during the treatment period will be documented. The results of this trial will be disseminated in peer-reviewed journals and presented at international meetings. NCT02491320. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Endocrine effects of adjuvant letrozole + triptorelin compared with tamoxifen + triptorelin in premenopausal patients with early breast cancer.

PubMed

Rossi, Emanuela; Morabito, Alessandro; De Maio, Ermelinda; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; Piccirillo, Maria Carmela; D'Aiuto, Giuseppe; D'Aiuto, Massimiliano; Rinaldo, Massimo; Botti, Gerardo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2008-01-10

To compare the endocrine effects of 6 months of adjuvant treatment with letrozole + triptorelin or tamoxifen + triptorelin in premenopausal patients with early breast cancer within an ongoing phase 3 trial (Hormonal Adjuvant Treatment Bone Effects study). Prospectively collected hormonal data were available for 81 premenopausal women, of whom 30 were assigned to receive tamoxifen + triptorelin and 51 were assigned letrozole + triptorelin +/- zoledronate. Serum 17-beta-estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), Delta4-androstenedione, testosterone, dehydroepiandrosterone-sulfate, progesterone, adrenocorticotropic hormone (ACTH), and cortisol were measured at baseline and after 6 months of treatment. For each hormone, 6-month values were compared between treatment groups by the Wilcoxon-Mann-Whitney exact test. Median age was 44 years for both groups of patients. Letrozole + triptorelin (+/- zoledronate) induced a stronger suppression of median E2 serum levels (P = .0008), LH levels (P = .0005), and cortisol serum levels (P < .0001) compared with tamoxifen + triptorelin. Median FSH serum levels were suppressed in both groups, but such suppression was lower among patients receiving letrozole, who showed significantly higher median FSH serum levels (P < .0001). No significant differences were observed for testosterone, progesterone, ACTH, androstenedione, and dehydroepiandrosterone between the two groups of patients. Letrozole in combination with triptorelin induces a more intense estrogen suppression than tamoxifen + triptorelin in premenopausal patients with early breast cancer.

Efficacy of Letrozole as First-Line Treatment of Postmenopausal Women with Hormone Receptor-Positive Metastatic Breast Cancer in Korea.

PubMed

Beom, Seung Hoon; Oh, Jisu; Kim, Tae-Yong; Lee, Kyung-Hun; Yang, Yaewon; Suh, Koung Jin; Moon, Hyeong-Gon; Han, Sae-Won; Oh, Do-Youn; Han, Wonshik; Kim, Tae-You; Noh, Dong-Young; Im, Seock-Ah

2017-04-01

Letrozole showed efficacy and generally favorable toxicities, along with the convenience of oral administration in postmenopausal patients with hormone receptor (HR)-positive metastatic breast cancer (MBC). To the best of our knowledge, there have been no reports of the clinical outcomes in Korean patients, although letrozole is widely used in practice. Therefore, this studywas conducted to affirm the efficacy and toxicities of letrozole in Korean patients. This study retrospectively analyzed 84 HR-positive MBC patients who had been treated with letrozole from January 2001 to December 2012. Clinicopathological characteristics and treatment history were extracted from medicalrecords. All patients received 2.5 mg letrozole once a day until there were disease progressions or unacceptable toxicity. Progression-free survival (PFS) was the primary endpoint, and secondary endpoints were overall survival (OS), objective response rate (ORR), and toxicity. The median age of the subjects was 59.3 years. Letrozole treatment resulted in a median PFS of 16.8 months (95% confidence interval [CI], 9.8 to 23.8) and a median OS of 56.4 months (95% CI, 38.1 to 74.7). The ORR was 36.9% for the 84 patients with measurable lesions. Multivariate analysis revealed symptomatic visceral disease (hazard ratio, 3.437; 95% CI, 1.576 to 7.495; p=0.002) and a disease-free interval ≤ 2 years (hazard ratio, 2.697; 95% CI, 1.262 to 5.762; p=0.010) were independently associated with shorter PFS. However, sensitivity to adjuvant hormone treatment was not related to PFS. Letrozole was generally well tolerated. Letrozole showed considerable efficacy and tolerability as a first-line treatment in postmenopausal patients with HR-positive MBC.

A Retrospective Study of Letrozole Treatment Prior to Human Chorionic Gonadotropin in Women with Polycystic Ovary Syndrome Undergoing In Vitro Fertilization at Risk of Ovarian Hyperstimulation Syndrome.

PubMed

Chen, Yilu; Yang, Tanchu; Hao, Cuifang; Zhao, Junzhao

2018-06-20

BACKGROUND Women with polycystic ovary syndrome (PCOS) undergoing in vitro fertilization (IVF) are given letrozole before a trigger injection of human chorionic gonadotropin (hCG) to lower estrogen (E2) levels, but can experience ovarian hyperstimulation syndrome (OHSS). The aim of this study was to evaluate the effect of oral letrozole, prior to administration of hCG, on the outcome of IVF and development of OHSS. MATERIAL AND METHODS Retrospective clinical review included 181 cases of women with PCOS who underwent IVF cycles with intracytoplasmic sperm injection (ICSI) and embryo transfer (ET) (IVF/ICSI-ET). The day before the use of hCG, cases were divided into a letrozole-treated group (N=78) and a non-letrozole group (N=103). An oral dose of 2.5 mg qd of letrozole was given when the peak level of E2 was ≥4000 pg/ml during ovarian stimulation and ceased before the day of egg retrieval. RESULTS The letrozole-treated group had a significant increase in the number of retrieved oocytes, viable embryos, and fresh ET rate (P>0.05); peak levels of E2, and E2 levels on the day of the egg retrieval, were significantly higher, and the fertilization rate was significantly lower (P<0.001). No significant differences were found in the rates of pregnancy, abortion, or ectopic pregnancy between the two groups (P>0.05). The incidence OHSS was lower in the letrozole-treated group, but this difference did not reach statistical significance (P>0.05). CONCLUSIONS Women with PCOS who underwent IVF, oral treatment with letrozole a day prior to treatment with hCG lowered E2 levels, but did not significantly reduce the incidence of OHSS.

Impact of palbociclib plus letrozole on patient-reported health-related quality of life: results from the PALOMA-2 trial.

PubMed

Rugo, H S; Diéras, V; Gelmon, K A; Finn, R S; Slamon, D J; Martin, M; Neven, P; Shparyk, Y; Mori, A; Lu, D R; Bhattacharyya, H; Bartlett, C Huang; Iyer, S; Johnston, S; Ettl, J; Harbeck, N

2018-04-01

Patient-reported outcomes are integral in benefit-risk assessments of new treatment regimens. The PALOMA-2 study provides the largest body of evidence for patient-reported health-related quality of life (QOL) for patients with metastatic breast cancer (MBC) receiving first-line endocrine-based therapy (palbociclib plus letrozole and letrozole alone). Treatment-naïve postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2-) MBC were randomized 2 : 1 to palbociclib plus letrozole (n = 444) or placebo plus letrozole (n = 222). Patient-reported outcomes were assessed at baseline, day 1 of cycles 2 and 3, and day 1 of every other cycle from cycle 5 using the Functional Assessment of Cancer Therapy (FACT)-Breast and EuroQOL 5 dimensions (EQ-5D) questionnaires. As of 26 February 2016, the median duration of follow-up was 23 months. Baseline scores were comparable between the two treatment arms. No significant between-arm differences were observed in change from baseline in FACT-Breast Total, FACT-General Total, or EQ-5D scores. Significantly greater improvement in pain scores was observed in the palbociclib plus letrozole arm (-0.256 versus -0.098; P = 0.0183). In both arms, deterioration of FACT-Breast Total score was significantly delayed in patients without progression versus those with progression and patients with partial or complete response versus those without. No significant difference was observed in FACT-Breast and EQ-5D index scores in patients with and without neutropenia. Overall, women with MBC receiving first-line endocrine therapy have a good QOL. The addition of palbociclib to letrozole maintains health-related QOL and improves pain scores in treatment-naïve postmenopausal patients with ER+/HER2- MBC compared with letrozole alone. Significantly greater delay in deterioration of health-related QOL was observed in patients without progression versus those who progressed and in

Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor–Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance)

PubMed Central

Barry, William T.; Cirrincione, Constance T.; Ellis, Matthew J.; Moynahan, Mary Ellen; Innocenti, Federico; Hurria, Arti; Rugo, Hope S.; Lake, Diana E.; Hahn, Olwen; Schneider, Bryan P.; Tripathy, Debasish; Carey, Lisa A.; Winer, Eric P.; Hudis, Clifford A.

2016-01-01

Purpose To investigate whether anti–vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor–positive metastatic breast cancer (MBC). Patients and Methods Women with hormone receptor–positive MBC were randomly assigned 1:1 in a multicenter, open-label, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided α = .025, a target sample size of 352 patients was planned. Results From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v 2%) and proteinuria (11% v 0%). Conclusion The addition of bevacizumab to letrozole improved PFS in hormone receptor–positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting. PMID:27138575

Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance).

PubMed

Dickler, Maura N; Barry, William T; Cirrincione, Constance T; Ellis, Matthew J; Moynahan, Mary Ellen; Innocenti, Federico; Hurria, Arti; Rugo, Hope S; Lake, Diana E; Hahn, Olwen; Schneider, Bryan P; Tripathy, Debasish; Carey, Lisa A; Winer, Eric P; Hudis, Clifford A

2016-08-01

To investigate whether anti-vascular endothelial growth factor therapy with bevacizumab prolongs progression-free survival (PFS) when added to first-line letrozole as treatment of hormone receptor-positive metastatic breast cancer (MBC). Women with hormone receptor-positive MBC were randomly assigned 1:1 in a multicenter, open-label, phase III trial of letrozole (2.5 mg orally per day) with or without bevacizumab (15 mg/kg intravenously once every 3 weeks) within strata defined by measurable disease and disease-free interval. This trial had 90% power to detect a 50% improvement in median PFS from 6 to 9 months. Using a one-sided α = .025, a target sample size of 352 patients was planned. From May 2008 to November 2011, 350 women were recruited; 343 received treatment and were observed for efficacy and safety. Median age was 58 years (range, 25 to 87 years). Sixty-two percent had measurable disease, and 45% had de novo MBC. At a median follow-up of 39 months, the addition of bevacizumab resulted in a significant reduction in the hazard of progression (hazard ratio, 0.75; 95% CI, 0.59 to 0.96; P = .016) and a prolongation in median PFS from 15.6 months with letrozole to 20.2 months with letrozole plus bevacizumab. There was no significant difference in overall survival (hazard ratio, 0.87; 95% CI, 0.65 to 1.18; P = .188), with median overall survival of 43.9 months with letrozole versus 47.2 months with letrozole plus bevacizumab. The largest increases in incidence of grade 3 to 4 treatment-related toxicities with the addition of bevacizumab were hypertension (24% v 2%) and proteinuria (11% v 0%). The addition of bevacizumab to letrozole improved PFS in hormone receptor-positive MBC, but this benefit was associated with a markedly increased risk of grade 3 to 4 toxicities. Research on predictive markers will be required to clarify the role of bevacizumab in this setting. © 2016 by American Society of Clinical Oncology.

Design, conduct, and analyses of Breast International Group (BIG) 1-98: a randomized, double-blind, phase-III study comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with receptor-positive, early breast cancer.

PubMed

Giobbie-Hurder, Anita; Price, Karen N; Gelber, Richard D

2009-06-01

Aromatase inhibitors provide superior disease control when compared with tamoxifen as adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer. To present the design, history, and analytic challenges of the Breast International Group (BIG) 1-98 trial: an international, multicenter, randomized, double-blind, phase-III study comparing the aromatase inhibitor letrozole with tamoxifen in this clinical setting. From 1998-2003, BIG 1-98 enrolled 8028 women to receive monotherapy with either tamoxifen or letrozole for 5 years, or sequential therapy of 2 years of one agent followed by 3 years of the other. Randomization to one of four treatment groups permitted two complementary analyses to be conducted several years apart. The first, reported in 2005, provided a head-to-head comparison of letrozole versus tamoxifen. Statistical power was increased by an enriched design, which included patients who were assigned sequential treatments until the time of the treatment switch. The second, reported in late 2008, used a conditional landmark approach to test the hypothesis that switching endocrine agents at approximately 2 years from randomization for patients who are disease-free is superior to continuing with the original agent. The 2005 analysis showed the superiority of letrozole compared with tamoxifen. The patients who were assigned tamoxifen alone were unblinded and offered the opportunity to switch to letrozole. Results from other trials increased the clinical relevance about whether or not to start treatment with letrozole or tamoxifen, and analysis plans were expanded to evaluate sequential versus single-agent strategies from randomization. Due to the unblinding of patients assigned tamoxifen alone, analysis of updated data will require ascertainment of the influence of selective crossover from tamoxifen to letrozole. BIG 1-98 is an example of an enriched design, involving complementary analyses addressing different questions several years

The discovery and mechanism of action of letrozole

PubMed Central

2007-01-01

Because estrogen contributes to the promotion and progression of breast cancer, a greater understanding of the role of estrogen in breast cancer has led to therapeutic strategies targeting estrogen synthesis, the estrogen receptor, and intracellular signaling pathways. The enzyme aromatase catalyses the final step in estrogen biosynthesis and was identified as an attractive target for selective inhibition. Modern third-generation aromatase inhibitors (AIs) effectively block the production of estrogen without exerting effects on other steroidogenic pathways. The discovery of letrozole (Femara®) achieved the goal of discovering a highly potent and totally selective AI. Letrozole has greater potency than other AIs, including anastrozole, exemestane, formestane, and aminoglutethimide. Moreover, letrozole produces near complete inhibition of aromatase in peripheral tissues and is associated with greater suppression of estrogen than is achieved with other AIs. The potent anti-tumor effects of letrozole were demonstrated in several animal models. Studies with MCF-7Ca xenografts successfully predicted that letrozole would be clinically superior to the previous gold standard tamoxifen and also indicated that it may be more effective than other AIs. An extensive program of randomized clinical trials has demonstrated the clinical benefits of letrozole across the spectrum of hormone-responsive breast cancer in postmenopausal women. PMID:17912633

Evaluating Letrozole and Tamoxifen Alone and in Sequence for Postmenopausal Women with Steroid Hormone Receptor-Positive Breast Cancer: the BIG 1-98 Randomized Clinical Trial at 8.1 years Median Follow-Up

PubMed Central

Regan, Meredith M.; Neven, Patrick; Giobbie-Hurder, Anita; Goldhirsch, Aron; Ejlertsen, Bent; Mauriac, Louis; Forbes, John F.; Smith, Ian; Láng, István; Wardley, Andrew; Rabaglio, Manuela; Price, Karen N.; Gelber, Richard D.; Coates, Alan S.; Thürlimann, Beat

2011-01-01

Background Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast cancer recurrence and death. Therefore, trials evaluating endocrine therapies for this patient population require extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8.1 years median follow-up. Methods BIG 1-98 is a randomized, phase III, double-blind trial of 8010 postmenopausal women with hormone receptor-positive early breast cancer that compares five years of tamoxifen or letrozole monotherapy or sequential treatment with two years of one of these agents followed by three years of the other. The primary efficacy endpoint is disease-free survival (DFS: events comprise invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without prior cancer event), and secondary endpoints are overall survival (OS), distant recurrence-free interval (DRFI) and breast cancer-free interval (BCFI). The monotherapy comparison includes patients randomized to tamoxifen × 5 years (n=2459) or letrozole × 5 years (n=2463). In 2005, after significant DFS benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of 619 patients in the tamoxifen arm. The comparison of sequential treatments to letrozole monotherapy includes patients enrolled in the four-arm option of the trial and randomized to letrozole × 5 years (n=1546), letrozole × 2 years followed by tamoxifen × 3 years (n=1540), or tamoxifen × 2 years followed by letrozole × 3 years (n=1548). All patients have completed study treatment; follow up is continuing for those enrolled in the four-arm option. BIG 1-98 is registered at

Ribociclib plus letrozole in early breast cancer: A presurgical, window-of-opportunity study.

PubMed

Curigliano, G; Gómez Pardo, P; Meric-Bernstam, F; Conte, P; Lolkema, M P; Beck, J T; Bardia, A; Martínez García, M; Penault-Llorca, F; Dhuria, S; Tang, Z; Solovieff, N; Miller, M; Di Tomaso, E; Hurvitz, S A

2016-08-01

Cyclin D-cyclin-dependent kinase (CDK) 4/6-inhibitor of CDK4/6-retinoblastoma (Rb) pathway hyperactivation is associated with hormone receptor-positive (HR+) breast cancer (BC). This study assessed the biological activity of ribociclib (LEE011; CDK4/6 inhibitor) plus letrozole compared with single-agent letrozole in the presurgical setting. Postmenopausal women (N = 14) with resectable, HR+, human epidermal growth factor receptor 2-negative (HER2-) early BC were randomized 1:1:1 to receive 2.5 mg/day letrozole alone (Arm 1), or with 400 or 600 mg/day ribociclib (Arm 2 or 3). Circulating tumor DNA and tumor biopsies were collected at baseline and, following 14 days of treatment, prior to or during surgery. The primary objective was to assess antiproliferative response per Ki67 levels in Arms 2 and 3 compared with Arm 1. Additional assessments included safety, pharmacokinetics, and genetic profiling. Mean decreases in the Ki67-positive cell fraction from baseline were: Arm 1 69% (range 38-100%; n = 2), Arm 2 96% (range 78-100%; n = 6), Arm 3 92% (range 75-100%; n = 3). Decreased phosphorylated Rb levels and CDK4, CDK6, CCND2, CCND3, and CCNE1 gene expression were observed following ribociclib treatment. Ribociclib and letrozole pharmacokinetic parameters were consistent with single-agent data. The ribociclib plus letrozole combination was well tolerated, with no Grade 3/4 adverse events over the treatment. The results suggest absence of a drug-drug interaction between ribociclib and letrozole and indicate ribociclib plus letrozole may reduce Ki67 expression in HR+, HER2- BC (NCT01919229). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate-resistant polycystic ovary syndrome.

PubMed

El-khayat, Waleed; Abdel Moety, Ghada; Al Mohammady, Maged; Hamed, Dalia

2016-02-01

To examine the efficacy of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone among women with polycystic ovary syndrome (PCOS) resistant to clomifene citrate. A prospective double-blind randomized controlled trial of women younger than 40 years who had primary/secondary infertility associated with PCOS and had not ovulated in response to clomifene citrate regimens previously was conducted at a center in Cairo, Egypt, between August 1, 2013, and December 31, 2014. Computer-generated random number tables and opaque envelopes were used to assign participants to group A or group B. Participants allocated to group A received 100mg clomifene citrate daily for 5 days from the third day of the menstrual cycle, whereas those in group B received 5mg letrozole daily in the same regimen. All patients received 850 mg metformin and 15 mg pioglitazone for 10 days from the first day of the menstrual cycle. The primary outcome was cumulative ovulation rate. Analyses were by intention to treat. Fifty women were assigned to each group. Ovulation occurred in 108 (92.3%) of 117 cycles in group A and 93 (86.9%) of 107 cycles in Group B (P=0.184). Combined treatment with letrozole, metformin, and pioglitazone was efficacious among women with PCOS resistant to clomifene citrate. ClinicalTrials.gov: NCT01909141. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Ribociclib with letrozole vs letrozole alone in elderly patients with hormone receptor-positive, HER2-negative breast cancer in the randomized MONALEESA-2 trial.

PubMed

Sonke, Gabe S; Hart, Lowell L; Campone, Mario; Erdkamp, Frans; Janni, Wolfgang; Verma, Sunil; Villanueva, Cristian; Jakobsen, Erik; Alba, Emilio; Wist, Erik; Favret, Anne M; Bachelot, Thomas; Hegg, Roberto; Wheatley-Price, Paul; Souami, Farida; Sutradhar, Santosh; Miller, Michelle; Germa, Caroline; Burris, Howard A

2018-02-01

Determine the efficacy and safety of first-line ribociclib plus letrozole in elderly patients with HR+, HER2- advanced breast cancer. 668 postmenopausal women with HR+, HER2- advanced breast cancer and no prior systemic therapy for advanced disease were enrolled in the Phase III MONALEESA-2 trial (NCT01958021); 295 patients were aged ≥ 65 years. Patients were randomized to ribociclib (600 mg/day; 3-weeks-on/1-week-off) plus letrozole (2.5 mg/day) or placebo plus letrozole until disease progression, unacceptable toxicity, death, or treatment discontinuation. The primary endpoint was PFS, which was evaluated in elderly (≥ 65 years) and younger (< 65 years) patients. Secondary endpoints included response rates and safety. Ribociclib plus letrozole significantly improved PFS vs placebo plus letrozole in elderly (hazard ratio: 0.608; 95% CI 0.394-0.937) and younger patients (hazard ratio: 0.523; 95% CI 0.378-0.723). Overall response rates were numerically higher in the ribociclib vs placebo arm, regardless of age. Ribociclib plus letrozole was well tolerated in elderly patients, with the safety profile similar to the overall study population. Nausea, vomiting, alopecia, and diarrhea were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm in both subgroups; most events were grade 1/2. In elderly patients, grade 1/2 anemia and fatigue were > 10% more frequent in the ribociclib plus letrozole vs placebo plus letrozole arm and discontinuation rates were similar in both arms. Addition of ribociclib to letrozole is a valid therapeutic option for elderly patients with HR+, HER2- advanced breast cancer in the first-line setting.

The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

PubMed

Finn, Richard S; Crown, John P; Lang, Istvan; Boer, Katalin; Bondarenko, Igor M; Kulyk, Sergey O; Ettl, Johannes; Patel, Ravindranath; Pinter, Tamas; Schmidt, Marcus; Shparyk, Yaroslav; Thummala, Anu R; Voytko, Nataliya L; Fowst, Camilla; Huang, Xin; Kim, Sindy T; Randolph, Sophia; Slamon, Dennis J

2015-01-01

Palbociclib (PD-0332991) is an oral, small-molecule inhibitor of cyclin-dependent kinases (CDKs) 4 and 6 with preclinical evidence of growth-inhibitory activity in oestrogen receptor-positive breast cancer cells and synergy with anti-oestrogens. We aimed to assess the safety and efficacy of palbociclib in combination with letrozole as first-line treatment of patients with advanced, oestrogen receptor-positive, HER2-negative breast cancer. In this open-label, randomised phase 2 study, postmenopausal women with advanced oestrogen receptor-positive and HER2-negative breast cancer who had not received any systemic treatment for their advanced disease were eligible to participate. Patients were enrolled in two separate cohorts that accrued sequentially: in cohort 1, patients were enrolled on the basis of their oestrogen receptor-positive and HER2-negative biomarker status alone, whereas in cohort 2 they were also required to have cancers with amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both. In both cohorts, patients were randomly assigned 1:1 via an interactive web-based randomisation system, stratified by disease site and disease-free interval, to receive continuous oral letrozole 2.5 mg daily or continuous oral letrozole 2.5 mg daily plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over 28-day cycles. The primary endpoint was investigator-assessed progression-free survival in the intention-to-treat population. Accrual to cohort 2 was stopped after an unplanned interim analysis of cohort 1 and the statistical analysis plan for the primary endpoint was amended to a combined analysis of cohorts 1 and 2 (instead of cohort 2 alone). The study is ongoing but closed to accrual; these are the results of the final analysis of progression-free survival. The study is registered with the ClinicalTrials.gov, number NCT00721409. Between Dec 22, 2009, and May 12, 2012, we randomly assigned 165 patients, 84 to palbociclib

Impact of palbociclib plus letrozole on patient-reported health-related quality of life: results from the PALOMA-2 trial

PubMed Central

Rugo, H S; Diéras, V; Gelmon, K A; Finn, R S; Slamon, D J; Martin, M; Neven, P; Shparyk, Y; Mori, A; Lu, D R; Bhattacharyya, H; Bartlett, C Huang; Iyer, S; Johnston, S; Ettl, J; Harbeck, N

2018-01-01

Abstract Background Patient-reported outcomes are integral in benefit–risk assessments of new treatment regimens. The PALOMA-2 study provides the largest body of evidence for patient-reported health-related quality of life (QOL) for patients with metastatic breast cancer (MBC) receiving first-line endocrine-based therapy (palbociclib plus letrozole and letrozole alone). Patients and methods Treatment-naïve postmenopausal women with estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2-negative (HER2−) MBC were randomized 2 : 1 to palbociclib plus letrozole (n = 444) or placebo plus letrozole (n = 222). Patient-reported outcomes were assessed at baseline, day 1 of cycles 2 and 3, and day 1 of every other cycle from cycle 5 using the Functional Assessment of Cancer Therapy (FACT)-Breast and EuroQOL 5 dimensions (EQ-5D) questionnaires. Results As of 26 February 2016, the median duration of follow-up was 23 months. Baseline scores were comparable between the two treatment arms. No significant between-arm differences were observed in change from baseline in FACT-Breast Total, FACT-General Total, or EQ-5D scores. Significantly greater improvement in pain scores was observed in the palbociclib plus letrozole arm (−0.256 versus −0.098; P = 0.0183). In both arms, deterioration of FACT-Breast Total score was significantly delayed in patients without progression versus those with progression and patients with partial or complete response versus those without. No significant difference was observed in FACT-Breast and EQ-5D index scores in patients with and without neutropenia. Conclusions Overall, women with MBC receiving first-line endocrine therapy have a good QOL. The addition of palbociclib to letrozole maintains health-related QOL and improves pain scores in treatment-naïve postmenopausal patients with ER+/HER2− MBC compared with letrozole alone. Significantly greater delay in deterioration of health-related QOL was observed

Effectiveness of co-treatment with traditional Chinese medicine and letrozole for polycystic ovary syndrome: a meta-analysis.

PubMed

Ma, Qian-Wen; Tan, Yong

2017-03-01

Polycystic ovary syndrome (PCOS) is an endocrine disease that affects gynecological health. Treatment of PCOS remains a big challenge for clinicians. This meta-analysis was developed to compare the efficacy of co-treatment with traditional Chinese medicine (TCM) and letrozole against letrozole monotherapy in the treatment of PCOS. Randomized controlled trials (RCTs) were electronically retrieved from PubMed, Cochrane Library, China Biomedical Literature Database, China National Knowledge Infrastructure and Wanfang Data; related papers that were not available electronically were manually checked. All papers were assessed according to the Cochrane Handbook for Systematic Reviews of Interventions and the valid data were analyzed using Revman software (The Cochrane Collaboration, Copenhagen, Denmark). We included RCTs that compared co-treatment with TCM and letrozole against letrozole monotherapy in women with PCOS, which was defined by anovulation, biochemical or clinical hyperandrogenemia and polycystic ovaries. We included trials from all sources. Two independent reviewers extracted data, and evaluated study quality according to the Cochrane Handbook for Systematic Reviews of Interventions criteria for RCT, including issues of patient randomization, blinding and bias. Eight RCTs, involving a total of 537 patients, were included in the present study. The meta-analysis showed that the cycle ovulation rate, the pregnancy rate and the total effective rate of symptom treatment were higher in treatments combining TCM with letrozole, compared with letrozole monotherapy. Although the rate of luteinizing hormone (LH)/follicle-stimulating hormone (FSH) and the body mass index of the group receiving combined therapy were lower than in letrozole monotherapy, no statistical difference was found in the LH and FSH level between the two groups. Available evidence showed that co-treatment with TCM and letrozole was more effective than letrozole monotherapy in the treatment of PCOS.

Comparison of the efficiency of clomiphene citrate and letrozole in combination with metformin in moderately obese clomiphene citrate-resistant polycystic ovarian syndrome patients.

PubMed

Bjelica, Artur; Trninić-Pjević, Aleksandra; Mladenović-Segedi, Ljiljana; Cetković, Nenad; Petrović, Djordje

2016-01-01

Polycystic ovary syndrome is the most common endocrinopathy in women of reproductive-age. Therapy for those who want to get pregnant involves ovulation induction using clomiphene citrate, metformin, letrozole and gonadotropins. The aim of the study was to compare the efficacy of combinations of clomiphene citrate-metformin and letrozole-metformin in obese patients who are resistant to clomiphene citrate alone. The investigation was conducted as a retrospective study involving 60 moderately obese patients with polycystic ovary syndrome. Thirty-one of them received the clomiphene citrate-metformin, and 29 letrozole-metformin therapy. Stimulation was carried out for the procedures of intrauterine insemination (IUI). The age of patients, duration of infertility, and body mass index in both groups were similar. There was statistically significant difference in the thickness of the endometrium in favor of the group having the letrozole-metformin therapy (8.9 ± 1.7 mm) compared with the group receiving the clomiphene citrate-metformin treatment (6.3 ± 1.3 mm). The number of follicles was not statistically significantly different. Pregnancy rate in the first cycle of IUI in the clomiphene citrate group was 6.4%, and 17.2% in the letrozole group, which also was not statistically different. After the third IUI cycle, the pregnancy rate was significantly higher in the letrozole group (20.6%), while in the clomiphene citrate group it was (9.6%). This retrospective study demonstrated the advantages of the use of letrozole over clomiphene citrate in combination with metformin in moderately obese patients with polycystic ovary syndrome who are resistant to stimulation with clomiphene citrate alone.

Extended high dose letrozole regimen versus short low dose letrozole regimen as an adjuvant to gonadotropin releasing hormone antagonist protocol in poor responders undergoing IVF-ET.

PubMed

Fouda, Usama M; Sayed, Ahmed M

2011-12-01

To compare the efficacy and cost-effectiveness of extended high dose letrozole regimen/HPuFSH-gonadotropin releasing hormone antagonist (GnRHant) protocol with short low dose letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET. In this randomized controlled trial, 136 women who responded poorly to GnRH agonist long protocol in their first IVF cycle were randomized into two equal groups using computer generated list and were treated in the second IVF cycle by either extended letrozole regimen (5 mg/day during the first 5 days of cycle and 2.5 mg/day during the subsequent 3 days) combined with HPuFSH-GnRHant protocol or short letrozole regimen (2.5 mg/day from cycle day 3-7) combined with HPuFSH-GnRHant protocol. There were no significant differences between both groups with regard to number of oocytes retrieved and clinical pregnancy rate (5.39 ± 2.08 vs. 5.20 ± 1.88 and 22.06% vs. 16.18%, respectively).The total gonadotropins dose and medications cost per cycle were significantly lower in extended letrozole group (44.87 ± 9.16 vs. 59.97 ± 14.91 ampoules and 616.52 ± 94.97 vs. 746.84 ± 149.21 US Dollars ($), respectively).The cost-effectiveness ratio was 2794 $ in extended letrozole group and 4616 $ in short letrozole group. Extended letrozole regimen/HPuFSH-GnRHant protocol was more cost-effective than short letrozole regimen/HPuFSH-GnRHant protocol in poor responders undergoing IVF-ET.

Assessment of letrozole and tamoxifen alone and in sequence for postmenopausal women with steroid hormone receptor-positive breast cancer: the BIG 1-98 randomised clinical trial at 8·1 years median follow-up.

PubMed

Regan, Meredith M; Neven, Patrick; Giobbie-Hurder, Anita; Goldhirsch, Aron; Ejlertsen, Bent; Mauriac, Louis; Forbes, John F; Smith, Ian; Láng, István; Wardley, Andrew; Rabaglio, Manuela; Price, Karen N; Gelber, Richard D; Coates, Alan S; Thürlimann, Beat

2011-11-01

Postmenopausal women with hormone receptor-positive early breast cancer have persistent, long-term risk of breast-cancer recurrence and death. Therefore, trials assessing endocrine therapies for this patient population need extended follow-up. We present an update of efficacy outcomes in the Breast International Group (BIG) 1-98 study at 8·1 years median follow-up. BIG 1-98 is a randomised, phase 3, double-blind trial of postmenopausal women with hormone receptor-positive early breast cancer that compares 5 years of tamoxifen or letrozole monotherapy, or sequential treatment with 2 years of one of these drugs followed by 3 years of the other. Randomisation was done with permuted blocks, and stratified according to the two-arm or four-arm randomisation option, participating institution, and chemotherapy use. Patients, investigators, data managers, and medical reviewers were masked. The primary efficacy endpoint was disease-free survival (events were invasive breast cancer relapse, second primaries [contralateral breast and non-breast], or death without previous cancer event). Secondary endpoints were overall survival, distant recurrence-free interval (DRFI), and breast cancer-free interval (BCFI). The monotherapy comparison included patients randomly assigned to tamoxifen or letrozole for 5 years. In 2005, after a significant disease-free survival benefit was reported for letrozole as compared with tamoxifen, a protocol amendment facilitated the crossover to letrozole of patients who were still receiving tamoxifen alone; Cox models and Kaplan-Meier estimates with inverse probability of censoring weighting (IPCW) are used to account for selective crossover to letrozole of patients (n=619) in the tamoxifen arm. Comparison of sequential treatments to letrozole monotherapy included patients enrolled and randomly assigned to letrozole for 5 years, letrozole for 2 years followed by tamoxifen for 3 years, or tamoxifen for 2 years followed by letrozole for 3 years

Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker.

PubMed

Sgroi, Dennis C; Carney, Erin; Zarrella, Elizabeth; Steffel, Lauren; Binns, Shemeica N; Finkelstein, Dianne M; Szymonifka, Jackie; Bhan, Atul K; Shepherd, Lois E; Zhang, Yi; Schnabel, Catherine A; Erlander, Mark G; Ingle, James N; Porter, Peggy; Muss, Hyman B; Pritchard, Katherine I; Tu, Dongsheng; Rimm, David L; Goss, Paul E

2013-07-17

Biomarkers to optimize extended adjuvant endocrine therapy for women with estrogen receptor (ER)-positive breast cancer are limited. The HOXB13/IL17BR (H/I) biomarker predicts recurrence risk in ER-positive, lymph node-negative breast cancer patients. H/I was evaluated in MA.17 trial for prognostic performance for late recurrence and treatment benefit from extended adjuvant letrozole. A prospective-retrospective, nested case-control design of 83 recurrences matched to 166 nonrecurrences from letrozole- and placebo-treated patients within MA.17 was conducted. Expression of H/I within primary tumors was determined by reverse-transcription polymerase chain reaction with a prespecified cutpoint. The predictive ability of H/I for ascertaining benefit from letrozole was determined using multivariable conditional logistic regression including standard clinicopathological factors as covariates. All statistical tests were two-sided. High H/I was statistically significantly associated with a decrease in late recurrence in patients receiving extended letrozole therapy (odds ratio [OR] = 0.35; 95% confidence interval [CI] = 0.16 to 0.75; P = .007). In an adjusted model with standard clinicopathological factors, high H/I remained statistically significantly associated with patient benefit from letrozole (OR = 0.33; 95% CI = 0.15 to 0.73; P = .006). Reduction in the absolute risk of recurrence at 5 years was 16.5% for patients with high H/I (P = .007). The interaction between H/I and letrozole treatment was statistically significant (P = .03). In the absence of extended letrozole therapy, high H/I identifies a subgroup of ER-positive patients disease-free after 5 years of tamoxifen who are at risk for late recurrence. When extended endocrine therapy with letrozole is prescribed, high H/I predicts benefit from therapy and a decreased probability of late disease recurrence.

Effects of letrozole on breast cancer micro-metastatic tumor growth in bone and lung in mice inoculated with murine 4T1 cells.

PubMed

Wang, Wendan; Belosay, Aashvini; Yang, Xujuan; Hartman, James A; Song, Huaxin; Iwaniec, Urszula T; Turner, Russell T; Churchwell, Mona I; Doerge, Daniel R; Helferich, William G

2016-06-01

Breast cancer (BC) is the leading cancer in women worldwide. Metastasis occurs in stage IV BC with bone and lung being common metastatic sites. Here we evaluate the effects of the aromatase inhibitor letrozole on BC micro-metastatic tumor growth in bone and lung metastasis in intact and ovariectomized (OVX) mice with murine estrogen receptor negative (ER-) BC cells inoculated in tibia. Forty-eight BALB/c mice were randomly assigned to one of four groups: OVX, OVX + Letrozole, Intact, and Intact + Letrozole, and injected with 4T1 cells intra-tibially. Letrozole was subcutaneously injected daily for 23 days at a dose of 1.75 µg/g body weight. Tumor progression was monitored by bioluminescence imaging (BLI). Following necropsy, inoculated tibiae were scanned via µCT and bone response to tumor was scored from 0 (no ectopic mineralization/osteolysis) to 5 (extensive ectopic mineralization/osteolysis). OVX mice had higher tibial pathology scores indicative of more extensive bone destruction than intact mice, irrespective of letrozole treatment. Letrozole decreased serum estradiol levels and reduced lung surface tumor numbers in intact animals. Furthermore, mice receiving letrozole had significantly fewer tumor colonies and fewer proliferative cells in the lung than OVX and intact controls based on H&E and Ki-67 staining, respectively. In conclusion, BC-inoculated OVX animals had higher tibia pathology scores than BC-inoculated intact animals and letrozole reduced BC metastases to lungs. These findings suggest that, by lowering systemic estrogen level and/or by interacting with the host organ, the aromatase inhibitor letrozole has the potential to reduce ER- BC metastasis to lung.

The effect of letrozole with misoprostol for medical termination of pregnancy on the expression of steroid receptors in the placenta.

PubMed

Lee, Vivian Chi-Yan; Gao, Jing; Lee, Kai-Fai; Ng, Ernest Hung-Yu; Yeung, William Shu-Biu; Ho, Pak-Chung

2013-11-01

What is the effect of letrozole on the expression of steroid receptors in the placentae in cases of termination of pregnancies? The expression of estrogen receptor-α (ERα) and progesterone receptor (PR) transcripts, as well as ERα protein, in placentae was suppressed by letrozole pretreatment in second trimester termination of pregnancy. There have been no data in the literature on the effect of letrozole in termination of human pregnancies. This study is part of a clinical randomized trial in which 50 subjects were recruited and 44 placentae were collected. Women (n = 50) requesting second trimester abortion between 12 and 20 gestational weeks were randomized to receive either letrozole or placebo pretreatment for 3 days before administration of vaginal misoprostol. Placentae were collected from both groups of women after the abortion. Total RNA from the frozen placenta samples was extracted and subjected to real-time RT-PCR analysis of ERα and estrogen receptor-β (ERβ), PR and glucocorticoid receptor (GR) transcripts. Immunohistochemical studies of ERα, ERβ, PR and GR expression, as well as Ki67 and PCNA staining for proliferation, were performed. TUNEL assays were performed to determine the extent of apoptosis. Real-time RT-PCR demonstrated that the median ERα {3.900 [95% confidence interval (CI): -0.643-8.443] in the letrozole group versus 4.714 (95% CI: 1.776-7.652) in the control group; P = 0.005} and the median PR [0.701 (95% CI: 0.333-1.069) in the letrozole group versus 1.774 (95% CI: 1.07-2.478) in the control group; P = 0.003] were significantly lower in the letrozole group compared with the control group. Furthermore, ERα protein levels, in both syncytiotrophoblasts and cytotrophoblasts but not in villous stromal cells, were significantly reduced [H-score of 113 (95% CI: 103-119) in the letrozole group versus 217 (95% CI: 214-290) in the control group, in syncytiotrophoblasts; 100 (95% CI: 98-105) in the letrozole group versus 210 (95% CI: 200

Minimal stimulation protocol using letrozole versus microdose flare up GnRH agonist protocol in women with poor ovarian response undergoing ICSI.

PubMed

Mohsen, Iman Abdel; El Din, Rasha Ezz

2013-02-01

To compare the IVF outcomes of letrozole/antagonist and microdose GnRH agonist flare up protocols in poor ovarian responders undergoing intracytoplasmic sperm injection. A randomized controlled trial was performed in patients with one or more previous failed IVF cycles in which four or less oocytes were retrieved when the gonadotrophin starting dose was at least 300 IU/day. Sixty patients were randomized by computer-generated list to receive either letrozole/antagonist (mild stimulation) n = 30 or GnRH-a protocol (microdose flare) n = 30. Both groups were similar with respect to background and hormonal characteristics (age, duration of infertility, BMI, FSH, LH and E2). The clinical pregnancy rate per cycle was similar in both groups (13.3 vs. 16.6%; OR = 0.769; 95% CI = 0.185, 3.198). The doses of used gonadotropins and the number of stimulation days were significantly lower in the letrozole/antagonist protocol. The peak E2 level on the day of hCG, the endometrial thickness, the retrieved oocytes, the number of fertilized oocytes, the number of transferred embryos and the cancellation rate were statistically similar in both groups. The letrozole/antagonist protocol is a cost-effective and patient-friendly protocol that may be used in poor ovarian responders for IVF/ICSI.

Preclinical Pharmacological Evaluation of Letrozole as a Novel Treatment for Gliomas

PubMed Central

Dave, Nimita; Chow, Lionel M.L.; Gudelsky, Gary A.; LaSance, Kathleen; Qi, Xiaoyang; Desai, Pankaj B.

2015-01-01

We present data that letrozole, an extensively used aromatase inhibitor in the treatment of estrogen receptor-positive breast tumors in postmenopausal women, may be potentially used in the treatment of glioblastomas. First, we measured the in vitro cytotoxicity of letrozole and aromatase (CYP19A1) expression and activity in human LN229, T98G, U373MG, U251MG, and U87MG, and rat C6 glioma cell lines. Estrogen receptor (ER)positive MCF-7 and ER-negative MDA-MB-231 cells served as controls. Cytotoxicity was determined employing the MTT assay, and aromatase activity using an immunoassay that measures the conversion of testosterone to estrogen. Second, in vivo activity of letrozole was assessed in Sprague-Dawley rats orthotopically implanted with C6 gliomas. The changes in tumor volume with letrozole treatment (4 mg/kg/day) were assessed employing μPET/CT imaging, employing [18F]-fluorodeoxyglucose (F18-FDG) as the radiotracer. Brain tissues were collected for histologic evaluations. All glioma cell lines included here expressed CYP19A1 and letrozole exerted considerable cytotoxicity and decrease in aromatase activity against these cells (IC50, 0.1–3.5 μmol/L). Imaging analysis employing F18-FDG μPET/CT demonstrated a marked reduction of active tumor volume (>75%) after 8 days of letrozole treatment. Immunohistochemical analysis revealed marked reduction in aromatase expression in tumoral regions of the brain after letrozole treatment. Thus, employing multifaceted tools, we demonstrate that aromatase may be a novel target for the treatment of gliomas and that letrozole, an FDA-approved drug with an outstanding record of safety may be repurposed for the treatment of such primary brain tumors, which currently have few therapeutic options. PMID:25695958

Preclinical pharmacological evaluation of letrozole as a novel treatment for gliomas.

PubMed

Dave, Nimita; Chow, Lionel M L; Gudelsky, Gary A; LaSance, Kathleen; Qi, Xiaoyang; Desai, Pankaj B

2015-04-01

We present data that letrozole, an extensively used aromatase inhibitor in the treatment of estrogen receptor-positive breast tumors in postmenopausal women, may be potentially used in the treatment of glioblastomas. First, we measured the in vitro cytotoxicity of letrozole and aromatase (CYP19A1) expression and activity in human LN229, T98G, U373MG, U251MG, and U87MG, and rat C6 glioma cell lines. Estrogen receptor (ER)-positive MCF-7 and ER-negative MDA-MB-231 cells served as controls. Cytotoxicity was determined employing the MTT assay, and aromatase activity using an immunoassay that measures the conversion of testosterone to estrogen. Second, in vivo activity of letrozole was assessed in Sprague-Dawley rats orthotopically implanted with C6 gliomas. The changes in tumor volume with letrozole treatment (4 mg/kg/day) were assessed employing μPET/CT imaging, employing [(18)F]-fluorodeoxyglucose (F18-FDG) as the radiotracer. Brain tissues were collected for histologic evaluations. All glioma cell lines included here expressed CYP19A1 and letrozole exerted considerable cytotoxicity and decrease in aromatase activity against these cells (IC50, 0.1-3.5 μmol/L). Imaging analysis employing F18-FDG μPET/CT demonstrated a marked reduction of active tumor volume (>75%) after 8 days of letrozole treatment. Immunohistochemical analysis revealed marked reduction in aromatase expression in tumoral regions of the brain after letrozole treatment. Thus, employing multifaceted tools, we demonstrate that aromatase may be a novel target for the treatment of gliomas and that letrozole, an FDA-approved drug with an outstanding record of safety may be repurposed for the treatment of such primary brain tumors, which currently have few therapeutic options. ©2015 American Association for Cancer Research.

The effect of 7 days of letrozole pretreatment combined with misoprostol on the expression of progesterone receptor and apoptotic factors of placental and decidual tissues from first-trimester abortion: a randomized controlled trial.

PubMed

Yung, Sofie Shuk Fei; Lee, Vivian Chi Yan; Chiu, Philip Chi Ngong; Li, Hang Wun Raymond; Ng, Ernest Hung Yu; Yeung, William Shu Biu; Ho, Pak Chung

2016-04-01

To evaluate if letrozole-induced suppression of estradiol reduces progesterone receptor expression and apoptosis in the first-trimester placenta. We performed a double-blinded, randomized, placebo-controlled trial. We randomized 20 women requesting first-trimester abortion with gestation up to 63 days to receive either letrozole 10 mg daily or placebo pretreatment for 7 days before administrating 400 mcg of vaginal misoprostol followed by suction abortion. We collected the placental and decidual tissues on which we performed immunohistochemical staining for progesterone receptor and apoptotic markers (active caspase 3, caspase 3, Bcl2, CD95, fas ligand) and determined H-scores of each based on the intensities of staining. We performed terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) assay for apoptosis in the samples of four women to confirm the findings from apoptotic markers. We excluded one woman in the letrozole group from the analysis because she had passage of abortus after taking letrozole, leaving 19 women (9 in the letrozole group, 10 in the placebo group) for analysis. There was no significant difference in the H-scorings of progesterone receptor and apoptotic markers, as well as proportion of apoptotic cells on TUNEL assay between the two groups. The H-scores for the progesterone receptor were 8.17 ± 2.67 (mean ± SD) in the letrozole group and 9.01 ± 2.82 in the placebo group (p=0.36). We did not detect a difference in the expression of progesterone receptor and apoptotic markers in placental and decidual tissues after letrozole pretreatment for 7 days in first-trimester abortion. We did not confirm the hypothesis that letrozole reduces progesterone receptor expression and induces apoptosis in the first-trimester placenta. Further studies are required to allow better understanding of the mechanism by which estrogen suppression following the use of letrozole can lead to improved abortion rate in the first

Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer.

PubMed

Robarge, Jason D; Desta, Zereunesay; Nguyen, Anne T; Li, Lang; Hertz, Daniel; Rae, James M; Hayes, Daniel F; Storniolo, Anna M; Stearns, Vered; Flockhart, David A; Skaar, Todd C; Henry, N Lynn

2017-02-01

Inter-individual differences in estrogen concentrations during treatment with aromatase inhibitors (AIs) may contribute to therapeutic response and toxicity. The aim of this study was to determine plasma concentrations of estradiol (E2), estrone (E1), and estrone sulfate (E1S) in a large cohort of AI-treated breast cancer patients. In a randomized, multicenter trial of postmenopausal women with early-stage breast cancer starting treatment with letrozole (n = 241) or exemestane (n = 228), plasma estrogen concentrations at baseline and after 3 months were quantitated using a sensitive mass spectrometry-based assay. Concentrations and suppression below the lower limit of quantification (LLOQ) were compared between estrogens and between drugs. The ranges of baseline estrogen concentrations were letrozole: 86.9%, p = 0.51). However, patients on letrozole were more likely to achieve suppression below the LLOQ of both E1 (exemestane: 80.1%, letrozole: 90.1%, p = 0.005) and E1S (exemestane: 17.4%, letrozole: 54.9%, p = 4.34e-15). After 3 months of AI therapy, the ranges of estrogen concentrations were Letrozole had greater suppression of plasma E1 and E1S than exemestane, though the response was highly variable among patients. Additional research is required to examine the clinical relevance of differential estrogen suppression.

Evaluation of effect of letrozole prior to misoprostol in comparison with misoprostol alone in success rate of induced abortion.

PubMed

Behroozi-Lak, T; Derakhshan-Aydenloo, S; Broomand, F

2018-03-01

Abortion, spontaneous or induced, is a common complication of pregnancy and exploration of available and safe regimens for medical abortion in developing countries seems crucial. The present study was aimed to assess the effect of letrozole in combination with misoprostol in women eligible for legal therapeutic abortion with gestational age ≤14weeks. This clinical randomized trial was conducted on 78 women who were candidate of medical abortion and eligible for legal abortion with gestational age ≤14 weeks that were randomly divided into two groups of case and controls. Case group received daily oral dose of 10mg letrozole for three days followed by vaginal misoprostol. In control group the patients received only vaginal misoprostol. The rate of complete abortion, induction-of-abortion time, and side-effects were assessed. Complete abortion was observed in 30 patients (76.9%) in case group and 9 (23.1%) cases were failed. In control group there was 16 (41.03%) complete abortions and 23 (58.97%) cases were failed to abort. Patients with gestational age of between 6 and 10 weeks did not show significant difference in both groups (P=0.134). Regarding pregnancy remnants there were significant differences between two groups (P=0.034). The time form admission to discharge in case groups were significantly shorter than those in control group (P=0.001). The indication for curettage in case group was significantly less than control group (P=0.001). A 3-day course of letrozole (10mg/daily) followed by misoprostol was associated with a higher complete abortion and lower curettage rates and reduction in time from admission to discharge in women with gestational age ≤14 weeks compared to misoprostol alone. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Stopping treatment can reverse acquired resistance to letrozole

PubMed Central

Sabnis, Gauri J; Macedo, Luciana F; Goloubeva, Olga; Schayowitz, Adam; Brodie, Angela MH

2008-01-01

Using the intra tumoral aromatase xenograft model, we have observed that despite long lasting growth inhibition tumors eventually begin to grow during continued letrozole treatment. In cells isolated from these Long Term Letrozole Treated tumors (LTLT-Ca), ERα levels were decreased whereas signaling proteins in the MAPK cascade were upregulated along with Her-2. In the current study we evaluated the effect of discontinuing the letrozole treatment on the growth of letrozole resistant cells and tumors. The cells formed tumors equally well in the absence or presence of letrozole and had similar growth rates. After treatment was discontinued for six weeks, letrozole was administered again. Marked tumor regression was observed with this second course of letrozole treatment. Similarly in MCF-7Ca xenografts, a six-week break in letrozole treatment prolonged the responsiveness of the tumors to letrozole. To understand the mechanisms of this effect, LTLT-Ca cells were cultured in the absence of letrozole for 16 weeks. The resulting cell line (RLT-Ca) exhibited properties similar to MCF-7Ca cells. The cell growth was inhibited by letrozole and stimulated by estradiol. The expression of p-MAPK was reduced and ERα and aromatase increased compared to levels in LTLT-Ca cells and were similar to the levels in MCF-7Ca cells. These results indicate that discontinuing treatment can reverse letrozole resistance. This could be a beneficial strategy to prolong responsiveness to AIs for breast cancer patients. PMID:18559495

No increased risk of major congenital anomalies or adverse pregnancy or neonatal outcomes following letrozole use in assisted reproductive technology.

PubMed

Tatsumi, T; Jwa, S C; Kuwahara, A; Irahara, M; Kubota, T; Saito, H

2017-01-01

Does letrozole use increase the risk of major congenital anomalies and adverse pregnancy and neonatal outcomes in fresh, single-embryo transfer? Letrozole significantly decreases the risk of miscarriage and does not increase the risk of major congenital anomalies or adverse pregnancy or neonatal outcomes compared with natural cycles in patients undergoing ART. Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART. However, its safety in terms of pregnancy and neonatal outcomes is unclear. This retrospective cohort study used data from the Japanese national ART registry from 2011 to 2013. A total of 3136 natural cycles and 792 letrozole-induced cycles associated with fresh, single-embryo transfer and resulting in a clinical pregnancy were included in the analysis. The main pregnancy outcomes were miscarriage, ectopic pregnancy and still birth, and the neonatal outcomes were preterm delivery, low birth weight, small/large for gestational age and major congenital anomalies. Terminated pregnancies were included in the analysis of major congenital anomalies. Odds ratios (ORs) and 95% CIs were calculated using multivariate logistic regression analysis adjusted for maternal age and calendar year. The risk of miscarriage was significantly lower in women administered letrozole (adjusted OR [aOR], 0.37, 95% CI, 0.30-0.47, P < 0.001). There was no significant difference in the overall risk of major congenital anomalies between the two groups (natural cycle 1.5% vs letrozole 1.9%, aOR, 1.24, 95% CI, 0.64-2.40, P = 0.52), and no increased risk for any specific organ system. Subgroup analysis demonstrated that the risk of major congenital anomalies was not increased in patients who underwent either in vitro fertilization or ICSI, or in those who received early cleavage stage or blastocyst embryo transfer. All other pregnancy and neonatal outcomes were comparable between the two groups. Despite the large sample size, we were only able to

Congenital malformations among babies born following letrozole or clomiphene for infertility treatment.

PubMed

Sharma, Sunita; Ghosh, Sanghamitra; Singh, Soma; Chakravarty, Astha; Ganesh, Ashalatha; Rajani, Shweta; Chakravarty, B N

2014-01-01

Clomiphene citrate (CC) is the first line drug for ovulation induction but because of its peripheral antiestrogenic effect, letrozole was introduced as the 2nd line drug. It lacks the peripheral antiestrogenic effect and is associated with similar or even higher pregnancy rates. Since letrozole is a drug for breast cancer, its use for the purpose of ovulation induction became controversial in the light of studies indicating an increased incidence of congenital malformations. To evaluate and compare the incidence of congenital malformations among offsprings of infertile couples who conceived naturally or with clomiphene citrate or letrozole treatment. A retrospective cohort study done at a tertiary infertility centre. A total of 623 children born to infertile women who conceived naturally or following clomiphene citrate or letrozole treatment were included in this study. Subjects were sorted out from medical files of both mother and newborn and follow up study was done based on the information provided by parents through telephonic conversations. Babies with suspected anomaly were called and examined by specialists for the presence of major and minor congenital malformations. Other outcomes like multiple pregnancy rate and birth weight were also studied. Overall, congenital malformations, chromosomal abnormalities were found in 5 out of 171 (2.9%) babies in natural conception group and 5 out of 201 babies in the letrozole group (2.5%) and in 10 of 251 babies in the CC group (3.9%). There was no significant difference in the overall rate of congenital malformations among children born to mothers who conceived naturally or after letrozole or CC treatment. Congenital malformations have been found to be comparable following natural conception, letrozole and clomiphene citrate. Thus, the undue fear against letrozole may be uncalled for.

Hyperandrogenemia Induced by Letrozole Treatment of Pubertal Female Mice Results in Hyperinsulinemia Prior to Weight Gain and Insulin Resistance.

PubMed

Skarra, Danalea V; Hernández-Carretero, Angelina; Rivera, Alissa J; Anvar, Arya R; Thackray, Varykina G

2017-09-01

Women with polycystic ovary syndrome (PCOS) diagnosed with hyperandrogenism and ovulatory dysfunction have an increased risk of developing metabolic disorders, including type 2 diabetes and cardiovascular disease. We previously developed a model that uses letrozole to elevate endogenous testosterone levels in female mice. This model has hallmarks of PCOS, including hyperandrogenism, anovulation, and polycystic ovaries, as well as increased abdominal adiposity and glucose intolerance. In the current study, we further characterized the metabolic dysfunction that occurs after letrozole treatment to determine whether this model represents a PCOS-like metabolic phenotype. We focused on whether letrozole treatment results in altered pancreatic or liver function as well as insulin resistance. We also investigated whether hyperinsulinemia occurs secondary to weight gain and insulin resistance in this model or if it can occur independently. Our study demonstrated that letrozole-treated mice developed hyperinsulinemia after 1 week of treatment and without evidence of insulin resistance. After 2 weeks of letrozole treatment, mice became significantly heavier than placebo mice, demonstrating that weight gain was not required to develop hyperinsulinemia. After 5 weeks of letrozole treatment, mice exhibited blunted glucose-stimulated insulin secretion, insulin resistance, and impaired insulin-induced phosphorylation of AKT in skeletal muscle. Moreover, letrozole-treated mice exhibited dyslipidemia after 5 weeks of treatment but no evidence of hepatic disease. Our study demonstrated that the letrozole-induced PCOS mouse model exhibits multiple features of the metabolic dysregulation observed in obese, hyperandrogenic women with PCOS. This model will be useful for mechanistic studies investigating how hyperandrogenemia affects metabolism in females. Copyright © 2017 Endocrine Society.

Bone effect of adjuvant tamoxifen, letrozole or letrozole plus zoledronic acid in early-stage breast cancer: the randomized phase 3 HOBOE study.

PubMed

Nuzzo, F; Gallo, C; Lastoria, S; Di Maio, M; Piccirillo, M C; Gravina, A; Landi, G; Rossi, E; Pacilio, C; Labonia, V; Di Rella, F; Bartiromo, A; Buonfanti, G; De Feo, G; Esposito, G; D'Aniello, R; Maiolino, P; Signoriello, S; De Maio, E; Tinessa, V; Colantuoni, G; De Laurentiis, M; D'Aiuto, M; Di Bonito, M; Botti, G; Giordano, P; Daniele, G; Morabito, A; Normanno, N; de Matteis, A; Perrone, F

2012-08-01

To measure bone mineral density (BMD) reduction produced by letrozole as compared with tamoxifen and the benefit of the addition of zoledronic acid. A phase 3 trial comparing tamoxifen, letrozole or letrozole+zoledronic acid in patients with hormone receptor-positive early breast cancer was conducted; triptorelin was given to premenopausal patients. Two comparisons were planned: letrozole versus tamoxifen and letrozole+zoledronic acid versus letrozole. Primary end point was the difference in 1-year change of T-score at lumbar spine (LTS) measured by dual energy X-ray absorptiometry scan. Out of 483 patients enrolled, 459 were available for primary analyses. Median age was 50 (range 28-80). The estimated mean difference (95% confidence interval [CI]) in 1-year change of LTS was equal to -0.30 (95% CI -0.44 to -0.17) in the letrozole versus tamoxifen comparison (P<0.0001) and to +0.60 (95% CI +0.46 to +0.77) in the letrozole+zoledronic acid versus letrozole comparison (P<0.0001). Bone damage by letrozole decreased with increasing baseline body mass index in premenopausal, but not postmenopausal, patients (interaction test P=0.004 and 0.47, respectively). In the HOBOE (HOrmonal BOne Effects) trial, the positive effect of zoledronic acid on BMD largely counteracts damage produced by letrozole as compared with tamoxifen. Letrozole effect is lower among overweight/obese premenopausal patients.

Meta-analysis of letrozole versus clomiphene citrate in polycystic ovary syndrome.

PubMed

He, Donghong; Jiang, Fengyan

2011-07-01

The aim of this study was to systematically compare the clinical efficacy and safety of letrozole with clomiphene citrate for ovulation induction in women with polycystic ovary syndrome (PCOS). The Cochrane Central Register of Controlled Trials, PubMed, EMbase, CBMdisc and CNKI were searched for eligible randomized controlled trials (RCT) comparing letrozole with clomiphene citrate in PCOS patients. Two reviewers independently extracted information and evaluated methodological quality according to the Cochrane Handbook 5.0. Meta-analysis was performed with the fixed-effects model or random-effects model according to the heterogeneity. Six eligible RCT involving 841 patients were included. Letrozole was associated with a number of lower mature follicles per cycle (standardized mean difference (SMD) -1.41; 95% confidence intervales (CI) -1.54 to -1.28; P<0.00001) compared with clomiphene citrate. There were no significant differences in pregnancy rate (relative risk (RR) 0.97; 95% CI 0.79 to 1.18), abortion rate (RR 1.38; 95% CI 0.48 to -3.96) and multiple pregnancy rate (RR 0.34; 95% CI 0.07 to -1.72) between the two groups. The evidence from ovulation rates was not enough to support either letrozole or clomiphene citrate. In conclusion, letrozole is as effective as clomiphene citrate for ovulation induction in patients with PCOS. Copyright © 2011 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Impact of palbociclib plus letrozole on pain severity and pain interference with daily activities in patients with estrogen receptor-positive/human epidermal growth factor receptor 2-negative advanced breast cancer as first-line treatment.

PubMed

Bell, T; Crown, J P; Lang, I; Bhattacharyya, H; Zanotti, G; Randolph, S; Kim, S; Huang, X; Huang Bartlett, C; Finn, R S; Slamon, D

2016-05-01

Background Palbociclib is a recently approved drug for use in combination with letrozole as initial endocrine-based therapy for the treatment of postmenopausal women with advanced estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER+/HER2-) breast cancer. This report assesses the impact of palbociclib in combination with letrozole versus letrozole alone on patient-reported outcomes of pain. Methods Palbociclib was evaluated in an open-label, randomized, phase II study (PALOMA-1/TRIO-18) among postmenopausal women with advanced ER+/HER2- breast cancer who had not received prior systemic treatment for their advanced disease. Patients received continuous oral letrozole 2.5 mg daily alone or the same letrozole dose and schedule plus oral palbociclib 125 mg, given once daily for 3 weeks followed by 1 week off over repeated 28-day cycles. The primary study endpoint was investigator-assessed progression-free survival in the intent-to-treat population, and these results have recently been published (Finn et al., Lancet Oncol 2015;16:25-35). One of the key secondary endpoints was the evaluation of pain, as measured using the Brief Pain Inventory (BPI) patient-reported outcome tool. The BPI was administered at baseline and on day 1 of every cycle thereafter until disease progression and/or treatment discontinuation. Clinical trial registration This study is registered with ClinicalTrials.gov (NCT00721409). Results There were no statistically significant differences in Pain Severity or Pain Interference scores of the BPI between the two treatment groups for the overall population or among those with any bone disease at baseline. A limitation of the study is that results were not adjusted for the concomitant use of opioids or other medications used to control pain. Conclusions The addition of palbociclib to letrozole was associated with increased efficacy without negatively impacting pain severity or pain interference with daily activities.

Glyceollin I reverses epithelial to mesenchymal transition in letrozole resistance

USDA-ARS?s Scientific Manuscript database

Although aromatase inhibitors, such as letrozole; are standard endocrine therapy for postmenopausal women with early stage metastatic estrogen-dependent breast cancer, the major limitation in managing this disease is the development of drug resistance; therefore, a better understanding of this proce...

The Gut Microbiome Is Altered in a Letrozole-Induced Mouse Model of Polycystic Ovary Syndrome

PubMed Central

Kelley, Scott T.; Skarra, Danalea V.; Rivera, Alissa J.; Thackray, Varykina G.

2016-01-01

Women with polycystic ovary syndrome (PCOS) have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. The large intestine contains a complex community of microorganisms (the gut microbiome) that is dysregulated in humans with obesity and type 2 diabetes. Using a letrozole-induced PCOS mouse model, we demonstrated significant diet-independent changes in the gut microbial community, suggesting that gut microbiome dysbiosis may also occur in PCOS women. Letrozole treatment was associated with a time-dependent shift in the gut microbiome and a substantial reduction in overall species and phylogenetic richness. Letrozole treatment also correlated with significant changes in the abundance of specific Bacteroidetes and Firmicutes previously implicated in other mouse models of metabolic disease in a time-dependent manner. Our results suggest that the hyperandrogenemia observed in PCOS may significantly alter the gut microbiome independently of diet. PMID:26731268

Effects of cisplatin and letrozole on surgically induced endometriosis and comparison of the two medications in a rat model.

PubMed

Li, Zhanfei; Liu, Huibing; He, Zhengxing; Zhang, Guorui; Lang, Jinghe

2016-10-10

This study was to investigate the effects of cisplatin (CDDP) and letrozole on surgically induced endometriosis and comparison of the two drugs in a rat model. Endometriosis was surgically induced by autologous transplantation of endometrial pieces. Thirty model rats were divided into three groups, randomly. Group 1 (n=10) served as control and received no medication. Group 2 (n=10) received 0.2mg/kg/day of oral letrozole. Group 3 (n=10) received 35mg/m(2) CDDP via peritoneal perfusion every four days. All the rats were treated for 24days. The growth and histologic score of the implants were evaluated. The proliferation- and angiogenesis-associated proteins were assessed using immunohistochemistry and western blotting. The serum sex hormones were assayed using ELISA. After the medication, the growth and histologic score of the implants were significantly lower in the 2 and 3 groups than in the control group. The protein expressions of vascular endothelial growth factor (VEGF), aromatase P450 (P450arom), transforming growth factor-beta (TGF-β), and matrix metalloproteinase (MMP)-2, were significantly lower in groups 2 and 3 than in the control group. Further, the P450arom level was lower in the letrozole group than in the CDDP group. The TGF-β and MMP-2 levels were lower in the CDDP group than in the letrozole group. Serum T level was significantly higher in the letrozole group, and serum E2 level was lower in the letrozole group. In conclusion, cisplatin and letrozole caused similar regression of the implants in the endometriosis model rats. But their effects on the proliferation- and angiogenesis-associated protein expressions and the serum sex hormone levels were different. Cisplatin and letrozole might cause the effects in the endometriotic foci through different mechanism. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of raloxifene against letrozole-induced bone loss in chemically-induced model of menopause in mice.

PubMed

Kalam, Abul; Talegaonkar, Sushama; Vohora, Divya

2017-01-15

The deleterious effects of letrozole, an aromatase inhibitor, used in the adjuvant treatment of breast cancer in postmenopausal women, on bone are well-documented and represent a major drawback to its clinical use. Raloxifene, a selective estrogen receptor modulator and a clinically approved anti-osteoporotic drug, has been recently demonstrated to be efficacious in women with breast cancer. The present study evaluated the effects of preventive and curative treatment with raloxifene on letrozole-induced alterations of bone microarchitecture and turnover markers in a chemically-induced menopause model in mice. Swiss strain albino female mice were made menopausal by inducing ovotoxicity using vinyl cyclohexene di epoxide (VCD, 160 mg/kg for 15 days followed by 30 days drug-free period) confirmed by ovarian histology and serum estradiol levels. Effects on femoral and lumbar bones were evaluated by micro CT determination of bone volume, trabecular number, separation, thickness, connective density and trabecular pattern factor and bone turnover markers including ALP, TRAP5b, hydroxyproline and RANKL. In addition to these, markers of Wnt signaling (sclerostin and dickkopf-1) were also evaluated. To rule out the involvement of pharmacokinetic interaction, plasma levels of letrozole and raloxifene were measured following drugs alone and in combination. Though bone loss was observed in VCD treated mice (as indicated by micro CT measurements), it was further enhanced with letrozole administration (1 mg/kg) for one month particularly in epiphysis of femoral bones. Raloxifene (15 mg/kg), whether administered concurrently or post-letrozole was able to revert the structural alterations and changes in turnover markers caused by letrozole to varying degrees (p < 0.01 or p < 0.001). Further, estrogen deficiency following letrozole treatment in ovotoxic mice was associated with significant increase in sclerostin and dickkopf-1 in both lumbar and femur bones (p < 0

Letrozole increases ovarian growth and Cyp17a1 gene expression in the rat ovary

PubMed Central

Ortega, Israel; Sokalska, Anna; Villanueva, Jesus A.; Cress, Amanda B.; Wong, Donna H.; Stener-Victorin, Elisabet; Stanley, Scott D.; Duleba, Antoni J.

2012-01-01

Objective To evaluate the effects of letrozole on ovarian size and steroidogenesis in vivo, as well as on proliferation and steroidogenesis of theca-interstitial cells alone and in coculture with granulosa cells using an in vitro model. Design In vivo and in vitro studies. Setting Research laboratory. Animal(s) Immature Sprague-Dawley female rats. Intervention(s) In vivo effects of letrozole were studied in intact rats receiving either letrozole (90-day continuous-release SC pellets, 400 µg/d) or placebo pellets (control group). In in vitro experiments, theca cells were cultured alone or in coculture with granulosa cells in the absence or presence of letrozole. Main Outcome Measure(s) Deoxyribonucleic acid synthesis was determined by thymidine incorporation assay; steroidogenesis by mass spectrometry; and steroidogenic enzyme messenger RNA (mRNA) expression by polymerase chain reaction. Result(s) In vivo, letrozole induced an increase in ovarian size compared with the control group and also induced a profound increase of androgen, LH levels, and Cyp17a1 mRNA expression. Conversely, a decrease in Star, Cyp11a1, and Hsd3b1 transcripts was observed in letrozole-exposed rats. In vitro, letrozole did not alter either theca cell proliferation or Cyp17a1 mRNA expression. Similarly, letrozole did not affect Cyp17a1 transcripts in granulosa-theca cocultures. Conclusion(s) These findings suggest that letrozole exerts potent, but indirect, effect on growth of rat ovary and dramatically increases androgen levels and Cyp17a1 mRNA expression, the key enzyme regulating the androgen biosynthesis pathway. The present findings reveal novel mechanisms of action of letrozole in the rat ovary. PMID:23200686

Neoadjuvant letrozole in postmenopausal estrogen and/or progesterone receptor positive breast cancer: A phase IIb/III trial to investigate optimal duration of preoperative endocrine therapy

PubMed Central

Krainick-Strobel, Ute E; Lichtenegger, Werner; Wallwiener, Diethelm; Tulusan, Augustinus H; Jänicke, Fritz; Bastert, Gunther; Kiesel, Ludwig; Wackwitz, Birgit; Paepke, Stefan

2008-01-01

Background In recent years, preoperative volume reduction of locally advanced breast cancers, resulting in higher rates of breast-conserving surgery (BCS), has become increasingly important also in postmenopausal women. Clinical interest has come to center on the third-generation nonsteroidal aromatase inhibitors (AIs), including letrozole, for such neoadjuvant endocrine treatment. This usually lasts 3–4 months and has been extended to up to 12 months, but optimal treatment duration has not been fully established. Methods This study was designed as a multicenter, open-label, single-arm, exploratory phase IIb/III clinical trial of letrozole 2.5 mg, one tablet daily, for 4–8 months. The primary objective was to investigate the effect of neoadjuvant treatment duration on tumor regression and BCS eligibility to identify optimal treatment duration. Tumor regression (by clinical examination, mammography, and ultrasound), shift towards BCS eligibility, and safety assessments were the main outcome measures. Standard parametric and nonparametric descriptive statistics were performed. Results Letrozole treatment was received by 32 of the enrolled 33 postmenopausal women (median (range): 67.0 (56–85) years) with unilateral, initially BCS-ineligible primary breast cancer (clinical stage ≥ T2, N0, M0). Letrozole treatment duration in the modified intent-to-treat (ITT; required 4 months' letrozole treatment) analysis population (29 patients) was 4 months in 14 patients and > 4 months in 15 patients. The respective per-protocol (PP) subgroup sizes were 14 and 11. The majority of partial or complete responses were observed at 4 months, though some beneficial responses occurred during prolonged letrozole treatment. Compared with baseline, median tumor size in the ITT population was reduced by 62.5% at Month 4 and by 70.0% at final study visit (Individual End). Similarly, in the PP population, respective reductions were 64.0% and 67.0%. Whereas initially all patients were

Updated results from MONALEESA-2, a phase III trial of first-line ribociclib plus letrozole versus placebo plus letrozole in hormone receptor-positive, HER2-negative advanced breast cancer.

PubMed

Hortobagyi, G N; Stemmer, S M; Burris, H A; Yap, Y S; Sonke, G S; Paluch-Shimon, S; Campone, M; Petrakova, K; Blackwell, K L; Winer, E P; Janni, W; Verma, S; Conte, P; Arteaga, C L; Cameron, D A; Mondal, S; Su, F; Miller, M; Elmeliegy, M; Germa, C; O'Shaughnessy, J

2018-04-27

The phase III MONALEESA-2 study demonstrated significantly prolonged progression-free survival (PFS) and a manageable toxicity profile for first-line ribociclib plus letrozole versus placebo plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer. Here we report updated efficacy and safety data, together with exploratory biomarker analyses, from the MONALEESA-2 study. A total of 668 postmenopausal women with HR+, HER2- recurrent/metastatic breast cancer were randomized (1:1; stratified by presence/absence of liver and/or lung metastases) to ribociclib (600 mg/day; 3-weeks-on/1-week-off; 28-day treatment cycles) plus letrozole (2.5 mg/day; continuous) or placebo plus letrozole. The primary endpoint was locally assessed PFS. The key secondary endpoint was overall survival (OS). Other secondary endpoints included overall response rate (ORR) and safety. Biomarker analysis was an exploratory endpoint. At the time of the second interim analysis, the median duration of follow-up was 26.4 months. Median PFS was 25.3 months (95% confidence interval [CI], 23.0-30.3) for ribociclib plus letrozole and 16.0 months (95% CI, 13.4-18.2) for placebo plus letrozole (hazard ratio 0.568; 95% CI, 0.457-0.704; log-rank P=9.63 × 10-8). Ribociclib treatment benefit was maintained irrespective of PIK3CA or TP53 mutation status, total Rb, Ki67, or p16 protein expression, and CDKN2A, CCND1, or ESR1 mRNA levels. Ribociclib benefit was more pronounced in patients with wild-type versus altered receptor tyrosine kinase genes. OS data remain immature, with 116 deaths observed; 50 in the ribociclib arm and 66 in the placebo arm (hazard ratio: 0.746; 95% CI, 0.517-1.078). The ORR was 42.5% versus 28.7% for all patients treated with ribociclib plus letrozole versus placebo plus letrozole, respectively, and 54.5% versus 38.8%, respectively, for patients with measurable disease. Safety results, after a

Comparative Efficacy and Safety of Adjuvant Letrozole Versus Anastrozole in Postmenopausal Patients With Hormone Receptor-Positive, Node-Positive Early Breast Cancer: Final Results of the Randomized Phase III Femara Versus Anastrozole Clinical Evaluation (FACE) Trial.

PubMed

Smith, Ian; Yardley, Denise; Burris, Howard; De Boer, Richard; Amadori, Dino; McIntyre, Kristi; Ejlertsen, Bent; Gnant, Michael; Jonat, Walter; Pritchard, Kathleen I; Dowsett, Mitch; Hart, Lowell; Poggio, Susan; Comarella, Lisa; Salomon, Herve; Wamil, Barbara; O'Shaughnessy, Joyce

2017-04-01

Purpose The Letrozole (Femara) Versus Anastrozole Clinical Evaluation (FACE) study compared the efficacy and safety of adjuvant letrozole versus anastrozole in postmenopausal patients with hormone receptor (HR) -positive and node-positive early breast cancer (eBC). Methods Postmenopausal women with HR-positive and node-positive eBC were randomly assigned to receive adjuvant therapy with either letrozole (2.5 mg) or anastrozole (1 mg) once per day for 5 years or until recurrence of disease. Patients were stratified on the basis of the number of lymph nodes and human epidermal growth factor receptor 2 status. The primary end point was 5-year disease-free survival (DFS), and the key secondary end points were overall survival and safety. Results A total of 4,136 patients were randomly assigned to receive either letrozole (n = 2,061) or anastrozole (n = 2,075). The final analysis was done at 709 DFS events (letrozole, 341 [16.5%]; anastrozole, 368 [17.7%]). The 5-year estimated DFS rate was 84.9% for letrozole versus 82.9% for anastrozole arm (hazard ratio, 0.93; 95% CI, 0.80 to 1.07; P = .3150). Exploratory analysis showed similar DFS with letrozole and anastrozole in all evaluated subgroups. The 5-year estimated overall survival rate was 89.9% for letrozole versus 89.2% for anastrozole arm (hazard ratio, 0.98; 95% CI, 0.82 to 1.17; P = .7916). Most common grade 3 to 4 adverse events (> 5% of patients) reported for letrozole versus anastrozole were arthralgia (3.9% v 3.3%, and 48.2% v 47.9% for all adverse events), hypertension (1.2% v 1.0%), hot flushes (0.8% v 0.4%), myalgia (0.8% v 0.7%), dyspnea (0.8% v 0.5%), and depression (0.8% v 0.6%). Conclusion Letrozole did not demonstrate significantly superior efficacy or safety compared with anastrozole in postmenopausal patients with HR-positive, node-positive eBC.

Letrozole is superior to anastrozole in suppressing breast cancer tissue and plasma estrogen levels.

PubMed

Geisler, Jürgen; Helle, Hilgegunn; Ekse, Dagfinn; Duong, Nhat K; Evans, Dean B; Nordbø, Yngve; Aas, Turid; Lønning, Per E

2008-10-01

To evaluate the influence of the third-generation aromatase inhibitor letrozole (Femara) on breast cancer tissue levels of estrone (E(1)), estradiol (E(2)), and estrone sulfate (E(1)S) in postmenopausal women undergoing primary treatment for locally advanced estrogen receptor/progesterone receptor-positive breast cancers. Breast cancer tissue samples were collected before and following 4 months of neoadjuvant therapy with letrozole (2.5 mg o.d.), and tissue estrogen levels measured using a highly sensitive RIA after high-pressure liquid chromatography purification. Letrozole suppressed pretreatment tumor levels of E(2), E(1), and E(1)S by 97.6%, 90.7%, and 90.1%, respectively. These data reveal that letrozole suppresses tissue estrogen levels significantly below what has previously been recorded with anastrozole (89.0%, 83.4%, and 72.9% suppression, respectively) using the same methods. To confirm the differential effect of letrozole and anastrozole on each plasma estrogen fraction, we re-analyzed plasma samples obtained from a previous intrapatient cross-over study comparing letrozole and anastrozole using an improved RIA (detection limits of 0.67, 1.14, and 0.55 pmol/L for E(2), E(1), and E(1)S, respectively). Letrozole consistently suppressed each plasma estrogen fraction below the levels recorded for anastrozole: E(2) (average suppression by 95.2% versus 92.8%; P = 0.018), E(1) (98.8% suppression versus 96.3%; P = 0.003), and E(1)S (98.9% suppression versus 95.3%; P = 0.003). Our data reveals that letrozole (2.5 mg o.d.) is more effective compared with anastrozole (1.0 mg o.d.) with respect to tissue as well as plasma estrogen suppression in patients with postmenopausal breast cancer.

Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

PubMed Central

Wolff, Antonio C.; Lazar, Ann A.; Bondarenko, Igor; Garin, August M.; Brincat, Stephen; Chow, Louis; Sun, Yan; Neskovic-Konstantinovic, Zora; Guimaraes, Rodrigo C.; Fumoleau, Pierre; Chan, Arlene; Hachemi, Soulef; Strahs, Andrew; Cincotta, Maria; Berkenblit, Anna; Krygowski, Mizue; Kang, Lih Lisa; Moore, Laurence; Hayes, Daniel F.

2013-01-01

Purpose Recent data showed improvement in progression-free survival (PFS) when adding everolimus to exemestane in patients with advanced breast cancer experiencing recurrence/progression after nonsteroidal aromatase inhibitor (AI) therapy. Here, we report clinical outcomes of combining the mammalian target of rapamycin (mTOR) inhibitor temsirolimus with letrozole in AI-naive patients. Patients and Methods This phase III randomized placebo-controlled study tested efficacy/safety of first-line oral letrozole 2.5 mg daily/temsirolimus 30 mg daily (5 days every 2 weeks) versus letrozole/placebo in 1,112 patients with AI-naive, hormone receptor–positive advanced disease. An independent data monitoring committee recommended study termination for futility at the second preplanned interim analysis (382 PFS events). Results Patients were balanced (median age, 63 years; 10% stage III, 40% had received adjuvant endocrine therapy). Those on letrozole/temsirolimus experienced more grade 3 to 4 events (37% v 24%). There was no overall improvement in primary end point PFS (median, 9 months; hazard ratio [HR], 0.90; 95% CI, 0.76 to 1.07; P = .25) nor in the 40% patient subset with prior adjuvant endocrine therapy. An exploratory analysis showed improved PFS favoring letrozole/temsirolimus in patients ≤ age 65 years (9.0 v 5.6 months; HR, 0.75; 95% CI, 0.60 to 0.93; P = .009), which was separately examined by an exploratory analysis of 5-month PFS using subpopulation treatment effect pattern plot methodology (P = .003). Conclusion Adding temsirolimus to letrozole did not improve PFS as first-line therapy in patients with AI-naive advanced breast cancer. Exploratory analyses of benefit in younger postmenopausal patients require external confirmation. PMID:23233719

THE PREGNANCY IN POLYCYSTIC OVARY SYNDROME II (PPCOS II) TRIAL: RATIONALE AND DESIGN OF A DOUBLE-BLIND RANDOMIZED TRIAL OF CLOMIPHENE CITRATE AND LETROZOLE FOR THE TREATMENT OF INFERTILITY IN WOMEN WITH POLYCYSTIC OVARY SYNDROME

PubMed Central

Legro, Richard S.; Kunselman, Allen R.; Brzyski, Robert G.; Casson, Peter R.; Diamond, Michael P.; Schlaff, William D.; Christman, Gregory M.; Coutifaris, Christos; Taylor, Hugh S.; Eisenberg, Esther; Santoro, Nanette; Zhang, Heping

2012-01-01

Polycystic Ovary Syndrome (PCOS) is a common cause of female infertility and first line treatment is currently oral clomiphene citrate, a selective estrogen receptor modulator, which results in both a high nonresponse rate and multiple pregnancy rate. Aromatase inhibitors such as letrozole may have more favorable ovarian and endometrial effects. The goal of the Pregnancy in Polycystic Ovary Syndrome II (PPCOSII) study is to determine the safety and efficacy of clomiphene citrate (CC) compared to letrozole, in achieving live birth in infertile women with PCOS. The population will consist of 750 infertile women with PCOS. Additionally, the couple will have no other major infertility factor. This will be a multi-center, prospective, double-blind clinical trial of CC vs. letrozole for 5 treatment cycles (or approximately up to 25 weeks). The randomization scheme will be coordinated through the central data coordinating center (DCC) and the randomization is stratified by each participating site. After progestin withdrawal as needed, 750 women will be equally randomized to two different treatment arms: A) CC 50 mg every day for 5 days (day 3–7 of cycle), or B) letrozole 2.5 mg every day for 5 days (day 3–7 of cycle), for a total of 5 cycles or 25 weeks. The dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of CC a day (× 5 days) or 7.5 mg of letrozole a day (× 5 days). The primary analysis will use an intent-to-treat approach to examine differences in the live birth rate in the two treatment arms. PMID:22265923

Gonadotropin-Releasing Hormone Agonist Combined With a Levonorgestrel-Releasing Intrauterine System or Letrozole for Fertility-Preserving Treatment of Endometrial Carcinoma and Complex Atypical Hyperplasia in Young Women.

PubMed

Zhou, Huimei; Cao, Dongyan; Yang, Jiaxin; Shen, Keng; Lang, Jinghe

2017-07-01

The aim of this study was to evaluate the efficacy and safety with gonadotropin-releasing hormone agonist (GnRHa) combined with a levonorgestrel-releasing intrauterine system or an aromatase inhibitor (letrozole) in young women with well-differentiated early endometrial carcinoma (EC) and complex atypical hyperplasia (CAH). We performed a retrospective analysis including the clinical characteristics of 29 patients younger than 45 years with early well-differentiated endometrioid adenocarcinoma of the uterus (EC) or CAH who were treated at the Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, from January 2012 to April 2016. Eighteen patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with the levonorgestrel intrauterine hormonal system (Mirena® Bayer Health Care Pharmaceutical Inc, Wayne, NY) was inserted. Eleven patients were treated with the combination of intramuscular injections of GnRHa every 4 weeks with oral letrozole 2.5 mg daily. The patients underwent follow-up with endometrial sampling by hysteroscopy and curettage for endometrial response every 3 months. After a median follow-up of 18.7 months (range, 5.6-54.9 months), 15 women (88.2%) in the EC group and 12 women (100%) in the CAH group had complete response (CR) after GnRHa combination treatment. Among the women who achieved CR, 1 woman (8.3%) with CAH and 1 woman (5.9%) with EC had recurrence after CR, and they finally underwent a hysterectomy. Time to CR was similar in the 2 groups (4.5 ± 1.9 months in the CAH group vs 5.0 ± 2.9 months in the EC group). Ten women (34.5%) had CR after the first 3 months, 8 women (27.6%) had CR after 6 months, and 9 women (31.0%) had CR after 9 months. Both GnRHa with the levonorgestrel-releasing intrauterine system and GnRHa with letrozole are alternative treatments for women with CAH and EC who desire fertility preservation. A larger multicenter trial of the fertility-preserving treatment is

A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

PubMed Central

2010-01-01

Background Aromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC. Methods We analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood. Results Thirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009). Conclusions Our study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients. PMID:20144226

The Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) trial: rationale and design of a double-blind randomized trial of clomiphene citrate and letrozole for the treatment of infertility in women with polycystic ovary syndrome.

PubMed

Legro, Richard S; Kunselman, Allen R; Brzyski, Robert G; Casson, Peter R; Diamond, Michael P; Schlaff, William D; Christman, Gregory M; Coutifaris, Christos; Taylor, Hugh S; Eisenberg, Esther; Santoro, Nanette; Zhang, Heping

2012-05-01

Polycystic Ovary Syndrome (PCOS) is a common cause of female infertility and first line treatment is currently oral clomiphene citrate, a selective estrogen receptor modulator, which results in both a high nonresponse rate and multiple pregnancy rate. Aromatase inhibitors such as letrozole may have more favorable ovarian and endometrial effects. The goal of the Pregnancy in Polycystic Ovary Syndrome II (PPCOSII) study is to determine the safety and efficacy of clomiphene citrate (CC) compared to letrozole, in achieving live birth in infertile women with PCOS. The population will consist of 750 infertile women with PCOS. Additionally, the couple will have no other major infertility factor. This will be a multi-center, prospective, double-blind clinical trial of CC vs. letrozole for 5 treatment cycles (or approximately up to 25 weeks). The randomization scheme will be coordinated through the central data coordinating center (DCC) and the randomization is stratified by each participating site. After progestin withdrawal as needed, 750 women will be equally randomized to two different treatment arms: A) CC 50mg every day for 5 days (days 3-7 of cycle), or B) letrozole 2.5mg every day for 5 days (days 3-7 of cycle), for a total of 5 cycles or 25 weeks. The dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of CC a day (×5 days) or 7.5mg of letrozole a day (×5 days). The primary analysis will use an intent-to-treat approach to examine differences in the live birth rate in the two treatment arms. Copyright © 2012 Elsevier Inc. All rights reserved.

Adjuvant letrozole versus tamoxifen according to centrally-assessed ERBB2 status for postmenopausal women with endocrine-responsive early breast cancer: supplementary results from the BIG 1-98 randomised trial.

PubMed

Rasmussen, Birgitte B; Regan, Meredith M; Lykkesfeldt, Anne E; Dell'Orto, Patrizia; Del Curto, Barbara; Henriksen, Katrine L; Mastropasqua, Mauro G; Price, Karen N; Méry, Eliane; Lacroix-Triki, Magali; Braye, Stephen; Altermatt, Hans J; Gelber, Richard D; Castiglione-Gertsch, Monica; Goldhirsch, Aron; Gusterson, Barry A; Thürlimann, Beat; Coates, Alan S; Viale, Giuseppe

2008-01-01

The Breast International Group (BIG) 1-98 trial (a randomised double-blind phase III trial) has shown that letrozole significantly improves disease-free survival (DFS) compared with tamoxifen in postmenopausal women with endocrine-responsive early breast cancer. Our aim was to establish whether the benefit of letrozole versus tamoxifen differs according to the ERBB2 status of tumours. The BIG 1-98 trial consists of four treatment groups that compare 5 years of monotherapy with letrozole or tamoxifen, and sequential administration of one drug for 2 years followed by the other drug for 3 years. Our study includes data from the 4922 patients randomly assigned to the two monotherapy treatment groups (letrozole or tamoxifen for 5 years; 51 months median follow-up [range <1 to 90 months]). A central assessment of oestrogen receptor (ER), progesterone receptor (PgR) and ERBB2 status using paraffin-embedded primary tumour material was possible for 3650 (74%) patients. ER, PgR, and ERBB2 expression were measured by immunohistochemistry (IHC) and ERBB2-positivity was confirmed by fluorescence in-situ hybridisation (FISH). Positive staining in at least 1% of cells was considered to show presence of ER or PgR expression. Tumours were deemed ERBB2-positive if amplified by FISH, or, for the few tumours with unassessable or unavailable FISH results, if they were IHC 3+. Hazard ratios (HR) estimated by Cox modelling were used to compare letrozole with tamoxifen for DFS, which was the primary endpoint, and to assess treatment-by-covariate interactions. The BIG 1-98 trial is registered on the clinical trials site of the US National Cancer Institute website http://www.clinicaltrials.gov/ct/show/NCT00004205. By central assessment 7% (257 of 3650) of tumours were classified as ERBB2-positive. In 3533 patients with tumours confirmed to express ER, DFS was poorer in patients with ERBB2-positive tumours (n=239) than in those with ERBB2-negative tumours (n=3294; HR 2.09 [95% CI 1

Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1.

PubMed

Carriere, Patrick P; Llopis, Shawn D; Naiki, Anna C; Nguyen, Gina; Phan, Tina; Nguyen, Mary M; Preyan, Lynez C; Yearby, Letitia; Pratt, Jamal; Burks, Hope; Davenport, Ian R; Nguyen, Thu A; Parker-Lemieux, KiTani; Payton-Stewart, Florastina; Williams, Christopher C; Boué, Stephen M; Burow, Matthew E; Collins-Burow, Bridgette; Hilliard, Aaron; Davidson, A Michael; Tilghman, Syreeta L

2015-12-22

Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a -3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer.

Glyceollin I Reverses Epithelial to Mesenchymal Transition in Letrozole Resistant Breast Cancer through ZEB1

PubMed Central

Carriere, Patrick P.; Llopis, Shawn D.; Naiki, Anna C.; Nguyen, Gina; Phan, Tina; Nguyen, Mary M.; Preyan, Lynez C.; Yearby, Letitia; Pratt, Jamal; Burks, Hope; Davenport, Ian R.; Nguyen, Thu A.; Parker-Lemieux, KiTani; Payton-Stewart, Florastina; Williams, Christopher C.; Boué, Stephen M.; Burow, Matthew E.; Collins-Burow, Bridgette; Hilliard, Aaron; Davidson, A. Michael; Tilghman, Syreeta L.

2015-01-01

Although aromatase inhibitors are standard endocrine therapy for postmenopausal women with early-stage metastatic estrogen-dependent breast cancer, they are limited by the development of drug resistance. A better understanding of this process is critical towards designing novel strategies for disease management. Previously, we demonstrated a global proteomic signature of letrozole-resistance associated with hormone-independence, enhanced cell motility and implications of epithelial mesenchymal transition (EMT). Letrozole-resistant breast cancer cells (LTLT-Ca) were treated with a novel phytoalexin, glyceollin I, and exhibited morphological characteristics synonymous with an epithelial phenotype and decreased proliferation. Letrozole-resistance increased Zinc Finger E-Box Binding Homeobox 1 (ZEB1) expression (4.51-fold), while glyceollin I treatment caused a −3.39-fold reduction. Immunofluorescence analyses resulted of glyceollin I-induced increase and decrease in E-cadherin and ZEB1, respectively. In vivo studies performed in ovariectomized, female nude mice indicated that glyceollin treated tumors stained weakly for ZEB1 and N-cadherin and strongly for E-cadherin. Compared to letrozole-sensitive cells, LTLT-Ca cells displayed enhanced motility, however in the presence of glyceollin I, exhibited a 68% and 83% decrease in invasion and migration, respectively. These effects of glyceollin I were mediated in part by inhibition of ZEB1, thus indicating therapeutic potential of glyceollin I in targeting EMT in letrozole resistant breast cancer. PMID:26703648

Controlled ovarian hyperstimulation with sequential letrozole co-treatment in normo/high responders.

PubMed

Ecemis, Tolga; Tasci, Yasemin; Caglar, Gamze Sinem

2016-01-01

To investigate the effect of co-administration of letrozole in an ovarian stimulation protocol using recombinant FSH and GnRH antagonists for ICSI in normo/high responders. Computerized data of 320 antagonist ICSI/ET cycles with or without letrozole were retrospectively analyzed. In 105 cases, letrozole (5 mg/day) was started at the second day of the cycle continued for 5 days. At the second day of letrozole, gonadotropins were added. The remaining 215 cases were stimulated with recombinant FSH only. In all cases on day 6, GnRH antagonist was started. Ovarian stimulation protocols with or without letrozole were compared for cycle outcome parameters. In cycles with letrozole, significantly lower gonadotropin consumption and lower peak estradiol levels were found. In cycles with letrozole, mean number of metaphase II and fertilized oocytes retrieved were significantly higher compared to cycles without letrozole. The pregnancy and clinical pregnancy rates were similar. Should the number of oocytes retrieved being higher in letrozole group might indicate that letrozole might contribute to successful ovarian stimulation with a lower dosage of gonadotropins. Despite the lower peak estradiol levels, pregnancy rates being similar to other group also support the idea that letrozole can contribute to normal potential of implantation.

Approval summary: letrozole (Femara® tablets) for adjuvant and extended adjuvant postmenopausal breast cancer treatment: conversion of accelerated to full approval.

PubMed

Cohen, Martin H; Johnson, John R; Justice, Robert; Pazdur, Richard

2011-01-01

On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor-positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77-0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76-1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen.

GP88 (PC-Cell Derived Growth Factor, progranulin) stimulates proliferation and confers letrozole resistance to aromatase overexpressing breast cancer cells

PubMed Central

2011-01-01

Background Aromatase inhibitors (AI) that inhibit breast cancer cell growth by blocking estrogen synthesis have become the treatment of choice for post-menopausal women with estrogen receptor positive (ER+) breast cancer. However, some patients display de novo or acquired resistance to AI. Interactions between estrogen and growth factor signaling pathways have been identified in estrogen-responsive cells as one possible reason for acquisition of resistance. Our laboratory has characterized an autocrine growth factor overexpressed in invasive ductal carcinoma named PC-Cell Derived Growth Factor (GP88), also known as progranulin. In the present study, we investigated the role GP88 on the acquisition of resistance to letrozole in ER+ breast cancer cells Methods We used two aromatase overexpressing human breast cancer cell lines MCF-7-CA cells and AC1 cells and their letrozole resistant counterparts as study models. Effect of stimulating or inhibiting GP88 expression on proliferation, anchorage-independent growth, survival and letrozole responsiveness was examined. Results GP88 induced cell proliferation and conferred letrozole resistance in a time- and dose-dependent fashion. Conversely, naturally letrozole resistant breast cancer cells displayed a 10-fold increase in GP88 expression when compared to letrozole sensitive cells. GP88 overexpression, or exogenous addition blocked the inhibitory effect of letrozole on proliferation, and stimulated survival and soft agar colony formation. In letrozole resistant cells, silencing GP88 by siRNA inhibited cell proliferation and restored their sensitivity to letrozole. Conclusion Our findings provide information on the role of an alternate growth and survival factor on the acquisition of aromatase inhibitor resistance in ER+ breast cancer. PMID:21658239

Endocrine effects of adjuvant letrozole compared with tamoxifen in hormone-responsive postmenopausal patients with early breast cancer: the HOBOE trial.

PubMed

Rossi, Emanuela; Morabito, Alessandro; Di Rella, Francesca; Esposito, Giuseppe; Gravina, Adriano; Labonia, Vincenzo; Landi, Gabriella; Nuzzo, Francesco; Pacilio, Carmen; De Maio, Ermelinda; Di Maio, Massimo; Piccirillo, Maria Carmela; De Feo, Gianfranco; D'Aiuto, Giuseppe; Botti, Gerardo; Chiodini, Paolo; Gallo, Ciro; Perrone, Francesco; de Matteis, Andrea

2009-07-01

PURPOSE We compared the endocrine effects of 6 and 12 months of adjuvant letrozole versus tamoxifen in postmenopausal patients with hormone-responsive early breast cancer within an ongoing phase III trial. PATIENTS AND METHODS Patients were randomly assigned to receive tamoxifen, letrozole, or letrozole plus zoledronic acid. Serum values of estradiol, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, dehydroepiandrosterone-sulphate (DHEA-S), progesterone, and cortisol were measured at baseline and after 6 and 12 months of treatment. For each hormone, changes from baseline at 6 and 12 months were compared between treatment groups, and differences over time for each group were analyzed. Results Hormonal data were available for 139 postmenopausal patients with a median age of 62 years, with 43 patients assigned to tamoxifen and 96 patients assigned to letrozole alone or combined with zoledronic acid. Baseline values were similar between the two groups for all hormones. Many significant changes were observed between drugs and for each drug over time. Namely, three hormones seemed significantly affected by one drug only: estradiol that decreased and progesterone that increased with letrozole and cortisol that increased with tamoxifen. Both drugs affected FSH (decreasing with tamoxifen and slightly increasing with letrozole), LH (decreasing more with tamoxifen than with letrozole), testosterone (slightly increasing with letrozole but not enough to differ from tamoxifen), and DHEA-S (increasing with both drugs but not differently between them). Zoledronic acid did not have significant impact on hormonal levels. CONCLUSION Adjuvant letrozole and tamoxifen result in significantly distinct endocrine effects. Such differences can explain the higher efficacy of letrozole as compared with tamoxifen.

Intratumoral concentration of estrogens and clinicopathological changes in ductal carcinoma in situ following aromatase inhibitor letrozole treatment

PubMed Central

Takagi, K; Ishida, T; Miki, Y; Hirakawa, H; Kakugawa, Y; Amano, G; Ebata, A; Mori, N; Nakamura, Y; Watanabe, M; Amari, M; Ohuchi, N; Sasano, H; Suzuki, T

2013-01-01

Background: Estrogens have important roles in ductal carcinoma in situ (DCIS) of the breast. However, the significance of presurgical aromatase inhibitor treatment remains unclear. Therefore, we examined intratumoral concentration of estrogens and changes of clinicopathological factors in DCIS after letrozole treatment. Methods: Ten cases of postmenopausal oestrogen receptor (ER)-positive DCIS were examined. They received oral letrozole before the surgery, and the tumour size was evaluated by ultrasonography. Surgical specimens and corresponding biopsy samples were used for immunohistochemistry. Snap-frozen specimens were also available in a subset of cases, and used for hormone assays and microarray analysis. Results: Intratumoral oestrogen levels were significantly lower in DCIS treated with letrozole compared with that in those without the therapy. A great majority of oestrogen-induced genes showed low expression levels in DCIS treated with letrozole by microarray analysis. Moreover, letrozole treatment reduced the greatest dimension of DCIS, and significantly decreased Ki-67 and progesterone receptor immunoreactivity in DCIS tissues. Conclusion: These results suggest that estrogens are mainly produced by aromatase in DCIS tissues, and aromatase inhibitors potently inhibit oestrogen actions in postmenopausal ER-positive DCIS through rapid deprivation of intratumoral estrogens. PMID:23756858

HDAC inhibitor entinostat restores responsiveness of letrozole resistant MCF-7Ca xenografts to AIs through modulation of Her-2

PubMed Central

Sabnis, Gauri J.; Goloubeva, Olga G.; Kazi, Armina A.; Shah, Preeti; Brodie, Angela H.

2013-01-01

We previously showed that in innately resistant tumors, silencing of the estrogen receptor (ER) could be reversed by treatment with a histone deacetylase (HDAC) inhibitor entinostat (ENT). Tumors were then responsive to aromatase inhibitor (AIs) letrozole. Here, we investigated whether ER in the acquired letrozole resistant tumors could be restored with ENT. Ovariectomized athymic mice were inoculated with MCF-7Ca cells, supplemented with androstenedione (Δ4A), the aromatizable substrate. When the tumors reached ~300mm3, the mice were treated with letrozole. After initial response to letrozole, the tumors eventually became resistant (doubled their initial volume). The mice then were grouped to receive letrozole, exemestane (250μg/day), ENT (50μg/day) or the combination of ENT with letrozole or exemestane for 26 weeks. The growth rates of tumors of mice treated with the combination of ENT with letrozole or exemestane were significantly slower than with the single agent (p<0.05). Analysis of the letrozole resistant tumors showed ENT increased ERα expression and aromatase activity but downregulated Her-2, p-Her-2, p-MAPK and p-Akt. However, the mechanism of action of ENT in reversing acquired resistance did not involve epigenetic silencing, but rather included post-translational as well as transcriptional modulation of Her-2. ENT treatment reduced the association of the Her-2 protein with HSP-90, possibly by reducing the stability of Her-2 protein. In addition, ENT also reduced Her-2 mRNA levels and its stability. Our results suggest that the HDAC inhibitor may reverse letrozole resistance in cells and tumors by modulating Her-2 expression and activity. PMID:24092810

Effect of age and single versus multiple dose pharmacokinetics of letrozole (Femara) in breast cancer patients.

PubMed

Pfister, C U; Martoni, A; Zamagni, C; Lelli, G; De Braud, F; Souppart, C; Duval, M; Hornberger, U

2001-07-01

Letrozole (trademark Femara) is a new orally active, potent and selective aromatase inhibitor for the hormonal treatment of advanced breast cancer in postmenopausal women. The pharmacokinetics of letrozole and the suppression of peripheral estrogens were studied in 28 breast cancer patients after a single dose and at steady state. The pharmacokinetics of two distinct age groups (> or =50, < or =65, N=15 and > or =70 years old, N=9) were compared. There were no significant differences in area under the curve (AUC) or terminal half-life between the two age groups neither after a single dose nor at steady state. However, when comparing steady state to single dose kinetics, half-life and AUC increased significantly by 42% (90% CI: 1.13, 1.78) and 28% (90% CI: 1.12, 1.47), respectively. This deviation from linearity was probably due to a partial saturation or auto-inhibition of the dominant metabolic clearance mechanism of letrozole. At steady state, approximately 70% of the administered dose was excreted in urine as unchanged letrozole (6.0+/-3.8%) or as the glucuronide of the major, pharmacologically inactive metabolite CGP44645 (64.2+/-22.7%). A single dose of letrozole caused suppression of serum estrogen levels close to the quantification limit of the assay. No difference between single dose suppression and suppression at steady state could be detected. Copyright 2001 John Wiley & Sons, Ltd.

Effects of Letrozole-HMG and Clomiphene-HMG on Incidence of Luteinized Unruptured Follicle Syndrome in Infertile Women Undergoing Induction Ovulation and Intrauterine Insemination: A Randomised Trial.

PubMed

Azmoodeh, Azra; Pejman Manesh, Mansoureh; Akbari Asbagh, Firouzeh; Ghaseminejad, Azizeh; Hamzehgardeshi, Zeinab

2015-09-01

Luteinized unruptured follicle (LUF) syndrome is considered a cause of ovulation failure and a subtle cause of infertility. Preovulatory injection of human chorionic gonadotropin (HCG) prevents or treats LUF syndrome, but it has also occurred after the induction of ovulation with clomiphene/HMG and HCG. This study was designed for evaluation and comparison of LUF incidence in eligible infertile women undergoing two stimulation protocols (clomiphene + HMG and letrozole + HMG) in addition to intrauterine insemination (IUI). Some related factors were compared between LUF and non-LUF cycles as secondary outcomes. The study was designed as a prospective randomized controlled trial. Patients were randomized using a table of random numbers into two equal protocol groups. For group A, (n = 90) clomiphene citrate was administrated orally in doses of 100 mg/day, and group B (n = 90) orally received letrozole 5 mg/day from day 3 to 7 of the menstrual cycle. Then HMG 75IU/day was administered intramuscularly in both groups on day 8 of the menstrual cycle and the dose was adjusted on the basis of ovarian response. The optimum size of preovulatory follicles for the injection of HCG (10,000 IU) was considered 18-23 mm. The number and size of preovulatory follicles were assessed by vaginal ultrasound 12 h before HCG (D0). Endometrial thickness was measured as well. IUI was performed on all patients 38-40 h after HCG. The second ultrasound examination was performed to observe the evidence of oocyte releasing at the time of IUI (D1). If the follicles were unruptured, a third sonography was performed on day 7 after HCG (D7) to observe LUF syndrome. There was a significant difference between clomiphene-HMG and letrozole-HMG in LUF (p = 0.021) and pregnancy (p = 0.041). The complete LUF in letrozole-HMG was lower than the alternative group and the pregnancy rate was higher. The patients in the non-LUF group had higher midluteal progesterone and a thicker endometrium compared to LUF

Differences between the non-steroidal aromatase inhibitors anastrozole and letrozole--of clinical importance?

PubMed

Geisler, J

2011-03-29

Aromatase inhibition is the gold standard for treatment of early and advanced breast cancer in postmenopausal women suffering from an estrogen receptor-positive disease. The currently established group of anti-aromatase compounds comprises two reversible aromatase inhibitors (anastrozole and letrozole) and on the other hand, the irreversible aromatase inactivator exemestane. Although exemestane is the only widely used aromatase inactivator at this stage, physicians very often have to choose between either anastrozole or letrozole in general practice. These third-generation aromatase inhibitors (letrozole/Femara (Novartis Pharmaceuticals, Basel, Switzerland) and anastrozole/Arimidex (AstraZeneca, Pharmaceuticals, Macclesfield, Cheshire, UK)), have recently demonstrated superior efficacy compared with tamoxifen as initial therapy for early breast cancer improving disease-free survival. However, although anastrozole and letrozole belong to the same pharmacological class of agents (triazoles), an increasing body of evidence suggests that these aromatase inhibitors are not equipotent when given in the clinically established doses. Preclinical and clinical evidence indicates distinct pharmacological profiles. Thus, this review focuses on the differences between the non-steroidal aromatase inhibitors allowing physicians to choose between these compounds based on scientific evidence. Although we are waiting for the important results of a still ongoing head-to-head comparison in patients with early breast cancer at high risk for relapse (Femara Anastrozole Clinical Evaluation trial; 'FACE-trial'), clinicians have to make their choices today. On the basis of available evidence summarised here and until FACE-data become available, letrozole seems to be the best choice for the majority of breast cancer patients whenever a non-steroidal aromatase inhibitor has to be chosen in a clinical setting. The background for this recommendation is discussed in the following chapters.

5-year follow-up of a randomized controlled trial of immediate versus delayed zoledronic acid for the prevention of bone loss in postmenopausal women with breast cancer starting letrozole after tamoxifen: N03CC (Alliance) trial.

PubMed

Wagner-Johnston, Nina D; Sloan, Jeff A; Liu, Heshan; Kearns, Ann E; Hines, Stephanie L; Puttabasavaiah, Suneetha; Dakhil, Shaker R; Lafky, Jacqueline M; Perez, Edith A; Loprinzi, Charles L

2015-08-01

Postmenopausal women with breast cancer receiving aromatase inhibitors are at an increased risk of bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report described the 5-year follow-up results. A total of 551 postmenopausal women with breast cancer who completed tamoxifen treatment and were undergoing daily letrozole treatment were randomized to either upfront (274 patients) or delayed (277 patients) ZA at a dose of 4 mg intravenously every 6 months. In the patients on the delayed treatment arm, ZA was initiated for a postbaseline bone mineral density T-score of <-2.0 or fracture. The incidence of a 5% decrease in the total lumbar spine bone mineral density at 5 years was 10.2% in the upfront treatment arm versus 41.2% in the delayed treatment arm (P<.0001). A total of 41 patients in the delayed treatment arm were eventually started on ZA. With the exception of increased NCI Common Toxicity Criteria (CTC) grade 1/2 elevated creatinine and fever in the patients treated on the upfront arm and cerebrovascular ischemia among those in the delayed treatment arm, there were no significant differences observed between arms with respect to the most common adverse events of arthralgia and back pain. Osteoporosis occurred less frequently in the upfront treatment arm (2 vs 8 cumulative cases), although this difference was not found to be statistically significant. Bone fractures occurred in 24 patients in the upfront treatment arm versus 25 patients in the delayed treatment arm. Immediate treatment with ZA prevented bone loss compared with delayed treatment in postmenopausal women receiving letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not found to be significantly different between treatment arms. © 2015 American Cancer Society.

Proteomic Signatures of Acquired Letrozole Resistance in Breast Cancer: Suppressed Estrogen Signaling and Increased Cell Motility and Invasiveness*

PubMed Central

Tilghman, Syreeta L.; Townley, Ian; Zhong, Qiu; Carriere, Patrick P.; Zou, Jin; Llopis, Shawn D.; Preyan, Lynez C.; Williams, Christopher C.; Skripnikova, Elena; Bratton, Melyssa R.; Zhang, Qiang; Wang, Guangdi

2013-01-01

Aromatase inhibitors, such as letrozole, have become the first-line treatment for postmenopausal women with estrogen-dependent breast cancer. However, acquired resistance remains a major clinical obstacle. Previous studies demonstrated constitutive activation of the MAPK signaling, overexpression of HER2, and down-regulation of aromatase and ERα in letrozole-resistant breast cancer cells. Given the complex signaling network involved in letrozole-refractory breast cancer and the lack of effective treatment for hormone resistance, further investigation of aromatase inhibitor resistance by a novel systems biology approach may reveal previously unconsidered molecular changes that could be utilized as therapeutic targets. This study was undertaken to characterize for the first time global proteomic alterations occurring in a letrozole-resistant cell line. A quantitative proteomic analysis of the whole cell lysates of LTLT-Ca (resistant) versus AC-1 cells (sensitive) was performed to identify significant protein expression changes. A total of 1743 proteins were identified and quantified, of which 411 were significantly up-regulated and 452 significantly down-regulated (p < 0.05, fold change > 1.20). Bioinformatics analysis revealed that acquired letrozole resistance is associated with a hormone-independent, more aggressive phenotype. LTLT-Ca cells exhibited 84% and 138% increase in migration and invasion compared with the control cells. The ROCK inhibitor partially abrogated the enhanced migration and invasion of the letrozole-resistant cells. Flow cytometric analyses also demonstrated an increase in vimentin and twist expression in letrozole-resistance cells, suggesting an onset of epithelial to mesenchymal transition (EMT). Moreover, targeted gene expression arrays confirmed a 28-fold and sixfold up-regulation of EGFR and HER2, respectively, whereas ERα and pS2 were dramatically reduced by 28-fold and 1100-fold, respectively. Taken together, our study revealed global

Approval Summary: Letrozole (Femara® Tablets) for Adjuvant and Extended Adjuvant Postmenopausal Breast Cancer Treatment: Conversion of Accelerated to Full Approval

PubMed Central

Johnson, John R.; Justice, Robert; Pazdur, Richard

2011-01-01

On April 30, 2010, the U.S. Food and Drug Administration converted letrozole (Femara®; Novartis Pharmaceuticals Corporation, East Hanover, NJ) from accelerated to full approval for adjuvant and extended adjuvant (following 5 years of tamoxifen) treatment of postmenopausal women with hormone receptor–positive early breast cancer. The initial accelerated approvals of letrozole for adjuvant and extended adjuvant treatment on December 28, 2005 and October 29, 2004, respectively, were based on an analysis of the disease-free survival (DFS) outcome of patients followed for medians of 26 months and 28 months, respectively. Both trials were double-blind, multicenter studies. Both trials were unblinded early when an interim analysis showed a favorable letrozole effect on DFS. In updated intention-to-treat analyses of both trials, the risk for a DFS event was lower with letrozole than with tamoxifen (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.77–0.99; p = .03) in the adjuvant trial and was lower than with placebo (HR, 0.89; 95% CI, 0.76–1.03; p = .12) in the extended adjuvant trial. The latter analysis ignores the interim switch of 60% of placebo-treated patients to letrozole. Bone fractures and osteoporosis were reported more frequently following treatment with letrozole whereas tamoxifen was associated with a higher risk for endometrial proliferation and endometrial cancer. Myocardial infarction was more frequently reported with letrozole than with tamoxifen, but the incidence of thromboembolic events was higher with tamoxifen than with letrozole. Lipid-lowering medications were required for 25% of patients on letrozole and 16% of patients on tamoxifen. PMID:22089970

Outcomes of special histotypes of breast cancer after adjuvant endocrine therapy with letrozole or tamoxifen in the monotherapy cohort of the BIG 1-98 trial.

PubMed

Munzone, E; Giobbie-Hurder, A; Gusterson, B A; Mallon, E; Viale, G; Thürlimann, B; Ejlertsen, B; MacGrogan, G; Bibeau, F; Lelkaitis, G; Price, K N; Gelber, R D; Coates, A S; Goldhirsch, A; Colleoni, M

2015-12-01

We investigated the outcomes of postmenopausal women with hormone receptor-positive, early breast cancer with special histotypes (mucinous, tubular, or cribriform) enrolled in the monotherapy cohort of the BIG 1-98 trial. The intention-to-treat BIG 1-98 monotherapy cohort (5 years of therapy with tamoxifen or letrozole) included 4922 women, of whom 4091 had central pathology review. Histotype groups were defined as: mucinous (N = 100), tubular/cribriform (N = 83), ductal (N = 3257), and other (N = 651). Of 183 women with either mucinous or tubular/cribriform tumors, 96 were randomly assigned to letrozole and 87 to tamoxifen. Outcomes assessed were disease-free survival (DFS), overall survival (OS), breast cancer-free interval (BCFI), and distant recurrence-free interval (DRFI). Median follow-up in the analytic cohort was 8.1 years. Women with tubular/cribriform breast cancer had the best outcomes for all end points compared with the other three histotypes, and had less breast cancer recurrence (97.5% 5-year BCFI) than those with mucinous (93.5%), ductal (88.9%), or other (89.9%) histotypes. Patients with mucinous or tubular/cribriform carcinoma had better DRFI (5-year rates 97.8% and 98.8%, respectively) than those with ductal (90.9%) or other (92.1%) carcinomas. Within the subgroup of women with special histotypes, we observed a nonsignificant increase in the hazard of breast cancer recurrence with letrozole [hazard (letrozole versus tamoxifen): 3.31, 95% confidence interval 0.94-11.7; P = 0.06]. Women with mucinous or tubular/cribriform breast cancer have better outcomes than those with other histotypes, although the observation is based on a limited number of events. In postmenopausal women with these histotypes, the magnitude of the letrozole advantage compared with tamoxifen may not be as large in patients with mucinous or tubular/cribriform disease. NCT00004205. © The Author 2015. Published by Oxford University Press on behalf of the European Society for

Joint symptoms associated with anastrozole and letrozole in patients with breast cancer: a retrospective comparative study.

PubMed

Morimoto, Yoshihito; Sarumaru, Shuhei; Oshima, Yuko; Tsuruta, Chiho; Watanabe, Kazuhiro

2017-01-01

Joint symptoms are a common side effect of aromatase inhibitors. However, it is not known if the risk of these symptoms varies between the members of this drug class. The aim of this study was to compare the frequency of joint symptoms associated with anastrozole and that associated with letrozole. We retrospectively reviewed patients with breast cancer who were treated with anastrozole or letrozole at Tsukiji Breast Clinic, Japan, between April 2008 and July 2014. Joint symptoms were deemed to include both joint pain and painless joint symptoms. The time to onset of joint symptoms in the anastrozole group was compared with that in the letrozole group using Kaplan-Meier curves and the log-rank test. Of 141 patients identified to have received aromatase inhibitors, 70 had been treated with anastrozole and 71 with letrozole. Joint symptoms occurred in 60.3% of the 141 patients (60.0% in the anastrozole group and 60.6% in the letrozole group; p  = 1). Median time to appearance of joint symptoms was 583 days, with no significant difference between the anastrozole and letrozole groups ( p  = 0.962). There was no significant difference in time to onset of joint pain ( p  = 0.139); however, time to onset of painless joint symptoms was significantly shorter in the anastrozole group ( p  = 0.022). The sites at which joint symptoms occurred were similar in the two groups. The results of this study indicate that there is no difference in the pattern of occurrence of joint symptoms caused by anastrozole and those caused by letrozole. Trial registration was not required for this study because of its retrospective nature and lack of intervention.

Multivariate analysis to predict letrozole efficacy in improving sperm count of non-obstructive azoospermic and cryptozoospermic patients: a pilot study

PubMed Central

Cavallini, Giorgio; Biagiotti, Giulio; Bolzon, Elisa

2013-01-01

We tested the hypothesis that letrozole increases sperm count in non-obstructive azoospermic or cryptozoospermic patients with a testosterone (T)/17-beta-2-oestradiol (E2) ratio <10. Forty-six patients with no chromosomal aberrations were randomized into two groups: 22 received letrozole 2.5 mg per day for 6 months (Group 1: 6 azoospermic+16 cryptozoospermic patients), while 24 received a placebo (Group 2: 5 azoospermic+19 cryptozoospermic patients). The following data were collected: two semen analyses, clinical history, scrotal Duplex scans, body mass index (BMI), Y microdeletion, karyotype and cystic fibrosis screens and follicle-stimulating hormone (FSH), luteinizing hormone (LH), E2, T and prolactin levels. Both before and after letrozole or placebo administration, the patients underwent two semen analyses and hormonal assessments. The differences were evaluated using the Mann–Whitney U test. The relationships between sperm concentration after letrozole administration with respect to FSH, T/E2 ratio, bilateral testicle volume and BMI before letrozole administration were assessed using multivariate analysis. The side effects were assessed using the chi-square test. Group 1 had sperm concentration (medians: 400–1.290×106 ml−1; P<0.01) and motility (medians: class A from 2% to 15% P<0.01), FSH, LH and T significantly increased, while Group 2 did not. E2 levels diminished significantly in Group 1, but not in Group 2. Eight patients in Group 1 demonstrated side effects, whereas no patient side effects were observed in Group 2. The sperm concentration after letrozole administration is inversely related to T/E2, FSH and BMI; a direct relationship emerged between sperm concentration and testicular volume. PMID:24121976

Efficacy and safety of palbociclib in combination with letrozole as first-line treatment of ER-positive, HER2-negative, advanced breast cancer: expanded analyses of subgroups from the randomized pivotal trial PALOMA-1/TRIO-18.

PubMed

Finn, Richard S; Crown, John P; Ettl, Johannes; Schmidt, Marcus; Bondarenko, Igor M; Lang, Istvan; Pinter, Tamas; Boer, Katalin; Patel, Ravindranath; Randolph, Sophia; Kim, Sindy T; Huang, Xin; Schnell, Patrick; Nadanaciva, Sashi; Bartlett, Cynthia Huang; Slamon, Dennis J

2016-06-28

Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6. In the randomized, open-label, phase II PALOMA-1/TRIO-18 trial, palbociclib in combination with letrozole improved progression-free survival (PFS) compared with letrozole alone as first-line treatment of estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, advanced breast cancer (20.2 months versus 10.2 months; hazard ratio (HR) = 0.488, 95 % confidence interval (CI) 0.319-0.748; one-sided p = 0.0004). Grade 3-4 neutropenia was the most common adverse event (AE) in the palbociclib + letrozole arm. We now present efficacy and safety analyses based on several specific patient and tumor characteristics, and present in detail the clinical patterns of neutropenia observed in the palbociclib + letrozole arm of the overall safety population. Postmenopausal women (n = 165) with ER+, HER2-negative, advanced breast cancer who had not received any systemic treatment for their advanced disease were randomized 1:1 to receive either palbociclib in combination with letrozole or letrozole alone. Treatment continued until disease progression, unacceptable toxicity, consent withdrawal, or death. The primary endpoint was PFS. We now analyze the difference in PFS for the treatment populations by subgroups, including age, histological type, history of prior neoadjuvant/adjuvant systemic treatment, and sites of distant metastasis, using the Kaplan-Meier method. HR and 95 % CI are derived from a Cox proportional hazards regression model. A clinically meaningful improvement in median PFS and clinical benefit response (CBR) rate was seen with palbociclib + letrozole in every subgroup evaluated. Grade 3-4 neutropenia was the most common AE with palbociclib + letrozole in all subgroups. Analysis of the frequency of neutropenia by grade during the first six cycles of treatment showed that there was a downward trend in Grade 3-4 neutropenia

Extended letrozole regimen versus clomiphene citrate for superovulation in patients with unexplained infertility undergoing intrauterine insemination: A randomized controlled trial

PubMed Central

2011-01-01

Background The aim of this randomized controlled trial was to compare the efficacy of extended letrozole regimen with clomiphene citrate in women with unexplained infertility undergoing superovulation and intrauterine insemination (IUI). Methods Two hundred and fourteen patients with unexplained infertility were randomized into two equal groups using computer generated list and were treated by either letrozole 2.5 mg/day from cycle day 1 to 9 (extended letrozole group, 211 cycles) or clomiphene citrate 100 mg/day from cycle day 3 to 7 (clomiphene citrate group,210 cycles). Intrauterine insemination was performed 36 to 40 hours after HCG administration. Results Both groups were comparable with regard to number of mature follicles (2.24 +/- 0.80 Vs 2.13 +/- 0.76) and the day of HCG administration. Serum estradiol was significantly greater in clomiphene citrate group (356 +/- 151 Vs 822 +/- 302 pg/ml, P = < 0.001) and the endometrial thickness was significantly greater in extended letrozole group (9.10 +/- 1.84 Vs 8.18 +/- 1.93 mm, P = < 0.001).The pregnancy rate per cycle and cumulative pregnancy rate were significantly greater in extended letrozole group (18.96% Vs 11.43% and 37.73% Vs 22.86%, respectively). Conclusion The extended letrozole regimen had a superior efficacy as compared with clomiphene citrate in patients of unexplained infertility undergoing superovulation and IUI. Trial registration ClinicalTrials.gov, NCT01232075 PMID:21693030

Differences between the non-steroidal aromatase inhibitors anastrozole and letrozole – of clinical importance?

PubMed Central

Geisler, J

2011-01-01

Aromatase inhibition is the gold standard for treatment of early and advanced breast cancer in postmenopausal women suffering from an estrogen receptor-positive disease. The currently established group of anti-aromatase compounds comprises two reversible aromatase inhibitors (anastrozole and letrozole) and on the other hand, the irreversible aromatase inactivator exemestane. Although exemestane is the only widely used aromatase inactivator at this stage, physicians very often have to choose between either anastrozole or letrozole in general practice. These third-generation aromatase inhibitors (letrozole/Femara (Novartis Pharmaceuticals, Basel, Switzerland) and anastrozole/Arimidex (AstraZeneca, Pharmaceuticals, Macclesfield, Cheshire, UK)), have recently demonstrated superior efficacy compared with tamoxifen as initial therapy for early breast cancer improving disease-free survival. However, although anastrozole and letrozole belong to the same pharmacological class of agents (triazoles), an increasing body of evidence suggests that these aromatase inhibitors are not equipotent when given in the clinically established doses. Preclinical and clinical evidence indicates distinct pharmacological profiles. Thus, this review focuses on the differences between the non-steroidal aromatase inhibitors allowing physicians to choose between these compounds based on scientific evidence. Although we are waiting for the important results of a still ongoing head-to-head comparison in patients with early breast cancer at high risk for relapse (Femara Anastrozole Clinical Evaluation trial; ‘FACE-trial'), clinicians have to make their choices today. On the basis of available evidence summarised here and until FACE-data become available, letrozole seems to be the best choice for the majority of breast cancer patients whenever a non-steroidal aromatase inhibitor has to be chosen in a clinical setting. The background for this recommendation is discussed in the following chapters

Tolerance of adjuvant letrozole outside of clinical trials.

PubMed

Fontaine, C; Meulemans, A; Huizing, M; Collen, C; Kaufman, L; De Mey, J; Bourgain, C; Verfaillie, G; Lamote, J; Sacre, R; Schallier, D; Neyns, B; Vermorken, J; De Grève, J

2008-08-01

Recently aromatase inhibitors have become a standard care as an adjuvant treatment for many postmenopausal patients with hormone receptor positive early breast cancer. Adjuvant letrozole was made available either immediately postoperative, after 2-3 years of tamoxifen, or as an extended treatment after 5 years of tamoxifen. Between October 2003 and October 2005, we analyzed the subjective tolerance in 185 postoperative early breast cancer patients receiving letrozole outside of a clinical trial. The most prominent toxicity was musculoskeletal pain. In addition hot flushes, increased fatigue, nausea, vomiting, anorexia, mood disturbances, vaginal dryness, hair loss and rash were also recorded. In contrast to the prospective randomized clinical trials, a high drop-out rate of 20% was documented, mainly due to aromatase inhibitor-associated arthralgia syndrome interfering significantly with the daily life of our patients. Although adjuvant aromatase inhibitors have proven to be generally superior to tamoxifen in the adjuvant setting, it is important to focus attention on the tolerance during the adjuvant therapy and to balance this against the potential benefit in individual patients. Alternative options including switching to tamoxifen remain available.

The pharmacokinetics of letrozole: association with key body mass metrics.

PubMed

Jin, Seok-Joon; Jung, Jin Ah; Cho, Sang-Heon; Kim, Un-Jib; Choe, Sangmin; Ghim, Jong-Lyul; Noh, Yook-Hwan; Park, Hyun-Jung; Kim, Jung-Chul; Jung, Jin-A; Lim, Hyeong-Seok; Bae, Kyun-Seop

2012-08-01

To characterize the pharmacokinetics (PK) of letrozole by noncompartmental and mixed effect modeling analysis with the exploration of effect of body compositions on the PK. The PK data of 52 normal healthy male subjects with intensive PK sampling from two separate studies were included in this analysis. Subjects were given a single oral administration of 2.5 mg letrozole (Femara®), an antiestrogenic aromatase inhibitor used to treat breast cancer. Letrozole concentrations were measured using validated high-performance liquid chromatography with tandem mass spectrometry. PK analysis was performed using NONMEM® 7.2 with first-order conditional estimation with interaction method. The association of body composition (body mass index, soft lean mass, fat free mass, body fat mass), CYP2A6 genotype (*1/*1, *1/*4), and CYP3A5 genotype (*1/*1, *1/*3, *3/*3) with the PK of letrozole were tested. A two-compartment model with mixed first and zero order absorption and first order elimination best described the letrozole concentration-time profile. Body weight and body fat mass were significant covariates for central volume of distribution and peripheral volume of distribution (Vp), respectively. In another model built using more readily available body composition measures, body mass index was also a significant covariate of Vp. However, no significant association was shown between CYP2A6 and CYP3A5 genetic polymorphism and the PK of letrozole in this study. Our results indicate that body weight, body fat mass, body mass index are associated with the volume of distribution of letrozole. This study provides an initial step toward the development of individualized letrozole therapy based on body composition.

An assessment of current clinical attitudes toward letrozole use in reproductive endocrinology practices.

PubMed

Malloch, Lindsay; Rhoton-Vlasak, Alice

2013-12-01

To assess the clinical use and practice attitudes among Society for Assisted Reproductive Technology (SART) members regarding the use of letrozole for ovulation induction and infertility treatment. The SART clinic physicians were mailed a cover letter and consent form, a two-page survey, and return envelope. The surveys were returned and analyzed using descriptive statistics. Not applicable. None. A 13-question survey. Reproductive endocrinology and infertility physicians use patterns and attitudes regarding letrozole. A total of 77.9% of physician prescribe letrozole. Of those who do not, 32.4% cited concern about the US Food and Drug Administration warning, 35.1% cited satisfaction with current medications, 25.7% cited both reasons, and 6.8% cited no experience with letrozole. Physicians (11.5%) were unaware of the US Food and Drug Administration warning. Physicians (99.7%) were aware that ovulation induction is an off-label use of letrozole. The most common use was for ovulation induction in patients with polycystic ovary syndrome (PCOS). Physicians (14.9%) prescribe letrozole as first-line ovulation therapy prior to clomid, 47.9% use for clomid failures, and 25.7% reported use in both situations. Most physicians surveyed use letrozole for ovulation induction despite the current US Food and Drug Administration warning. Even when accounting for nonrespondents, more than 25% of physicians indicated success with letrozole use. Questions regarding doses and clinical concerns about letrozole revealed no standardized manner of letrozole administration despite wide interest, therefore additional research is warranted. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Sex-dependent effects of letrozole on anxiety in middle-aged rats.

PubMed

Borbélyová, Veronika; Domonkos, Emese; Csongová, Melinda; Kačmárová, Mária; Ostatníková, Daniela; Celec, Peter; Hodosy, Július

2017-12-01

Aromatase catalyzes the conversion of testosterone to estradiol and is involved in the physiological effects of sex hormones on brain function. Animal experiments have shown that the aromatase inhibitor, letrozole, can induce anxiety in young ovariectomized females that are used as a model of aging. Whether or not these effects would be similar in intact middle-aged animals is unknown. The aim of our study was to analyze the effects of letrozole on anxiety in middle-aged rats of both sexes. Fifteen month old male and female rats were treated daily with either letrozole or vehicle for 2 weeks. The elevated plus maze was used to test anxiety-like behaviour. Sex differences were found not only in plasma concentrations of testosterone but also in the effects of letrozole treatment on plasma testosterone (P<.05). The interaction between sex and treatment was also proven in locomotor activity (P<.05) and time spent in the open arms of the elevated plus maze (P<.05). Letrozole-treated male rats spent 95% less time in the open arms of the elevated plus maze than the control rats did (P<.05) suggesting an anxiogenic effect of aromatase inhibition. This difference was not found between letrozole-treated and vehicle-treated females. In contrast to previous experiments on young animals, letrozole seems to induce anxiety in male but not in female middle-aged rats. This sex-specific effect might be related to sex differences of oestrogen and androgen signalling in aging brains. These results should be taken into account in clinical applications of letrozole, especially in men. © 2017 John Wiley & Sons Australia, Ltd.

Therapeutic potentials of Quercetin in management of polycystic ovarian syndrome using Letrozole induced rat model: a histological and a biochemical study.

PubMed

Jahan, Sarwat; Abid, Abira; Khalid, Sidra; Afsar, Tayyaba; Qurat-Ul-Ain; Shaheen, Ghazala; Almajwal, Ali; Razak, Suhail

2018-04-03

PCOS is a leading endocrinopathy of young women instigating androgens elevation, insulin resistance, obesity, cardiometabolic and menstrual complications. The study investigated the effects of quercetin in a letrozole induced rat model of polycystic ovarian syndrome, which displayed both clinical and metabolic features as in PCOS women. Female Sprague Dawley (SD) rats were divided into four groups; control group received aqueous solution of carboxymethyl (CMC 0.5%); PCOS group administered with letrozole (1 mg/kg) dissolved in solution (CMC 0.5%); Metformin group given with metformin (20 mg/kg) + letrozole (1 mg/kg); and Quercetin group provided with quercetin (30 mg/kg) + letrozole (1 mg/kg). All doses were given orally via gavage, for 21 consecutive days and colpocytological analysis was carried till end. After 21rst day, blood was taken out, centrifuged and plasma was kept for biochemical analysis (ELISA, anti-oxidant enzymes, lipid profile) and the reproductive organs were dissected out for histopathological evaluation. Quercetin as a chief member of flavonoid, showed beneficial effects by decreasing body weight, ovarian diameter, cysts and restoring healthy follicles, follicle's extra-glandular layers, and corpora lutea in contrast to the positive control. Additionally, lipid profile and anti-oxidant status were also maintained to baseline which was very high in diseased rats (p < 0.001).Quercetin depicted a mark regulation in steroidogenesis by decreasing the levels of testosterone (0.78 ng/ml ± 0.14 in quercetin vs. PCOS positive control 1.69 ng/ml ± 0.17, p < 0.001) and estradiol (8.85 pg/ml ± 0.19 in quercetin vs. PCOS positive 1.61 pg/ml ± 0.29) and increasing progesterone levels (34.47 ng/ml ± 1.65 in quercetin vs. 11.08 ng/ml ± 1.17 in PCOS positive). The effects of quercetin were moderately parallel to the standard drug available in market i.e. metformin. The present study has confirmed that

Clomiphene citrate combined with metformin versus letrozole for induction of ovulation in clomiphene-resistant polycystic ovary syndrome: a randomized clinical trial.

PubMed

Rezk, Mohamed; Shaheen, Abd-Elhamid; Saif El-Nasr, Ibrahim

2018-04-01

A total of 202 patients with clomiphene citrate (CC) -resistant polycystic ovary syndrome (PCOS) were randomly allocated into two arms of induction of ovulation; the first group (n = 102) received CC 100 mg and metformin 500 mg while the second group (n = 100) received letrozole 2.5 mg with ovulation rate, clinical pregnancy rate, adverse effects, and acceptability were assessed. Patients in the letrozole arm experienced higher rate of ovulation (82% versus 43.1%, p < .001), more dominant follicles (p < .05), better endometrial thickness (p < .001), higher clinical pregnancy rate (36% versus 9.8%, p < .001), higher multiple pregnancy rate (p < .05), lesser adverse effects (p < .05) and higher acceptability (p < .001) compared to patients in the CC and metformin arm. In conclusion; letrozole is better and more acceptable than combined CC and metformin for inducing ovulation in patients with CC-resistant PCOS with higher clinical pregnancy rate and unexpectedly higher multiple pregnancy rate.

Effect of letrozole in carcinogen-plus-estrogen-induced endometrial hyperplasia in mice.

PubMed

Lara, Alessandra Cerávolo; Cândido, Eduardo Batista; Vidigal, Paula Vieira; Rocha, Ana Luiza Lunardi; Carvalho-Macedo, Alessandra Costa; Carneiro, Márcia Mendonça; Silva-Filho, Agnaldo Lopes

2016-04-01

To evaluate the effects of letrozole (Ltz) in carcinogen+estrogen-induced endometrial hyperplasia. BALB/c female mice were divided into four groups of 12 animals each receiving an intrauterine dose of N-ethyl-N-nitrosourea (ENU) and weekly subcutaneous injections of estradiol hexaidrobenzoate (EHB), except for group I(control). The groups were divided in I (control), II (ENU+EHB), III (ENU+EHB+MPA) and IV (ENU+EHB+Ltz). Group III also received intramuscular injections of MPA (medroxy progesterone acetate) every four weeks, while group IV received oral doses of Ltz daily. At the end of 16 weeks, the animals were sacrificed, and blood samples were collected for the measurement of serum estradiol and progesterone levels. Uterine histological sections were made to evaluate the presence of endometrial proliferative lesions. Differences between groups were evaluated with student's t test, ANOVA and chi-square test. Groups ENU+EHB, ENU+EHB+MPA and ENU+EHB+Ltz showed varying degrees of endometrial hyperplasia. The incidence of hyperplasia in groups ENU+EHB and ENU+EHB+Ltz was higher and more severe than in group ENU+EHB+MPA. Control group showed lower levels of serum estradiol than the other groups. There was no evidence that letrozole could act as an antiestrogenic drug in the development of endometrial proliferative lesions.

Use of letrozole in assisted reproduction: a systematic review and meta-analysis

PubMed Central

Requena, Antonio; Herrero, Julio; Landeras, José; Navarro, Esperanza; Neyro, José L.; Salvador, Cristina; Tur, Rosa; Callejo, Justo; Checa, Miguel A.; Farré, Magí; Espinós, Juan J.; Fábregues, Francesc; Graña-Barcia, María

2008-01-01

BACKGROUND Letrozole is the third-generation aromatase inhibitor (AI) most widely used in assisted reproduction. AIs induce ovulation by inhibiting estrogen production; the consequent hypoestrogenic state increases GnRH release and pituitary follicle-stimulating hormone (FSH) synthesis. METHODS A systematic search of the literature was performed for both prospective and retrospective studies. Meta-analyses of randomized clinical trials (RCTs) were performed for three comparisons: letrozole versus clomiphene citrate (CC), letrozole + FSH versus FSH in intrauterine insemination (IUI) and letrozole + FSH versus FSH in IVF. In the absence of RCTs, non-randomized studies were pooled. RESULTS Nine studies were included in the meta-analysis. Four RCTs compared the overall effect of letrozole with CC in patients with polycystic ovary syndrome. The pooled result was not significant for ovulatory cycles (OR = 1.17; 95% CI 0.66–2.09), or for pregnancy rate per cycle (OR = 1.47; 95% CI 0.73–2.96) or for pregnancy rate per patient (OR = 1.37; 95% CI 0.70–2.71). In three retrospective studies which compared L + FSH with FSH in ovarian stimulation for IUI, the pooled OR was 1.15 (95% CI 0.78−1.71). A final meta-analysis included one RCT and one cohort study that compared letrozole + gonadotrophin versus gonadotrophin alone: the pooled pregnancy rate per patient was not significantly different (OR = 1.40; 95% CI 0.67–2.91). CONCLUSIONS Letrozole is as effective as other methods of ovulation induction. Further randomized-controlled studies are warranted to define more clearly the efficacy and safety of letrozole in human reproduction. PMID:18812422

Effect of aromatase inhibitor letrozole on the proliferation of spermatogonia by regulating the MAPK pathway.

PubMed

Wang, Shunde; Wang, Shuhong; Li, Hang; Li, Xiaoxia; Xie, Menglin; Wen, Jiayu; Li, Meicai; Long, Tengbo

2018-06-01

The molecular mechanism of the aromatase inhibitor letrozole was investigated. It promotes the proliferation of spermatogonia by regulating the mitogen-activated protein kinase (MAPK) pathway. Six different concentrations were selected for letrozole in order to incubate mouse spermatogonia [GC-1 spermatogonia (spg)] for 24, 48 and 72 h, respectively. Cell Counting Kit-8 (CCK-8) was used to observe the effect of letrozole on the proliferation of GC-1 spg cells, and the effect was further verified by cell plate clone formation assay. Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were used to detect the effects of letrozole on MAPK signaling pathways [Ras/extracellular signal-regulated kinase 1 (ERK1)/c-Myc], proliferation indexes [Ki-67 and proliferating cell nuclear antigen (PCNA)]. Bromodeoxyuridine (BrdU) staining was used to study the effects of letrozole and MAPK signaling pathways on cell proliferation. The results of CCK-8 showed that the proliferation rate of GC-1 spg cells was improved. Study results also revealed a significant increase in letrozole concentration along with the time of action. The results of plate clone formation assay further indicated that letrozole could significantly promote the proliferation capacity of GC-1 spg cells (p<0.05). The results of RT-PCR and western blot analysis confirmed letrozole significantly activated the expression of Ras/ERK1/c-Myc in the classical MAPK pathway. A significant increase was noted in the protein levels of Ki-67 and PCNA (p<0.05). By contrast, inhibition of the MAPK pathway resulted in a significant decrease in the levels of the above indexes (p<0.05). The number of BrdU cells in the letrozole group was also higher than that of the control group, while the number of BrdU-stained cells in the letrozole + MAPK inhibition group showed a significant decrease in comparison to the letrozole group. In conclusion, letrozole activated the MAPK signaling pathway and promoted the

Comparison of Success of Clomiphene citrate and Letrozole in Ovulation Induction.

PubMed

Saha, J; Akhter, S; Prasad, I; Siddiq, S

2016-01-01

The study was carried out to evaluate which drug is better in ovulation induction between clomiphene citrate and letrozole. The study was carried out in the infertility unit of Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka and Centre for Assisted Reproduction (CARE) at Bangladesh Institute of Research and Rehabilitation in Diabetes Endocrine and Metabolic Disorders (BIRDEM), Dhaka from January 2007 to December 2007. One hundred and sixty five cases were taken for the study. It was a prospective interventional comparative study of clomiphene citrate and letrozole in infertile cases. The patients were divided into three groups. Group I--newly detected cases of sub fertility studied with clomiphene citrate. Group II--clomiphene citrate resistant cases studied with letrozole, Group III--newly detected cases of sub fertility studied with letrozole. The cases were followed up for outcome; (ovulation). The TVS was done on 12th or 13th day of menstruation and level of serum progesterone on 21st day of menstrual cycle to see the evidence of ovulation. Endometrial thickness was also measured. The data was collected on a predesigned questionnaire. The variables that influenced the study were-age, occupation, socioeconomic status, menstrual cycle, marital age, parity, history of MR, history of abortion, past medical and surgical history. In the current study it was observed that the signs of ovulation were significantly (p<0.05) higher in Group I treated with clomiphene citrate in comparison to Group II clomiphene citrate resistant cases treated with letrozole. The rate of ovulation was higher in Group I than that of Group III treated with letrozole, but the difference was not statistically significant (p>0.05). The signs of ovulation were present in 45(81.8%) cases in Group I, 33(60.0%) cases in Group II and 37(67.3%) cases in Group III. This findings of the study suggested that clomiphene citrate is higher successful than letrozole though not statistically

Fertility Preservation Success Subsequent to Concurrent Aromatase Inhibitor Treatment and Ovarian Stimulation in Women With Breast Cancer

PubMed Central

Oktay, Kutluk; Turan, Volkan; Bedoschi, Giuliano; Pacheco, Fernanda S.; Moy, Fred

2015-01-01

Purpose We have previously reported an approach to ovarian stimulation for the purpose of fertility preservation (FP) in women with breast cancer via embryo freezing with the concurrent use of letrozole. The aim of this study was to provide the pregnancy and FP outcomes when embryos generated with the same protocol are used. Patients and Methods In all, 131 women with stage ≤ 3 breast cancer underwent ovarian stimulation and received concurrent letrozole 5 mg per day before receiving adjuvant chemotherapy and cryopreserving embryos. Results Thirty-three of the 131 women underwent 40 attempts to transfer embryos to their own uterus (n = 18) or via the use of a gestational carrier (n = 22) at a mean age of 41.5 ± 4.3 years with a median 5.25 years after embryo cryopreservation. The overall live birth rate per embryo transfer was similar to the US national mean among infertile women of a similar age undergoing in vitro fertilization–embryo transfer (45.0 v 38.2; P = .2). Seven (38.8%) of the 18 pregnancies were twins with no higher-order pregnancies being encountered. No fetal anomalies or malformations were reported in 25 children after a mean follow-up of 40.4 ± 26.4 months. Seventeen of the 33 women attempting pregnancy had at least one child, translating into an FP rate of 51.5% per attempting woman. Conclusion Embryo cryopreservation after ovarian stimulation with the letrozole and follicle-stimulating hormone protocol preserves fertility in women with breast cancer and results in pregnancy rates comparable to those expected in a noncancer population undergoing in vitro fertilization. PMID:26101247

Repression of ESR1 transcription by MYOD potentiates letrozole-resistance in ERα-positive breast cancer cells.

PubMed

Zhang, Qiang; Liu, Xiao-Yan; Li, Shuang; Zhao, Zhao; Li, Juan; Cui, Ming-Ke; Wang, En-Hua

2017-10-21

Transcriptional silencing of estrogen receptor α (ERα) expression is an important etiology contributing to the letrozole-resistance in ERα-positive breast cancer (BCa) cells, but the transcription factors responsible for this transcriptional repression remain largely unidentified. Here we report that the expression of the basic helix-loop-helix myogenic regulatory factor MYOD was abnormally up-regulated in letrozole-resistant BCa tissues and in experimentally-induced letrozole-resistant BCa cells. Overexpression of the exogenous MYOD impaired ERα expression and potentiated letrozole-resistance in letrozole-sensitive MCF7 cells, whereas MYOD knockdown could effectively restore ERα expression and thereby promote letrozole-sensitivity in letrozole-resistant MCF-7/LR cells. Mechanistically, MYOD was shown to be a potent corepressor of ESR1 transcription, and this transcriptional repression was significantly enhanced in the presence of letrozole treatment. Thus, targeted inhibition of MYOD may restore ERα level and lead to resensitization to letrozole-based hormone therapy, providing a novel therapeutic strategy for relapsed ERα-positive BCa patients. Our data also underscore an unexpected chemotherapeutic facet of MYOD, which may operate as a novel regulator of BCa biology. Copyright © 2017 Elsevier Inc. All rights reserved.

Comparison of the effects of letrozole and cabergoline on vascular permeability, ovarian diameter, ovarian tissue VEGF levels, and blood PEDF levels, in a rat model of ovarian hyperstimulation syndrome.

PubMed

Şahin, Nur; Apaydın, Nesin; Töz, Emrah; Sivrikoz, Oya Nermin; Genç, Mine; Turan, Gülüzar Arzu; Cengiz, Hakan; Eskicioğlu, Fatma

2016-05-01

To evaluate the effects of letrozole and cabergoline in a rat model of ovarian hyperstimulation syndrome (OHSS). In this prospective, controlled experimental study, the 28 female Wistar rats were divided into four subgroups (one non-stimulated control and three OHSS-positive groups: placebo, letrozole, and cabergoline). To induce OHSS, rats were injected with 10 IU of pregnant mare serum gonadotropin from day 29 to day 32 of life, followed by subcutaneous injection of 30 IU hCG on day 33. Letrozole rats received with a single dose of 0.1 mg/kg letrozole via oral gavage, on the hCG day. Cabergoline rats received with a single dose of 100 µg/kg cabergoline via oral gavage, on the hCG day. All animals were compared in terms of body weight, vascular permeability (VP), ovarian diameter, ovarian tissue VEGF expression (assessed via immunohistochemical staining), and blood pigment epithelium-derived growth factor (PEDF) levels. The OHSS-positive placebo group (group 2) exhibited the highest VP, ovarian diameter, extent of VEGF staining, and lowest PEDF level, as expected. No significant difference was evident between the letrozole and cabergoline groups in terms of any of body weight; VP; PEDF level; ovarian diameter; or the staining intensity of, or percentage staining for, VEGF in ovarian tissues. Letrozole and cabergoline were equally effective to prevent OHSS, reducing the ovarian diameter, VP, and PEDF and VEGF levels to similar extents.

Effects of vitamin D and calcium supplementation on side effects profile in patients of breast cancer treated with letrozole.

PubMed

Arul Vijaya Vani, S; Ananthanarayanan, P H; Kadambari, D; Harichandrakumar, K T; Niranjjan, R; Nandeesha, H

2016-08-01

Vitamin D deficiency (<10ng/mL) and insufficiency (10-30ng/mL) may contribute to musculoskeletal symptoms observed in patients taking letrozole. This study was undertaken to assess the vitamin D status in breast cancer patients who received letrozole for >2months and to see the effects of vitamin D3 and calcium supplementation on them. Eighty-two breast cancer patients were included. Baseline serum 25-hydroxy vitamin D concentrations were assayed and standard questionnaire was completed. They were given vitamin D3 and calcium supplementation (2000IU/1000 mg and 4000IU/1000mg) based on their baseline serum 25-hydroxy vitamin D concentration for 12weeks. Baseline serum 25-hydroxy vitamin D concentrations showed that 13.4% of patients were deficient and 73.2% of patients were insufficient in 25-hydroxy vitamin D. There was an increase in the concentrations of calcium, phosphorus and decrease in the concentrations of parathyroid hormone, alkaline phosphatase as the concentration of serum 25-hydroxy vitamin D increases. Patients who received letrozole for a longer duration had a low concentration of serum 25 (OH) vitamin D. Vitamin D3 and calcium supplementation increased the concentrations of calcium, phosphorous and decreased the concentrations of parathyroid hormone and alkaline phosphatase. Patients who had low serum 25-hydroxy vitamin D concentrations had more musculoskeletal symptoms which was improved following supplementation (9.14 vs 8.10 p=0.000). Vitamin D3 supplementation significantly improved serum 25-hydroxy vitamin D concentrations and decreased letrozole-induced arthralgia. Copyright © 2016 Elsevier B.V. All rights reserved.

Aromatase inhibitors for subfertile women with polycystic ovary syndrome.

PubMed

Franik, Sebastian; Kremer, Jan A M; Nelen, Willianne L D M; Farquhar, Cindy

2014-02-24

Polycystic ovary syndrome (PCOS) is the most common cause of infrequent periods (oligomenorrhoea) and absence of periods (amenorrhoea). It affects about 4% to 8% of women worldwide and often leads to anovulatory subfertility. Aromatase inhibitors (AIs) are a novel class of drugs that were introduced for ovulation induction in 2001. Over the last ten years clinical trials have reached differing conclusions as to whether the AI letrozole is at least as effective as the first-line treatment clomiphene citrate (CC). To evaluate the effectiveness and safety of aromatase inhibitors for subfertile women with anovulatory PCOS. We searched the following sources from inception to 24/10/2013 to identify relevant randomised controlled trials (RCTs): the Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, PsycINFO, Pubmed, LILACS, Web of Knowledge, the World Health Organisation (WHO) clinical trials register and Clinicaltrials.gov. Furthermore, we manually searched the references of relevant articles.The search was not restricted by language or publication status. We included all RCTs of aromatase inhibitors used alone or with other medical therapies for ovulation induction in women of reproductive age with anovulatory PCOS. Two review authors independently selected trials, extracted the data and assessed trial quality. Studies were pooled where appropriate using a fixed effect model to calculate pooled odds ratios (ORs) and 95% confidence intervals (CIs) for most outcomes and risk differences (RDs) for ovarian hyperstimulation syndrome (OHSS). The primary outcomes were live birth and OHSS. Secondary outcomes were pregnancy, miscarriage and multiple pregnancy. The quality of the evidence for each comparison was assessed using GRADE methods. We included 26 RCTs (5560 women). In all studies the aromatase inhibitor was letrozole. Live birth (12 RCTs) One RCT compared letrozole with placebo in women

miR-1271 inhibits ERα expression and confers letrozole resistance in breast cancer.

PubMed

Yu, Tao; Yu, Hai-Ru; Sun, Jia-Yi; Zhao, Zhao; Li, Shuang; Zhang, Xin-Feng; Liao, Zhi-Xuan; Cui, Ming-Ke; Li, Juan; Li, Chan; Zhang, Qiang

2017-12-05

Attenuation of estrogen receptor α (ERα) expression via unknown mechanism(s) is a hallmark of endocrine-resistant breast cancer (BCa) progression. Here, we report that miR-1271 was significantly down-regulated in letrozole-resistant BCa tissues and in letrozole-resistant BCa cells. miR-1271 directly targeted the chromatin of DNA damage-inducible transcript 3 (DDIT3) gene. miR-1271 expression level was inversely correlated to DDIT3 mRNA level in BCa biopsies. Form a mechanistic standpoint, reintroduction of exogenous miR-1271 could effectively restore ERα level via inhibiting DDIT3 expression, thereby potentiating letrozole sensitivity in BCa cells. Moreover, DDIT3 deregulation promoted letrozole-resistance by acting as a potent corepressor of ESR1 transcription. Taken together, we have identified that disruption of the miR-1271/DDIT3/ERα cascade plays a causative role in the pathogenesis of letrozole resistance in BCa.

Alteration at transcriptional level of cardiac renin-angiotensin system by letrozole treatment.

PubMed

Shekarforoush, Shahnaz; Koohpeyma, Farhad; Safari, Fatemeh

2018-06-17

The use of aromatase inhibitors (AIs) for breast cancer led to a marked change in ventricular function. Since accumulating evidence indicates that overactivation of the cardiac renin-angiotensin system (RAS) plays an important role in the development of cardiovascular diseases such as hypertrophy and remodelling, we aimed to investigate whether letrozole alters the transcription level of RAS related genes in the cardiac tissue. Twenty four rats were randomly divided into four groups (n = 6 per group): two groups were letrozole treated (1 and 2 mg/kg/day orally), one group was vehicle treated (DMSO) and one group was the control group without any treatment. 12 weeks after beginning treatment with letrozole, we examined the rate of transcription of renin, angiotensinogen, AngII type 1a and 1b (AT1a and AT1b) and type 2 receptors (AT2) in the rat heart using real-time polymerase chain reaction. The cardiac mRNA levels of several components of the RAS in the rats treated with letrozole were significantly increased including AT1a receptor (80%), renin (51%), and angiotensinogen (33%). Though not significant, AT2 receptor levels were observed to decrease with increasing doses of letrozole. Letrozole can induce significant changes in some RAS related genes. These alterations are important to understand the pathways and consequences beyond cardiac events induced by breast cancer treatments.

Coadministrating luteolin minimizes the side effects of the aromatase inhibitor letrozole.

PubMed

Li, Fengjuan; Wong, Tsz Yan; Lin, Shu-mei; Chow, Simon; Cheung, Wing-hoi; Chan, Franky L; Chen, Shiuan; Leung, Lai K

2014-11-01

Aromatase inhibitors (AIs) have been used as adjuvant therapeutic agents for breast cancer. Their adverse side effect on blood lipid is well documented. Some natural compounds have been shown to be potential AIs. In the present study, we compared the efficacy of the flavonoid luteolin to the clinically approved AI letrozole (Femara; Novartis Pharmaceuticals, East Hanover, NJ) in a cell and a mouse model. In the in vitro experimental results for aromatase inhibition, the Ki values of luteolin and letrozole were estimated to be 2.44 µM and 0.41 nM, respectively. Both letrozole and luteolin appeared to be competitive inhibitors. Subsequently, an animal model was used for the comparison. Aromatase-expressing MCF-7 cells were transplanted into ovariectomized athymic mice. Luteolin was given by mouth at 5, 20, and 50 mg/kg, whereas letrozole was administered by intravenous injection. Similar to letrozole, luteolin administration reduced plasma estrogen concentrations and suppressed the xenograft proliferation. The regulation of cell cycle and apoptotic proteins-such as a decrease in the expression of Bcl-xL, cyclin-A/D1/E, CDK2/4, and increase in that of Bax-was about the same in both treatments. The most significant disparity was on blood lipids. In contrast to letrozole, luteolin increased fasting plasma high-density lipoprotein concentrations and produced a desirable blood lipid profile. These results suggested that the flavonoid could be a coadjuvant therapeutic agent without impairing the action of AIs. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Ovarian Stimulation in Patients With Cancer: Impact of Letrozole and BRCA Mutations on Fertility Preservation Cycle Outcomes.

PubMed

Turan, Volkan; Bedoschi, Giuliano; Emirdar, Volkan; Moy, Fred; Oktay, Kutluk

2018-01-01

Aromatase inhibitors (AI) have been introduced to reduce estrogen exposure in women with estrogen-sensitive cancer undergoing ovarian stimulation for oocyte/embryo cryopreservation. There have been questions regarding whether the addition of AI and the presence of BRCA mutations affect cycle outcomes. We sought to determine the impact of letrozole and BRCA mutations on fertility preservation (FP) cycle outcomes of patients undergoing ovarian stimulation with an antagonist protocol. The data were generated by the secondary analysis of a prospective database of all females diagnosed with cancer who underwent embryo or oocyte cryopreservation for FP. The final analysis included 145 patients stimulated with an antagonist protocol either using letrozole combined with recombinant follicle-stimulating hormone (rFSH; LF, n = 118) or rFSH alone (FA, n = 24). The mean number of total (15.6 [7.9] vs 10.2 [7.8]; P = .004) and mature oocytes (10.4 [5.1] vs 7.8 [3.5]; P = .044) and embryos frozen (7.7 [5.3] vs 5.3 [2.7]; P = .043) were significantly higher after LF stimulation versus FA. In the LF group, women with BRCA mutations produced significantly fewer oocytes (11.0 [8.0] vs 16.4 [7.7], P = .015) and embryos (5.1 [4.4] vs 8.2 [4.7], P = .013), compared to those who were mutation negative. After adjusting for age, body mass index, baseline FSH level, and BRCA status, LF protocol still resulted in higher number of total oocytes (95% confidence interval [CI]: 1.9 to 3.6; P = .002) mature oocyte (95% CI: 0.3 to 1.4; P = .028), and embryo yield (95% CI: 0.7 to 1.4; P = .015). In women with cancer undergoing FP, letrozole appears to enhance response to ovarian stimulation while the presence of BRCA mutations is associated with lower oocyte and embryo yield.

Quality of Life From Canadian Cancer Trials Group MA.17R: A Randomized Trial of Extending Adjuvant Letrozole to 10 Years.

PubMed

Lemieux, Julie; Brundage, Michael D; Parulekar, Wendy R; Goss, Paul E; Ingle, James N; Pritchard, Kathleen I; Celano, Paul; Muss, Hyman; Gralow, Julie; Strasser-Weippl, Kathrin; Whelan, Kate; Tu, Dongsheng; Whelan, Timothy J

2018-02-20

Purpose MA.17R was a Canadian Cancer Trials Group-led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor as adjuvant therapy for hormone receptor-positive breast cancer. Quality of life (QOL) was a secondary outcome measure of the study, and here, we report the results of these analyses. Methods QOL was measured using the Short Form-36 (SF-36; two summary scores and eight domains) and menopause-specific QOL (MENQOL; four symptom domains) at baseline and every 12 months up to 60 months. QOL assessment was mandatory for Canadian Cancer Trials Group centers but optional for centers in other groups. Mean change scores from baseline were calculated. Results One thousand nine hundred eighteen women were randomly assigned, and 1,428 women completed the baseline QOL assessment. Compliance with QOL measures was > 85%. Baseline summary scores for the SF-36 physical component summary (47.5 for letrozole and 47.9 for placebo) and mental component summary (55.5 for letrozole and 54.8 for placebo) were close to the population norms of 50. No differences were seen between groups in mean change scores for the SF-36 physical and mental component summaries and the other eight QOL domains except for the role-physical subscale. No difference was found in any of the four domains of the MENQOL Conclusion No clinically significant differences were seen in overall QOL measured by the SF-36 summary measures and MENQOL between the letrozole and placebo groups. The data indicate that continuation of aromatase inhibitor therapy after 5 years of prior treatment in the trial population was not associated with a deterioration of overall QOL.

Quality of Life From Canadian Cancer Trials Group MA.17R: A Randomized Trial of Extending Adjuvant Letrozole to 10 Years

PubMed Central

Brundage, Michael D.; Parulekar, Wendy R.; Goss, Paul E.; Ingle, James N.; Pritchard, Kathleen I.; Celano, Paul; Muss, Hyman; Gralow, Julie; Strasser-Weippl, Kathrin; Whelan, Kate; Tu, Dongsheng; Whelan, Timothy J.

2018-01-01

Purpose MA.17R was a Canadian Cancer Trials Group–led phase III randomized controlled trial comparing letrozole to placebo after 5 years of aromatase inhibitor as adjuvant therapy for hormone receptor–positive breast cancer. Quality of life (QOL) was a secondary outcome measure of the study, and here, we report the results of these analyses. Methods QOL was measured using the Short Form-36 (SF-36; two summary scores and eight domains) and menopause-specific QOL (MENQOL; four symptom domains) at baseline and every 12 months up to 60 months. QOL assessment was mandatory for Canadian Cancer Trials Group centers but optional for centers in other groups. Mean change scores from baseline were calculated. Results One thousand nine hundred eighteen women were randomly assigned, and 1,428 women completed the baseline QOL assessment. Compliance with QOL measures was > 85%. Baseline summary scores for the SF-36 physical component summary (47.5 for letrozole and 47.9 for placebo) and mental component summary (55.5 for letrozole and 54.8 for placebo) were close to the population norms of 50. No differences were seen between groups in mean change scores for the SF-36 physical and mental component summaries and the other eight QOL domains except for the role-physical subscale. No difference was found in any of the four domains of the MENQOL Conclusion No clinically significant differences were seen in overall QOL measured by the SF-36 summary measures and MENQOL between the letrozole and placebo groups. The data indicate that continuation of aromatase inhibitor therapy after 5 years of prior treatment in the trial population was not associated with a deterioration of overall QOL. PMID:29328860

Pregnancy and neonatal outcomes following letrozole use in frozen-thawed single embryo transfer cycles.

PubMed

Tatsumi, T; Jwa, S C; Kuwahara, A; Irahara, M; Kubota, T; Saito, H

2017-06-01

Are pregnancy and neonatal outcomes following letrozole use comparable with natural and HRT cycles in patients undergoing single frozen-thawed embryo transfer (FET)? Letrozole use was significantly associated with higher rates of clinical pregnancy, clinical pregnancy with fetal heart beat and live birth, and with a lower rate of miscarriage, compared with natural and HRT cycles. Letrozole is the most commonly used aromatase inhibitor for mild ovarian stimulation in ART. However, the effect of letrozole on pregnancy and neonatal outcomes in FET are not well known. A retrospective cohort study was conducted using data from the Japanese national ART registry between 2012 and 2013. A total of 110 722 single FET cycles with letrozole (n = 2409), natural (n = 41 470) or HRT cycles (n = 66 843) were included. The main outcomes were the rates of clinical pregnancy, clinical pregnancy with fetal heart beat, miscarriage and live birth. Adjusted odds ratios and relative risks (RRs) were calculated using a generalized estimating equation adjusting for correlations within clinics. The rates of clinical pregnancy, clinical pregnancy with fetal heart beat, and live birth were significantly higher, while the rate of miscarriage was significantly lower in the letrozole group compared with the natural and HRT groups. In blastocyst stage transfers, the adjusted RRs for clinical pregnancy with fetal heart beat of letrozole compared with natural and HRT cycles were 1.48 (95% CI: 1.41-1.55) and 1.62 (95% CI: 1.54-1.70), respectively. Similarly, the adjusted RRs of letrozole for miscarriage compared with natural and HRT cycles were 0.91 (95% CI: 0.88-0.93) and 0.84 (95% CI: 0.82-0.87), respectively. Neonatal outcomes were mostly similar in letrozole, natural and HRT cycles. Important limitations of this study included the lack of information concerning the reasons for selecting the specific FET method, parity, the number of previous ART failures, embryo quality and the dose and duration

Effect of vehicle and route of administration of letrozole on ovarian function in a bovine model.

PubMed

Yapura, M J; Mapletoft, R J; Pierson, R A; Singh, J; Adams, G P

2014-10-01

The objective of this study was to determine the effects of vehicle and route of administration of letrozole on ovarian function in sexually mature beef heifers. On Day 3 (Day 0=ovulation), heifers were assigned randomly to four treatment groups and given 1mgkg(-1) letrozole intravenously (iv, n=10) or intramuscularly (im, n=10) or given a placebo iv (control iv, n=5) or im (control im, n=5). The interwave interval was longer in heifers treated with letrozole im than in im and iv controls (11.7±0.30 vs 9.5±0.50 and 10±0.43, respectively; P<0.05). Corpus luteum diameter profiles and plasma progesterone concentrations were greater (P<0.03 and P<0.05, respectively) in heifers treated with letrozole im compared with control im. Plasma oestradiol concentrations were lower in both letrozole-treated groups compared with controls (P≤0.03). Plasma LH concentrations tended to be elevated at the time of wave emergence in heifers treated with letrozole im compared with other groups (group-by-day interaction, P=0.06) and plasma FSH concentrations tended to be greater (P<0.09) in heifers treated with letrozole by either route compared with a single control group. We conclude that intramuscular administration of letrozole in oil is a feasible route and vehicle for the development of a letrozole-based treatment protocol for herd synchronisation in cattle.

Synthesis and PET studies of [(11)C-cyano]letrozole (Femara), an aromatase inhibitor drug.

PubMed

Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J; Fowler, Joanna S

2009-02-01

Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone into estrone and estradiol, respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole; Femara) is a high-affinity aromatase inhibitor (K(i)=11.5 nM) that has Food and Drug Administration approval for breast cancer treatment. Here we report the synthesis of carbon-11-labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile) were prepared in a two-step synthesis from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [(11)C]cyano group was introduced via tetrakis(triphenylphosphine)palladium(0)-catalyzed coupling of [(11)C]cyanide with the bromo precursor. Positron emission tomography (PET) studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. Log D, the free fraction of letrozole in plasma and the [(11)C-cyano]letrozole fraction in arterial plasma were also measured. [(11)C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79-80%, with a radiochemical purity greater than 98% and a specific activity of 4.16+/-2.21 Ci/mumol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance, followed by slow clearance of carbon-11 from the brain, with no difference between brain regions. Brain kinetics was not affected by coinjection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9%, and log D was 1.84. [(11)C-cyano]Letrozole is readily synthesized via a palladium-catalyzed coupling reaction with [(11)C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase, as revealed by the absence of regional specificity and saturability in brain regions such as amygdala, which are known to

A comparison of the effect of short-term aromatase inhibitor (letrozole) and GnRH agonist (triptorelin) versus case control on pregnancy rate and symptom and sign recurrence after laparoscopic treatment of endometriosis.

PubMed

Alborzi, Saeed; Hamedi, Bahareh; Omidvar, Azizeh; Dehbashi, Sedigheh; Alborzi, Soroosh; Alborzi, Mehrnoosh

2011-07-01

To compare the role of an aromatase inhibitor (letrozole) with a GnRH agonist (triptorelin) versus case control on the pregnancy rate and recurrence of symptoms and signs in patients with endometriosis. In a prospective randomized clinical trial, after treatment of 144 infertile women in their reproductive age by laparoscopy (whose endometriosis was confirmed by prior laparoscopy), they were divided into 3 groups: group 1 (47 cases) who received letrozole for 2 months, group 2 (40 patients) who were prescribed triptorelin for 2 months and group 3 who were 57 patients in the control group and did not receive any medication. We followed up each group at least for 12 months after their restoration of regular cycle. Pregnancy rate was 23.4% in group 1, 27.5% in group 2, and 28.1% in group 3. The results did not show significant differences among the 3 groups. Recurrence rate of endometriosis was 6.4% in group 1, 5% group 2 and 5.3% in group 3, which was not statistically significantly different as well. Pregnancy rate and endometriosis recurrence rate are comparable among the 3 groups.

Letrozole versus clomiphene citrate in polycystic ovary syndrome: systematic review and meta-analysis.

PubMed

Roque, Matheus; Tostes, Ana C I; Valle, Marcello; Sampaio, Marcos; Geber, Selmo

2015-01-01

The objective of the present systematic review and meta-analysis was to examine the literature and to identify the results of randomized controlled trials (RCTs) comparing the use of letrozole to clomiphene citrate (CC) for ovulation induction in patients with polycystic ovary syndrome (PCOS). An exhaustive electronic literature search was performed using the MEDLINE and EMBASE databases until October 2014. Seven prospective RCTs comparing the use of letrozole to CC in PCOS patients met the inclusion criteria. Overall, the seven included studies accounted for 1833 patients (906 in the letrozole group and 927 in the CC group) and for 4999 ovulation induction cycles (2455 in the letrozole group and 2544 in the CC group). Five of the included studies reported data on live birth rates. There was a statistically significant increase in the live birth and pregnancy rates in the letrozole group when compared to the CC group, with a relative risk (RR) = 1.55 (95% confidence interval (CI): 1.26-1.90; I(2) = 0%) and RR = 1.38 (95% CI: 1.05-1.83; I(2) = 61%), respectively. There were no differences in the multiple pregnancy, miscarriage and ovulation rates between the two groups. Our study found that letrozole is superior to CC when considering the live birth and pregnancy rates in patients with PCOS.

Folate Conjugated Hybrid Nanocarrier for Targeted Letrozole Delivery in Breast Cancer Treatment.

PubMed

Hemati Azandaryani, Abbas; Kashanian, Soheila; Derakhshandeh, Katayoun

2017-12-01

Letrozole as a steroidal anticancer drug with hydrophobic nature is usually administrated by oral route for patient treatment and the injectable formulation for this drug has not still been reported. In this study, a new letrozole incorporated folate-conjugated polymer - lipid hybrid nanoparticles - is introduced for cancer treatment. Nanoparticles were fabricated via modified oil in water ionic gelation method using optimization parameters and then were coupled to folic acid using carbodiimide activation. The physicochemical characterization in vitro drug release, cytotoxicity, and then ex vivo study of obtained carrier was investigated. Both thermal and crystallography studies proved the amorphous loading of drug in the nanocarrier. The cytotoxicity investigation with an average IC 50 value of 79 ± 2.40 nM proved the efficiency of the coupled folic acid carrier for the intracellular uptake of letrozole on the breast cancer line. Ex vivo, the study proved the positive effect of the letrozole entrapment on the drug bioavailability. The obtained targeted nanocarrier could overcome the limitations associated with the LTZ as a potent non-steroidal drug. Both the entrapment and therapeutic efficiency of letrozole in the amphiphilic carrier were increased using the lipid nanoparticles and the surface modification, respectively.

ESR1 and ESR2 polymorphisms in the BIG 1-98 trial comparing adjuvant letrozole versus tamoxifen or their sequence for early breast cancer.

PubMed

Leyland-Jones, Brian; Gray, Kathryn P; Abramovitz, Mark; Bouzyk, Mark; Young, Brandon; Long, Bradley; Kammler, Roswitha; Dell'Orto, Patrizia; Biasi, Maria Olivia; Thürlimann, Beat; Harvey, Vernon; Neven, Patrick; Arnould, Laurent; Maibach, Rudolf; Price, Karen N; Coates, Alan S; Goldhirsch, Aron; Gelber, Richard D; Pagani, Olivia; Viale, Giuseppe; Rae, James M; Regan, Meredith M

2015-12-01

Estrogen receptor 1 (ESR1) and ESR2 gene polymorphisms have been associated with endocrine-mediated physiological mechanisms, and inconsistently with breast cancer risk and outcomes, bone mineral density changes, and hot flushes/night sweats. DNA was isolated and genotyped for six ESR1 and two ESR2 single-nucleotide polymorphisms (SNPs) from tumor specimens from 3691 postmenopausal women with hormone receptor-positive breast cancer enrolled in the BIG 1-98 trial to receive tamoxifen and/or letrozole for 5 years. Associations with recurrence and adverse events (AEs) were assessed using Cox proportional hazards models. 3401 samples were successfully genotyped for five SNPs. ESR1 rs9340799(XbaI) (T>C) variants CC or TC were associated with reduced breast cancer risk (HR = 0.82,95% CI = 0.67-1.0), and ESR1 rs2077647 (T>C) variants CC or TC was associated with reduced distant recurrence risk (HR = 0.69, 95% CI = 0.53-0.90), both regardless of the treatments. No differential treatment effects (letrozole vs. tamoxifen) were observed for the association of outcome with any of the SNPs. Letrozole-treated patients with rs2077647 (T>C) variants CC and TC had a reduced risk of bone AE (HR = 0.75, 95% CI = 0.58-0.98, P interaction = 0.08), whereas patients with rs4986938 (G>A) genotype variants AA and AG had an increased risk of bone AE (HR = 1.37, 95% CI = 1.01-1.84, P interaction = 0.07). We observed that (1) rare ESR1 homozygous polymorphisms were associated with lower recurrence, and (2) ESR1 and ESR2 SNPs were associated with bone AEs in letrozole-treated patients. Genes that are involved in estrogen signaling and synthesis have the potential to affect both breast cancer recurrence and side effects, suggesting that individual treatment strategies can incorporate not only oncogenic drivers but also SNPs related to estrogen activity.

Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome.

PubMed

Estrada, Andrea; Boyce, Alison M; Brillante, Beth A; Guthrie, Lori C; Gafni, Rachel I; Collins, Michael T

2016-11-01

McCune-Albright syndrome (MAS) is a rare disorder with a broad spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP. Retrospective cohort analysis. Clinical data, including history and physical examination, bone age, and pelvic ultrasounds, were reviewed on 28 letrozole-treated girls. Adult height was reviewed for 42 historical controls. Outcomes included rate of skeletal maturation, growth velocity, predicted adult height and adult height. Twenty-eight girls received letrozole treatment. Treatment duration was 4.1 ± 2.6 years (mean ± 1 s.d.) (range: 0.5-10.9) and mean follow-up was 6.0 ± 3.3 years (range: 0.5-15.0), for a total of 135.9 person-years of follow-up. Letrozole treatment was highly effective at decreasing the rate of skeletal maturation, with a decline in change in bone age over change in chronological age (ΔBA/ΔCA) from 1.7 (IQR: 2.3) to 0.5 (IQR: 0.4) (P < 0.0001), and growth velocity Z-scores, which declined from 2.2 ± 2.3 to -0.6 ± 1.6 (P = 0.0004). Predicted adult height Z-scores increased significantly from -2.9 ± 3.2 to -0.8 ± 1.5 for subjects on treatment (P = 0.004). Four subjects who completed treatment reached adult height Z-scores ranging from -1.5 to 1.7 (median: -0.6), which were increased in comparison with untreated historical controls (P = 0.02). There was no change in uterine size or ovarian volumes, and no adverse events over the treatment period. In this study with the longest follow-up to date, letrozole treatment resulted in sustained beneficial effects on skeletal maturation, growth velocity and predicted adult height. © 2016 European Society of Endocrinology.

Long-term Outcomes of Letrozole Treatment for Precocious Puberty in Girls with McCune-Albright Syndrome

PubMed Central

Brillante, Beth A.; Guthrie, Lori C.; Gafni, Rachel I.; Collins, Michael T.

2016-01-01

Objective McCune-Albright syndrome (MAS) is a rare disorder with a spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP. Design Retrospective cohort analysis. Methods Clinical data were reviewed, including history and physical, bone age, and pelvic ultrasounds on 28 letrozole-treated girls. Adult height was reviewed for 42 historical controls. Outcomes included rate of skeletal maturation, growth velocity, predicted adult height, and adult height. Results Twenty-eight girls received letrozole treatment. Treatment duration was 4.1 ± 2.6 years (mean ± 1SD) (0.5–10.9, range) and mean follow-up was 6.0 ± 3.3 years (range 0.5-15.0), for a total of 135.9 person-years of follow-up. Letrozole was highly effective at decreasing the rate of skeletal maturation, with a decline in change in bone age over change in chronological age (ΔBA/ΔCA) from 1.7 (IQR 2.3) to 0.5 (IQR 0.4) (p<0.0001), and growth velocity Z-scores, which declined from 2.2 ± 2.3 to −0.6 ± 1.6 (p = 0.0004). Predicted adult height Z-scores increased significantly from −2.9 ± 3.2 to −0.8 ± 1.5 for subjects on treatment (p = 0.004). Four subjects who completed treatment reached adult height Z-scores ranging from −1.5 to 1.7 (median −0.6), which was increased in comparison to untreated historical controls (p=0.02). There was no change in uterine size or ovarian volumes, and no adverse events over the treatment period. Conclusions In this study with the longest follow-up to date, letrozole treatment resulted in sustained beneficial effects on skeletal maturation, growth velocity and predicted adult height. PMID:27562402

Synthesis and PET studies of [11C-cyano]letrozole (Femara®), an aromatase inhibitor drug

PubMed Central

Kil, Kun-Eek; Biegon, Anat; Ding, Yu-Shin; Fischer, Andre; Ferrieri, Richard A.; Kim, Sung Won; Pareto, Deborah; Schueller, Michael J.; Fowler, Joanna S.

2011-01-01

Introduction Aromatase, a member of the cytochrome P450 family, converts androgens such as androstenedione and testosterone to estrone and estradiol respectively. Letrozole (1-[bis-(4-cyanophenyl)methyl]-1H-1,2,4-triazole, Femara®) is a high affinity aromatase inhibitor (Ki=11.5 nM) which has FDA approval for breast cancer treatment. Here we report the synthesis of carbon-11 labeled letrozole and its assessment as a radiotracer for brain aromatase in the baboon. Methods Letrozole and its precursor (4-[(4-bromophenyl)-1H-1,2,4-triazol-1-ylmethyl]benzonitrile, 3) were prepared in two-step syntheses from 4-cyanobenzyl bromide and 4-bromobenzyl bromide, respectively. The [11C]cyano group was introduced via the tetrakis(triphenylphosphine)palladium(0) catalyzed coupling of [11C]cyanide with the bromo-precursor (3). PET studies in the baboon brain were carried out to assess regional distribution and kinetics, reproducibility of repeated measures and saturability. The free fraction of letrozole in the plasma, log D, and the [11C-cyano]letrozole fraction in the arterial plasma were also measured. Results [11C-cyano]Letrozole was synthesized in 60 min with a radiochemical yield of 79–80%, with a radiochemical purity greater than 98% and a specific activity of 4.16±2.21 Ci/μmol at the end of bombardment (n=4). PET studies in the baboon revealed initial rapid and high uptake and initial rapid clearance followed by slow clearance of carbon-11 from the brain with no difference between brain regions. The brain kinetics was not affected by co-injection of unlabeled letrozole (0.1 mg/kg). The free fraction of letrozole in plasma was 48.9% and log D was 1.84. Conclusion [11C-cyano]Letrozole is readily synthesized via a palladium catalyzed coupling reaction with [11C]cyanide. Although it is unsuitable as a PET radiotracer for brain aromatase as revealed by the absence of regional specificity and saturability in brain regions, such as amygdala, which are known to contain

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

PubMed

Nabieva, N; Kellner, S; Fehm, T; Häberle, L; de Waal, J; Rezai, M; Baier, B; Baake, G; Kolberg, H-C; Guggenberger, M; Warm, M; Harbeck, N; Wuerstlein, R; Deuker, J-U; Dall, P; Richter, B; Wachsmann, G; Brucker, C; Siebers, J W; Fersis, N; Kuhn, T; Wolf, C; Vollert, H-W; Breitbach, G-P; Janni, W; Landthaler, R; Kohls, A; Rezek, D; Noesselt, T; Fischer, G; Henschen, S; Praetz, T; Heyl, V; Kühn, T; Krauss, T; Thomssen, C; Hohn, A; Tesch, H; Mundhenke, C; Hein, A; Rauh, C; Bayer, C M; Jacob, A; Schmidt, K; Belleville, E; Brucker, S Y; Kümmel, S; Beckmann, M W; Wallwiener, D; Hadji, P; Fasching, P A

2018-01-01

Patients' compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Drug Use Evaluation of Letrozole in Breast Cancer Patients at Regional Cancer Hospitals in Thailand.

PubMed

Ketkaew, Chaninun; Kiatying-Angsulee, Niyada

2015-01-01

Medication policy development in Thailand is continually promoting rational drug use. Letrozole, an endocrine therapy drug, is usually prescribed for post-menopausal status early and advanced stage breast cancer. After Ministry of Public Health announced Letrozole as compulsory licensed drug in 2009, more breast cancer patients can access to this drug at low cost especially those within universal coverage schemes. To ensure that Letrozole is rationally prescribed, the drug utilization study was conducted. The aim of this study was to describe the appropriate use of Letrozole in breast cancer and the relationship between appropriate use and health benefit schemes. A retrospective study to evaluate use of Letrozole in breast cancer patients was performed for six months between January - June 2010 in seven regional cancer hospitals, Thailand. All prescriptions of Letrozole were identified from pharmacy dispensing databases and prescription papers. A medical record review was also performed to evaluate appropriate use referring to the drug use evaluation criteria. The approved criterion of this study was referred from the guideline of Thai National Formulary version 2010. There were 681 prescriptions of Letrozole for 254 breast cancer patients with an average age of 58.6 ± 10.0 years. The patients in universal coverage scheme (UCS), civil servant medication benefit scheme (CSMBS) and social security scheme (SSS) were 77.7%, 18.5% and 8.7% respectively. 10.6% were prescribed Letrozole for the first time. Letrozole were prescribed by oncologists (82.8%). The average number of tablets per prescription was 58 ± 10. Calcium supplements were prescribed concomitant with Letrozole for 19.4%. To assess drug use evaluation criteria, 45 prescriptions were excluded because of uncompleted clinical data, 636 prescriptions were evaluated. The study showed 86 prescriptions (13.5%) with inappropriate use including 6 (0.9%) not prescribed for estrogen receptor (ER) and/or progesterone

Progesterone levels in letrozole associated controlled ovarian stimulation for fertility preservation in breast cancer patients.

PubMed

Goldrat, O; Gervy, C; Englert, Y; Delbaere, A; Demeestere, I

2015-09-01

Are progesterone levels after letrozole-associated controlled ovarian stimulation (COS) for fertility preservation in breast cancer patients, lower than after standard in vitro fertilization (IVF) cycles? During the luteal phase of letrozole-associated COS cycles (triggered with human chorionic gonadotrophin (hCG)) progesterone levels are similarly elevated to those obtained after standard COS without letrozole. Current fertility preservation strategies for breast cancer patients include association of COS with the aromatase inhibitor letrozole to harvest several mature oocytes while maintaining low estradiol levels. Data on progesterone levels are however lacking despite growing evidence of the role of progesterone in breast tumorigenesis. This is a prospective observational study comparing estradiol and progesterone levels of 21 breast cancer patients undergoing letrozole-associated COS with 21 infertile patients undergoing standard COS for IVF and/or intra cytoplasmic sperm injection (ICSI). All patients underwent COS with a GnRH antagonist protocol. In the fertility preservation group, ovulation induction was started in the follicular or luteal phase depending on the chemotherapy schedule and in 10 cases a GnRH antagonist was administered during luteal phase to induce luteolysis. Final oocyte maturation was induced by hCG in all patients. Estradiol and progesterone levels were measured on the day of hCG, at oocyte retrieval, and on days 3 and 8 after oocyte retrieval. Hormone levels in fertility preservation patients were compared with those observed in infertility patients. While estradiol levels were significantly lower in the fertility preservation group compared with the control group (P < 0.001), progesterone levels were similar at all times, including patients receiving a GnRH antagonist during the luteal phase. The studied populations (breast cancer and infertile patients) are different, which may induce selection bias. The small sample size limits the

Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence.

PubMed

Chirgwin, Jacquie H; Giobbie-Hurder, Anita; Coates, Alan S; Price, Karen N; Ejlertsen, Bent; Debled, Marc; Gelber, Richard D; Goldhirsch, Aron; Smith, Ian; Rabaglio, Manuela; Forbes, John F; Neven, Patrick; Láng, István; Colleoni, Marco; Thürlimann, Beat

2016-07-20

To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor-positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Both aspects of low adherence (early cessation of letrozole and a compliance score of < 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence. © 2016 by American Society of Clinical Oncology.

Treatment Adherence and Its Impact on Disease-Free Survival in the Breast International Group 1-98 Trial of Tamoxifen and Letrozole, Alone and in Sequence

PubMed Central

Giobbie-Hurder, Anita; Coates, Alan S.; Price, Karen N.; Ejlertsen, Bent; Debled, Marc; Gelber, Richard D.; Goldhirsch, Aron; Smith, Ian; Rabaglio, Manuela; Forbes, John F.; Neven, Patrick; Láng, István; Colleoni, Marco; Thürlimann, Beat

2016-01-01

Purpose To investigate adherence to endocrine treatment and its relationship with disease-free survival (DFS) in the Breast International Group (BIG) 1-98 clinical trial. Methods The BIG 1-98 trial is a double-blind trial that randomly assigned 6,193 postmenopausal women with hormone receptor–positive early breast cancer in the four-arm option to 5 years of tamoxifen (Tam), letrozole (Let), or the agents in sequence (Let-Tam, Tam-Let). This analysis included 6,144 women who received at least one dose of study treatment. Conditional landmark analyses and marginal structural Cox proportional hazards models were used to evaluate the relationship between DFS and treatment adherence (persistence [duration] and compliance with dosage). Competing risks regression was used to assess demographic, disease, and treatment characteristics of the women who stopped treatment early because of adverse events. Results Both aspects of low adherence (early cessation of letrozole and a compliance score of < 90%) were associated with reduced DFS (multivariable model hazard ratio, 1.45; 95% CI, 1.09 to 1.93; P = .01; and multivariable model hazard ratio, 1.61; 95% CI, 1.08 to 2.38; P = .02, respectively). Sequential treatments were associated with higher rates of nonpersistence (Tam-Let, 20.8%; Let-Tam, 20.3%; Tam 16.9%; Let 17.6%). Adverse events were the reason for most trial treatment early discontinuations (82.7%). Apart from sequential treatment assignment, reduced adherence was associated with older age, smoking, node negativity, or prior thromboembolic event. Conclusion Both persistence and compliance are associated with DFS. Toxicity management and, for sequential treatments, patient and physician awareness, may improve adherence. PMID:27217455

Formestane, a steroidal aromatase inhibitor after failure of non-steroidal aromatase inhibitors (anastrozole and letrozole): is a clinical benefit still achievable?

PubMed

Carlini, P; Frassoldati, A; De Marco, S; Casali, A; Ruggeri, E M; Nardi, M; Papaldo, P; Fabi, A; Paoloni, F; Cognetti, F

2001-11-01

There are few clinical data on the sequential use of aromatase inhibitors (AI). This paper focuses on the relevance of clinical benefit CB (CR + PR + SD > or = 6 months) in postmenopausal metastatic breast cancer (MBC) patients treated with the steroidal aromatase inhibitor (SAI) formestane (FOR). who had already received non-steroidal aromatase inhibitor (nSAI): letrozole (LTZ) or anastrozole (ANZ). Twenty postmenopausal women with MBC were analysed in this retrospective two-centre study with the sequence nSAI-FOR. When receiving ANZ, 1 of 11 achieved a complete response and 9 of 11 a stable disease > or = 6 months, and receiving LTZ 1 of 9 achieved a partial response and 4 of 9 a stable disease > or = 6 months. The analysis of the entire population treated with FOR showed an overall CB of 55% (11 of 20) with a median duration of 15 months and median time to progression (TTP) of 6 months. Formestane 250 mg once bi-weekly seems to be an attractive alternative third-line hormonal therapy for the treatment of patients with MBC, previously treated with nSAI.

Comparison of clomiphene citrate and letrozole for ovulation induction in women with polycystic ovary syndrome: a prospective randomized trial.

PubMed

Liu, Chang; Feng, Guimei; Huang, Wei; Wang, Qiuyi; Yang, Shiyuan; Tan, Jing; Fu, Jing; Liu, Dong

2017-11-01

To compare the therapeutic efficacy of clomiphene citrate (CC) and letrozole (LE) on ovulation, pregnancy, and live birth in women with polycystic ovary syndrome (PCOS); and to ensure if LE can replace CC as the first-line therapy for ovulation induction in these women. This is a prospectively, randomized, controlled trial in the tertiary hospital. Two-hundred and sixty-eight anovulatory PCOS patients were treated by CC or CC plus metformin and LE or LE plus metformin for three continuous cycles or conception; their ovulation rates, pregnancy rates, and live birth rates were calculated and compared. No significant difference was noted among the four groups regarding to the baseline data of clinical manifestations, serum sex hormone levels, and serum insulin levels. A total of 240 patients completed the therapies. The ovulation rate was significantly higher in the group LE than the group CC; however, no significant difference was noted between the groups LE and CC, CC, and CC + MET, or LE and LE + MET in the pregnancy rate, abortion rate, and live birth rate. No birth defect was found in the total of 63 newborns. CC regimen was still recommended to be the first-line therapy of ovulation induction for PCOS.

Ovulation induction and controlled ovarian stimulation using letrozole gonadotropin combination: A single center retrospective cohort study.

PubMed

Arya, Sushila; Kupesic-Plavsic, Sanja; Mulla, Zuber D; Dwivedi, Alok K; Crisp, Zeni; Jose, Jisha; Noble, Luis S

2017-11-01

To assess the effect of letrozole in combination with low dose gonadotropins for ovulation induction in anovulatory infertility from polycystic ovary syndrome (PCOS) and controlled ovarian stimulation for endometriosis, and unexplained infertility patients. Retrospective cohort study in a setting of private Reproductive Endocrinology and Infertility Clinic affiliated with the University. Three hundred couples (650 cycles) requiring OI/COS for PCOS (92 patients, 195 cycles), endometriosis (89 patients, 217 cycles), and unexplained infertility (119 patients, 238 cycles). Patients received 2.5mg or 5mg letrozole for 5days (D3-D7) and recombinant follicle-stimulating hormone on alternating D3-D7 and human menopausal gonadotropin-highly purified alternating D5-D10 until growth of ideally 2 mature follicles. Ovulation was triggered with 10,000 IU of HCG. Maximum number of cycles per patient was four. Main outcome measures were clinical pregnancy rates, multiple order pregnancy rates, miscarriage rates, number of follicles and endometrial thickness on the day of HCG administration. The cumulative incidence of pregnancy was estimated as 35% (95%CI: 29%-41%) overall and was highest in patients with PCOS (36.6%), followed by unexplained infertility (34.6%) and endometriosis (32.5%). The pregnancy rates per cycle in PCOS, endometriosis and unexplained infertility patients were 17%, 13.2% and 17.2% respectively, no statistically significant difference between the groups. There were three twin pregnancies in PCOS, and one in unexplained infertility group. Monofolliculogenesis was noted in 48% of patients. Letrozole-low dose gonadotropins combination appears to be effective across different causes of infertility for superovulation. The letrozole-low dose gonadotropin combination resulted in high rate of monofolliculogenesis, low occurrence of multiple gestations and no case of OHSS or cycle cancellation. Published by Elsevier B.V.

Aromatase inhibition by letrozole attenuates kainic acid-induced seizures but not neurotoxicity in mice.

PubMed

Iqbal, Ramsha; Jain, Gaurav K; Siraj, Fouzia; Vohora, Divya

2018-07-01

Evidence shows neurosteroids play a key role in regulating epileptogenesis. Neurosteroids such as testosterone modulate seizure susceptibility through its transformation to metabolites which show proconvulsant and anticonvulsant effects, respectively. Reduction of testosterone by aromatase generates proconvulsant 17-β estradiol. Alternatively, testosterone is metabolized into 5α-dihydrotestosterone (5α-DHT) by 5α-reductase, which is then reduced by 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR) to form anticonvulsant metabolite 3α-androstanediol (3α-Diol), a potent GABA A receptor modulating neurosteroid. The present study evaluated whether inhibition of aromatase inhibitor letrozole protects against seizures and neuronal degeneration induced by kainic acid (KA) (10 mg/kg, i.p.) in Swiss albino mice. Letrozole (1 mg/kg, i.p.) administered one hour prior to KA significantly increased the onset time of seizures and reduced the% incidence of seizures. Pretreatment with finasteride, a selective inhibitor of 5α-reductase and indomethacin, a selective inhibitor of 3α-hydroxysteroid oxidoreductase enzyme (3α-HSOR), reversed the protective effects of letrozole in KA-induced seizures in mice. Microscopic examination using cresyl violet staining revealed that letrozole did not modify KA-induced neurotoxicity in the CA1, CA3 and DG region of the hippocampus. Letrozole treatment resulted in the reduced levels of 17-β estradiol and elevated the levels of 5α-dihydrotestosterone (DHT) and 3α-Diol in the hippocampus. Finasteride and indomethacin attenuated letrozole-induced elevations of 5α-DHT and 3α-Diol. Our results indicate the potential anticonvulsant effects of letrozole against KA-induced seizures in mice that might be mediated by inhibiting aromatization of testosterone to 17β-estradiol, a proconvulsant hormone and by redirecting the synthesis to anticonvulsant metabolites, 5α-DHT and 3α-Diol. Acute aromatase inhibition, thus, might be used as an

Reduced estradiol synthesis by letrozole, an aromatase inhibitor, is protective against development of pentylenetetrazole-induced kindling in mice.

PubMed

Rashid, Davood; Panda, B P; Vohora, Divya

2015-11-01

Neurosteroids, such as testosterone and their metabolites, are known to modulate neuronal excitability. The enzymes regulating the metabolism of these neurosteroids, thus, may be targeted as a noval strategy for the development of new antiepileptic drugs. The present work targeted two such enzymes i,e aromatase and 5α-reductase in order to explore the potential of letrozole (an aromatase inhibitor) on pentylenetetrazole (PTZ)-induced kindling in mice and the ability of finasteride (a 5α-reductase inhibitor) to modulate any such effects. PTZ (30 mg/kg, i.p.), when administered once every two days (for a total of 24 doses) induced kindling in Swiss albino mice. Letrozole (1 mg/kg, p.o.), administered prior to PTZ, significantly reduced the % incidence of kindling, delayed mean onset time of seizures and reduced seizure severity score. Letrozole reduced the levels of plasma 17β-estradiol after induction of kindling. The concurrent administration of finasteride and letrozole produced effects similar to letrozole on PTZ-kindling and on estradiol levels. This implies that the ability of letrozole to redirect the synthesis of dihydrotestosterone (DHT) and 5α-androstanediol from testosterone doesn't appear to play a significant role in the protective effects of letrozole against PTZ kindling. Letrozole, however, increased the levels of 5α-DHT in mice plasma. The aromatase inhibitors, thus, may be exploited for inhibiting the synthesis of proconvulsant (17β-estradiol) and/or redirecting the synthesis of anticonvulsant (DHT and 5α-androstanediol) neurosteroids. Copyright © 2015 Elsevier Ltd. All rights reserved.

Interpreting Breast International Group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer.

PubMed

Regan, Meredith M; Price, Karen N; Giobbie-Hurder, Anita; Thürlimann, Beat; Gelber, Richard D

2011-05-26

The Breast International Group (BIG) 1-98 study is a four-arm trial comparing 5 years of monotherapy with tamoxifen or with letrozole or with sequences of 2 years of one followed by 3 years of the other for postmenopausal women with endocrine-responsive early invasive breast cancer. From 1998 to 2003, BIG -98 enrolled 8,010 women. The enhanced design f the trial enabled two complementary analyses of efficacy and safety. Collection of tumor specimens further enabled treatment comparisons based on tumor biology. Reports of BIG 1-98 should be interpreted in relation to each individual patient as she weighs the costs and benefits of available treatments. Clinicaltrials.gov ID: NCT00004205.

Interpreting breast international group (BIG) 1-98: a randomized, double-blind, phase III trial comparing letrozole and tamoxifen as adjuvant endocrine therapy for postmenopausal women with hormone receptor-positive, early breast cancer

PubMed Central

2011-01-01

The Breast International Group (BIG) 1-98 study is a four-arm trial comparing 5 years of monotherapy with tamoxifen or with letrozole or with sequences of 2 years of one followed by 3 years of the other for postmenopausal women with endocrine-responsive early invasive breast cancer. From 1998 to 2003, BIG -98 enrolled 8,010 women. The enhanced design f the trial enabled two complementary analyses of efficacy and safety. Collection of tumor specimens further enabled treatment comparisons based on tumor biology. Reports of BIG 1-98 should be interpreted in relation to each individual patient as she weighs the costs and benefits of available treatments. Clinicaltrials.gov ID: NCT00004205. PMID:21635709

In vitro fertilization treatments with the use of clomiphene citrate or letrozole.

PubMed

Haas, Jigal; Casper, Robert F

2017-10-01

There has been increasing interest in combining the oral agents clomiphene citrate (CC) and letrozole with gonadotropins in IVF: for poor responders to reduce the amount of gonadotropins used, and in normal responders to reduce the incidence of ovarian hyperstimulation (OHSS). In normal responders, mild stimulation with the use of CC and gonadotropins was found to decrease the number of oocytes retrieved and result in good pregnancy rates, but in most studies the cumulative pregnancy rate was lower compared with conventional ovarian stimulation when frozen embryo transfers were considered. Coadministration of letrozole and gonadotropins has mainly been used in patients with breast cancer to prevent the massive elevation of serum E 2 concentrations with the use of standard controlled ovarian hyperstimulation. CC and letrozole have both been used with gonadotropins in poor responders and have been shown to reduce the amount of gonadotropin used without reducing the pregnancy rate. Letrozole use with gonadotropins in IVF cycles may increase endometrial receptivity by increasing integrin expression in the endometrium and by lowering estrogen concentrations to more physiologic levels. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Treatment strategies for women with WHO group II anovulation: systematic review and network meta-analysis

PubMed Central

Kim, Bobae V; van Wely, Madelon; Johnson, Neil P; Costello, Michael F; Zhang, Hanwang; Ng, Ernest Hung Yu; Legro, Richard S; Bhattacharya, Siladitya; Norman, Robert J; Mol, Ben Willem J

2017-01-01

Objective To compare the effectiveness of alternative first line treatment options for women with WHO group II anovulation wishing to conceive. Design Systematic review and network meta-analysis. Data sources Cochrane Central Register of Controlled Trials, Medline, and Embase, up to 11 April 2016. Study selection Randomised controlled trials comparing eight ovulation induction treatments in women with WHO group II anovulation: clomiphene, letrozole, metformin, clomiphene and metformin combined, tamoxifen, gonadotropins, laparoscopic ovarian drilling, and placebo or no treatment. Study quality was measured on the basis of the methodology and categories described in the Cochrane Collaboration Handbook. Pregnancy, defined preferably as clinical pregnancy, was the primary outcome; live birth, ovulation, miscarriage, and multiple pregnancy were secondary outcomes. Results Of 2631 titles and abstracts initially identified, 57 trials reporting on 8082 women were included. All pharmacological treatments were superior to placebo or no intervention in terms of pregnancy and ovulation. Compared with clomiphene alone, both letrozole and the combination of clomiphene and metformin showed higher pregnancy rates (odds ratio 1.58, 95% confidence interval 1.25 to 2.00; 1.81, 1.35 to 2.42; respectively) and ovulation rates (1.99, 1.38 to 2.87; 1.55, 1.02 to 2.36; respectively). Letrozole led to higher live birth rates when compared with clomiphene alone (1.67, 1.11 to 2.49). Both letrozole and metformin led to lower multiple pregnancy rates compared with clomiphene alone (0.46, 0.23 to 0.92; 0.22, 0.05 to 0.92; respectively). Conclusions In women with WHO group II anovulation, letrozole and the combination of clomiphene and metformin are superior to clomiphene alone in terms of ovulation and pregnancy. Compared with clomiphene alone, letrozole is the only treatment showing a significantly higher rate of live birth. Systematic review registration PROSPERO CRD42015027579. PMID

FemZone trial: a randomized phase II trial comparing neoadjuvant letrozole and zoledronic acid with letrozole in primary breast cancer patients

PubMed Central

2014-01-01

Background The objective of this prospectively randomized phase II trial (Trial registration: EUCTR2004-004007-37-DE) was to compare the clinical response of primary breast cancer patients to neoadjuvant therapy with letrozole alone (LET) or letrozole and zoledronic acid (LET + ZOL). Methods Patients were randomly assigned to receive either LET 2.5 mg/day (n = 79) or the combination of LET 2.5 mg/day and a total of seven infusions of ZOL 4 mg every 4 weeks (n = 89) for 6 months. Primary endpoint was clinical response rate as assessed by mammogram readings. The study was terminated prematurely due to insufficient recruitment. We report here on an exploratory analysis of this data. Results Central assessment of tumor sizes during the treatment period was available for 131 patients (66 LET, 65 LET + ZOL). Clinical responses (complete or partial) were seen in 54.5% (95% CI: 41.8-66.9) of the patients in the LET arm and 69.2% (95% CI: 56.6-80.1) of those in the LET + ZOL arm (P = 0.106). A multivariate model showed an OR of 1.72 (95% CI: 0.83-3.59) for the experimental arm. Conclusion No increase in the clinical response rate was observed with the addition of ZOL to a neoadjuvant treatment regimen with LET. However a trend towards a better reponse in the LET + ZOL arm could be observed. This trend is consistent with previous studies that have investigated the addition of ZOL to chemotherapy, and it may support the evidence for a direct antitumor action of zoledronic acid. PMID:24499441

Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications.

PubMed

Glaser, Rebecca L; York, Anne E; Dimitrakakis, Constantine

2017-07-01

Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy. A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to "testosterone-letrozole" and subsequently, "testosterone-letrozole with chemotherapy" was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated. There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported. Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.

Effect of dietary administration of letrozole and tamoxifen on gonadal development, sex differentiation and biochemical changes in common carp (Cyprinus carpio L.).

PubMed

Singh, Atul K; Srivastava, P P; Verma, Rita; Srivastava, Sharad C; Kumar, Dinesh; Ansari, Abubakar

2015-03-01

The effect of letrozole and tamoxifen on the specific growth rate (SGR; % day(-1)), gonado-somatic index (GSI), total haemoglobin (g%), gonadal and serum protein as well as lipid, sex differentiation and 17β-oestradiol levels were studied in sexually undifferentiated Cyprinus carpio fingerlings 30 days post fertilisation (30 dpf) for 60 days. Results showed decreased GSI with tamoxifen treatment whereas letrozole increased it. There were reduced protein, lipid, triglyceride and cholesterol levels after treatment with tamoxifen and letrozole during gonadal development. Tamoxifen (200mgkg(-1) feed) induced 82.5% masculinisation, whereas letrozole in the same dose produced 98.5% males. Gonadal 17β-oestradiol significantly declined from 86.0±1.41pg per 100mg (control) to 45.5±1.94pg per 100mg with tamoxifen and 36.0±0.72pg per 100mg with letrozole treatment. Similarly, serum 17β-oestradiol levels also decreased after tamoxifen and letrozole treatments. Testicular development in 37.8% of fish treated with tamoxifen and letrozole was found to be more advanced (spermatocytes) than in the control (spermatogonium); however, there was reduced ovarian growth and increased atresia. It was concluded that letrozole and tamoxifen both significantly affect sex differentiation and gonadal maturity in C. carpio leading to the production of sex-reversed males, yet the effect of letrozole was more potent.

Associations between genetic variants and the effect of letrozole and exemestane on bone mass and bone turnover.

PubMed

Oesterreich, Steffi; Henry, N Lynn; Kidwell, Kelley M; Van Poznak, Catherine H; Skaar, Todd C; Dantzer, Jessica; Li, Lang; Hangartner, Thomas N; Peacock, Munro; Nguyen, Anne T; Rae, James M; Desta, Zeruesenay; Philips, Santosh; Storniolo, Anna M; Stearns, Vered; Hayes, Daniel F; Flockhart, David A

2015-11-01

Adjuvant therapy for hormone receptor (HR) positive postmenopausal breast cancer patients includes aromatase inhibitors (AI). While both the non-steroidal AI letrozole and the steroidal AI exemestane decrease serum estrogen concentrations, there is evidence that exemestane may be less detrimental to bone. We hypothesized that single nucleotide polymorphisms (SNP) predict effects of AIs on bone turnover. Early stage HR-positive breast cancer patients were enrolled in a randomized trial of exemestane versus letrozole. Effects of AI on bone mineral density (BMD) and bone turnover markers (BTM), and associations between SNPs in 24 candidate genes and changes in BMD or BTM were determined. Of the 503 enrolled patients, paired BMD data were available for 123 and 101 patients treated with letrozole and exemestane, respectively, and paired BTM data were available for 175 and 173 patients, respectively. The mean change in lumbar spine BMD was significantly greater for letrozole-treated (-3.2 %) compared to exemestane-treated patients (-1.0 %) (p = 0.0016). Urine N-telopeptide was significantly increased in patients treated with exemestane (p = 0.001) but not letrozole. Two SNPs (rs4870061 and rs9322335) in ESR1 and one SNP (rs10140457) in ESR2 were associated with decreased BMD in letrozole-treated patients. In the exemestane-treated patients, SNPs in ESR1 (Rs2813543) and CYP19A1 (Rs6493497) were associated with decreased bone density. Exemestane had a less negative impact on bone density compared to letrozole, and the effects of AI therapy on bone may be impacted by genetic variants in the ER pathway.

Effects of Exercise Intervention on Preventing Letrozole-Exposed Rats From Polycystic Ovary Syndrome.

PubMed

Cao, Si-Fan; Hu, Wen-Long; Wu, Min-Min; Jiang, Li-Yan

2017-03-01

Polycystic ovary syndrome (PCOS) is a prevalent endocrinological disorder in reproductive-age women and is often associated with a metabolic syndrome. To investigate whether exercise intervention promotes PCOS prevention, a rat model was used. Polycystic ovary syndrome was induced by letrozole administration, and animals presented with obesity, sex hormone disorder, no ovulation, large cystic follicles, and increasing fasting insulin (FINS) and leptin levels. The intervention was set at 3 different intensities of swimming exercise: low (0.5 h/d), moderate (1 h/d), and high (2 h/d), and compared with a PCOS model group (letrozole administration without exercise intervention) and a control group. The exercise intervention in the low-intensity group did not produce changes in obesity, testosterone, progesterone (P), and follicle-stimulating hormone (FSH) levels. Moderate-intensity exercise reduced body weight, retained ovulation, and P levels were increased but remained lower than those in the control group. The FSH levels were significantly higher, and FINS and leptin levels were lower than in the model group ( P < 0.05) but not in the control group. The high-intensity group demonstrated the greatest effect of PCOS prevention. Testosterone, luteinizing hormone, FINS, and leptin levels were significantly lower in the high-intensity group, and FSH and P levels were higher compared with the model group. These results suggest that high-intensity exercise intervention can effectively prevent PCOS development.

Increased pathological complete response rate after a long-term neoadjuvant letrozole treatment in postmenopausal oestrogen and/or progesterone receptor-positive breast cancer

PubMed Central

Allevi, G; Strina, C; Andreis, D; Zanoni, V; Bazzola, L; Bonardi, S; Foroni, C; Milani, M; Cappelletti, M R; Gussago, F; Aguggini, S; Giardini, R; Martinotti, M; Fox, S B; Harris, A L; Bottini, A; Berruti, A; Generali, D

2013-01-01

Background: The objective of this study was to determine the optimal scheduling of 2.5 mg daily letrozole in neoadjuvant breast cancer patients to obtain pathological complete response (pathCR) and assess Ki-67 expression as an early predictor of response. Patients and methods: This single institution study comprised 120 oestrogen receptor (ER)-positive postmenopausal women with primary breast cancer (clinical stage ⩾T2, N0–1), from three sequential cohorts (cohort A of 40, cohort B of 40 and cohort C of 40 patients, respectively) based on different duration of the neoadjuvant letrozole. Biological markers such as ER, progesterone receptor, HER2 and Ki-67 expression were tested at diagnosis and at definitive surgery. Results: A total of 89 patients (75.4%) achieved an objective response with 44 (37.3%) clinical CRs and 45 (38.1%) partial responses. The clinical CRs were significantly observed in cohort C (23 out of 40 patients, 57.5%) and B (16 out of 38 patients, 42.1%) compared with cohort A (5 out of 40 patients, 12.5%) (P-value for trend <0.001). Letrozole induced a similar significant reduction in Ki-67 index after treatment in all cohorts. The pathCR rate was significantly more frequent in cohort C (7 out of 40 patients, 17.5%) than in cohort A (1 out of 40 patients, 2.5%) and B (2 out of 40 patients, 5.0%) (P-value for trend <0.04). Conclusion: One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure. PMID:23579222

Aromatase inhibitor letrozole downregulates steroid receptor coactivator-1 in specific brain regions that primarily related to memory, neuroendocrine and integration.

PubMed

Bian, Chen; Zhao, Yangang; Guo, Qiang; Xiong, Ying; Cai, Wenqin; Zhang, Jiqiang

2014-05-01

As one of the third generation of aromatase inhibitors, letrozole is a favored drug for the treatment of hormone receptor-positive breast cancer with some adverse effects on the nervous system, but the knowledge is limited and the results are controversial, the mechanism underlying its central action is also unclear. Accumulated evidences have demonstrated that estrogens derived from androgens by aromatase play profound roles in the brain through their receptors, which needs coactivator for the transcription regulation, among which steroid receptor coactivator-1 (SRC-1) has been shown to be multifunctional potentials in the brain, but whether it is regulated by letrozole is currently unknown. In this study, we examined letrozole regulation on SRC-1 expression in adult mice brain using immunohistochemistry. The results showed that letrozole induced dramatic decrease of SRC-1 in the medial septal, hippocampus, medial habenular nucleus, arcuate hypothalamic nucleus and superior colliculus (p<0.01). Significant decrease was detected in the dorsal lateral septal nucleus, bed nucleus of stria terminalis, ventral taenia tecta, dorsomedial and ventromedial hypothalamic nuclei, dorsomedial periaqueductal gray, superior paraolivary nucleus and pontine nucleus (p<0.05). In the hippocampus, levels of estradiol content, androgen receptor, estrogen receptor α and β also decreased significantly after letrozole injection. The above results demonstrated letrozole downregulation of SRC-1 in specific regions that are primarily related to learning and memory, cognition and mood, neuroendocrine as well as information integration, indicating that SRC-1 may be one important downstream central target of letrozole. Furthermore, these potential central adverse effects of letrozole should be taken into serious considerations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Letrozole combined with low dose highly purified HMG for ovulation induction in clomiphene citrate-resistant infertile Chinese women with polycystic ovary syndrome: a prospective study.

PubMed

Zhao, Yue; Ruan, Xiangyan; Mueck, Alfred O

2017-06-01

There are still open questions about ovulation induction in clomiphene citrate-(CC)-resistant infertile women. Especially little is known about efficacy and safety of letrozole (LTZ) combined with low-dose highly purified human menopausal gonadotropin (Hp-HMG) in women with polycystic ovary syndrome (PCOS). Prospective, single-arm single-center trial in 200 infertile PCOS patients refractory for at least three CC-treatment cycles. Women with hyperandrogenism took Diane-35 for at least 3 months. All patients got LTZ on day 3 for 5 d in combination with Hp-HMG, starting with 75 IU from cycle day 7 and maintained for up to 3 d. The maximum dose was 150 IU. Primary end-points were ongoing and clinical pregnancy rate, secondary end-points mono-follicular development, ovulation rate, OHSS, multiple pregnancy and early pregnancy loss. Major safety end-point was the incidence of adverse events. Within 395 cycles the ongoing pregnancy rate was 28.24%, for cycles 35.23%, for patients 68%. The rate of ovulation per cycle was 97.7%, percentage of mono-follicular development 70.9%. No severe OHSS, multiple pregnancy, local or systemic side effects were seen. LTZ combined with low-dose Hp-HMG is an effective and safe choice for reducing hyperstimulation and increasing pregnancy rate in CC-resistant women with PCOS.

Tetragonia tetragonioides (Pall.) Kuntze Regulates Androgen Production in a Letrozole-Induced Polycystic Ovary Syndrome Model.

PubMed

Pyun, Bo-Jeong; Yang, Hyun; Sohn, Eunjin; Yu, Song Yi; Lee, Dongoh; Jung, Dong Ho; Ko, Byoung Seob; Lee, Hye Won

2018-05-14

Tetragonia tetragonioides (Pall.) Kuntze (TTK) is a medicinal plant traditionally used to treat various diseases such as diabetic, inflammatory, and female-related disorders. Polycystic ovary syndrome (PCOS) is a common endocrinological disorder in women of reproductive age, and hyperandrogenism is a prominent feature of PCOS resulting in anovulation and infertility. In this study, we investigated the effects of a TTK extract on androgen generation and regulation of steroidogenic enzymes in vitro and in vivo. Human adrenocortical NCI-H295R cells were used to assess the effects of TTK extract on production of dehydroepiandrosterone and testosterone, as well as the protein expression of steroidogenic enzymes. Further, a letrozole-induced PCOS rat model was used in vivo to assess whether dietary administration of TTK extract restores normal hormones and reduces PCOS symptoms. TTK extract significantly inhibited forskolin (FOR)-induced androgen production in NCI-H295R cells and serum luteinizing hormone, testosterone, and follicular cysts, but not estradiol, were reduced in letrozole-induced PCOS rats orally administered the TTK extract. In addition, TTK extract inhibits androgen biosynthesis through the ERK-CREB signaling pathway, which regulates CYP17A1 or HSD3B2 expression. TTK extract could be utilized for the prevention and treatment of hyperandrogenism and other types of PCOS.

The Effect of Undaria pinnatifida Fucoidan on the Pharmacokinetics of Letrozole and Tamoxifen in Patients With Breast Cancer.

PubMed

Tocaciu, Shreya; Oliver, Lesley J; Lowenthal, Ray M; Peterson, Gregory M; Patel, Rahul; Shastri, Madhur; McGuinness, Georgia; Olesen, Inger; Fitton, J Helen

2018-03-01

Although the use of complementary and alternative medicines is widespread in cancer patients, clinical evidence of their benefits is sparse. Furthermore, while they are often assumed to be safe with regard to concurrent use of anticancer therapies, few studies have been carried out to investigate possible interactions. Fucoidans are a group of sulfated carbohydrates, derived from marine brown algae, which have long been used as dietary supplements due to their reported medicinal properties, including anticancer activity. The aim of this study was to investigate the effect of co-administration of fucoidan, derived from Undaria pinnatifida, on the pharmacokinetics of 2 commonly used hormonal therapies, letrozole and tamoxifen, in patients with breast cancer. This was an open label non-crossover study in patients with active malignancy taking letrozole or tamoxifen (n = 10 for each group). Patients took oral fucoidan, given in the form of Maritech extract, for a 3-week period (500 mg twice daily). Trough plasma concentrations of letrozole, tamoxifen, 4-hydroxytamoxifen, and endoxifen were measured using HPLC-CAD (high-performance liquid chromatography charged aerosol detector), at baseline and after concomitant administration with fucoidan. No significant changes in steady-state plasma concentrations of letrozole, tamoxifen, or tamoxifen metabolites were detected after co-administration with fucoidan. In addition, no adverse effects of fucoidan were reported, and toxicity monitoring showed no significant differences in all parameters measured over the study period. Administration of Undaria pinnatifida fucoidan had no significant effect on the steady-state trough concentrations of letrozole or tamoxifen and was well tolerated. These results suggest that fucoidan in the studied form and dosage could be taken concomitantly with letrozole and tamoxifen without the risk of clinically significant interactions.

Long-Term Outcome of Aromatase Inhibitor Therapy With Letrozole in Patients With Advanced Low-Grade Endometrial Stromal Sarcoma.

PubMed

Yamaguchi, Munekage; Erdenebaatar, Chimeddulam; Saito, Fumitaka; Motohara, Takeshi; Miyahara, Yo; Tashiro, Hironori; Katabuchi, Hidetaka

2015-11-01

There has been no consensus on the indications for the treatment of advanced low-grade endometrial stromal sarcoma (LGESS), and the possible effects of hormonal treatment including progestins and aromatase inhibitors have been reported. The aim of this study was to investigate the efficacy of aromatase inhibitor therapy with letrozole for patients with residual or recurrent LGESS. We retrospectively reviewed the clinical response of patients with advanced LGESS who had been treated with letrozole. We also analyzed the adverse effects after the administration of letrozole. The expression levels of estrogen receptor and aromatase in the tumors were immunohistochemically examined. In 5 patients who had been treated for unresectable LGESS lesions after initial or repeat surgical procedures, residual lesions in 3 patients and recurrence lesions in 2 patients were the indications for hormonal therapy with letrozole. The median duration of letrozole exposure at retrospective analysis was 53 (10-96) months. The clinical outcomes were classified as complete response in 2 patients, partial response in 1 patient, and stable disease in 2 patients. Myalgias, hot flashes, and arthralgias were not observed during the follow-up period in any patients. The median serum levels of estradiol were <5.0 (cutoff value, <0.5-11.8) pg/mL. The median age-matched bone mineral densities were 92% (79%-123%). The LGESS tissues in all 5 patients were positive for estrogen receptor and aromatase expression. Letrozole as well as progestins could be the first choice of treatment for patients with recurrent or residual LGESS, which is difficult to resect surgically because of its efficacy and minimal adverse effects.

Seribantumab, an Anti-ERBB3 Antibody, Delays the Onset of Resistance and Restores Sensitivity to Letrozole in an Estrogen Receptor-Positive Breast Cancer Model.

PubMed

Curley, Michael D; Sabnis, Gauri J; Wille, Lucia; Adiwijaya, Bambang S; Garcia, Gabriela; Moyo, Victor; Kazi, Armina A; Brodie, Angela; MacBeath, Gavin

2015-11-01

Heregulin-driven ERBB3 signaling has been implicated as a mechanism of resistance to cytotoxic and antiendocrine therapies in preclinical breast cancer models. In this study, we evaluated the effects of seribantumab (MM-121), a heregulin-blocking anti-ERBB3 monoclonal antibody, alone and in combination with the aromatase inhibitor letrozole, on cell signaling and tumor growth in a preclinical model of postmenopausal estrogen receptor-positive (ER(+)) breast cancer. In vitro, heregulin treatment induced estrogen receptor phosphorylation in MCF-7Ca cells, and long-term letrozole-treated (LTLT-Ca) cells had increased expression and activation levels of EGFR, HER2, and ERBB3. Treatment with seribantumab, but not letrozole, inhibited basal and heregulin-mediated ERBB receptor phosphorylation and downstream effector activation in letrozole-sensitive (MCF-7Ca) and -refractory (LTLT-Ca) cells. Notably, in MCF-7Ca-derived xenograft tumors, cotreatment with seribantumab and letrozole had increased antitumor activity compared with letrozole alone, which was accompanied by downregulated PI3K/MTOR signaling both prior to and after the development of resistance to letrozole. Moreover, the addition of an MTOR inhibitor to this treatment regimen did not improve antitumor activity and was not well tolerated. Our results demonstrate that heregulin-driven ERBB3 signaling mediates resistance to letrozole in a preclinical model of ER(+) breast cancer, suggesting that heregulin-expressing ER(+) breast cancer patients may benefit from the addition of seribantumab to antiendocrine therapy. ©2015 American Association for Cancer Research.

Letrozole dispersed on poly (vinyl alcohol) anchored maleic anhydride grafted low density polyethylene: a controlled drug delivery system for treatment of breast cancer.

PubMed

Siddiqa, Akhtar Jahan; Chaudhury, Koel; Adhikari, Basudam

2014-04-01

The present work focuses on the design of a drug delivery system for systemic, controlled release of the poorly soluble breast cancer drug, letrozole. The drug delivery system was prepared in two steps: a low density polyethylene (LDPE) substrate surface was grafted with maleic anhydride (MA) via solution grafting technique. Next, the grafted substrate was used to anchor a hydrophilic polymeric drug release system consisting of poly (vinyl alcohol) (PVA). The PVA anchored MA grafted LDPE (PVA/MA-g-LDPE) drug release system was used for the controlled release of letrozole. This system was characterized using ATR-FTIR spectrophotometry, surface profilometry, and scanning electron microscopy. Biocompatibility studies were also carried out. In vitro release studies of letrozole from the system were performed in distilled water and phosphate buffer saline (PBS) at 37°C. Release of ∼90% letrozole from hydrophilic PVA matrix was observed within a period of 35 days. A high correlation coefficient (R(2)=0.99) was seen between the release of letrozole in distilled water and PBS. Cytotoxicity studies using MTT colorimetric assay suggested that all samples were biocompatible. It is concluded that the letrozole delivery system appears to overcome the limitations associated with letrozole by providing enhanced drug dissolution rate, controlled release and improved bioavailability of the incorporated drug and, therefore, seems to have extended therapeutic effects. Copyright © 2014 Elsevier B.V. All rights reserved.

A randomized, controlled clinical trial comparing the effects of aromatase inhibitor (letrozole) and gonadotropin-releasing hormone agonist (triptorelin) on uterine leiomyoma volume and hormonal status.

PubMed

Parsanezhad, Mohammad Ebrahim; Azmoon, Mina; Alborzi, Saeed; Rajaeefard, Abdoreza; Zarei, Afsun; Kazerooni, Talieh; Frank, Vivian; Schmidt, Ernst Hienrich

2010-01-01

To examine and compare the efficacy and safety of GnRH agonist (GnRHa) vs. aromatase inhibitor in premenopausal women with leiomyomas. Multicenter, randomized, controlled clinical trial. University hospitals. A total of 70 subjects with a single uterine myoma measuring >or=5 cm. Subjects were randomized into two groups with use of a random table. They were treated with aromatase inhibitor (group A) or GnRHa (group B). Group A received letrozole (2.5 mg/d) for 12 weeks. Group B received triptorelin (3.75 mg/mo) for 12 weeks. Measurement of myoma volume and E(2), FSH, LH, and T levels. Total myoma volume decreased by 45.6% in group A and 33.2% in group B. Reductions in myoma volume in the two groups were statistically significant. There was no significant change in hormonal milieu in group A. The serum level of hormones significantly decreased in group B by the 12th week of treatment. Uterine myoma volume was successfully reduced by use of an aromatase inhibitor. Rapid onset of action and avoidance of initial gonadotropin flare with an aromatase inhibitor may be advantageous for short-term management of women with myomas of any size who are to be managed transiently and who wish to avoid surgical intervention, specifically women with unexplained infertility having uterine myoma. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Pregnancy Rate Following Luteal Phase Support in Iranian Women with Polycystic Ovarian Syndrome

PubMed Central

Foroozanfard, Fatemeh; Saberi, Hamidreza; Moraveji, Seyed Alireza; Bazarganipour, Fatemeh

2014-01-01

Background To assess the efficacy of luteal phase support (LPS) using intravaginal progesterone (P) on pregnancy rate in Iranian women with polycystic ovarian syndrome (PCOS) who used a combination for ovulation induction consisting of letrozole or clomi- phene citrate (CC) and human menopausal gonadotropin (HMG). Materials and Methods This was a randomized clinical trial undertaken in a fertility clinic in Kashan, Isfahan Province, Iran. A total of 198 patients completed treatment and follow up. Base on chosen ovulation induction programs, they were divided into two following group: i. CC group (n=98) used a combination consisting of CC (100 mg×5 day) and HMG (150 IU×5 day) and ii. letrozole group (n=100) used a combination consisting of letrozole (5 mg×5 day) and HMG (150 IU×5 day). After human chorionic gonadotropin (hCG) administration (5000 IU), the patients (n=122) who randomly re- ceived intravaginal P (Cyclogest, 400 mg daily) were included in LPS group, while the rest (n=123) were included in non-P cycles group. The outcome was the comparison of chemical pregnancy rate between the groups. Results Our findings showed that LPS was associated with a 10% higher pregnancy rate than in non-P cycles, although this difference did not reach statistical significant (p=0.08). LPS improved pregnancy rate in both CC (4%) and letrozole (6%) groups. In addition, patients who used letrozole for ovulation induction along with intravaginal P showed higher pregnancy rates than CC group. Conclusion Administration of vaginal P for LPS may improve the pregnancy rate in women with PCOS using letrozole or CC in combination with HMG for ovulation induc- tion (Registration Number: IRCT201206072967N4). PMID:25379150

Kisspeptin expression features in the arcuate and anteroventral periventricular nuclei of hypothalamus of letrozole-induced polycystic ovarian syndrome in rats.

PubMed

Aliabadi, Elham; Namavar, Mohammad Reza; Mortezaee, Keywan; Toolee, Heidar; Keshtgar, Sara; Mirkhani, Hossein; Akbari, Mohammad; Rastegar, Tayebeh; Solhjoo, Somayeh

2017-11-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of the reproductive system characterized by polycystic ovaries and androgen excess. Letrozole is a nonsteroidal aromatase inhibitor that is used in experimental research to induce PCOS. Kisspeptin is an essential protein in regulation of cyclicity. Kisspeptin receptor is expressed in the hypothalamus and pituitary glands, and kisspeptin containing neurons are affected from sex steroid hormones. We aimed to investigate the number of kisspeptin-positive cells in the arcuate (Arc) and anteroventral periventricular nuclei (AVPV) of hypothalamus in the letrozole-induced PCOS. 40 female Wistar rats were divided into the proestrus control, diestrus control, proestrus vehicle, diestrus vehicle and letrozole. Animals were sacrificed after 3 weeks, and sera, ovary and brain samples were harvested for further evaluations. Letrozole group had high weight gain, high numbers of ovarian follicular cysts, high levels of luteinizing hormone and testosterone and increase number of kisspeptin-positive cells in the Arc nucleus, as compared with the control groups (P ≤ 0.05 vs. proestrus control and proestrus vehicle). Letrozole group showed a decrease in the number of kisspeptin-positive cells in the AVPV nucleus (P ≤ 0.05 vs. proestrus control and proestrus vehicle). Our findings show that the number of kisspeptin-positive cells may be affected from letrozole, and that the changes in the number of these cells may be in favor of the appearance of PCOS features in this group.

Preparation and characterization of two new forced degradation products of letrozole and development of a stability-indicating RP-LC method for its determination.

PubMed

Elkady, Ehab Farouk; Fouad, Marwa Ahmed

2015-11-01

Two new hydrolytic products of letrozole were identified and proved to be true degradation products obtained by alkaline and acidic degradation of the drug. The acid and amide forms of the nitrile groups of letrozole were prepared and identified by IR and mass spectroscopic techniques. Subsequently, a simple, precise and selective stability-indicating RPLC method was developed and validated for the determination of letrozole in the presence of its degradation products. Letrozole was subjected to alkali and acid hydrolysis, oxidation, thermal degradation and photo-degradation. The degradation products were well isolated from letrozole. The chromatographic method was achieved using gradient elution of the drug and its degradation products on a reversed phase Zorbax Eclipse C18 column (100mm x 4.6mm, 3.5 μm) using a mobile phase consisting of 0.01M KH₂PO₄and methanol at a flow rate of 1 mL min⁻¹. Quantitation was achieved with UV detection at 230 nm. Linearity, accuracy and precision were found to be acceptable over the concentration range of 0.01-80 μgmL⁻¹. The proposed method was successfully applied to the determination of letrozole in bulk, plasma and in its pharmaceutical preparation.

Inhibition of drug metabolizing cytochrome P450s by the aromatase inhibitor drug letrozole and its major oxidative metabolite 4,4′-methanol-bisbenzonitrile in vitro

PubMed Central

Jeong, Seongwook; Woo, Margaret M.; Flockhart, David A.

2009-01-01

Purpose To determine the inhibitory potency of letrozole and its main human metabolite, 4,4′-methanol-bisbenzonitrilee, on the activities of eight cytochrome P450 (CYP) enzymes. Methods Letrozole and its metabolite were incubated with human liver microsomes (HLMs) (or expressed CYP isoforms) and NADPH in the absence (control) and presence of the test inhibitor. Results Letrozole was a potent competitive inhibitor of CYP2A6 (Ki 4.6 ± 0.05 μM and 5.0 ± 2.4 μM in HLMs and CYP2A6, respectively) and a weak inhibitor of CYP2C19 (Ki 42.2 μM in HLMs and 33.3 μM in CYP2C19), while its metabolite showed moderate inhibition of CYP2C19 and CYP2B6. Letrozole or its metabolite had negligible effect on other CYPs. Conclusions Based on the in vitro Ki values, letrozole is predicted to be a weak inhibitor of CYP2A6 in vivo. Letrozole and its major human metabolite show inhibitory activity towards other CYPs, but clinically relevant drug interactions seem less likely as the Ki values are above the therapeutic plasma concentrations of letrozole. PMID:19198839

Observation versus late reintroduction of letrozole as adjuvant endocrine therapy for hormone receptor-positive breast cancer (ANZ0501 LATER): an open-label randomised, controlled trial.

PubMed

Zdenkowski, N; Forbes, J F; Boyle, F M; Kannourakis, G; Gill, P G; Bayliss, E; Saunders, C; Della-Fiorentina, S; Kling, N; Campbell, I; Mann, G B; Coates, A S; Gebski, V; Davies, L; Thornton, R; Reaby, L; Cuzick, J; Green, M

2016-05-01

Despite the effectiveness of adjuvant endocrine therapy in preventing breast cancer recurrence, breast cancer events continue at a high rate for at least 10 years after completion of therapy. This randomised open label phase III trial recruited postmenopausal women from 29 Australian and New Zealand sites, with hormone receptor-positive early breast cancer, who had completed ≥4 years of endocrine therapy [aromatase inhibitor (AI), tamoxifen, ovarian suppression, or sequential combination] ≥1 year prior, to oral letrozole 2.5 mg daily for 5 years, or observation. Treatment allocation was by central computerised randomisation, stratified by institution, axillary node status and prior endocrine therapy. The primary outcome was invasive breast cancer events (new invasive primary, local, regional or distant recurrence, or contralateral breast cancer), analysed by intention to treat. The secondary outcomes were disease-free survival (DFS), overall survival, and safety. Between 16 May 2007 and 14 March 2012, 181 patients were randomised to letrozole and 179 to observation (median age 64.3 years). Endocrine therapy was completed at a median of 2.6 years before randomisation, and 47.5% had tumours of >2 cm and/or node positive. At 3.9 years median follow-up (interquartile range 3.1-4.8), 2 patients assigned letrozole (1.1%) and 17 patients assigned observation (9.5%) had experienced an invasive breast cancer event (difference 8.4%, 95% confidence interval 3.8% to 13.0%, log-rank test P = 0.0004). Twenty-four patients (13.4%) in the observation and 14 (7.7%) in the letrozole arm experienced a DFS event (log-rank P = 0.067). Adverse events linked to oestrogen depletion, but not serious adverse events, were more common with letrozole. These results should be considered exploratory, but lend weight to emerging data supporting longer duration endocrine therapy for hormone receptor-positive breast cancer, and offer insight into reintroduction of AI therapy. Australian New

The role of hormonal therapy in patients with relapsed high-grade ovarian carcinoma: a retrospective series of tamoxifen and letrozole.

PubMed

George, Angela; McLachlan, Jennifer; Tunariu, Nina; Della Pepa, Chiara; Migali, Cristina; Gore, Martin; Kaye, Stan; Banerjee, Susana

2017-06-30

Hormonal therapy is used as a treatment option in high-grade ovarian carcinoma (HGOC), but the role and choice of treatment remains unclear. Agents used include tamoxifen and aromatase inhibitors. Our aim was to evaluate the efficacy of tamoxifen (T) and letrozole (L) in HGOC in clinical practice and investigate factors influencing clinical outcome. A retrospective review of patients with relapsed HGOC treated with either tamoxifen or letrozole at the Royal Marsden Hospital between 2007 and 2012 was performed. The primary endpoint of the study was objective response rate (ORR). Secondary endpoints included CA125 response, clinical benefit rate (CBR) and duration of response. Platinum-sensitivity and ER-status were evaluated as predictors of treatment response. 97 patients were included (43 T, 54 L); median age 63 years (20-92); 91% high-grade serous; median number of lines of prior chemotherapy 3 (1-8); 60% platinum-resistant, 40% platinum-sensitive; 52% ER + ve, 1% ER-ve, 47% unknown. 14 patients (6 T, 8 L) achieved a partial response, with ORR (RECIST) of 14% (T) and 15% (L). The CBR for ≥3 months was 65% (22/43) for tamoxifen and 56% (22/54) for letrozole. There was no significant difference in ORR (p = 0.99) or CBR (p = 0.14) between tamoxifen and letrozole. 22 patients (23%) had a CA-125 response with hormonal therapy (10 T - 23% and 12 L - 22%). ORR did not differ by platinum sensitivity (p = 0.42); or ER-status (positive vs unknown, p = 0.12). Responders to letrozole had longer durations of response than responders to tamoxifen (26 vs 11.5 months, p = 0.03), but equivalent disease stability duration (9.6 vs 7.2 months respectively, p = 0.11). Within the constraints of a retrospective study, we identified that patients treated with letrozole had a significantly longer duration of response than those treated with tamoxifen. Treatment with either tamoxifen or letrozole is a rational treatment option for patients with ER + ve HGOC

The VEGF and PEDF levels in the follicular fluid of patients co- treated with LETROZOLE and gonadotropins during the stimulation cycle.

PubMed

Haas, Jigal; Bassil, Rawad; Gonen, Noa; Meriano, Jim; Jurisicova, Andrea; Casper, Robert F

2018-05-29

Previous studies have shown that androgens, in addition to serving as precursors for ovarian estrogen synthesis, also have a fundamental role in primate ovarian follicular development by augmentation of FSH receptor expression on granulosa cells. Recent studies have shown that aromatase inhibitor, letrozole, improves ovarian response to FSH in normal and poor responder patients, possibly by increasing intraovarian androgen levels. Studies in mice also showed an effect of letrozole to increase pigment epithelium-derived factor (PEDF) and to lower vascular epithelial growth factor (VEGF), which might be expected to reduce the risk of ovarian hyperstimulation syndrome (OHSS) with stimulation. The aim of this study was to compare the VEGF and PEDF levels in the follicular fluids of normal responders treated with letrozole and gonadotropins during the ovarian stimulation with patients treated with gonadotropins only. A single center, prospective clinical trial. We collected follicular fluid from 26 patients, on a GnRH antagonist protocol, dual triggered with hCG and GnRH agonist. The patients in one group were co-treated with letrozole and gonadotropins during the ovarian stimulation and the patients in the other group were treated with gonadotropins only. VEGF, PEDF, estrogen, progesterone and testosterone levels were measured by ELISA kits. The age of the patients, the total dose of gonadotropins and the number of oocytes were comparable between the two groups. In the follicular fluid, the estrogen levels (2209 nmol/l vs. 3280 nmol/l, p = 0.02) were significantly decreased, and the testosterone levels (246.5 nmol/l vs. 40.7 nmol/l, p < 0.001) were significantly increased in the letrozole group compared to the gonadotropin only group. The progesterone levels (21.4 μmol/l vs. 17.5 p = NS) were comparable between the two groups. The VEGF levels (2992 pg/ml vs. 1812 pg/ml p = 0.02) were significantly increased and the PEDF levels (9.7 ng/ml vs 17

Mentally disordered women in jail: who receives services?

PubMed Central

Teplin, L A; Abram, K M; McClelland, G M

1997-01-01

OBJECTIVES: Many jail inmates have severe psychiatric disorders (e.g., schizophrenia, major affective disorders). The courts have mandated that detainees have a constitutional right to treatment. We investigated what proportion of female jail detainees needed mental health services, what proportion received services, and what variables predicted who received services. METHODS: Trained interviewers administered a psychiatric evaluation (the NIMH Diagnostic Interview Schedule) to 1272 randomly selected female jail detainees during jail intake in a large Midwestern city. Project staff then documented whether women subsequently received services, using records and case files. RESULTS: Of the women who needed services, 23.5% received them while they were in jail. Type of disorder, treatment history, and socio-demographic variables all affected the odds of a mentally ill woman's receiving services. CONCLUSIONS: Correctional health care is a growing national public health problem. The magnitude of mental health service needs far exceeds current resources. PMID:9146439

Functional activation of the estrogen receptor-α and aromatase by the HDAC inhibitor, entinostat, sensitizes of ER-negative tumors to letrozole

PubMed Central

Sabnis, Gauri J; Goloubeva, Olga; Chumsri, Saranya; Nguyen, Nguyen; Sukumar, Saraswati; Brodie, Angela MH

2011-01-01

Approximately 25% of breast cancers do not express the estrogen receptor (ERα) and consequently do not respond to endocrine therapy. In these tumors, ERα repression is often due to epigenetic modifications such as methylation and histone deacetylation. For this reason, we investigated the ability of the histone deacetylase inhibitor entinostat (ENT) to trigger re-expression of ERα and aromatase in breast cancer cells, with the notion that this treatment would restore sensitivity to the aromatase inhibitor letrozole. ENT treatment of tumor cells increased expression of ERα and aromatase along with the enzymatic activity of aromatase, in a dose-dependent manner both in vitro and in vivo. Notably, ERα and aromatase upregulation resulted in sensitization of breast cancer cells to estrogen and letrozole. Tumor growth rate was significantly lower in tumor xenografts following treatment with ENT alone and in combination with letrozole compared to control tumors (p >0.001). ENT plus letrozole also prevented lung colonization and growth of tumor cells with a significant reduction (p>0.03) in both visible and microscopic foci. Our results demonstrate that ENT treatment can be used to restore the letrozole responsiveness of ER-negative tumors. More generally, they provide a strong rationale for immediate clinical evaluation of combinations of histone deacetylase and aromatase inhibitors to treat ER-negative and endocrine-resistant breast cancers. PMID:21245100

Women's experiences receiving abnormal prenatal chromosomal microarray testing results.

PubMed

Bernhardt, Barbara A; Soucier, Danielle; Hanson, Karen; Savage, Melissa S; Jackson, Laird; Wapner, Ronald J

2013-02-01

Genomic microarrays can detect copy-number variants not detectable by conventional cytogenetics. This technology is diffusing rapidly into prenatal settings even though the clinical implications of many copy-number variants are currently unknown. We conducted a qualitative pilot study to explore the experiences of women receiving abnormal results from prenatal microarray testing performed in a research setting. Participants were a subset of women participating in a multicenter prospective study "Prenatal Cytogenetic Diagnosis by Array-based Copy Number Analysis." Telephone interviews were conducted with 23 women receiving abnormal prenatal microarray results. We found that five key elements dominated the experiences of women who had received abnormal prenatal microarray results: an offer too good to pass up, blindsided by the results, uncertainty and unquantifiable risks, need for support, and toxic knowledge. As prenatal microarray testing is increasingly used, uncertain findings will be common, resulting in greater need for careful pre- and posttest counseling, and more education of and resources for providers so they can adequately support the women who are undergoing testing.

Long-Term Safety of Letrozole and Gonadotropin Stimulation for Fertility Preservation in Women With Breast Cancer

PubMed Central

Kim, Jayeon; Turan, Volkan

2016-01-01

Context and Objective: There has been increased attention to the issue of fertility preservation (FP). We aimed to investigate the long-term safety of FP via controlled ovarian stimulation with letrozole supplementation (COSTLES) prior to breast cancer treatment. Design, Setting, and Participants: This is a prospective, nonrandomized, controlled study conducted between the years 2002 and 2014. A total of 337 women diagnosed with stage 3 or less invasive breast cancer were enrolled during a FP consultation before chemotherapy. Of those, 120 elected to undergo COSTLES for FP prior to chemotherapy (FP group). The remaining 217 patients did not undergo any FP procedure and served as the controls. Main Outcome Measure: The primary end point was cancer recurrence defined as the detection of locoregional tumor (chest wall, regional nodal disease), distant metastases, or contralateral invasive breast cancer. Results: The baseline characteristics at enrollment were similar between the FP and control groups except for the less frequent lymph node involvement (P = .02) in the former. The mean follow-up after diagnosis was 5.0 years in the FP group and 6.9 years in the control group. In the FP group, the hazard ratio for recurrence after ovarian stimulation was 0.77 (95% confidence interval 0.28–2.13), and the survival was not compromised compared with controls (P = .61). Neither BRCA gene mutation status (P = .57) nor undergoing FP before or after breast surgery (P = .44) affected survival outcomes in the FP group. Likewise, none of the tumor characteristics including the estrogen receptor status affected the survival rates after the COSTLES. Conclusion: COSTLES is unlikely to cause a substantially increased recurrence risk in breast cancer during the 5 years after diagnosis. PMID:26751194

FDA Approval: Palbociclib for the Treatment of Postmenopausal Patients with Estrogen Receptor-Positive, HER2-Negative Metastatic Breast Cancer.

PubMed

Beaver, Julia A; Amiri-Kordestani, Laleh; Charlab, Rosane; Chen, Wei; Palmby, Todd; Tilley, Amy; Zirkelbach, Jeanne Fourie; Yu, Jingyu; Liu, Qi; Zhao, Liang; Crich, Joyce; Chen, Xiao Hong; Hughes, Minerva; Bloomquist, Erik; Tang, Shenghui; Sridhara, Rajeshwari; Kluetz, Paul G; Kim, Geoffrey; Ibrahim, Amna; Pazdur, Richard; Cortazar, Patricia

2015-11-01

On February 3, 2015, the FDA granted accelerated approval to palbociclib (IBRANCE, Pfizer Inc.), an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4 and CDK6), for use in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, HER2-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. The approval is based on a randomized, multicenter, open-label phase I/II trial (PALOMA-1) in 165 patients randomized to palbociclib (125 mg orally daily for 21 consecutive days, followed by 7 days off treatment) plus letrozole (2.5 mg orally daily) or letrozole alone. The phase II portion of the trial was divided into two cohorts: cohort 1 enrolled 66 biomarker-unselected patients and cohort 2 enrolled 99 biomarker-positive patients. The major efficacy outcome measure was investigator-assessed progression-free survival (PFS). A large magnitude of improvement in PFS was observed in patients receiving palbociclib plus letrozole compared with patients receiving letrozole alone (HR, 0.488; 95% confidence interval, 0.319-0.748). Multiple sensitivity analyses were supportive of clinical benefit. The most common adverse reaction in patients receiving palbociclib plus letrozole was neutropenia. This article summarizes the FDA thought process and data supporting accelerated approval based on PALOMA-1 that may be contingent upon verification and description of clinical benefit in the ongoing and fully accrued confirmatory trial PALOMA-2. ©2015 American Association for Cancer Research.

[Clinical Efficacy of Alternate-Day S-1/Letrozole Combination Therapy for Advanced Breast Cancer with Gastric Metastasis--A Case Report].

PubMed

Nakayama, Ichiro; Muranishi, Yumi; Fujita, Yoko

2015-07-01

We report a case of Stage IV breast cancer in a 62-year-old woman who responded well to alternate-day S-1/letrozole combination therapy. She was admitted to our hospital because of appetite loss and vomiting, and was diagnosed with invasive lobular carcinoma (ER+/HER2-) with gastric metastasis. After gastrointestinal stenting was performed, we initiated oral administration of S-1 (100 mg/body) and letrozole (2.5 mg) as systemic therapy. To reduce adverse effects, we administered S-1 on alternate days. Computed tomography and endoscopic examination revealed that the patient has been showing partial response since 1 year after initiating treatment. Therefore, we conclude that alternate-day S-1/letrozole combination therapy could be an effective and sustainable treatment for advanced ER-positive, HER2-negative breast cancer.

Antiandrogen Treatment Ameliorates Reproductive and Metabolic Phenotypes in the Letrozole-Induced Mouse Model of PCOS.

PubMed

Ryan, Genevieve E; Malik, Shaddy; Mellon, Pamela L

2018-04-01

Polycystic ovary syndrome (PCOS), the most common endocrinopathy in women of reproductive age, is characterized by hyperandrogenism, anovulation, and polycystic ovaries. Although its etiology is unknown, excess androgens are thought to be a critical factor driving the pathology of PCOS. We previously demonstrated that continuous exposure to the aromatase inhibitor letrozole (LET) in mice produces many hallmarks of PCOS, including elevated testosterone (T) and luteinizing hormone, anovulation, and obesity. In the current study, we sought to determine whether androgen receptor (AR) actions are responsible for any of the phenotypes observed in LET mice. C57BL/6 female mice were subcutaneously implanted with LET or placebo control and subsequently treated with the nonsteroidal AR antagonist flutamide or vehicle control. Flutamide treatment in LET females reversed elevated T levels and restored ovarian expression of Cyp17a1 (critical for androgen synthesis) to normal levels. Pituitary expression of Lhb was decreased in LET females that received flutamide treatment, with no changes in expression of Fshb or Gnrhr. Flutamide treatment also restored estrous cycling and reduced the number of ovarian cyst-like follicles in LET females. Furthermore, body weight and adipocyte size were decreased in flutamide-treated LET females. Altogether, our findings provide strong evidence that AR signaling is responsible for many key reproductive and metabolic PCOS phenotypes and further establish the LET mouse model as an important tool for the study of androgen excess.

Postpartum wound and bleeding complications in women who received peripartum anticoagulation.

PubMed

Limmer, Jane S; Grotegut, Chad A; Thames, Elizabeth; Dotters-Katz, Sarah K; Brancazio, Leo R; James, Andra H

2013-07-01

The objective of this study was to compare wound and bleeding complications between women who received anticoagulation after cesarean delivery due to history of prior venous thromboembolic disease, arterial disease, or being a thrombophilia carrier with adverse pregnancy outcome, to women not receiving anticoagulation. Women in the Duke Thrombosis Center Registry who underwent cesarean delivery during 2003-2011 and received postpartum anticoagulation (anticoagulation group, n=77), were compared with a subset of women who delivered during the same time period, but did not receive anticoagulation (no anticoagulation group, n=77). The no anticoagulation group comprised women who were matched to the anticoagulation group by age, body mass index, type of cesarean (no labor vs. labor), and date of delivery. Bleeding and wound complications were compared between the two groups. A multivariable logistic regression model was constructed to determine if anticoagulation was an independent predictor of wound complication. Women who received anticoagulation during pregnancy had a greater incidence of wound complications compared to those who did not (30% vs. 8%, p<0.001). Using multivariable logistic regression, while controlling for race, diabetes, chorioamnionitis, and aspirin use, anticoagulation predicted the development of any wound complication (OR 5.8, 95% CI 2.2, 17.6), but there were no differences in the mean estimated blood loss at delivery (782 vs. 778 ml, p=0.91), change in postpartum hematocrit (5.4 vs. 5.2%, p=0.772), or percent of women receiving blood products (6.5 vs. 1.3%, p=0.209) between the two groups. Anticoagulation following cesarean delivery is associated with an increased risk of post-cesarean wound complications, but not other postpartum bleeding complications. Copyright © 2013 Elsevier Ltd. All rights reserved.

Prenatal administration of letrozole reduces SDN and SCN volume and cell number independent of partner preference in the male rat.

PubMed

Olvera-Hernández, Sandra; Tapia-Rodríguez, Miguel; Swaab, Dick F; Fernández-Guasti, Alonso

2017-03-15

During development, the exposure to testosterone, and its conversion to estradiol by an enzyme complex termed aromatase, appears to be essential in adult male rats for the expression of typical male sexual behavior and female-sex preference. Some hypothalamic areas are the supposed neural bases of sexual preference/orientation; for example, male-oriented rams have a reduced volume of the sexually dimorphic nucleus (oSDN), while in homosexual men this nucleus does not differ from that of heterosexual men. In contrast, homosexual men showed a larger number of vasopressinergic cells in the suprachiasmatic nucleus (SCN). Interestingly, male rats perinatally treated with an aromatase inhibitor, 1,4,6-androstatriene-3,17-dione (ATD), also showed bisexual preference and an increased number of vasopressinergic neurons in the SCN. However, this steroidal aromatase inhibitor has affinity for all three steroid receptors. Recently, we reported that the prenatal administration of the selective aromatase inhibitor, letrozole, produced a subpopulation of males with same-sex preference. The aim of this study was to compare the volume and number of cells of the SDN and SCN (the latter nucleus was immunohistochemically stained for vasopressin) between males treated with letrozole with same-sex preference, males treated with letrozole with female preference and control males with female preference. Results showed that all males prenatally treated with letrozole have a reduced volume and estimated cell number in the SDN and SCN, independent of their partner preference. These results indicate that the changes in these brain areas are not related to sexual preference, but rather to the effects of letrozole. The divergent results may be explained by species differences as well as by the critical windows during which the aromatase inhibitor was administered. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Letrozole, a selective aromatase inhibitor, on testicular activities in adult mice: Both in vivo and in vitro study.

PubMed

Verma, Rachna; Krishna, Amitabh

2017-01-15

The aim of present study was to evaluate the significance of estradiol (E2) in testicular activities and to find out the mechanism by which E2 regulates spermatogenesis in mice. To achieve this, both in vivo and in vitro effect of Letrozole on testis of adult mice was investigated. Letrozole-induced changes in testicular histology, cell proliferation (proliferating cell nuclear antigen; PCNA), cell survival (B cell lymphoma factor-2; Bcl2), apoptotic (cysteine-aspartic proteases; caspase-3), steroidogenic (side chain cleavage; SCC, 3β-hydroxy steroid dehydrogenase enzyme; 3β HSD, steroidogenic acute regulatory protein; StAR, aromatase and luteinizing hormone receptor; LH-R) markers, glucose level, and rate of expression of glucose transporter (GLUT) 8 and insulin receptor (IR) proteins in the testis along with changes in serum E2 and testosterone (T) levels were evaluated. Letrozole acts on testis and caused significant decrease in E2 synthesis, but increase in testosterone level and showed regressive changes in the spermatogenesis. Letrozole-induced changes in various testicular markers were compared with the changes in serum E2 level. The correlation study showed that decreased circulating E2 level may be responsible for decreased insulin receptor (IR) level in the testis. The decreased effects of insulin inhibited the glucose transport in the testis by suppressing GLUT8. The decreased level of testicular glucose may produce less lactate as energy support to developing germ cells consequently resulting in decreased cell proliferation and cell survival, but increased apoptosis. Thus, Letrozole suppresses spermatogenesis by reducing insulin sensitivity and glucose transport in the testis, but significantly increased testosterone level by promoting gonadotrophin release by decreased E2. Copyright © 2016 Elsevier Inc. All rights reserved.

Does daily co-administration of letrozole and gonadotropins during ovarian stimulation improve IVF outcome?

PubMed

Haas, Jigal; Bassil, Rawad; Meriano, Jim; Samara, Nivin; Barzilay, Eran; Gonen, Noa; Casper, Robert F

2017-08-30

For the last year we have been treating normal responders with gonadotropins and letrozole during the whole stimulation in order to improve response to FSH by increasing the intrafollicular androgen concentration, and to reduce circulating estrogen concentrations. The aim of this study was to compare the IVF outcome of normal responders treated with letrozole and gonadotropins during ovarian stimulation with patients treated with gonadotropins only. A single centre retrospective cohort study of 174 patients (87 in each group). The age of the patients was comparable between the groups. Estradiol levels were significantly higher in the control group (6760 pmol/L vs. 2420 pmol/L respectively, p < 0.01), and the number of follicles ≥15 mm at the trigger day was significantly lower in the control group (7.9 vs. 10, p = 0.02). The number of retrieved oocytes (10 vs. 14.5, p < 0.01), MII oocytes (7.9 vs. 11.2, p < 0.01) and blastocysts (2.7 vs. 4.0, p = 0.02) was significantly higher in the study group. We found no significant differences in the cumulative pregnancy outcome between the two groups (65.2% vs 58.3% p = NS). We conclude that co-treatment with letrozole improves the IVF outcome in normal responders in terms of increased number of blastocysts obtained without increasing the pregnancy rate or the risk of OHSS.

Life satisfaction and social support received by women in the perinatal period.

PubMed

Gebuza, Grażyna; Kaźmierczak, Marzena; Mieczkowska, Estera; Gierszewska, Małgorzata; Kotzbach, Roman

2014-01-01

Birth of a baby has a big impact on women's lives. The presence and help of loved ones favours wellbeing, health, coping with difficult situations. The aim of this study was to determine whether women's satisfaction with life changes during pregnancy and after delivery, and to identify correlates of life satisfaction. Life satisfaction was measured using The Satisfaction with Life Scale - SWLS and received social support was assessed using the Berlin Social Support Scales - BSSS. The study was conducted in the third trimester of pregnancy and during the postpartum period, before discharge from the hospital. The research sample included a total of 199 women in the third trimester of pregnancy and 188 of initially participating women, who had physiological births or caesarean sections. The results clearly show a significant increase in life satisfaction in the postpartum period (p < 0.0001). An important correlate of life satisfaction in the third trimester of pregnancy is social support received (p < 0.0001). During pregnancy such a correlate is emotional support received, and in the postnatal period- instrumental support received. An increase in instrumental support received (p = 0.031) and informational (p = 0.013) has been observed in the postpartum period. The assessment of life satisfaction and received social support seem to be needed to gain a full picture of women's situation during birth, which will allow for planning and implementing maternity care appropriate to the needs of women.

Current Proportion of Women Receiving Perinatal Psychosocial or Psychological Intervention in Japan

PubMed Central

Suzuki, Shunji; Kuribayashi, Yasushi; Matsuda, Hideo; Asakawa, Yasuyuki; Sekizawa, Akihiko; Tanaka, Masanobu; Okai, Takashi; Kinoshita, Katsuyuki

2016-01-01

Background In this study, we examined the current status of psychosocial or psychological intervention for women during pregnancy and the postpartum period in Japan. Methods We estimated the number of women receiving perinatal psychosocial or psychological intervention in Japan. On December 2015, we requested 2,462 obstetrical facilities that are members of the Japan Association of Obstetricians and Gynecologists (JAOG) to provide information on women who received psychosocial or psychological intervention during pregnancy, the hospitalization period for childbirth and the puerperal 1 month in 2014. A total of 1,305 (53.0%) of the 2,462 obstetrical facilities responded with valid information on a total of 515,373 women, accounting for approximately 52% of all deliveries that occurred in Japan during the study period. Results The number of women who received psychosocial or psychological intervention during pregnancy, the hospitalization period for childbirth and the puerperal 1 month were 4,843 (0.94%), 4,791 (0.93%) and 3,015 (0.59%), respectively. In total, 8,743 women (1.70%) received psychosocial or psychological intervention in 2014. Conclusion Considering the response rate, the number of women requiring perinatal psychosocial or psychological intervention was estimated to be 16,000 per year in Japan. PMID:27222675

Zoledronic Acid Inhibits Aromatase Activity and Phosphorylation: Potential Mechanism for Additive Zoledronic Acid and Letrozole Drug Interaction

PubMed Central

Schech, Amanda J.; Nemieboka, Brandon E.; Brodie, Angela H.

2012-01-01

Zoledronic acid (ZA), a bisphosphonate originally indicated for use in osteoporosis, has been reported to exert a direct effect on breast cancer cells, although the mechanism of this effect is currently unknown. Data from the ABCSG-12 and ZO-FAST clinical trials suggest that treatment with the combination of ZA and aromatase inhibitors (AI) result in increased disease free survival in breast cancer patients over AI alone. To determine whether the mechanism of this combination involved inhibition of aromatase, AC-1 cells (MCF-7 human breast cancer cells transfected with an aromatase construct) were treated simultaneously with combinations of ZA and AI letrozole for 72 hours. This combination significantly increased inhibition of aromatase activity of AC-1 cells by compared to letrozole alone. Combination treatment of 1nM letrozole and 1μM and 10μM zoledronic acid resulted in an additive drug interaction on inhibiting cell viability, as measured by MTT assay. Treatment with ZA was found to inhibit phosphorylation of aromatase on serine 473. Zoledronic acid was also shown to be more effective in inhibiting cell viability in aromatase transfected AC-1 cells when compared to inhibition of cell viability observed in non-transfected MCF-7. Estradiol was able to partially rescue the effect of 1μM and 10μM ZA on cell viability following treatment for 72 hours, as shown by a shift to the right in the estradiol dose response curve. In conclusion, these results indicate that the combination of ZA and letrozole results in an additive inhibition of cell viability. Furthermore, ZA alone can inhibit aromatase activity through inhibition of serine phosphorylation events important for aromatase enzymatic activity and contributes to inhibition of cell viability. PMID:22659283

Socioeconomic Outcomes of Women Who Receive and Women Who Are Denied Wanted Abortions in the United States

PubMed Central

Biggs, M. Antonia; Ralph, Lauren; Gerdts, Caitlin; Roberts, Sarah; Glymour, M. Maria

2018-01-01

Objectives. To determine the socioeconomic consequences of receipt versus denial of abortion. Methods. Women who presented for abortion just before or after the gestational age limit of 30 abortion facilities across the United States between 2008 and 2010 were recruited and followed for 5 years via semiannual telephone interviews. Using mixed effects models, we evaluated socioeconomic outcomes for 813 women by receipt or denial of abortion care. Results. In analyses that adjusted for the few baseline differences, women denied abortions who gave birth had higher odds of poverty 6 months after denial (adjusted odds ratio [AOR] = 3.77; P < .001) than did women who received abortions; women denied abortions were also more likely to be in poverty for 4 years after denial of abortion. Six months after denial of abortion, women were less likely to be employed full time (AOR = 0.37; P = .001) and were more likely to receive public assistance (AOR = 6.26; P < .001) than were women who obtained abortions, differences that remained significant for 4 years. Conclusions. Women denied an abortion were more likely than were women who received an abortion to experience economic hardship and insecurity lasting years. Laws that restrict access to abortion may result in worsened economic outcomes for women. PMID:29345993

Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial.

PubMed

Metzger Filho, Otto; Giobbie-Hurder, Anita; Mallon, Elizabeth; Gusterson, Barry; Viale, Giuseppe; Winer, Eric P; Thürlimann, Beat; Gelber, Richard D; Colleoni, Marco; Ejlertsen, Bent; Debled, Marc; Price, Karen N; Regan, Meredith M; Coates, Alan S; Goldhirsch, Aron

2015-09-01

To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma. Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor-positive with high (luminal B [LB] -like) or low (luminal A [LA] -like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling. The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20). The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma. © 2015 by American Society of Clinical Oncology.

Rapid determination of letrozole, citalopram and their metabolites by high performance liquid chromatography-fluorescence detection in urine: Method validation and application to real samples.

PubMed

Rodríguez, J; Castañeda, G; Muñoz, L

2013-01-15

This work reports the validation of a high precision and accuracy method for the simultaneous determination of letrozole, citalopram and their metabolites in urine by high performance liquid chromatography with fluorescence detection. Dilution (urine:mobile phase, 1:2, v/v) was the only sample preparation step. The separation was carried out in a Kromasil C(18) (150mm×4.6mm) column, and the mobile phase was phosphate buffer 80mM (pH 3.0) and acetonitrile (65:35, v/v) at a flow rate of 1.0mL/min. The analytes were detected at 295nm after excitation at 230nm. Linearity was observed in the range of 1.0-1000ng/mL for letrozole and its metabolite and 2.5-1000ng/mL for citalopram and their metabolites, with limits of detection and quantification between 0.09-1.0 and 0.27-1.65ng/mL, respectively. The precisions were satisfactory with RSDs between 0.17 and 5.71%. The accuracy was studied by spiking three urines from healthy female volunteers, and the recoveries were from 85 to 103%. The method was applied to urine samples from women under treatment for breast cancer and depression diseases. Copyright © 2012 Elsevier B.V. All rights reserved.

Prognostic and predictive value of centrally reviewed Ki-67 labeling index in postmenopausal women with endocrine-responsive breast cancer: results from Breast International Group Trial 1-98 comparing adjuvant tamoxifen with letrozole.

PubMed

Viale, Giuseppe; Giobbie-Hurder, Anita; Regan, Meredith M; Coates, Alan S; Mastropasqua, Mauro G; Dell'Orto, Patrizia; Maiorano, Eugenio; MacGrogan, Gaëtan; Braye, Stephen G; Ohlschlegel, Christian; Neven, Patrick; Orosz, Zsolt; Olszewski, Wojciech P; Knox, Fiona; Thürlimann, Beat; Price, Karen N; Castiglione-Gertsch, Monica; Gelber, Richard D; Gusterson, Barry A; Goldhirsch, Aron

2008-12-01

To evaluate the prognostic and predictive value of Ki-67 labeling index (LI) in a trial comparing letrozole (Let) with tamoxifen (Tam) as adjuvant therapy in postmenopausal women with early breast cancer. Breast International Group (BIG) trial 1-98 randomly assigned 8,010 patients to four treatment arms comparing Let and Tam with sequences of each agent. Of 4,922 patients randomly assigned to receive 5 years of monotherapy with either agent, 2,685 had primary tumor material available for central pathology assessment of Ki-67 LI by immunohistochemistry and had tumors confirmed to express estrogen receptors after central review. The prognostic and predictive value of centrally measured Ki-67 LI on disease-free survival (DFS) were assessed among these patients using proportional hazards modeling, with Ki-67 LI values dichotomized at the median value of 11%. Higher values of Ki-67 LI were associated with adverse prognostic factors and with worse DFS (hazard ratio [HR; high:low] = 1.8; 95% CI, 1.4 to 2.3). The magnitude of the treatment benefit for Let versus Tam was greater among patients with high tumor Ki-67 LI (HR [Let:Tam] = 0.53; 95% CI, 0.39 to 0.72) than among patients with low tumor Ki-67 LI (HR [Let:Tam] = 0.81; 95% CI, 0.57 to 1.15; interaction P = .09). Ki-67 LI is confirmed as a prognostic factor in this study. High Ki-67 LI levels may identify a patient group that particularly benefits from initial Let adjuvant therapy.

Relationship of Catastrophizing to Fatigue Among Women Receiving Treatment for Breast Cancer

ERIC Educational Resources Information Center

Jacobsen, Paul B.; Andrykowski, Michael A.; Thors, Christina L.

2004-01-01

This study examined the relationship of catastrophizing to fatigue in 80 women receiving chemotherapy (CT) or radiotherapy (RT) for treatment of early stage breast cancer. Findings revealed expected relationships between catastrophizing and fatigue among women receiving RT but not CT. Among RT patients, those high in catastrophizing reported…

Relative Effectiveness of Letrozole Compared With Tamoxifen for Patients With Lobular Carcinoma in the BIG 1-98 Trial

PubMed Central

Metzger Filho, Otto; Giobbie-Hurder, Anita; Mallon, Elizabeth; Gusterson, Barry; Viale, Giuseppe; Winer, Eric P.; Thürlimann, Beat; Gelber, Richard D.; Colleoni, Marco; Ejlertsen, Bent; Debled, Marc; Price, Karen N.; Regan, Meredith M.; Coates, Alan S.; Goldhirsch, Aron

2015-01-01

Purpose To evaluate the relative effectiveness of letrozole compared with tamoxifen for patients with invasive ductal or lobular carcinoma. Patients and Methods Patients diagnosed with early-stage invasive ductal carcinoma (IDC) or classic invasive lobular carcinoma (ILC) who were randomly assigned onto the Breast International Group (BIG) 1-98 trial and who had centrally reviewed pathology data were included (N = 2,923). HER2-negative IDC and ILC were additionally classified as hormone receptor–positive with high (luminal B [LB] –like) or low (luminal A [LA] –like) proliferative activity by Ki-67 labeling index. Survival analyses were performed with weighted Cox models that used inverse probability of censoring weighted modeling. Results The median follow-up time was 8.1 years. In multivariable models for disease-free survival (DFS), significant interactions between treatment and histology (ILC or IDC; P = .006) and treatment and subgroup (LB like or LA like; P = .01) were observed. In the ILC subset, there was a 66% reduction in the hazard of a DFS event with letrozole for LB (hazard ratio [HR], 0.34; 95% CI, 0.21 to 0.55) and a 50% reduction for LA subtypes (HR, 0.50; 95% CI, 0.32 to 0.78). In the IDC subset, there was a significant 35% reduction in the hazard of a DFS event with letrozole for the LB subtype (HR, 0.65; 95% CI, 0.53 to 0.79), but no difference between treatments was noted for IDC and the LA subtype (HR, 0.95; 95% CI, 0.76 to 1.20). Conclusion The magnitude of benefit of adjuvant letrozole is greater for patients diagnosed with lobular carcinoma versus ductal carcinoma. PMID:26215945

Letrozole versus clomiphene citrate in polycystic ovary syndrome: a meta-analysis of randomized controlled trials.

PubMed

Hu, Shifu; Yu, Qiong; Wang, Yingying; Wang, Mei; Xia, Wei; Zhu, Changhong

2018-05-01

Polycystic ovary syndrome (PCOS) is a common endocrine disturbance affecting women in the reproductive age group. The present study aimed to compare the effects of letrozole (LE) and clomiphene citrate (CC) for ovulation induction in women with PCOS. The PUBMED, Web of Science, and EMBASE databases were screened systematically for randomized controlled trials (RCTs) published from database inception to July 2017. Eleven RCTs involving 2255 patients were included, and data were independently extracted and analyzed using 95% risk ratios (RRs) and confidence intervals (CIs) based on a random- or fixed-effect model (as appropriate). Meta-analyses of nine RCTs comparing LE and CC ovulation induction, followed by timed intercourse, indicated that the former significantly increased the ovulation rate (RR = 1.18; 95% CI 1.03-1.36, P = 0.01), pregnancy rate (RR = 1.34; 95% CI 1.09-1.64, P = 0.006), and live birth rate (RR = 1.55; 95% CI 1.28-1.88, P < 0.00001). However, LE and CC did not differ significantly in terms of the multiple pregnancy and abortion rates. Furthermore, LE for ovulation induction significantly improved the pregnancy rate after IUI. LE is superior to CC for ovulation induction in patients with PCOS.

Preparation, characterization, and biodistribution of letrozole loaded PLGA nanoparticles in Ehrlich Ascites tumor bearing mice.

PubMed

Mondal, Nita; Halder, Kamal Krishna; Kamila, Madan Mohan; Debnath, Mita Chatterjee; Pal, Tapan K; Ghosal, Saroj K; Sarkar, Bharat R; Ganguly, Shantanu

2010-09-15

Letrozole (LTZ) incorporated PLGA nanoparticles were prepared by solvent displacement technique and characterized by transmission electron microscopy, poly-dispersity index and zeta potential measurement. Radiolabeling of free LTZ and LTZ-loaded PLGA NPs was performed with technetium-99m with high labeling efficiency. The labeled complex showed good in vitro stability as verified by DTPA challenge test. The labeled complexes also showed significant in vivo stability when incubated in rat serum for 24 h. Biodistribution studies of (99m)Tc-labeled complexes were performed after intravenous administration in normal mice and Ehrlich Ascites tumor bearing mice. Compared to free LTZ, LTZ-loaded PLGA NPs exhibited significantly lower uptake by the organs of RES. The tumor concentration of LTZ-loaded PLGA NPs was 4.65 times higher than that of free LTZ at 4 h post-injection. This study indicates the capability of PLGA nanopartcles in enhancing the tumor uptake of letrozole. Copyright 2010 Elsevier B.V. All rights reserved.

Feasibility Trial of Letrozole in Combination With Bevacizumab in Patients With Metastatic Breast Cancer

PubMed Central

Traina, Tiffany A.; Rugo, Hope S.; Caravelli, James F.; Patil, Sujata; Yeh, Benjamin; Melisko, Michele E.; Park, John W.; Geneus, Stephanie; Paulson, Matthew; Grothusen, Jill; Seidman, Andrew D.; Fornier, Monica; Lake, Diana; Dang, Chau; Robson, Mark; Theodoulou, Maria; Flombaum, Carlos D.; Norton, Larry; Hudis, Clifford A.; Dickler, Maura N.

2010-01-01

Purpose Preclinical models suggest that the use of anti–vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor–positive metastatic breast cancer (MBC). Methods Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease. Results Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease ≥ 24 weeks was noted in 67%. Median PFS was 17.1 months. Conclusion Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503). PMID:19841327

Feasibility trial of letrozole in combination with bevacizumab in patients with metastatic breast cancer.

PubMed

Traina, Tiffany A; Rugo, Hope S; Caravelli, James F; Patil, Sujata; Yeh, Benjamin; Melisko, Michele E; Park, John W; Geneus, Stephanie; Paulson, Matthew; Grothusen, Jill; Seidman, Andrew D; Fornier, Monica; Lake, Diana; Dang, Chau; Robson, Mark; Theodoulou, Maria; Flombaum, Carlos D; Norton, Larry; Hudis, Clifford A; Dickler, Maura N

2010-02-01

Preclinical models suggest that the use of anti-vascular endothelial growth factor (anti-VEGF) therapy with antiestrogens may prevent or delay the development of endocrine therapy resistance. We therefore performed a feasibility study to evaluate the safety of letrozole plus bevacizumab in patients with hormone receptor-positive metastatic breast cancer (MBC). Patients with locally advanced breast cancer or MBC were treated with the aromatase inhibitor (AI) letrozole (2.5 mg orally daily) and the anti-VEGF antibody bevacizumab (15 mg/kg intravenously every 3 weeks). The primary end point was safety, defined by grade 4 toxicity using the National Cancer Institute Common Toxicity Criteria, version 3.0. Secondary end points included response rate, clinical benefit rate, and progression-free survival (PFS). Prior nonsteroidal AIs (NSAIs) were permitted in the absence of progressive disease. Forty-three patients were treated. After a median of 13 cycles (range, 1 to 71 cycles), select treatment-related toxicities included hypertension (58%; grades 2 and 3 in 19% and 26%), proteinuria (67%; grades 2 and 3 in 14% and 19%), headache (51%; grades 2 and 3 in 16% and 7%), fatigue (74%; grades 2 and 3 in 19% and 2%), and joint pain (63%; grades 2 and 3 in 19% and 0%). Eighty-four percent of patients had at least stable disease on an NSAI, confounding efficacy results. Partial responses were seen in 9% of patients and stable disease >or= 24 weeks was noted in 67%. Median PFS was 17.1 months. Combination letrozole and bevacizumab was feasible with expected bevacizumab-related events of hypertension, headache, and proteinuria. Phase III proof-of-efficacy trials of endocrine therapy plus bevacizumab are in progress (Cancer and Leukemia Group B 40503).

Hydrolysis of Letrozole catalyzed by macrocyclic Rhodium (I) Schiff-base complexes.

PubMed

Reddy, P Muralidhar; Shanker, K; Srinivas, V; Krishna, E Ravi; Rohini, R; Srikanth, G; Hu, Anren; Ravinder, V

2015-03-15

Ten mononuclear Rhodium (I) complexes were synthesized by macrocyclic ligands having N4 and N2O2 donor sites. Square planar geometry is assigned based on the analytical and spectral properties for all complexes. Rh(I) complexes were investigated as catalysts in hydrolysis of Nitrile group containing pharmaceutical drug Letrozole. A comparative study showed that all the complexes are efficient in the catalysis. The percent yields of all the catalytic reaction products viz. drug impurities were determined by spectrophotometric procedures and characterized by spectral studies. Copyright © 2014 Elsevier B.V. All rights reserved.

Body mass index and circulating oestrone sulphate in women treated with adjuvant letrozole★

PubMed Central

Sini, V; Lunardi, G; Cirillo, M; Turazza, M; Bighin, C; Giraudi, S; Levaggi, A; Piccioli, P; Bisagni, G; Gnoni, R; Stridi, G; Porpiglia, M; Picardo, E; Ponzone, R; Marenco, D; Mansutti, M; Puglisi, F; Del Mastro, L

2014-01-01

Background: Obesity is an independent adverse prognostic factor in early breast cancer patients, but it is still controversial whether obesity may affect adjuvant endocrine therapy efficacy. The aim of our study (ancillary to the two clinical trials Gruppo Italiano Mammella (GIM)4 and GIM5) was to investigate whether the circulating oestrogen levels during treatment with the aromatase inhibitor letrozole are related to body mass index (BMI) in postmenopausal women with breast cancer. Methods: Plasma concentration of oestrone sulphate (ES) was evaluated by radioimmunoassay in 370 patients. Plasma samples were obtained after at least 6 weeks of letrozole therapy (steady-state time). Patients were divided into four groups according to BMI. Differences among the geometric means (by ANOVA and ANCOVA) and correlation (by Spearman's rho) between the ES levels and BMI were assessed. Results: Picomolar geometric mean values (95% confidence interval, n=patients) of circulating ES during letrozole were 58.6 (51.0–67.2, n=150) when BMI was <25.0 kg m−2; 65.6 (57.8–74.6, n=154) when 25.0–29.9 kg m−2; 59.3 (47.1–74.6, n=50) when 30.0–34.9 kg m−2; and 43.3 (23.0–81.7, n=16) when ⩾35.0 kg m−2. No statistically significant difference in terms of ES levels among groups and no correlation with BMI were observed. Conclusions: Body mass index does not seem to affect circulating oestrogen levels in letrozole-treated patients. PMID:24448359

Mental health measurement among women veterans receiving co-located, collaborative care services.

PubMed

Lilienthal, Kaitlin R; Buchholz, Laura J; King, Paul R; Vair, Christina L; Funderburk, Jennifer S; Beehler, Gregory P

2017-12-01

Routine use of measurement to identify patient concerns and track treatment progress is critical to high quality patient care. This is particularly relevant to the Primary Care Behavioral Health model, where rapid symptom assessment and effective referral management are critical to sustaining population-based care. However, research suggests that women who receive treatment in co-located collaborative care settings utilizing the PCBH model are less likely to be assessed with standard measures than men in these settings. The current study utilized regional retrospective data obtained from the Veterans Health Administration's electronic medical record system to: (1) explore rates of mental health measurement for women receiving co-located collaborative care services (N = 1008); and (2) to identify predictors of mental health measurement in women veterans in these settings. Overall, only 8% of women had documentation of standard mental health measures. Measurement was predicted by diagnosis, facility size, length of care episode and care setting. Specifically, women diagnosed with depression were less likely than those with anxiety disorders to have standard mental health measurement documented. Several suggestions are offered to increase the quality of mental health care for women through regular use of measurement in integrated care settings.

Colposcopy information leaflets: what women want to know and when they want to receive this information.

PubMed

Byrom, J; Dunn, P D J; Hughes, G M; Lockett, J; Johnson, A; Neale, J; Redman, C W E

2003-01-01

To evaluate whether the information leaflets produced by UK colposcopy clinics provide women with the information they desire and to determine when they would like to receive this information. Questionnaire study and structured evaluation. The colposcopy clinic of a UK cancer centre. Forty-two women attending a pre-colposcopy counselling session and 100 consecutive women attending the colposcopy clinic. Thirty-eight standards derived from the concerns/questions asked by women attending a pre-colposcopy counselling session were used to assess locally produced colposcopy clinic leaflets from UK colposcopy clinics, the leaflets produced by the Royal College of Obstetricians and Gynaecologists and the National Health Service Cervical Screening Programme (NHSCSP), and two "leaflets" obtained from internet sites. The Gunning fog test was used to assess the leaflets' readability. A questionnaire survey of 100 women attending the colposcopy clinic was used to determine when women wanted to receive information about colposcopy. Percentage of questions answered by a given leaflet and Gunning fog scores for readability. The information leaflets of 128 colposcopy clinics were received and assessed. Thirty-two clinics only sent women the NHSCSP leaflet. No leaflet answered all 38 questions. Less than half (36/100) of the leaflets answered more than 50% of the questions. In addition to the lack of advice given, different leaflets frequently gave conflicting advice. The average Gunning fog score was 9.7 (range 5.5-15.5). The majority of women (70%) wanted to receive information about colposcopy at or prior to the time of receiving their abnormal smear test result, although only 42% of women actually received information at this time. Many UK colposcopy clinics do not appear to be providing women with the information they require to understand their condition and the procedure that they are about to undergo. Furthermore, this information is often not provided at the appropriate

[Women's education according to the first women to receive doctorates in medicine from Spanish universities, 1882].

PubMed

Flecha Garcia, C

1999-01-01

This study looks at the topic of women's education as considered by the first two women to receive the degree of Doctor in Medicine from a Spanish university. Delores Aleu and Martina Castells decided to present as a doctoral thesis the development of an issue of particular relevance during the final decades of the 19th century. The importance given to public education and the difficulties young women encountered in participating under the same conditions as young men led these two women--who both held a bachelor's degree--to raise the issue and defend personal and social reasons that justified their full participation in different levels of education.

Influencing Factors of Intention to Receive Pap Tests in Vietnamese Women who Immigrated to Taiwan for Marriage.

PubMed

Lee, Fang-Hsin; Wang, Hsiu-Hung; Yang, Yung-Mei; Huang, Joh-Jong; Tsai, Hsiu-Min

2016-09-01

This study aimed to explore the factors associated with the intention to receive a Pap test among married immigrant women of Vietnamese origin living in Taiwan. This was a cross-sectional community-based study. We enrolled 281 women aged 30 years and over in the study, from July 2013 to January 2014. The participants' characteristics, cervical cancer knowledge, Pap test knowledge, attitudes toward cervical cancer, barriers to receiving a Pap test, fatalism, and intention to receive a Pap test, were measured using self-report questionnaires. Hierarchical multiple regression analyses were performed to examine the variables associated with participants' intentions to receive a Pap test. Vietnamese women with low scores on the measures of cervical cancer knowledge and perceived barriers to receiving a Pap test were more willing to receive the test, as were those with high scores on the measures of Pap test knowledge and fatalism. Women who received a Pap test in the previous year were more willing to receive a Pap test within the next 3 years. Preventive healthcare for immigrant women should be a focus of nurses. The development of culturally appropriate health education and strategies should enhance their knowledge of Pap tests and reduce perceived barriers to Pap test participation. This study's results can be a reference for nurses who work with immigrant women. Copyright © 2016. Published by Elsevier B.V.

Disparities in unmet dental need and dental care received by pregnant women in Maryland.

PubMed

Singhal, Astha; Chattopadhyay, Amit; Garcia, A Isabel; Adams, Amy B; Cheng, Diana

2014-09-01

To examine prenatal dental care needs, utilization and oral health counseling among Maryland women who delivered a live infant during 2001-2003 and identify the factors associated with having a dental visit and having an unmet dental need during pregnancy. Pregnancy Risk Assessment Monitoring System is an ongoing population based surveillance system that collects information of women's attitudes and experiences before, during, and shortly after pregnancy. Logistic regression was used to model dental visits and unmet dental need using predictor variables for Maryland 2001-2003 births. Less than half of all women reported having a dental visit and receiving oral health advice during pregnancy. Twenty-five percent of women reported a need for dental care, of which 33 % did not receive dental care despite their perceived need. Multivariate modeling revealed that racial minorities, women who were not married and those with annual income <$40,000 were least likely to have a dental visit. Women who were not married, had low annual income, were older than 40 years of age, had an unintended pregnancy and received prenatal care later than desired were most likely to have an unmet dental need during pregnancy. Despite reported needs and existing recommendations to include oral health as a component of prenatal care, less than half of pregnant women have a dental visit during their pregnancy. One-third of women with a dental problem did not have a dental visit highlighting the unmet need for dental care during pregnancy.

Psychological Well-Being Among Women Who Experienced Intimate Partner Violence and Received Civil Legal Services.

PubMed

Renner, Lynette M; Hartley, Carolyn Copps

2018-05-01

Intimate partner violence (IPV) victimization is often associated with negative mental health outcomes; yet, little is known about the psychological well-being of women who experience IPV and receive civil legal services. Civil legal services are not specifically designed to focus on women's mental health needs but Sullivan's Social and Emotional Well-Being Framework helps to explain why women receiving this type of formal assistance may demonstrate positive changes in psychological well-being. Using a panel study design and data from 85 women who experienced IPV and sought civil legal services, we examined women's psychological well-being over a one-year period of time. Approximately two thirds of the women received assistance from Iowa Legal Aid (ILA) for a civil protective order ( n = 56) and the rest were represented in a family law matter. We used measures of mental health (depression, posttraumatic stress disorder [PTSD]) and well-being (social support, resilience, goal directed thinking, empowerment). Our hypotheses that women would experience a decrease in mental health symptoms and an increase in well-being were partially supported. Women reported a decrease in depressive and PTSD symptoms over one year but there were no changes in their goal-oriented thinking or resilience. Implications for practice and future research are included.

Meanings of being received and met by others as experienced by women with MS

PubMed Central

Olsson, Malin; Skär, Lisa; Söderberg, Siv

2011-01-01

In order to elucidate meanings of being received and met by others as experienced by women with multiple sclerosis (MS) we conducted a qualitative inquiry. We interviewed 15 women with MS and analysed the interviews with a phenomenological hermeneutic interpretation. The findings were presented in two themes: experiencing oneself as a valuable person and experiencing oneself as diminished. Meanings of being received and met by others, as experienced by women with MS, can be understood as containing two dimensions where treatment from others can mean recognising oneself through confirmation, as well as being ignored due to missing togetherness with others. PMID:21394245

Soy isoflavones exert beneficial effects on letrozole-induced rat polycystic ovary syndrome (PCOS) model through anti-androgenic mechanism.

PubMed

Rajan, Ravi Kumar; M, Siva Selva Kumar; Balaji, Bhaskar

2017-12-01

Soy is the main source of phytoestrogens, which has long been used as traditional food. One major subtype of phytoestrogens includes isoflavones and they are scientifically validated for their beneficial actions on many hormone-dependent conditions. The present study examines the effect of soy isoflavones on letrozole-induced polycystic ovary syndrome (PCOS) rat model. PCOS was induced in Sprague-Dawley rats with of 1 mg/kg letrozole, p.o. once daily for 21 consecutive days. Soy isoflavones (50 and 100 mg/kg) was administered for 14 days after PCOS induction. Physical parameters (body weight, oestrous cycle determination, ovary and uterus weight) metabolic parameters (oral glucose tolerance test, total cholesterol), steroidal hormone profile (testosterone and 17β-oestradiol), steroidogenic enzymes (3β-hydroxy steroid dehydrogenase (HSD) and 17β-HSD), oxidative stress and histopathology of ovary were studied. Soy isoflavones (100 mg/kg) treatment significantly altered the letrozole-induced PCOS symptoms as observed by decreased body weight gain (p < 0.05), percentage diestrous phase (p < 0.001), testosterone (p < 0.001), 3β-HSD (p < 0.01) and 17β-HSD (p < 0.001) enzyme activity and oxidative stress. Histological results reveal that soy isoflavones treatment in PCOS rats resulted in well-developed antral follicles and normal granulosa cell layer in rat ovary. Treatment with soy isoflavones exerts beneficial effects in PCOS rats (with decreased aromatase activity) which might be due to their ability to decrease testosterone concentration in the peripheral blood. Analysis of physical, biochemical and histological evidences shows that soy isoflavones may be beneficial in PCOS.

Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women

DOE Office of Scientific and Technical Information (OSTI.GOV)

Biegon, Anat; Fowler, Joanna S.; Alexoff, David L.

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with ¹¹C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aims to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathological situations can be studied. Methods: ¹¹C-vorozole (111-296 MBq/subject) was injected I.V in 13 men and 20 women (age range 23 to 67). PET data were acquired over a 90 minute period. Each subject had 4 scans, 2/day separated by 2-6 weeks, including brain and torso or pelvismore » scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned following pretreatment with a clinical dose of the aromatase inhibitor letrozole (“blocking” studies). Time activity curves were obtained and standard uptake values (SUV) calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole body radiation exposures were calculated using Olinda software. Results: Liver uptake was higher than all other organs, but was not blocked by pretreatment with letrozole. Mean SUVs in men were higher than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than all other organs (ranging from 0.48±0.05 in lungs to 1.5±0.13 in kidneys). Mean ovarian SUVs (3.08±0.7) were comparable to brain levels and higher than all other organs. Furthermore, ovarian SUVs In young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, while aging and cigarette smoking reduced ¹¹C-vorozole uptake. Conclusions: PET with ¹¹C-vorozole is useful for assessing physiological changes in estrogen synthesis capacity in the

Aromatase imaging with [N-methyl-C-11]vorozole PET in healthy men and women

DOE PAGES

Biegon, Anat; Fowler, Joanna S.; Alexoff, David L.; ...

2015-02-19

Aromatase, the last and obligatory enzyme catalyzing estrogen biosynthesis from androgenic precursors, can be labeled in vivo with ¹¹C-vorozole. Aromatase inhibitors are widely used in breast cancer and other endocrine conditions. The present study aims to provide baseline information defining aromatase distribution in healthy men and women, against which its perturbation in pathological situations can be studied. Methods: ¹¹C-vorozole (111-296 MBq/subject) was injected I.V in 13 men and 20 women (age range 23 to 67). PET data were acquired over a 90 minute period. Each subject had 4 scans, 2/day separated by 2-6 weeks, including brain and torso or pelvismore » scans. Young women were scanned at 2 discrete phases of the menstrual cycle (midcycle and late luteal). Men and postmenopausal women were also scanned following pretreatment with a clinical dose of the aromatase inhibitor letrozole (“blocking” studies). Time activity curves were obtained and standard uptake values (SUV) calculated for major organs including brain, heart, lungs, liver, kidneys, spleen, muscle, bone and male and female reproductive organs (penis, testes, uterus, ovaries). Organ and whole body radiation exposures were calculated using Olinda software. Results: Liver uptake was higher than all other organs, but was not blocked by pretreatment with letrozole. Mean SUVs in men were higher than in women, and brain uptake was blocked by letrozole. Male brain SUVs were also higher than all other organs (ranging from 0.48±0.05 in lungs to 1.5±0.13 in kidneys). Mean ovarian SUVs (3.08±0.7) were comparable to brain levels and higher than all other organs. Furthermore, ovarian SUVs In young women around the time of ovulation (midcycle) were significantly higher than those measured in the late luteal phase, while aging and cigarette smoking reduced ¹¹C-vorozole uptake. Conclusions: PET with ¹¹C-vorozole is useful for assessing physiological changes in estrogen synthesis capacity in the

Barriers to receiving substance abuse treatment among rural pregnant women in Kentucky.

PubMed

Jackson, Afton; Shannon, Lisa

2012-12-01

Research presenting outcomes for women who enter substance abuse treatment during pregnancy consistently shows benefits. While treatment has nearly universal benefits, there are many barriers to seeking substance abuse treatment for pregnant women. The purpose of this study is to explore barriers for rural pregnant women seeking substance abuse treatment. There were three eligibility criteria for study participation: (1) aged 18 and older, (2) pregnant, and (3) undergoing short-term inpatient detoxification at the University of Kentucky Chandler Medical Center. Eighty-five rural women (N = 85) were included in the analysis. Substance use history and previous treatment were assessed with measures adapted from the Addiction Severity Index. Treatment barriers were measured with three qualitative questions and were coded into four overarching categories: availability, accessibility, affordability, and acceptability barriers. This sample had an extensive substance use history. Almost all participants had used alcohol (98%), marijuana (98%), illicit opiates (99%), and cigarettes (97%). On average, participants reported about two barriers to receiving treatment (Mean = 1.8; SD = 1.3), with over 80% of the sample reporting having experienced any barrier to treatment. The majority experienced acceptability (51%) and accessibility (49%) barriers. Twenty-six percent (26%) of the sample reported availability barriers. A smaller percentage of participants reported affordability barriers (13%). Rural pregnant women seeking substance abuse treatment face many obstacles to receiving needed treatment. More studies on barriers to substance abuse treatment among rural pregnant women are needed. Identifying these barriers can help in improving treatment access and services.

CENTRAL SEROUS CHORIORETINOPATHY IN POSTMENOPAUSAL WOMEN RECEIVING EXOGENOUS TESTOSTERONE.

PubMed

Conway, Mandi D; Noble, Jason A; Peyman, Gholam A

2017-01-01

Central serous chorioretinopathy (CSR) is a serous detachment of the neurosensory retina commonly associated with male sex, Type-A personality and corticosteroid use. Exogenous administration of androgens and development of CSR in men has been reported. Only one case of CSR in a postmenopausal woman receiving exogenous androgen therapy has been reported. The authors describe three cases of chronic CSR in postmenopausal women receiving exogenous testosterone therapy. Diagnosis was based on characteristic clinical, fluorescein angiographic, and optical coherence tomography findings. The three women were being treated with exogenous testosterone and progesterone therapy for symptoms of menopause and libido loss. Average age at presentation was 54.7 years (53-56 years), average duration of exogenous androgen use was 61 months (36-87 months), with average 19.7-month follow-up. Resolution of symptoms seemed correlated with cessation of androgen use despite treatment with oscillatory photodynamic therapy and intravitreal pharmacotherapy with antivascular endothelial growth factor agents. Exogenous testosterone is increasingly prescribed for menopausal symptoms and libido loss. Treatment with oscillatory photodynamic therapy, supplemental bevacizumab intravitreal pharmacotherapy, and cessation of exogenous androgen therapy was successful in three cases of chronic, therapy-resistant CSR. Ophthalmologists should inquire about androgen usage in patients who present with CSR, especially in the setting of therapy resistance.

Anti-GD2-ch14.18/CHO coated nanoparticles mediate glioblastoma (GBM)-specific delivery of the aromatase inhibitor, Letrozole, reducing proliferation, migration and chemoresistance in patient-derived GBM tumor cells.

PubMed

Tivnan, Amanda; Heilinger, Tatjana; Ramsey, Joanne M; O'Connor, Gemma; Pokorny, Jenny L; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Boyd, Andrew W; Kim, Ella L; Lode, Holger N; Cryan, Sally-Ann; Prehn, Jochen H M

2017-03-07

Aromatase is a critical enzyme in the irreversible conversion of androgens to oestrogens, with inhibition used clinically in hormone-dependent malignancies. We tested the hypothesis that targeted aromatase inhibition in an aggressive brain cancer called glioblastoma (GBM) may represent a new treatment strategy. In this study, aromatase inhibition was achieved using third generation inhibitor, Letrozole, encapsulated within the core of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs). PLGA-NPs were conjugated to human/mouse chimeric anti-GD2 antibody ch14.18/CHO, enabling specific targeting of GD2-positive GBM cells. Treatment of primary and recurrent patient-derived GBM cells with free-Letrozole (0.1 μM) led to significant decrease in cell proliferation and migration; in addition to reduced spheroid formation. Anti-GD2-ch14.18/CHO-NPs displayed specific targeting of GBM cells in colorectal-glioblastoma co-culture, with subsequent reduction in GBM cell numbers when treated with anti-GD2-ch14.18-PLGA-Let-NPs in combination with temozolomide. As miR-191 is an estrogen responsive microRNA, its expression, fluctuation and role in Letrozole treated GBM cells was evaluated, where treatment with premiR-191 was capable of rescuing the reduced proliferative phenotype induced by aromatase inhibitor. The repurposing and targeted delivery of Letrozole for the treatment of GBM, with the potential role of miR-191 identified, provides novel avenues for target assessment in this aggressive brain cancer.

Anti-GD2-ch14.18/CHO coated nanoparticles mediate glioblastoma (GBM)-specific delivery of the aromatase inhibitor, Letrozole, reducing proliferation, migration and chemoresistance in patient-derived GBM tumor cells

PubMed Central

Tivnan, Amanda; Heilinger, Tatjana; Ramsey, Joanne M; O’Connor, Gemma; Pokorny, Jenny L; Sarkaria, Jann N; Stringer, Brett W; Day, Bryan W; Boyd, Andrew W; Kim, Ella L; Lode, Holger N; Cryan, Sally-Ann; Prehn, Jochen H.M

2017-01-01

Aromatase is a critical enzyme in the irreversible conversion of androgens to oestrogens, with inhibition used clinically in hormone-dependent malignancies. We tested the hypothesis that targeted aromatase inhibition in an aggressive brain cancer called glioblastoma (GBM) may represent a new treatment strategy. In this study, aromatase inhibition was achieved using third generation inhibitor, Letrozole, encapsulated within the core of biodegradable poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs). PLGA-NPs were conjugated to human/mouse chimeric anti-GD2 antibody ch14.18/CHO, enabling specific targeting of GD2-positive GBM cells. Treatment of primary and recurrent patient-derived GBM cells with free-Letrozole (0.1 μM) led to significant decrease in cell proliferation and migration; in addition to reduced spheroid formation. Anti-GD2-ch14.18/CHO-NPs displayed specific targeting of GBM cells in colorectal-glioblastoma co-culture, with subsequent reduction in GBM cell numbers when treated with anti-GD2-ch14.18-PLGA-Let-NPs in combination with temozolomide. As miR-191 is an estrogen responsive microRNA, its expression, fluctuation and role in Letrozole treated GBM cells was evaluated, where treatment with premiR-191 was capable of rescuing the reduced proliferative phenotype induced by aromatase inhibitor. The repurposing and targeted delivery of Letrozole for the treatment of GBM, with the potential role of miR-191 identified, provides novel avenues for target assessment in this aggressive brain cancer. PMID:28178667

Altered expression of miRNAs in the uterus from a letrozole-induced rat PCOS model.

PubMed

Li, Chunjin; Chen, Lu; Zhao, Yun; Chen, Shuxiong; Fu, Lulu; Jiang, Yanwen; Gao, Shan; Liu, Zhuo; Wang, Fengge; Zhu, Xiaoling; Rao, Jiahui; Zhang, Jing; Zhou, Xu

2017-01-20

Polycystic ovary syndrome (PCOS) causes female subfertility with ovarian disorders and may be associated with increased rate of early-pregnancy failure. Rat PCOS models were established using letrozole to understand the uterine pathogenesis of PCOS. The differential expression of microRNAs (miRNAs) was observed in rat uterus with PCOS. After estrous cycles were disrupted, significantly abnormal ovarian morphology and hormone level were observed in rats with PCOS. A total of 148 miRNAs differentially expressed were identified in the uterus from the letrozole-induced rat model compared with the control. These miRNAs included 111 upregulated miRNAs and 37 downregulated miRNAs. The differential expression of miR-484, miR-375-3p, miR-324-5p, and miR-223-3p was further confirmed by quantitative reverse transcription polymerase chain reaction. Bioinformatic analysis showed that these four miRNAs were predicted to regulate a large number of genes with different functions. Pathway analysis supported that target genes of miRNAs were involved in insulin secretion and signaling pathways, such as wnt, AMPK, PI3K-Akt, and Ras. These data indicated that miRNAs differentially expressed in rat uterus with PCOS may be associated with PCOS pathogenesis in the uterus. Our findings can help clarify the mechanism of uterine defects in PCOS. Copyright © 2016. Published by Elsevier B.V.

The perspectives of obese women receiving antenatal care: A qualitative study of women's experiences.

PubMed

Knight-Agarwal, Catherine R; Williams, Lauren T; Davis, Deborah; Davey, Rachel; Shepherd, Rebecca; Downing, Alice; Lawson, Kathryn

2016-04-01

The prevalence of overweight and obesity is increasing amongst women of child bearing age. Maternal obesity has implications for both mother and baby including increased health risks from gestational hypertensive disorders, caesarean section and stillbirth. Despite the increasing prevalence of maternal obesity little is known of the experiences of these women within the health care system. The aim of this research was to investigate the perspectives of pregnant women with a body mass index (BMI) of ≥30kg/m(2) receiving antenatal care. A qualitative study using individual interviews was undertaken. Sixteen pregnant women with a BMI ≥30kg/m(2) participated. Interviews were audio recorded, transcribed, cross checked for consistency and then entered into a word processing document for analysis. Data was analysed using Interpretative Phenomenological Analysis. In any phenomenological study the researcher's objective is to elicit the participant's views on their lived experiences. Four major themes emerged: (1) obese during pregnancy as part of a long history of obesity; (2) lack of knowledge of the key complications of obesity for both mother and child; (3) communication about weight and gestational weight gain can be conflicting, confusing and judgmental; (4) most women are motivated to eat well during pregnancy and want help to do so. Specialist lifestyle interventions for obese women should be a priority in antenatal care. Extra support is required to assist obese women in pregnancy achieve recommended nutritional and weight goals. Health professionals should approach the issue of maternal obesity in an informative but non-judgmental way. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Steroid receptor coactivator-1 mediates letrozole induced downregulation of postsynaptic protein PSD-95 in the hippocampus of adult female rats.

PubMed

Liu, Mengying; Huangfu, Xuhong; Zhao, Yangang; Zhang, Dongmei; Zhang, Jiqiang

2015-11-01

Hippocampus local estrogen which is converted from androgen that catalyzed by aromatase has been shown to play important roles in the regulation of learning and memory as well as cognition through action on synaptic plasticity, but the underlying mechanisms are poorly understood. Steroid receptor coactivator-1 (SRC-1) is one of the coactivators of steroid nuclear receptors; it is widely distributed in brain areas that related to learning and memory, reproductive regulation, sensory and motor information integration. Previous studies have revealed high levels of SRC-1 immunoreactivities in the hippocampus; it is closely related to the levels of synaptic proteins such as PSD-95 under normal development or gonadectomy, but its exact roles in the regulation of these proteins remains unclear. In this study, we used aromatase inhibitor letrozole in vivo and SRC-1 RNA interference in vitro to investigate whether SRC-1 mediated endogenous estrogen regulation of hippocampal PSD-95. The results revealed that letrozole injection synchronously decreased hippocampal SRC-1 and PSD-95 in a dose-dependant manner. Furthermore, when SRC-1 specific shRNA pool was applied to block the expression of SRC-1 in the primary hippocampal neuron culture, both immunocytochemistry and Western blot revealed that levels of PSD-95 were also decreased significantly. Taking together, these results provided the first evidence that SRC-1 mediated endogenous estrogen regulation of hippocampal synaptic plasticity by targeting the expression of synaptic protein PSD-95. Additionally, since letrozole is frequently used to treat estrogen-sensitive breast cancer, the above results also indicate its potential side effects in clinical administration. Copyright © 2015 Elsevier Ltd. All rights reserved.

Comfort and anxiety levels of women with early stage breast cancer who receive radiotherapy.

PubMed

Tuncer, Gamze; Yucel, Sebnem Cinar

2014-01-01

The aim of this planned research was to determine the comfort and anxiety levels of women with breast cancer receiving radiotherapy. This descriptive type study covered patients that applied to the radiation oncology breast polyclinic of our university hospital between January and May 2011. Patient Identification Form, Radiation Therapy Comfort Questionnaire (RTCQ), Spielberger State Trait Anxiety Inventory (STAI) were completed and analysed. The mean age of the women who participated in the study was 51.6 ± 10.4 years. Mean scores of women were 3.73 ± 0.31 for RTCQ, 29.1 ± 5.88 for SAI and 37.8±6.91 for TAI. While the comfort levels of the women with breast cancer receiving radiotherapy were moderate, they experienced only low levels of anxiety. By determining the comfort level of the patient before radiotherapy, besides providing comfort in this direction, eliminating/minimizing anxiety and stress will positively affect radiotherapy application. More attention of nurses to this issue is to be recommended.

Intent to receive an HPV vaccine among university men and women and implications for vaccine administration.

PubMed

Jones, Melissa; Cook, Robert

2008-01-01

In 2006, the authors examined intention to receive an HPV vaccine among 340 college students. A total of 138 men and 202 women completed questionnaires. The authors measured intention by asking participants how likely they would be to accept an HPV vaccine that prevented against (1) all HPV, (2) cervical cancer but not genital warts, (3) genital warts but not cervical cancer, and (4) both genital warts and cervical cancer. Men and women reported high intent to receive an HPV vaccine, although women did so at a significantly higher rate (77.5% vs 88.6%, respectively; p < .01). Men were less willing to receive a vaccine that prevents cervical cancer alone than they were to receive one that prevents cervical cancer and genital warts (34.1% vs 77.5%, p < .001). Intent to receive the vaccine was significantly greater among participants who reported more than 5 sex partners and correctly answered 2 or 3 HPV knowledge questions. Interest varied according to sexual history, according to knowledge about HPV, and (in men) according to vaccine target.

Beyond the verbal: Pregnant women's preferences for receiving influenza and Tdap vaccine information from their obstetric care providers.

PubMed

Ellingson, Mallory; Chamberlain, Allison T

2018-03-04

Prenatal providers are pregnant women's most trusted sources of health information, and a provider's recommendation is a strong predictor of maternal vaccine receipt. However, other ways women prefer receiving vaccine-related information from prenatal providers, aside from face-to-face conversations, is unclear. This study explores what secondary communication methods are preferred for receiving maternal vaccine-related information. Obstetric patients at four prenatal clinics around Atlanta, Georgia received a 27-item survey between May 5th, 2016 and June 15th, 2016. Participants were asked about sources they currently use to obtain prenatal health information and their preferences for receiving vaccine-related information from providers. Descriptive statistics were calculated and chi-square tests were used to evaluate associations between participant characteristics and outcomes. Women primarily reported using the CDC website (57.7%) and pregnancy-related websites (53.0%) to obtain vaccine information. Apart from clinical conversations, educational brochures (64.9%) and e-mails (54.7%) were the preferred methods of receiving vaccine information from providers, followed by their provider's practice website (42.1%). Communication preferences and interest in maternal immunization varied by race/ethnicity, age and education; white women were twice as likely to want information on a provider's practice website compared to African-American women (OR = 2.06; 95% CI: 1.31, 3.25). Pregnant women use the Internet for information about vaccines, but they still value input from their providers. While e-mails and brochures were the preferred secondary modes of receiving information, a provider's existing practice website offers a potential communications medium that capitalizes on women's information seeking behaviors and preferences while limiting burden on providers.

Characteristics of Transgender Women Living with HIV Receiving Medical Care in the United States.

PubMed

Mizuno, Yuko; Frazier, Emma L; Huang, Ping; Skarbinski, Jacek

2015-09-01

Little has been reported from population-based surveys on the characteristics of transgender persons living with HIV. Using Medical Monitoring Project (MMP) data, we describe the characteristics of HIV-infected transgender women and examine their care and treatment needs. We used combined data from the 2009 to 2011 cycles of MMP, an HIV surveillance system designed to produce nationally representative estimates of the characteristics of HIV-infected adults receiving medical care in the United States, to compare demographic, behavioral, and clinical characteristics, and met and unmet needs for supportive services of transgender women with those of non-transgender persons using Rao-Scott chi-square tests. An estimated 1.3% of HIV-infected persons receiving care in the United States self-identified as transgender women. Transgender women were socioeconomically more marginalized than non-transgender men and women. We found no differences between transgender women and non-transgender men and women in the percentages prescribed antiretroviral therapy (ART). However, a significantly lower percentage of transgender women compared to non-transgender men had 100% ART dose adherence (78.4% vs. 87.4%) and durable viral suppression (50.8% vs. 61.4%). Higher percentages of transgender women needed supportive services. No differences were observed in receipt of most of supportive services, but transgender women had higher unmet needs than non-transgender men for basic services such as food and housing. We found little difference between transgender women and non-transgender persons in regards to receipt of care, treatment, and most of supportive services. However, the noted disparities in durable viral suppression and unmet needs for basic services should be explored further.

Likelihood of women vs. men to receive bachelor's degrees in physics at Stanford, 1900-1929.

NASA Astrophysics Data System (ADS)

Nero, Anthony

2005-04-01

Work by K. Tolley indicates that girls in mid to late 19th century U.S. high schools were more likely to study mathematics and natural philosophy (i.e., physics and astronomy) than were boys (who pursued the classics).* She also found that after the turn of the century women were more likely than men to receive bachelor's degrees in math and biological sciences at Stanford, but her sampling of every fifth year yielded too few data to be conclusive about physics. Reexamination of graduation lists at Stanford, yielding data for each year from 1900 to 1929, shows that, while absolute numbers were small, women were as likely as men to receive bachelor's degrees in physics during the first decade of the century, in the second decade they were notably more likely, and in the third their likelihood decreased substantially, while that of men rose to exceed that of women. (Women were much more likely to receive bachelor's degrees in math, exceeding the likelihood for men by an order of magnitude during the second and third decades.) *K. Tolley, The Science Education of American Girls: A Historical Perspective (Routledge, N.Y.), 2003.

Experiences of older women with cancer receiving hospice care: significance for physical therapy.

PubMed

Mackey, K M; Sparling, J W

2000-05-01

The number of older adults with cancer is growing, increasing the need for professionals who are able to meet these patients' special needs. In palliative care settings, physical therapists strive to promote quality of life. Minimal research exists, however, to guide therapists working with patients with terminal illness. The purpose of this study was to gain knowledge that can be used by physical therapists to more effectively assess and treat older people with cancer receiving hospice care. A qualitative single-case study with replication was conducted with 3 older women with cancer who were receiving hospice care. Interview data were analyzed using grounded theory techniques. Four themes emerged as central to the experience of the informants: social relationships, spirituality, outlook on mortality, and meaningful physical activity. In addition to maintaining physical function, physical therapists, who attend to nonphysical as well as physical aspects of care, may foster social cohesion, help maximize life's meaning, and support stabilizing strategies of older women with cancer who receive hospice care.

The clinical and economic impact of nurse to patient staffing ratios in women receiving intrapartum oxytocin.

PubMed

Clark, Steven L; Saade, George A; Meyers, Janet A; Frye, Donna R; Perlin, Jonathan B

2014-02-01

To examine the relationship between nurse-to-patient staffing ratios and perinatal outcomes in women receiving oxytocin during labor. A retrospective analysis of perinatal outcomes in women receiving oxytocin for induction or augmentation of labor during 2010. Outcomes examined were fetal distress, birth asphyxia, primary cesarean delivery, chorioamnionitis, endomyometritis, and a composite of adverse events. Frequency of 1:1 nurse-to-patient staffing was determined for each hospital. Outcomes were compared between hospitals categorized into quartiles of staffing ratios. In 208,033 women delivering during 2010, there was no relation between frequency of 1:1 nurse-to-patient staffing ratio and improved perinatal outcomes. Adoption of universal 1:1 staffing in the United States would result in the need for an additional 27,000 labor nurses and a cost of $1.6 billion. Available data do not support the imposition of mandatory 1:1 nurse-to-patient staffing ratios for women receiving oxytocin in all U.S. facilities. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Comparing the case mix and survival of women receiving breast cancer care from one private provider with other London women with breast cancer: pilot data exchange and analyses.

PubMed

Davies, Elizabeth A; Coupland, Victoria H; Dixon, Steve; Mokbel, Kefah; Jack, Ruth H

2016-07-07

Data from providers of private cancer care are not yet formally included in English cancer registration data. This study aimed to test the exchange of breast cancer data from one Hospital Corporation of America International (HCAI) hospital in London with the cancer registration system and assess the suitability of these data for comparative analyses of case mix and adjusted survival. Data on 199 London women receiving 'only HCAI care', 278 women receiving 'some HCAI care' (HCAI and other services), and 31,234 other London women diagnosed between 2005 and 2011 could be identified and compared. Overall survival was estimated using the Kaplan-Meier method, and Cox regression was used to adjust for age, socioeconomic deprivation, year of diagnosis, stage of disease and recorded treatment. Women receiving 'only HCAI care' were younger, lived in areas of higher affluence (47.8 % vs 27.6 %) and appeared less likely to be recorded as having screen-detected (2.5 % vs 25.0 %) disease than other London women. Women receiving 'some HCAI care' were more similar to 'HCAI only' women. Although HCAI stage of disease data completeness improved during the study period, this was less complete overall than cancer registration data and limited the comparative survival analyses. An apparent survival advantage for 'HCAI only' women compared with other London women (hazard ratio 0.48, 95 % confidence interval (CI): 0.32-0.74) was attenuated and no longer statistically significant after adjustment (0.79, 95 % CI: 0.51-1.21). Women receiving 'some HCAI care' appeared to have higher survival (hazard ratio 0.24, 95 % CI 0.14-0.41) which was attenuated to 0.48 (95 % CI: 0.28-0.80) in the fully adjusted model. Exchange of data between the private cancer sector and the English cancer registration service can identify patients who receive all or some private care. The better survival of women receiving only or some HCAI breast cancer care appears to be at least partly explained by

Adjuvant anastrozole versus exemestane versus letrozole, upfront or after 2 years of tamoxifen, in endocrine-sensitive breast cancer (FATA-GIM3): a randomised, phase 3 trial.

PubMed

De Placido, Sabino; Gallo, Ciro; De Laurentiis, Michelino; Bisagni, Giancarlo; Arpino, Grazia; Sarobba, Maria Giuseppa; Riccardi, Ferdinando; Russo, Antonio; Del Mastro, Lucia; Cogoni, Alessio Aligi; Cognetti, Francesco; Gori, Stefania; Foglietta, Jennifer; Frassoldati, Antonio; Amoroso, Domenico; Laudadio, Lucio; Moscetti, Luca; Montemurro, Filippo; Verusio, Claudio; Bernardo, Antonio; Lorusso, Vito; Gravina, Adriano; Moretti, Gabriella; Lauria, Rossella; Lai, Antonella; Mocerino, Carmela; Rizzo, Sergio; Nuzzo, Francesco; Carlini, Paolo; Perrone, Francesco

2018-04-01

Uncertainty exists about the optimal schedule of adjuvant treatment of breast cancer with aromatase inhibitors and, to our knowledge, no trial has directly compared the three aromatase inhibitors anastrozole, exemestane, and letrozole. We investigated the schedule and type of aromatase inhibitors to be used as adjuvant treatment for hormone receptor-positive early breast cancer. FATA-GIM3 is a multicentre, open-label, randomised, phase 3 trial of six different treatments in postmenopausal women with hormone receptor-positive early breast cancer. Eligible patients had histologically confirmed invasive hormone receptor-positive breast cancer that had been completely removed by surgery, any pathological tumour size, and axillary nodal status. Key exclusion criteria were hormone replacement therapy, recurrent or metastatic disease, previous treatment with tamoxifen, and another malignancy in the previous 10 years. Patients were randomly assigned in an equal ratio to one of six treatment groups: oral anastrozole (1 mg per day), exemestane (25 mg per day), or letrozole (2·5 mg per day) tablets upfront for 5 years (upfront strategy) or oral tamoxifen (20 mg per day) for 2 years followed by oral administration of one of the three aromatase inhibitors for 3 years (switch strategy). Randomisation was done by a computerised minimisation procedure stratified for oestrogen receptor, progesterone receptor, and HER2 status; previous chemotherapy; and pathological nodal status. Neither the patients nor the physicians were masked to treatment allocation. The primary endpoint was disease-free survival. The minimum cutoff to declare superiority of the upfront strategy over the switch strategy was assumed to be a 2% difference in disease-free survival at 5 years. Primary efficacy analyses were done by intention to treat; safety analyses included all patients for whom at least one safety case report form had been completed. Follow-up is ongoing. This trial is registered with the

Women with Bulimic Eating Disorders: When Do They Receive Treatment for an Eating Problem?

ERIC Educational Resources Information Center

Mond, J. M.; Hay, P. J.; Darby, A.; Paxton, S. J.; Quirk, F.; Buttner, P.; Owen, C.; Rodgers, B.

2009-01-01

Variables associated with the use of health services were examined in a prospective, community-based study of women with bulimic-type eating disorders who did (n = 33) or did not (n = 58) receive treatment for an eating problem during a 12-month follow-up period. Participants who received treatment for an eating problem differed from those who did…

Update of the BIG 1-98 Trial: where do we stand?

PubMed

Joerger, Markus; Thürlimann, Beat

2009-10-01

There is accumulating data on the clinical benefit of aromatase inhibitors in the adjuvant treatment of early-stage breast cancer in postmenopausal women. The Breast International Group (BIG) 1-98 study is a randomized, phase 3, double-blind trial comparing four adjuvant endocrine treatments of 5 years duration in postmenopausal women with hormone-receptor-positive breast cancer: letrozole or tamoxifen monotherapy, sequential treatment with tamoxifen followed by letrozole, or vice versa. This article summarizes data presented at the 2009 St. Gallen early breast cancer conference: an update on the monotherapy arms of the BIG 1-98 study, and results from the sequential treatment arms. Implications for daily practice from BIG 1-98 and from other adjuvant trials will be discussed. Despite cross-over from tamoxifen to letrozole by 25% of the patients after unblinding of the tamoxifen monotherapy arm, the improvement of disease-free survival (HR 0.88, 0.78-0.99, p = 0.03) and time to distant recurrence (HR 0.85, 0.72-1.00, p = 0.05) for letrozole monotherapy as compared to tamoxifen monotherapy remained significant in the intention-to-treat (ITT) analysis. A trend for an overall survival advantage for letrozole was seen in the ITT analysis (HR 0.87, 0.75-1.02, p = 0.08). No statistically significant differences were found for the sequential treatment arms versus letrozole monotherapy, with respect to disease-free survival, time to distant recurrence or overall survival. Cumulative incidence analysis of breast cancer recurrence favors the initiation of adjuvant endocrine treatment with letrozole instead of tamoxifen, especially in patients at higher risk for early recurrence. Similarly, data suggest that patients commenced on letrozole can be switched to tamoxifen after 2 years, if required. The BIG 1-98 study update with median follow up of 76 months confirms a significant reduction in the risk of breast cancer recurrence and a trend towards improved overall survival

Three-month treatment with triptorelin, letrozole and ulipristal acetate before hysteroscopic resection of uterine myomas: prospective comparative pilot study.

PubMed

Bizzarri, Nicolò; Ghirardi, Valentina; Remorgida, Valentino; Venturini, Pier Luigi; Ferrero, Simone

2015-09-01

To compare the usefulness of preoperative treatment with triptorelin, letrozole or ulipristal acetate or no treatment before hysteroscopic removal of uterine submucosal myomas. Single center prospective non-randomized comparative pilot study. The study included consecutive premenopausal patients undergoing hysteroscopic resection of myomas graded as type 0, type 1 or type 2 according to the FIGO classification with diameter between 20 and 35 mm. Exclusion criteria were: associated polyps, associated non-hysteroscopic surgical procedures, >2 myomas requiring hysteroscopic resection. This study enrolled patients who underwent either direct surgery (group S; n=23) or 3-month preoperative treatment with triptorelin (3.75 mg every 28 days; group T; n=20), letrozole (2.5 mg/day; group L; n=11) or ulipristal acetate (5 mg/day; group U; n=7). Patients underwent hysteroscopic resection of the myomas. All medical treatments caused a significant decrease in the volume of myomas (group T, p<.001; group L, p<.001; group U, p=.006); however, the percentage decrease in myoma volume was lower in group U than in group T (p=.001) and in group L (p=.010). The hysteroscopy time was higher in group S than in group T (p<.001) and in group L (p=.001); there was no significant difference in the hysteroscopy time between group S and group U (p=.206). Fluid absorption was lower in group T than in group S (p=.002) and in group L than in group S (p=.048); fluid absorption was similar in group S and group U (p=.110). Intra- and postoperative complications, postoperative pain, and patient satisfaction were similar in the four study groups. Surgeon's evaluation of operative difficulty was better in group T than in group S (p<.005). Preoperative treatment with triptorelin and letrozole decreases the hysteroscopy time and the volume of fluid absorbed during hysteroscopic resection of uterine submucosal myomas. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Differential Expression of microRNAs in the Ovaries from Letrozole-Induced Rat Model of Polycystic Ovary Syndrome.

PubMed

Li, Dandan; Li, Chunjin; Xu, Ying; Xu, Duo; Li, Hongjiao; Gao, Liwei; Chen, Shuxiong; Fu, Lulu; Xu, Xin; Liu, Yongzheng; Zhang, Xueying; Zhang, Jingshun; Ming, Hao; Zheng, Lianwen

2016-04-01

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder. To understand the pathogenesis of PCOS, we established rat models of PCOS induced by letrozole and employed deep sequencing to screen the differential expression of microRNAs (miRNAs) in PCOS rats and control rats. We observed vaginal smear and detected ovarian pathological alteration and hormone level changes in PCOS rats. Deep sequencing showed that a total of 129 miRNAs were differentially expressed in the ovaries from letrozole-induced rat model compared with the control, including 49 miRNAs upregulated and 80 miRNAs downregulated. Furthermore, the differential expression of miR-201-5p, miR-34b-5p, miR-141-3p, and miR-200a-3p were confirmed by real-time polymerase chain reaction. Bioinformatic analysis revealed that these four miRNAs were predicted to target a large set of genes with different functions. Pathway analysis supported that the miRNAs regulate oocyte meiosis, mitogen-activated protein kinase (MAPK) signaling, phosphoinositide 3-kinase/Akt (PI3K-Akt) signaling, Rap1 signaling, and Notch signaling. These data indicate that miRNAs are differentially expressed in rat PCOS model and the differentially expressed miRNA are involved in the etiology and pathophysiology of PCOS. Our findings will help identify miRNAs as novel diagnostic markers and therapeutic targets for PCOS.

Contraceptive use and pregnancy rates among women receiving antiretroviral therapy in Malawi: a retrospective cohort study.

PubMed

Tweya, Hannock; Feldacker, Caryl; Gugsa, Salem; Phiri, Sam

2018-02-09

In 2011, family planning (FP) services were integrated at Martin Preuss Centre (MPC), in urban Lilongwe, Malawi. To date, no previous study evaluated pregnancy rates among HIV-positive women after the integration of FP services into HIV care at the facility. In this study, we investigated whether integration of FP services into HIV clinical care led to increased use of contraceptives and decreased pregnancy rates. This was a retrospective cohort analysis of HIV-positive women from 15 to 49 years of age who accessed antiretroviral therapy (ART) services at MPC. Ascertainment of FP needs, contraceptive methods and pregnancy status were done at ART initiation, and at each ART follow-up visit. Women were offered a wide range of contraceptive methods. Outcomes of interest were contraceptive use and rate of pregnancy. Incident pregnancy was ascertained through patient self-reports during clinic consultation. Trends of contraceptive use and pregnancy rates were analyzed using chi-square (χ2). A total of 10,472 women were included in the analysis and contributed 15,700 person-years of observation. Contraceptive use among all women receiving ART increased from 28% in 2012 to 62% in 2016 (p < 0.001). A total of 501 pregnancies occurred, including 13 multiple pregnancies, resulting in an overall pregnancy rates of 3.2 per 100 person-years. Rates of pregnancy decreased from 6.8 per 100 person-years in 2012 to 1.3 per 100 person-years in 2016 (p < 0.001). Integration of FP services into HIV care resulted in increased contraceptive use and, subsequently, decreased pregnancy rates in women receiving ART. HIV programs should consider offering FP services to women who are receiving ART.

Chinese women's motivation to receive future screening: the role of social-demographic factors, knowledge and risk perception of cervical cancer.

PubMed

Gu, Can; Chan, Carmen W H; He, Guo-Ping; Choi, K C; Yang, Sheng-Bo

2013-04-01

This paper adopted Protection Motivation Theory (PMT) to examine Chinese women's knowledge and perceptions of cervical cancer risk and factors influencing their motivation to receive future screening. A cross-sectional survey was conducted with 167 Chinese women (142 women were willing to receive a screening in the future and 25 women were not) in 2007 to collect women's socio-demographic information and sexual history, perceptions related to body health and knowledge about cervical cancer and screening, and Protection Motivation Theory measures. The majority of women stated they intended to receive future screening and response efficacy was significantly associated with their intention. However, no significant association was observed between sexual history and protection motivation. Using multivariate analysis, cancer in relatives (odds ratio, OR = 9.97, 95% CI [1.44-436.3], p = 0.010), a perception that visiting a doctor regularly is important to health (OR = 9.85, 95% CI [1.61-999.9], p = 0.009)), and ever attending for cervical screening during the previous three years (OR = 3.49, 95% CI [1.23-11.02], p = 0.016) were significantly associated with women' motivation to receive future screening. The findings of this study highlight the important role of women's beliefs in the value of cervical screening and previous screening experience in motivating them to receive a screening. Education intervention is needed to provide information and raise public awareness about the importance of cervical screening to women's health. Culture-related beliefs and social motivational processes in addition to those specified by PMT need to be addressed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Survival outcome of women with stage IV uterine carcinosarcoma who received neoadjuvant chemotherapy followed by surgery.

PubMed

Matsuo, Koji; Johnson, Marian S; Im, Dwight D; Ross, Malcolm S; Bush, Stephen H; Yunokawa, Mayu; Blake, Erin A; Takano, Tadao; Klobocista, Merieme M; Hasegawa, Kosei; Ueda, Yutaka; Shida, Masako; Baba, Tsukasa; Satoh, Shinya; Yokoyama, Takuhei; Machida, Hiroko; Ikeda, Yuji; Adachi, Sosuke; Miyake, Takahito M; Iwasaki, Keita; Yanai, Shiori; Takeuchi, Satoshi; Nishimura, Masato; Nagano, Tadayoshi; Takekuma, Munetaka; Shahzad, Mian M K; Pejovic, Tanja; Omatsu, Kohei; Kelley, Joseph L; Ueland, Frederick R; Roman, Lynda D

2018-03-01

To examine survival of women with stage IV uterine carcinosarcoma (UCS) who received neoadjuvant chemotherapy followed by hysterectomy. This is a nested case-control study within a retrospective cohort of 1192 UCS cases. Women who received neoadjuvant chemotherapy followed by hysterectomy based-surgery for stage IV UCS (n = 26) were compared to those who had primary hysterectomy-based surgery without neoadjuvant chemotherapy for stage IV UCS (n = 120). Progression-free survival (PFS) and cause-specific survival (CSS) were examined. The most common regimen for neoadjuvant chemotherapy was carboplatin/paclitaxel (53.8%). Median number of neoadjuvant chemotherapy cycles was 4. PFS was similar between the neoadjuvant chemotherapy group and the primary surgery group (unadjusted-hazard ratio [HR] 1.19, 95% confidence interval [CI] 0.75-1.89, P = 0.45). Similarly, CSS was comparable between the two groups (unadjusted-HR 1.13, 95%CI 0.68-1.90, P = 0.64). When the types of neoadjuvant chemotherapy regimens were compared, women who received a carboplatin/paclitaxel regimen had better survival outcomes compared to those who received other regimens: PFS, unadjusted-HR 0.38, 95%CI 0.15-0.93, P = 0.027; and CSS, unadjusted-HR 0.21, 95%CI 0.07-0.61, P = 0.002. Our study found that there is no statistically significant difference in survival between women with stage IV UCS who are tolerated neoadjuvant chemotherapy and those who undergo primary surgery. © 2017 Wiley Periodicals, Inc.

Symptoms Experienced and Information Needs of Women Receiving Chemotherapy.

PubMed

Uysal, Neşe; Toprak, Filiz Ünal; Kutlutsürkan, Sevinç; Erenel, Ayten Şentürk

2018-01-01

This study is carried out to determine the symptoms and information necessity on chemotherapy (CT) treatment of the women with breast cancer. A total of 170 women older than 18 years old, who receive CT with breast cancer diagnosis, are volunteered to participate in the study. Mixed method was used in the study. Data are collected using Descriptive Data Form, Interview Form and Memorial Symptom Assessment Scale. As a result of the cluster analysis, four clusters and the symptoms within have been obtained. These are: pain, lack of energy, feeling drowsy, sweat, swelling of hands, and feet in the first cluster; feeling nervous, difficulty sleeping, feeling sad, worrying in the second cluster; nausea, feeling bloating, change in the way food tastes, hair loss, constipation in the third cluster; vomiting, diarrhea, problems with sexual interest, lack of appetite, dizziness, and weight loss in the forth cluster. Women's information necessity related to the CT are follows: the effects of CT, other treatment options beyond CT, complementary methods, the effect of the CT treatment on reproductive health and sexuality, nutrition, and symptom control. The results of this study will enable determination of symptom clusters, which health professionals are easier to focus on these symptoms. An understanding information need of patients can help to ensure that individual's coping strategies and self-management.

Efficacy and mechanism of action of Proellex, an antiprogestin in aromatase overexpressing and Letrozole resistant T47D breast cancer cells.

PubMed

Gupta, Akash; Mehta, Rajeshwari; Alimirah, Fatouma; Peng, Xinjian; Murillo, Genoveva; Wiehle, Ronald; Mehta, Rajendra G

2013-01-01

Aromatase inhibitors (AI) are considered as a first line therapy for ER+PR+ breast cancers. However, many patients acquire resistance to AI. In this study, we determined the response of antiprogestin CDB-4124 (Proellex) on the aromatase overexpressing and Letrozole resistant cell lines and also studies its mechanism of action in inhibition of breast cancer cell proliferation. For these studies we generated aromatase overexpressing T47D (T47Darom) and respective control (T47Dcon) breast cancer cell lines by stable transfection with plasmid containing CYP19A1 gene, or empty vector respectively. Letrozole resistant cell line (T47DaromLR) was generated by incubating T47Darom for 75 weeks in the presence of 10 μM Letrozole. Cell proliferation was determined by MTT or crystal violet assays. Gene expressions were quantified by QRT-PCR whereas proteins were identified by western blot analyses, flow cytometry and immunofluorescence staining. Aromatase activity was determined by estradiol ELISA. The effects of Proellex on the anchorage independent growth were measured by soft agar colony formation. Statistical differences between the various groups were determined by Student's 't' test or ANOVA followed by Bonferroni's post hoc test. Results showed that T47Darom and T47DaromLR cell lines had significantly higher aromatase expression (mRNA; 80-90 fold and protein) and as a result exhibited increased aromatization of testosterone to estradiol as compared to T47Dcon. Both these cell lines showed enhanced growth in the presence of Testosterone (50-60%). In T47DaromLR cells increased PR-B and EGFR expression as compared to T47Dcon cells was observed. Proellex and other known aromatase inhibitors (Letrozole, Anastrozole, and Exemestane) inhibited testosterone induced cell proliferation and anchorage independent growth of T47Darom cells. Cell growth inhibition was significantly greater when cells were treated with Proellex alone or in combination with other AIs as compared to AIs

Distress among women receiving uninformative BRCA1/2 results: 12-month outcomes.

PubMed

O'Neill, Suzanne C; Rini, Christine; Goldsmith, Rachel E; Valdimarsdottir, Heiddis; Cohen, Lawrence H; Schwartz, Marc D

2009-10-01

Few data are available regarding the long-term psychological impact of uninformative BRCA1/2 test results. This study examines change in distress from pretesting to 12-months post-disclosure, with medical, family history, and psychological variables, such as pretesting perceived risk of carrying a deleterious mutation prior to testing and primary and secondary appraisals, as predictors. Two hundred and nine women with uninformative BRCA1/2 test results completed questionnaires at pretesting and 1-, 6-, and 12-month post-disclosure, including measures of anxiety and depression, cancer-specific and genetic testing distress. We used a mixed models approach to predict change in post-disclosure distress. Distress declined from pretesting to 1-month post-disclosure, but remained stable thereafter. Primary appraisals predicted all types of distress at 1-month post-disclosure. Primary and secondary appraisals predicted genetic testing distress at 1-month as well as change over time. Receiving a variant of uncertain clinical significance and entering testing with a high expectation for carrying a deleterious mutation predicted genetic testing distress that persisted through the year after testing. As a whole, women receiving uninformative BRCA1/2 test results are a resilient group. For some women, distress experienced in the month after testing does not dissipate. Variables, such as heightened pretesting perceived risk and cognitive appraisals, predict greater likelihood for sustained distress in this group and could be amenable to intervention.

A Novel Letrozole Model Recapitulates Both the Reproductive and Metabolic Phenotypes of Polycystic Ovary Syndrome in Female Mice1

PubMed Central

Kauffman, Alexander S.; Thackray, Varykina G.; Ryan, Genevieve E.; Tolson, Kristen P.; Glidewell-Kenney, Christine A.; Semaan, Sheila J.; Poling, Matthew C.; Iwata, Nahoko; Breen, Kellie M.; Duleba, Antoni J.; Stener-Victorin, Elisabet; Shimasaki, Shunichi; Webster, Nicholas J.; Mellon, Pamela L.

2015-01-01

Polycystic ovary syndrome (PCOS) pathophysiology is poorly understood, due partly to lack of PCOS animal models fully recapitulating this complex disorder. Recently, a PCOS rat model using letrozole (LET), a nonsteroidal aromatase inhibitor, mimicked multiple PCOS phenotypes, including metabolic features absent in other models. Given the advantages of using genetic and transgenic mouse models, we investigated whether LET produces a similar PCOS phenotype in mice. Pubertal female C57BL/6N mice were treated for 5 wk with LET, which resulted in increased serum testosterone and normal diestrus levels of estradiol, similar to the hyperandrogenemia and follicular phase estrogen levels of PCOS women. As in PCOS, ovaries from LET mice were larger, polycystic, and lacked corpora lutea versus controls. Most LET females were acyclic, and all were infertile. LET females displayed elevated serum LH levels and higher Lhb mRNA in the pituitary. In contrast, serum FSH and Fshb were significantly reduced in LET females, demonstrating differential effects on gonadotropins, as in PCOS. Within the ovary, LET females had higher Cyp17, Cyp19, and Fsh receptor mRNA expression. In the hypothalamus, LET females had higher kisspeptin receptor mRNA expression but lower progesterone receptor mRNA levels. LET females also gained more weight than controls, had increased abdominal adiposity and adipocyte size, elevated adipose inflammatory mRNA levels, and impaired glucose tolerance, mirroring the metabolic phenotype in PCOS women. This is the first report of a LET paradigm in mice that recapitulates both reproductive and metabolic PCOS phenotypes and will be useful to genetically probe the PCOS condition. PMID:26203175

[Clinical therapeutic effects of acupuncture combined with Chinese herbal medicine on infertility of polycystic ovary syndrome in the patients with ovulation induction with letrozole].

PubMed

Yin, Yan; Zhang, Yingchun; Zhang, Hua; Jiang, Duosheng; Guo, Guirong

2018-01-12

results in the group C were the best and those in the group B were the better in the comparison of the 3 groups. (2) After treatment, the menstrual cycle was remarkably shortened in the 3 groups (all P <0.05). The result in the group C was better than that in the group A ( P <0.05). After treatment, the body weight in the group B and group C was all reduced (both P <0.05). The reducing degree in the group C was better than that in the group A ( P <0.05). The differences in BMI were not significant statistically before and after treatment in each group as well as in comparison among the groups (all P >0.05). (3) After treatment, the levels of LH and LH/FSH were all reduced remarkably in the 3 groups (all P <0.05). The differences were not significant statistically in comparison among the three groups (all P >0.05). After treatment, in the group B and group C, the levels of T and AMH were all reduced remarkably (all P <0.05), in which, T value in the group C was lower than that in the group A and group B, that in the group B was lower than the group A (all P <0.05). AMH value in the group C was lower than that in the group A ( P <0.05). The differences were not significant statistically in FSH, E 2 and IHNB before and after treatment in each group as well as in comparison among the 3 groups (all P >0.05). (4) The luteinized unreuptured follicle syndrome (LUFS) did not happen in the group C. There were 3 cases of LUFS (7.5%) in the group B and 5 cases (12.5%) in the group A. For PCOS infertility patients receiving ovulation induction with letrozole, the combined treatment with the Chinese herbal formula for regulating menstruation and removing phlegm and EA remarkably improves the menstrual cycle, reduces body weight and the levels of LH, LH/FSH, T and AMH, improves ovulation and pregnancy rates. This therapy does not induce adverse reactions and the therapeutic effects are better than the simple application of letrozole or the combined therapy of letrozole and Chinese

Evaluation of the vaginal flora in pregnant women receiving opioid maintenance therapy: a matched case-control study.

PubMed

Farr, Alex; Kiss, Herbert; Hagmann, Michael; Holzer, Iris; Kueronya, Verena; Husslein, Peter W; Petricevic, Ljubomir

2016-08-05

Vaginal infections are a risk factor for preterm delivery. In this study, we sought to evaluate the vaginal flora of pregnant women receiving opioid maintenance therapy (OMT) in comparison to non-dependent, non-maintained controls. A total of 3763 women with singleton pregnancies who underwent routine screening for asymptomatic vaginal infections between 10 + 0 and 16 + 0 gestational weeks were examined. Vaginal smears were Gram-stained, and microscopically evaluated for bacterial vaginosis, candidiasis, and trichomoniasis. In a retrospective manner, data of 132 women receiving OMT (cases) were matched for age, ethnicity, parity, education, previous preterm delivery, and smoking status to the data of 3631 controls. The vaginal flora at antenatal screening served as the primary outcome measure. Secondary outcome measures were gestational age and birth weight. In the OMT group, 62/132 (47 %) pregnant women received methadone, 39/132 (29.5 %) buprenorphine, and 31/132 (23.5 %) slow-release oral morphine. Normal or intermediate flora was found in 72/132 OMT women (54.5 %) and 2865/3631 controls [78.9 %; OR 0.49 (95 % CI, 0.33-0.71); p < 0.001]. Candidiasis occurred more frequently in OMT women than in controls [OR 2.11 (95 % CI, 1.26-3.27); p < 0.001]. Findings were inconclusive regarding bacterial vaginosis (± candidiasis) and trichomoniasis. Compared to infants of the control group, those of women with OMT had a lower mean birth weight [MD -165.3 g (95 % CI, -283.6 to -46.9); p = 0.006]. Pregnant women with OMT are at risk for asymptomatic vaginal infections. As recurrent candidiasis is associated with preterm delivery, the vulnerability of this patient population should lead to consequent antenatal infection screening at early gestation.

Economic violence to women and girls: is it receiving the necessary attention?

PubMed

Fawole, Olufunmilayo I

2008-07-01

Most studies on gender-based violence (GBV) have focused on its physical, sexual, and psychological manifestations. This paper seeks to draw attention to the types of economic violence experienced by women, and describes its consequences on health and development. Economic violence experienced included limited access to funds and credit; controlling access to health care, employment, education, including agricultural resources; excluding from financial decision making; and discriminatory traditional laws on inheritance, property rights, and use of communal land. At work women experienced receiving unequal remuneration for work done equal in value to the men's, were overworked and underpaid, and used for unpaid work outside the contractual agreement. Some experienced fraud and theft from some men, illegal confiscation of goods for sale, and unlawful closing down of worksites. At home, some were barred from working by partners; while other men totally abandoned family maintenance to the women. Unfortunately, economic violence results in deepening poverty and compromises educational attainment and developmental opportunities for women. It leads to physical violence, promotes sexual exploitation and the risk of contracting HIV infection, maternal morbidity and mortality, and trafficking of women and girls. Economic abuse may continue even after the woman has left the abusive relationship. There is need for further large-scale studies on economic violence to women. Multi-strategy interventions that promote equity between women and men, provide economic opportunities for women, inform them of their rights, reach out to men and change societal beliefs and attitudes that permit exploitative behavior are urgently required.

Ribociclib as First-Line Therapy for HR-Positive, Advanced Breast Cancer.

PubMed

Hortobagyi, Gabriel N; Stemmer, Salomon M; Burris, Howard A; Yap, Yoon-Sim; Sonke, Gabe S; Paluch-Shimon, Shani; Campone, Mario; Blackwell, Kimberly L; André, Fabrice; Winer, Eric P; Janni, Wolfgang; Verma, Sunil; Conte, Pierfranco; Arteaga, Carlos L; Cameron, David A; Petrakova, Katarina; Hart, Lowell L; Villanueva, Cristian; Chan, Arlene; Jakobsen, Erik; Nusch, Arnd; Burdaeva, Olga; Grischke, Eva-Maria; Alba, Emilio; Wist, Erik; Marschner, Norbert; Favret, Anne M; Yardley, Denise; Bachelot, Thomas; Tseng, Ling-Ming; Blau, Sibel; Xuan, Fengjuan; Souami, Farida; Miller, Michelle; Germa, Caroline; Hirawat, Samit; O'Shaughnessy, Joyce

2016-11-03

The inhibition of cyclin-dependent kinases 4 and 6 (CDK4/6) could potentially overcome or delay resistance to endocrine therapy in advanced breast cancer that is positive for hormone receptor (HR) and negative for human epidermal growth factor receptor 2 (HER2). In this randomized, placebo-controlled, phase 3 trial, we evaluated the efficacy and safety of the selective CDK4/6 inhibitor ribociclib combined with letrozole for first-line treatment in 668 postmenopausal women with HR-positive, HER2-negative recurrent or metastatic breast cancer who had not received previous systemic therapy for advanced disease. We randomly assigned the patients to receive either ribociclib (600 mg per day on a 3-weeks-on, 1-week-off schedule) plus letrozole (2.5 mg per day) or placebo plus letrozole. The primary end point was investigator-assessed progression-free survival. Secondary end points included overall survival, overall response rate, and safety. A preplanned interim analysis was performed on January 29, 2016, after 243 patients had disease progression or died. Prespecified criteria for superiority required a hazard ratio of 0.56 or less with P<1.29×10 -5 . The duration of progression-free survival was significantly longer in the ribociclib group than in the placebo group (hazard ratio, 0.56; 95% CI, 0.43 to 0.72; P=3.29×10 -6 for superiority). The median duration of follow-up was 15.3 months. After 18 months, the progression-free survival rate was 63.0% (95% confidence interval [CI], 54.6 to 70.3) in the ribociclib group and 42.2% (95% CI, 34.8 to 49.5) in the placebo group. In patients with measurable disease at baseline, the overall response rate was 52.7% and 37.1%, respectively (P<0.001). Common grade 3 or 4 adverse events that were reported in more than 10% of the patients in either group were neutropenia (59.3% in the ribociclib group vs. 0.9% in the placebo group) and leukopenia (21.0% vs. 0.6%); the rates of discontinuation because of adverse events were 7.5% and 2

Ethnic Differences in HIV Risk Behaviors Among Methadone-Maintained Women Receiving Contingency Management for Cocaine Use Disorders

PubMed Central

Barry, Danielle; Weinstock, Jeremiah; Petry, Nancy M.

2008-01-01

Objective To identify ethnic differences in HIV risk behaviors among cocaine using women receiving methadone maintenance for opioid dependence, and to evaluate the efficacy of contingency management (CM) for cocaine use disorders in reducing HIV risk behaviors. Methods African American (N=47), Hispanic (N=47), and White women (N = 29) were randomized to standard methadone treatment or standard methadone treatment plus a CM intervention. They completed the HIV Risk Behavior Scale (HRBS) indicating frequency of drug use and sexual behaviors across the lifetime, in the month before baseline, and in the 3 months following clinical trial participation. Ethnic group differences and the effect of CM on change in HIV risk behaviors between baseline and follow-up were evaluated. Results White women reported significantly higher lifetime rates of risky drug use and sexual behaviors on the HRBS than African American women; neither group differed significantly from Hispanic women. No ethnic group differences in HIV risk behaviors were identified in the month prior to baseline. At follow-up, African American women reported fewer high-risk drug use behaviors than White or Hispanic women, and Hispanic women reported more high-risk sexual behaviors than White or African American women. CM was associated with reduction in high-risk drug use behaviors regardless of ethnicity, but did not affect high-risk sexual behaviors. Conclusions White women receiving methadone maintenance engage in more lifetime HIV risk behaviors than African American women. CM for cocaine use reduces risky drug use behaviors, but certain ethnic groups may benefit from additional targeted HIV prevention efforts. PMID:18684571

Satisfaction of healthy pregnant women receiving short message service via mobile phone for prenatal support: A randomized controlled trial.

PubMed

Jareethum, Rossathum; Titapant, Vitaya; Chantra, Tienthai; Sommai, Viboonchart; Chuenwattana, Prakong; Jirawan, Chatchainoppakhun

2008-04-01

The main objective was to compare the satisfaction levels of antenatal care between healthy pregnant women who received short message service (SMS) via mobile phone for prenatal support, and those who did not. The second objective was to compare the confidence, anxiety levels and also pregnancy outcomes. A randomized controlled trial. 68 healthy pregnant women who attended the antenatal clinic and delivered at Siriraj Hospital, who met the inclusion criterias between May 2007 and October 2007, were enrolled and randomly allocated into two random groups. The study group received two SMS messages per week from 28 weeks of gestation until giving birth. The other group was pregnant women who did not receive SMS. Both groups had the same antenatal and perinatal care. The satisfaction, confidence and anxiety scores were evaluated using a questionnaire at the postpartum ward. The pregnancy outcomes were also compared in these two groups. The satisfaction levels of the women who received prenatal support in SMS messages, were significantly higher than those of who did not receive the messages both in the antenatal period (9.25 vs. 8.00, p < 0.001) and during labor (9.09 vs. 7.90, p = 0.007). In the SMS using group, the confidence level was'higher (8.91 vs. 7.79, p = 0.001) and the anxiety level was lower (2.78 vs. 4.93, p = 0.002) than the control group n the antenatal period, however no diference in pregnancy outcomes were found. The present study shows the higher satisfaction level of pregnant women who received SMS via mobile phone during their antenatal service when compared with the general antenatal care group. The study also show the higher confidence level and lower anxiety level in the antenatal period but no difference in pregnancy outcomes.

A randomized controlled trial of mindfulness-based stress reduction for women with early-stage breast cancer receiving radiotherapy.

PubMed

Henderson, Virginia P; Massion, Ann O; Clemow, Lynn; Hurley, Thomas G; Druker, Susan; Hébert, James R

2013-09-01

To testthe relative effectiveness of a mindfulness-based stress reduction program (MBSR) compared with a nutrition education intervention (NEP) and usual care (UC) in women with newly diagnosed early-stage breast cancer (BrCA)undergoing radiotherapy. Datawere available from a randomized controlled trialof 172 women, 20 to 65 years old, with stage I or II BrCA. Data from women completing the 8-week MBSR program plus 3 additional sessions focuses on special needs associated with BrCA were compared to women receiving attention control NEP and UC. Follow-up was performed at 3 post-intervention points: 4 months, and 1 and 2 years. Standardized, validated self-administered questionnaires were used to assess psychosocial variables. Descriptive analyses compared women by randomization assignment. Regression analyses, incorporating both intention-to-treat and post hoc multivariable approaches, were used to control for potential confounding variables. A subset of 120 women underwent radiotherapy; 77 completed treatment prior to the study, and 40 had radiotherapy during the MBSR intervention. Women who actively received radiotherapy (art) while participating in the MBSR intervention (MBSR-art) experienced a significant (P < .05) improvement in 16 psychosocial variables compared with the NEP-art, UC-art, or both at 4 months. These included health-related, BrCA-specific quality of life and psychosocial coping, which were the primary outcomes, and secondary measures, including meaningfulness, helplessness, cognitive avoidance, depression, paranoid ideation, hostility, anxiety, global severity, anxious preoccupation, and emotional control. MBSR appears to facilitate psychosocial adjustment in BrCA patients receiving radiotherapy, suggesting applicability for MBSR as adjunctive therapy in oncological practice.

Predicting Optimal Dihydroartemisinin-Piperaquine Regimens to Prevent Malaria During Pregnancy for Human Immunodeficiency Virus-Infected Women Receiving Efavirenz.

PubMed

Wallender, Erika; Vucicevic, Katarina; Jagannathan, Prasanna; Huang, Liusheng; Natureeba, Paul; Kakuru, Abel; Muhindo, Mary; Nakalembe, Mirium; Havlir, Diane; Kamya, Moses; Aweeka, Francesca; Dorsey, Grant; Rosenthal, Philip J; Savic, Radojka M

2018-03-05

A monthly treatment course of dihydroartemisinin-piperaquine (DHA-PQ) effectively prevents malaria during pregnancy. However, a drug-drug interaction pharmacokinetic (PK) study found that pregnant human immunodeficiency virus (HIV)-infected women receiving efavirenz-based antiretroviral therapy (ART) had markedly reduced piperaquine (PQ) exposure. This suggests the need for alternative DHA-PQ chemoprevention regimens in this population. Eighty-three HIV-infected pregnant women who received monthly DHA-PQ and efavirenz contributed longitudinal PK and corrected QT interval (QTc) (n = 25) data. Population PK and PK-QTc models for PQ were developed to consider the benefits (protective PQ coverage) and risks (QTc prolongation) of alternative DHA-PQ chemoprevention regimens. Protective PQ coverage was defined as maintaining a concentration >10 ng/mL for >95% of the chemoprevention period. PQ clearance was 4540 L/day. With monthly DHA-PQ (2880 mg PQ), <1% of women achieved defined protective PQ coverage. Weekly (960 mg PQ) or low-dose daily (320 or 160 mg PQ) regimens achieved protective PQ coverage for 34% and >96% of women, respectively. All regimens were safe, with ≤2% of women predicted to have ≥30 msec QTc increase. For HIV-infected pregnant women receiving efavirenz, low daily DHA-PQ dosing was predicted to improve protection against parasitemia and reduce risk of toxicity compared to monthly dosing. NCT02282293. © The Author(s) 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Subjective cognitive complaints one year after ceasing adjuvant endocrine treatment for early-stage breast cancer.

PubMed

Ribi, K; Aldridge, J; Phillips, K-A; Thompson, A; Harvey, V; Thürlimann, B; Cardoso, F; Pagani, O; Coates, A S; Goldhirsch, A; Price, K N; Gelber, R D; Bernhard, J

2012-05-08

In the BIG 1-98 trial objective cognitive function improved in postmenopausal women 1 year after cessation of adjuvant endocrine therapy for breast cancer. This report evaluates changes in subjective cognitive function (SCF). One hundred postmenopausal women, randomised to receive 5 years of adjuvant tamoxifen, letrozole, or a sequence of the two, completed self-reported measures on SCF, psychological distress, fatigue, and quality of life during the fifth year of trial treatment (year 5) and 1 year after treatment completion (year 6). Changes between years 5 and 6 were evaluated using the Wilcoxon signed-rank test. Subjective cognitive function and its correlates were explored. Subjective cognitive function and the other patient-reported outcomes did not change significantly after cessation of endocrine therapy with the exception of improvement for hot flushes (P=0.0005). No difference in changes was found between women taking tamoxifen or letrozole. Subjective cognitive function was the only psychosocial outcome with a substantial correlation between year 5 and 6 (Spearman's R=0.80). Correlations between SCF and the other patient-reported outcomes were generally low. Improved objective cognitive function but not SCF occur following cessation of adjuvant endocrine therapy in the BIG 1-98 trial. The substantial correlation of SCF scores over time may represent a stable attribute.

The comparision of effect of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients.

PubMed

Ozcan Cenksoy, Pinar; Ficicioglu, Cem; Kizilkale, Ozge; Suhha Bostanci, Mehmet; Bakacak, Murat; Yesiladali, Mert; Kaspar, Cigdem

2014-07-01

To compare the effects of microdose GnRH-a flare-up, GnRH antagonist/aromatase inhibitor letrozole and GnRH antagonist/clomiphene citrate protocols on IVF outcomes in poor responder patients. Of 225 patients, 83 patients were in microdose flare-up group (Group 1), 70 patients were in GnRH antagonist/letrozole group (Group 2) and 72 patients were in GnRH antagonist/clomiphene citrate group (Group 3). Demographic and endocrine characteristics, the total number of oocytes retrieved, cancellation rate and clinical pregnancy rate were collected Results: Total dosage of gonadotropins (p=0.002) and serum E2 levels on the day of hCG administration (p=0.010) were significantly higher and duration of stimulations (p=0.03) was significantly longer in group 1. The number of oocytes retrieved was significantly greater in group 1 and 2 when compare to those of group 3 (p=0,000). There was a trend towards increasing cycle cancellation rates with GnRH antagonist/clomiphene citrate and GnRH antagonist/letrozole. Our finding suggest that the results of microdose flare-up protocol are better than other two used treatment protocols, in terms of maximum estradiol levels, number of mature oocytes retrieved, and cancellation rate and it still seems to be superior the ovarian stimulation regime for the poor responder patients.

Women receiving news of a family BRCA1/2 mutation: messages of fear and empowerment.

PubMed

Crotser, Cheryl B; Dickerson, Suzanne S

2010-12-01

Communication of genetic test results to healthy at-risk family members is complicated considering family dynamics and the complexity of cancer genetics. The purpose of this study was to understand the experience of family communication of BRCA1/2 results from the perspective of young and middle-aged women receiving the news. THEORETICAL RATIONALE: Individuals are self-interpretive beings influenced by family culture, history, and communication patterns. Humans express meaning through language and stories. Heideggerian hermeneutics guided in-depth interviews and team interpretation of data. Using purposive and network sampling, 19 women 18 to 50 years of age who received news of a family BRCA1/2 mutation from a biologic relative were recruited from support groups and two health facilities in upstate New York. Five themes emerged: (a) situating the story, (b) receiving the message from family, (c) responding to receipt of the message, (d) impacting family communication, and (e) advice for communicating risk. Two constitutive patterns were identified: (a) communicating risk as a message of fear and empowerment and (b) integrating the message by taking one step at a time. Healthcare professionals (HCPs) have an important role in provision of anticipatory guidance for communication of genetic test results, including the potential behavioral and emotional responses to family risk communication. Future research is indicated to understand the role of HCPs in family risk communication. Presentation of comprehensive and balanced information and the use of patient-centered communication is essential. HCPs need to view women as whole rather than as a person at risk. Continued support is needed for women who subsequently test positive or negative for the family BRCA1/2 mutation from HCPs and others, often outside the family network. © 2010 Sigma Theta Tau International.

Experiencing maternity care: the care received and perceptions of women from different ethnic groups.

PubMed

Henderson, Jane; Gao, Haiyan; Redshaw, Maggie

2013-10-22

According to the Office for National Statistics, approximately a quarter of women giving birth in England and Wales are from minority ethnic groups. Previous work has indicated that these women have poorer pregnancy outcomes than White women and poorer experience of maternity care, sometimes encountering stereotyping and racism. The aims of this study were to examine service use and perceptions of care in ethnic minority women from different groups compared to White women. Secondary analysis of data from a survey of women in 2010 was undertaken. The questionnaire asked about women's experience of care during pregnancy, labour and birth, and the postnatal period, as well as demographic factors. Ethnicity was grouped into eight categories: White, Mixed, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African, and Other ethnicity. A total of 24,319 women completed the survey. Compared to White women, women from minority ethnic groups were more likely to be younger, multiparous and without a partner. They tended to access antenatal care later in pregnancy, have fewer antenatal checks, fewer ultrasound scans and less screening. They were less likely to receive pain relief in labour and, Black African women in particular, were more likely to deliver by emergency caesarean section. Postnatally, women from minority ethnic groups had longer lengths of hospital stay and were more likely to breastfeed but they had fewer home visits from midwives. Throughout their maternity care, women from minority ethnic groups were less likely to feel spoken to so they could understand, to be treated with kindness, to be sufficiently involved in decisions and to have confidence and trust in the staff. Women in all minority ethnic groups had a poorer experience of maternity services than White women. That this was still the case following publication of a number of national policy documents and local initiatives is a cause for concern.

Neutropenia: occurrence and management in women with breast cancer receiving chemotherapy

PubMed Central

do Nascimento, Talita Garcia; de Andrade, Marceila; de Oliveira, Rosemeire Aparecida; de Almeida, Ana Maria; Gozzo, Thais de Oliveira

2014-01-01

Objectives to identify the prevalence, and describe the management of, neutropenia throughout the chemotherapy treatment among women with breast cancer. Methods observational study, cycles of chemotherapy. 116 neutropenic events were recorded, and 63.3% of the patients presented neutropenia at some point of their treatment, 46.5% of these presenting grade II. The management used was temporary suspension between the cycles and the mean number of delays was 6 days. The study was prospective and longitudinal, where the evaluation of the hematological toxicities was undertaken at each cycle of chemotherapy, whether neoadjuvant or adjuvant. Results 79 women were included, who received 572 cycles. However, the reasons for the suspensions were the lack of a space in the chemotherapy center, followed by neutropenia. Conclusion neutropenia is one of the most common and serious adverse events observed during the chemotherapy. Nursing must invest in research regarding this adverse event and in management strategies for organizing the public health system, so as to offer quality care. PMID:26107839

Social support received by women with intellectual and developmental disabilities during pregnancy and childbirth: An exploratory qualitative study.

PubMed

Potvin, Lynne A; Brown, Hilary K; Cobigo, Virginie

2016-06-01

this study aims to contribute to the development of a conceptual framework that will inform maternity care improvements for expectant mothers with intellectual and developmental disabilities (IDD) by exploring the structure, functions, and perceived quality of social support received by women with IDD during pregnancy and childbirth. using a grounded theory approach, we conducted an exploratory study set in Ontario, Canada in 2015. the sample included four adult women with IDD who had given birth in the last five years. data were collected using semi-structured interviews. the structure of social support received by women with IDD consisted of both formal and informal sources, but few or no friendships. Women with IDD reported high levels of informational and instrumental support and low levels of emotional support and social companionship. However, a high level of available support was not always perceived as beneficial. Emergent core categories suggest that social support is perceived as most effective when three conditions are met: (1) support is accessible, (2) support is provided by individuals expressing positive attitudes towards the pregnancy, and (3) autonomy is valued. our study confirms and identifies important gaps in the social support received by expectant mothers with IDD. Women with IDD currently lack accessible informational support, emotional support, and social companionship during pregnancy and childbirth. Additional findings regarding the structure and functions of social support are presented, and a preliminary conceptual framework of effective social support during pregnancy and childbirth, as perceived by women with IDD is also proposed. Findings suggest that increasing support accessibility should be a social and clinical priority; however, maternity care providers should be aware of stigmatizing attitudes and respect the autonomy of pregnant women with IDD as they prepare for motherhood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of ovarian stimulation response in patients with breast cancer undergoing ovarian stimulation with letrozole and gonadotropins to patients undergoing ovarian stimulation with gonadotropins alone for elective cryopreservation of oocytes†.

PubMed

Pereira, Nigel; Hancock, Kolbe; Cordeiro, Christina N; Lekovich, Jovana P; Schattman, Glenn L; Rosenwaks, Zev

2016-10-01

The primary objective of this study is to compare the oocyte yield in breast cancer patients undergoing controlled ovarian stimulation (COS) using letrozole and gonadotropins with patients undergoing COS with standard gonadotropins for elective cryopreservation of oocytes. Odds ratios (OR) for the number of mature oocytes were estimated. Pregnancy outcomes for breast cancer patients undergoing frozen-thawed 2-PN embryo transfers (FETs) after oncologic treatment were also noted. 220 and 451 cycles were identified in the breast cancer and the elective cryopreservation groups, respectively. Patients in the former group had lower peak estradiol levels [464.5 (315.5-673.8) pg/mL] compared to the latter [1696 (1058-2393) pg/mL; p < 0.01]. More oocytes were retrieved in the breast cancer group (12.3 ± 3.99) compared to the elective cryopreservation group (10.9 ± 3.86; p < 0.01). The odds for mature oocytes with letrozole and gonadotropins was 2.71 (95% CI 1.29-5.72; p = 0.01). Fifty-six FETs occurred in the breast cancer group. The clinical pregnancy and live birth rates per FET cycle were 39.7%, and 32.3%, respectively. Our findings suggest that COS with letrozole and gonadotropins yield more mature oocytes at lower estradiol levels compared to COS with gonadotropins alone. Breast cancer patients undergoing FET after oncologic treatment have live birth rates comparable to age-matched counterparts.

Experiencing maternity care: the care received and perceptions of women from different ethnic groups

PubMed Central

2013-01-01

Background According to the Office for National Statistics, approximately a quarter of women giving birth in England and Wales are from minority ethnic groups. Previous work has indicated that these women have poorer pregnancy outcomes than White women and poorer experience of maternity care, sometimes encountering stereotyping and racism. The aims of this study were to examine service use and perceptions of care in ethnic minority women from different groups compared to White women. Methods Secondary analysis of data from a survey of women in 2010 was undertaken. The questionnaire asked about women’s experience of care during pregnancy, labour and birth, and the postnatal period, as well as demographic factors. Ethnicity was grouped into eight categories: White, Mixed, Indian, Pakistani, Bangladeshi, Black Caribbean, Black African, and Other ethnicity. Results A total of 24,319 women completed the survey. Compared to White women, women from minority ethnic groups were more likely to be younger, multiparous and without a partner. They tended to access antenatal care later in pregnancy, have fewer antenatal checks, fewer ultrasound scans and less screening. They were less likely to receive pain relief in labour and, Black African women in particular, were more likely to deliver by emergency caesarean section. Postnatally, women from minority ethnic groups had longer lengths of hospital stay and were more likely to breastfeed but they had fewer home visits from midwives. Throughout their maternity care, women from minority ethnic groups were less likely to feel spoken to so they could understand, to be treated with kindness, to be sufficiently involved in decisions and to have confidence and trust in the staff. Conclusion Women in all minority ethnic groups had a poorer experience of maternity services than White women. That this was still the case following publication of a number of national policy documents and local initiatives is a cause for concern. PMID

Does seeking safety reduce PTSD symptoms in women receiving physical disability compensation?

PubMed

Anderson, Melissa L; Najavits, Lisa M

2014-08-01

This secondary analysis investigated the impact of 12 sessions of Seeking Safety (SS) on reducing posttraumatic stress disorder (PTSD) symptoms in a sample of dually diagnosed women with physical disabilities versus nondisabled (ND) women. SS is an evidence-based and widely implemented manualized therapy for PTSD and/or substance use disorder. It is a present-focused model that promotes coping skills and psychoeducation. As part of the National Institute on Drug Abuse Clinical Trials Network (NIDA CTN), 353 participants with current PTSD and substance use disorder (SUD) were randomly assigned to partial-dose SS or Women's Health Education (WHE) group therapy conducted in community-based substance abuse treatment programs. The women were categorized as participants with disabilities (PWD; n = 20) or ND (n = 333) based on the question, "Do you receive a pension for a physical disability?" PTSD was assessed on the Clinician-Administered PTSD Scale (CAPS) at baseline and follow-ups after treatment (1 week, 3 months, 6 months, and 12 months). PWD experienced sustained reductions in PTSD symptoms when treated with SS but not WHE. Indeed, PTSD symptoms of PWD in WHE returned to baseline levels of severity by 12-month follow-up. This pattern of results was not observed among ND women, who sustained improvements on PTSD in both treatment conditions. These results suggest strong potential for using SS to treat PTSD among women with physical disabilities, and speak to the genuine need to address trauma and PTSD more directly with PWD. Our results are also consistent with other findings from the NIDA CTN trial, in which virtually all significant results evidenced SS outperforming WHE.

Effect of clomiphene citrate on endometrial thickness, ovulation, pregnancy and live birth in anovulatory women: systematic review and meta-analysis.

PubMed

Gadalla, M A; Huang, S; Wang, R; Norman, R J; Abdullah, S A; El Saman, A M; Ismail, A M; van Wely, M; Mol, B W J

2018-01-01

To compare the impact of clomiphene citrate (CC) vs other drug regimens on mid-cycle endometrial thickness (EMT), ovulation, pregnancy and live birth rates in women with World Health Organization (WHO) group II ovulatory disorders. We searched MEDLINE, EMBASE, Scopus, Web of Science, The Cochrane Central Register of Clinical Trials (CENTRAL) and the non-MEDLINE subset of PubMed from inception to December 2016 and cross-checked references of relevant articles. We included only randomized controlled trials (RCTs) comparing CC used alone vs other drug regimens for ovulation induction in women with WHO group II anovulation. Outcomes were mid-cycle EMT, ovulation, pregnancy and live birth rates. We pooled weighted mean differences (WMD) with 95% confidence intervals (CI) for continuous variables (EMT) and risk ratios (RR) with 95% CI for binary variables (ovulation, pregnancy and live birth rates). We retrieved 1718 articles of which 33 RCTs (4349 women, 7210 ovulation induction cycles) were included. In 15 RCTs that compared CC with letrozole, EMT was lower in the CC group (1957 women, 3892 cycles; WMD, -1.39; 95% CI, -2.27 to -0.51; I 2  = 100%), ovulation rates after CC and letrozole were comparable (1710 women, 3217 cycles; RR, 0.97; 95% CI, 0.90-1.04; I 2  = 47%), while CC led to a lower pregnancy rate (1957 women, 3892 cycles; RR, 0.78; 95% CI, 0.63-0.95; I 2  = 43%) and a lower live birth rate (RR, 0.70; 95% CI, 0.49-0.98; I 2  = 35%). In two RCTs that compared CC with CC plus metformin, EMT, ovulation and pregnancy rates were comparable (101 women, 140 cycles; WMD, -0.23; 95% CI, -0.92 to 0.45; I 2  = 78%; RR, 0.84; 95% CI, 0.67-1.06; I 2  = 0%; and RR, 0.79; 95% CI, 0.33-1.87; I 2  = 0%). In three studies that compared CC with CC plus N-acetyl cysteine (NAC), EMT was lower in the CC group (340 women, 300 cycles; WMD, -1.51; 95% CI, -1.98 to -1.04; I 2  = 45%). In two studies that compared CC with CC + nitric oxide

High-fat diet exposure from pre-pubertal age induces polycystic ovary syndrome (PCOS) in rats.

PubMed

Patel, Roshni; Shah, Gaurang

2018-02-01

Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism, oligo-anovulation, polycystic ovaries and metabolic syndrome. Many researchers reported that PCOS often starts with menarche in adolescents. Presently available animal model focuses on ovarian but not metabolic features of PCOS. Therefore, we hypothesized that high-fat diet feeding to pre-pubertal female rats results in both reproductive and metabolic features of PCOS. Pre-pubertal female rats were divided into two groups: group I received normal pellet diet and group II received high-fat diet (HFD). In the letrozole study, adult female rats were divided into two groups: group I received 1% carboxy methyl cellulose and group II received 1 mg/kg letrozole orally. Oral glucose tolerance test, lipid profile, fasting glucose, insulin, estrus cycle, hormonal profile, ovary weight, luteinizing hormone (LH) receptor and follicle-stimulating hormone receptor expression were measured. Polycystic ovarian morphology was assessed through histopathological changes of ovary. Feeding of HFD gradually increase glucose intolerance and fasting insulin levels. Triglyceride level was higher in HFD study while total cholesterol level was higher in the letrozole study. Alteration in testosterone and estrogen levels was observed in both studies. LH receptor expression was upregulated only in HFD study. Histopathological changes like increase cystic follicle, diminished granulosa cell layer and thickened theca cell layer were observed in letrozole as well as HFD study. High-fat diet initiated at pre-puberty age in rats produces both metabolic disturbances and ovarian changes similar to that observed clinically in PCOS patients. Letrozole on the other hand induces change in ovarian structure and function. © 2018 Society for Reproduction and Fertility.

Direct and Indirect Messages African American Women Receive from Their Familial Networks about Intimate Relationships and Sex: The Intersecting Influence of Race, Gender, and Class

ERIC Educational Resources Information Center

Grange, Christina M.; Brubaker, Sarah Jane; Corneille, Maya A.

2011-01-01

This qualitative study examined the sexual socialization experienced by emerging adult, African American women, ages 18 to 26 years, who received services at a sexually transmitted infection clinic. Data obtained from in-depth interviews revealed that women received information about sex and relationships from three primary sources: women of the…

Placental malaria among HIV-infected and uninfected women receiving anti-folates in a high transmission area of Uganda

PubMed Central

2009-01-01

Background HIV infection increases the risk of placental malaria, which is associated with poor maternal and infant outcomes. Recommendations in Uganda are for HIV-infected pregnant women to receive daily trimethoprim-sulphamethoxazole (TS) and HIV-uninfected women to receive intermittent sulphadoxine-pyrimethamine (SP). TS decreases the risk of malaria in HIV-infected adults and children but has not been evaluated among pregnant women. Methods This was a cross sectional study comparing the prevalence of placental malaria between HIV-infected women prescribed TS and HIV-uninfected women prescribed intermittent preventive therapy with sulphadoxine-pyrimethamine (IPT-SP) in a high malaria transmission area in Uganda. Placental blood was evaluated for malaria using smear and PCR. Results Placentas were obtained from 150 HIV-infected women on TS and 336 HIV-uninfected women on IPT-SP. The proportion of HIV-infected and HIV-uninfected women with placental malaria was 19% vs. 26% for those positive by PCR and 6% vs. 9% for those positive by smear, respectively. Among all infants, smear+ placental malaria was most predictive of low birth weight (LBW). Primigravidae were at higher risk than multigravidae of having placental malaria among HIV-uninfected, but not HIV-infected, women. Adjusting for gravidity, age, and season at the time of delivery, HIV-infected women on TS were not at increased risk for placental malaria compared to HIV-uninfected women on IPT-SP, regardless of the definition used. Conclusion Prevalence of placental malaria was similar in HIV-infected women on TS and HIV-uninfected women on IPT-SP. Nonetheless, while nearly all of the women in this study were prescribed anti-folates, the overall risk of placental malaria and LBW was unacceptably high. The population attributable risk of placental malaria on LBW was substantial, suggesting that future interventions that further diminish the risk of placental malaria may have a considerable impact on the

Nutrition advice during pregnancy: do women receive it and can health professionals provide it?

PubMed

Lucas, Catherine; Charlton, Karen E; Yeatman, Heather

2014-12-01

A healthy diet during pregnancy is essential for normal growth and development of the foetus. Pregnant women may obtain nutrition information from a number of sources but evidence regarding the adequacy and extent of this information is sparse. A systematic literature review was conducted to identify sources of nutrition information accessed by pregnant women, their perceived needs for nutrition education, the perceptions of healthcare providers about nutrition education in pregnancy, and to assess the effectiveness of public health programs that aim to improve nutritional practices. The Scopus data base was searched during January, 2013 and in February 2014 to access both qualitative and quantitative studies published between 2002 and 2014 which focused on healthy pregnant women and their healthcare providers in developed countries. Articles were excluded if they focused on the needs of women with medical conditions, including obesity, gestational diabetes or malnutrition. Of 506 articles identified by the search terms, 25 articles were deemed to be eligible for inclusion. Generally, women were not receiving adequate nutrition education during pregnancy. Although healthcare practitioners perceived nutrition education to be important, barriers to providing education to clients included lack of time, lack of resources and lack of relevant training. Further well designed studies are needed to identify the most effective nutrition education strategies to improve nutrition knowledge and dietary behaviours for women during antenatal care.

Stimulation of the ovaries in women with breast cancer undergoing fertility preservation: Alternative versus standard stimulation protocols; the study protocol of the STIM-trial.

PubMed

Dahhan, T; Balkenende, E M E; Beerendonk, C C M; Fleischer, K; Stoop, D; Bos, A M E; Lambalk, C B; Schats, R; van Golde, R J T; Schipper, I; Louwé, L A; Cantineau, A E P; Smeenk, J M J; de Bruin, J P; Reddy, N; Kopeika, Y; van der Veen, F; van Wely, M; Linn, S C; Goddijn, M

2017-10-01

Chemotherapy for breast cancer may have a negative impact on reproductive function due to gonadotoxicity. Fertility preservation via banking of oocytes or embryos after ovarian stimulation with FSH can increase the likelihood of a future live birth. It has been hypothesized that elevated serum estrogen levels during ovarian stimulation may induce breast tumour growth. This has led to the use of alternative stimulation protocols with addition of tamoxifen or letrozole. The effectiveness of these stimulation protocols in terms of oocyte yield is unknown. Randomized open-label trial comparing ovarian stimulation plus tamoxifen and ovarian stimulation plus letrozole with standard ovarian stimulation in the course of fertility preservation. The study population consists of women with breast cancer who opt for banking of oocytes or embryos, aged 18-43years at randomisation. Primary outcome is the number of oocytes retrieved at follicle aspiration. Secondary outcomes are number of mature oocytes retrieved, number of oocytes or embryos banked and peak E2 levels during ovarian stimulation. Concerning the lack of evidence on which stimulation protocol should be used in women with breast cancer and the growing demand for fertility preservation, there is an urgent need to undertake this study. By performing this study, we will be able to closely monitor the effects of various stimulation protocols in women with breast cancer and pave the way for long term follow up on the safety of this procedure in terms of breast cancer prognosis. NTR4108. Copyright © 2017 Elsevier Inc. All rights reserved.

Centering prayer for women receiving chemotherapy for recurrent ovarian cancer: a pilot study.

PubMed

Johnson, Mary E; Dose, Ann M; Pipe, Teri Britt; Petersen, Wesley O; Huschka, Mashele; Gallenberg, Mary M; Peethambaram, Prema; Sloan, Jeff; Frost, Marlene H

2009-07-01

To explore the feasibility of implementing centering prayer in chemotherapy treatment and assess its influence on mood, spiritual well-being, and quality of life in women with recurrent ovarian cancer. Descriptive pilot study. Outpatient chemotherapy treatment suite in a large cancer center in the midwestern United States. A convenience sample of 10 women receiving outpatient chemotherapy for recurrent ovarian cancer. A centering prayer teacher led participants through three one-hour sessions over nine weeks. Data were collected prior to the first session, at the conclusion of the final session, and at three and six months after the final session. Feasibility and influence of centering prayer on mood, spiritual well-being, and quality of life. Most participants identified centering prayer as beneficial. Emotional well-being, anxiety, depression, and faith scores showed improvement. Centering prayer can potentially benefit women with recurrent ovarian cancer. Additional research is needed to assess its feasibility and effectiveness. Nurses may promote or suggest centering prayer as a feasible intervention for the psychological and spiritual adjustment of patients with recurrent ovarian cancer.

Expression profiles of mRNA and long noncoding RNA in the ovaries of letrozole-induced polycystic ovary syndrome rat model through deep sequencing.

PubMed

Fu, Lu-Lu; Xu, Ying; Li, Dan-Dan; Dai, Xiao-Wei; Xu, Xin; Zhang, Jing-Shun; Ming, Hao; Zhang, Xue-Ying; Zhang, Guo-Qing; Ma, Ya-Lan; Zheng, Lian-Wen

2018-05-30

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders in reproductive-aged women. However, the exact pathophysiology of PCOS remains largely unclear. We performed deep sequencing to investigate the mRNA and long noncoding RNA (lncRNA) expression profiles in the ovarian tissues of letrozole-induced PCOS rat model and control rats. A total of 2147 mRNAs and 158 lncRNAs were differentially expressed between the PCOS models and control. Gene ontology analysis indicated that differentially expressed mRNAs were associated with biological adhesion, reproduction, and metabolic process. Pathway analysis results indicated that these aberrantly expressed mRNAs were related to several specific signaling pathways, including insulin resistance, steroid hormone biosynthesis, PPAR signaling pathway, cell adhesion molecules, autoimmune thyroid disease, and AMPK signaling pathway. The relative expression levels of mRNAs and lncRNAs were validated through qRT-PCR. LncRNA-miRNA-mRNA network was constructed to explore ceRNAs involved in the PCOS model and were also verified by qRTPCR experiment. These findings may provide insight into the pathogenesis of PCOS and clues to find key diagnostic and therapeutic roles of lncRNA in PCOS. Copyright © 2018 Elsevier B.V. All rights reserved.

Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole.

PubMed

Gyanchandani, Rekha; Kota, Karthik J; Jonnalagadda, Amruth R; Minteer, Tanya; Knapick, Beth A; Oesterreich, Steffi; Brufsky, Adam M; Lee, Adrian V; Puhalla, Shannon L

2017-09-15

ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC. However, the incidence and impact of ESR1 mutations on clinical outcome in patients treated with CDK4/6 inhibitors have not been defined. In this study, we evaluated the frequency of ESR1 mutations in cfDNA from 16 patients with MBC undergoing palbociclib and letrozole therapy. Four common ESR1 mutations (D538G, Y537C, Y537N, and Y537S) were analyzed in serial blood draws using ddPCR. Mutation rate was 31.3% (5/16) (n=3; de novo , n=2; acquired). D538G was the most frequent mutation (n=3), followed by Y537N and Y537S (n=2). One patient showed multiple ESR1 mutations. Mutations were enriched during therapy. Progression-free survival (PFS) and overall survival (OS) were similar in patients with and without mutation detected at any given time during treatment. However, PFS was significantly shorter in patients with ESR1 mutation at initial blood draw (3.3 versus 9.0 months, P-value=0.038). In conclusion, ESR1 mutation prevalence is consistent with recent studies in hormone-refractory breast cancer. Further, treatment with palbociclib and letrozole does not prevent selection of ESR1 mutations in later lines of therapy. Larger studies are warranted to validate these findings.

Detection of ESR1 mutations in circulating cell-free DNA from patients with metastatic breast cancer treated with palbociclib and letrozole

PubMed Central

Gyanchandani, Rekha; Kota, Karthik J.; Jonnalagadda, Amruth R.; Minteer, Tanya; Knapick, Beth A.; Oesterreich, Steffi; Brufsky, Adam M.; Lee, Adrian V.; Puhalla, Shannon L.

2017-01-01

ESR1 mutations are frequently acquired in hormone-resistant metastatic breast cancer (MBC). CDK4/6 inhibition along with endocrine therapy is a promising strategy in hormone receptor-positive MBC. However, the incidence and impact of ESR1 mutations on clinical outcome in patients treated with CDK4/6 inhibitors have not been defined. In this study, we evaluated the frequency of ESR1 mutations in cfDNA from 16 patients with MBC undergoing palbociclib and letrozole therapy. Four common ESR1 mutations (D538G, Y537C, Y537N, and Y537S) were analyzed in serial blood draws using ddPCR. Mutation rate was 31.3% (5/16) (n=3; de novo, n=2; acquired). D538G was the most frequent mutation (n=3), followed by Y537N and Y537S (n=2). One patient showed multiple ESR1 mutations. Mutations were enriched during therapy. Progression-free survival (PFS) and overall survival (OS) were similar in patients with and without mutation detected at any given time during treatment. However, PFS was significantly shorter in patients with ESR1 mutation at initial blood draw (3.3 versus 9.0 months, P-value=0.038). In conclusion, ESR1 mutation prevalence is consistent with recent studies in hormone-refractory breast cancer. Further, treatment with palbociclib and letrozole does not prevent selection of ESR1 mutations in later lines of therapy. Larger studies are warranted to validate these findings. PMID:28978004

Higher placental anti-inflammatory IL-10 cytokine expression in HIV-1 infected women receiving longer zidovudine prophylaxis associated with nevirapine.

PubMed

Pornprasert, Sakorn; Mary, Jean-Yves; Faye, Albert; Leechanachai, Pranee; Limtrakul, Aram; Rugpao, Sungwal; Sirivatanapa, Pannee; Gomuthbutra, Vorapin; Matanasaravoot, Wanmanee; Le Coeur, Sophie; Lallemant, Marc; Barré-Sinoussi, Françoise; Menu, Elisabeth; Ngo-Giang-Huong, Nicole

2009-03-01

Placental cytokine balance may be critical for the control of mother-to-child transmission (MTCT) of HIV. We assessed whether the type and duration of antiretrovirals used for prevention of HIV-1-MTCT modified the inflammatory cytokine profile. We investigated the levels of cytokine expression in the placentas of 61 HIV-1-infected women who received zidovudine (ZDV) plus single dose nevirapine (SD-NVP) or ZDV only for prevention of MTCT. Placentas of 38 HIV-1-uninfected women were included as controls. All placentas were obtained after vaginal delivery. Levels of mRNA and cytokine expression were quantified using real-time PCR and ELISA, respectively, in placental explants and 24-hour culture supernatants and analyzed in relation to the women's characteristics and the type and duration of antiretroviral prophylaxis. HIV-1-infected and uninfected women did not show any differences in the expression of placental cytokine secretion except for a trend toward lower TNF-alpha mRNA levels in HIV-1-infected women. Within the HIV-1-infected group, women who were exposed to a long duration of ZDV (>72 days) or received SD-NVP less than 5h prior to delivery, more frequently expressed detectable levels of IL-10 in their placentas (32% versus 7% (p = 0.01) and 32% versus 5% (p = 0.02), respectively). No infant was found to be HIV-1-infected. Our results showed a normalization of the placental cytokine balance in HIV-1-infected women receiving antiretroviral prophylaxis. Furthermore, the type and duration of antiretroviral prophylaxis have an impact on the placental anti-inflammatory IL-10 expression level, which may contribute to controlling HIV replication at the placental level, thus reducing MTCT of HIV-1.

Comparing the rubella seronegativity in pregnant women who received one dose of rubella vaccine at different ages in Taiwan.

PubMed

Shih, Ching-Tang; Chang, Yuan-Chun; Wang, Huey-Lan; Lin, Ching-Chiang

2016-09-14

Vaccination is the best strategy to prevent rubella and congenital rubella. The aim of our study was to assess the immunity to rubella and determine rubella virus antibody titers in pregnant women who were offered a single dose of rubella vaccine at different ages of their lives. A total 15,067 rubella IgG antibody test results for Taiwanese pregnant women who received routine prenatal checkup at Fooyin University Hospital from 1999 to 2014 were analyzed in this study. The women were divided into five birth cohorts in order to compare their rubella seronegativities and antibody titers according to the different period of rubella vaccination policy in Taiwan. The total rubella seronegativity rate was 11.2% (95% CI: 10.7-11.7%) and the mean rubella antibody titers was 51.0IU/mL (SD=54.7IU/mL). The junior school cohort has the lowest rubella seronegativity of 7.6% (95% CI: 6.9-8.2%). The seronegativities were significantly high in the preschool cohort and in the 15-month-old cohort, 14.9% (95% CI: 13.2-16.6%) and 14.8% (95% CI: 11.5-18.1%), respectively. The OR values were 2.1 (95% CI: 1.8-2.5, p<0.001) in the preschool cohort and 2.2 (95% CI: 1.6-2.8, p<0.001) in the 15-month-old cohort, respectively, against the junior school cohort. Women in the 15-month-old cohort have lowest average rubella IgG titer, 25.4IU/mL. The total rubella seronegativity rate was 11.2% in all native pregnant women. Women who received one dose rubella vaccine at preschool and 15-month-old have highest seronegativities. The 15-month-old cohort has the lowest average rubella IgG titer. We recommend a revised catch-up immunization policy to women who received one dose rubella vaccine at a younger age. Copyright © 2016 Elsevier Ltd. All rights reserved.

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study

PubMed Central

Gaß, Paul; Fasching, Peter A.; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W.; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M.; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y.; Beckmann, Matthias W.; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R.

2016-01-01

Background Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Methods Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. Results In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. Conclusion There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues. PMID:27920623

Factors Influencing Decision-Making for or against Adjuvant and Neoadjuvant Chemotherapy in Postmenopausal Hormone Receptor-Positive Breast Cancer Patients in the EvAluate-TM Study.

PubMed

Gaß, Paul; Fasching, Peter A; Fehm, Tanja; de Waal, Johann; Rezai, Mahdi; Baier, Bernd; Baake, Gerold; Kolberg, Hans-Christian; Guggenberger, Martin; Warm, Mathias; Harbeck, Nadia; Wuerstlein, Rachel; Deuker, Jörg-Uwe; Dall, Peter; Richter, Barbara; Wachsmann, Grischa; Brucker, Cosima; Siebers, Jan W; Fersis, Nikos; Kuhn, Thomas; Wolf, Christopher; Vollert, Hans-Walter; Breitbach, Georg-Peter; Janni, Wolfgang; Landthaler, Robert; Kohls, Andreas; Rezek, Daniela; Noesselt, Thomas; Fischer, Gunnar; Henschen, Stephan; Praetz, Thomas; Heyl, Volker; Kühn, Thorsten; Krauss, Thomas; Thomssen, Christoph; Hohn, Andre; Tesch, Hans; Mundhenke, Christoph; Hein, Alexander; Rauh, Claudia; Bayer, Christian M; Jacob, Adib; Schmidt, Katja; Belleville, Erik; Hadji, Peyman; Brucker, Sara Y; Beckmann, Matthias W; Wallwiener, Diethelm; Kümmel, Sherko; Löhberg, Christian R

2016-10-01

Decision-making for or against neoadjuvant or adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive breast cancer does not follow any clear guidelines, and some patients may unnecessarily undergo chemotherapy and be exposed to the associated toxicity. The aim of this study was to identify the patient population for whom this issue may bear relevance. Patients being treated with letrozole in the prospective multicenter noninterventional EvAluate-TM study were recruited. The percentage of patients receiving chemotherapy and factors associated with chemotherapy administration were identified. In all, 3,924 (37.4%) patients received chemotherapy before treatment with letrozole. Of these, 293 (20%) underwent neoadjuvant therapy. Younger age was predictive for both adjuvant and neoadjuvant therapy. Overall, decisions in favor of administering chemotherapy are more likely to be made in patients with a higher body mass index (BMI), and neoadjuvant chemotherapy is administered at a higher rate in women with a lower BMI. Concomitant medication influenced the overall decision-making regarding chemotherapy, irrespective of whether it was given on a neoadjuvant or adjuvant basis. There is an ongoing debate as to whether all of the many patients who receive chemotherapy actually benefit from it. Neoadjuvant chemotherapy is frequently administered in this patient population, and this should encourage further research to resolve current clinical and research issues.

The Effect of Mindfulness-Based Music Therapy on Attention and Mood in Women Receiving Adjuvant Chemotherapy for Breast Cancer: A Pilot Study.

PubMed

Lesiuk, Teresa

2015-05-01

To explore the efficacy of mindfulness-
based music therapy (MBMT) to improve attention and decrease mood distress experienced by women with breast cancer receiving adjuvant chemotherapy. Quantitative, descriptive, longitudinal approach. A comprehensive cancer hospital and a university in southern Florida. 15 women with a diagnosis of breast cancer, stages I-III, receiving adjuvant chemotherapy. Participants individually received MBMT for one hour per week for four weeks. The sessions consisted of varied music activities accompanied by mindfulness attitudes, or mental strategies that enhance moment-to-moment awareness, and weekly homework. Demographic information was collected at baseline. Attention was measured using Conners' Continuous Performance Test II. Mood was measured using the Profile of Mood States-Brief Form. Narrative comments collected from the homework assignments served to reinforce quantitative data. Repeated measures analysis of variance showed that attention improved significantly over time. Although all mood states significantly improved from the beginning to the end of each MBMT session, the mood state of fatigue decreased significantly more than the other mood states. MBMT enhances attention and mood, particularly the mood state of fatigue, in women with breast cancer receiving adjuvant chemotherapy. 
. A preferred music listening and mindfulness exercise may be offered to women with breast cancer who experience attention problems and mood distress.

The Breast International Group 1-98 trial: big results for women with hormone-sensitive early breast cancer.

PubMed

Monnier, Alain M

2007-05-01

As there is a risk for relapse in early breast cancer, especially at 1-3 years post surgery, the need for adjuvant therapy is clear. In terms of disease-free survival, aromatase inhibitors have emerged as superior to tamoxifen for the adjuvant treatment of hormone-sensitive breast cancer in several Phase III clinical trials. Of these trials, the Breast International Group (BIG) 1-98 trial stands out as unique in design, as it is the only trial to address whether an aromatase inhibitor is more effective as initial adjuvant therapy or as sequential therapy with an aromatase inhibitor and tamoxifen in either order and in rigor of end points and safety evaluations. When compared with tamoxifen, letrozole has been shown to significantly reduce recurrence risk in the overall population by 19% and also significantly reduced recurrence risk in the patient subgroups at increased risk: node-positive and previously chemotherapy-treated patients. Letrozole is the only aromatase inhibitor to demonstrate a significant 27% reduction in the risk of distant metastases (p = 0.001) in the clinically relevant, hormone receptor-positive population in the initial adjuvant setting. Recent results also suggest that letrozole in particular reduces the risk of distant metastases early on after initial surgery for breast cancer. This is important, as early distant metastatic events compose the majority of early recurrences and are a well-recognized predictor of breast cancer death. Letrozole has been found to be well tolerated in the initial adjuvant treatment setting, and these data have been confirmed by long-term safety data from the monotherapy analysis in the BIG 1-98 study. Thus far, the results from the BIG 1-98 trial provide clear support for the use of letrozole in the initial adjuvant treatment of breast cancer. Future studies will provide the definitive answer to questions of which initial adjuvant therapy is superior (i.e., anastrozole or letrozole) and information as to the

Chemotherapy-induced nausea and vomiting in Asian women with breast cancer receiving anthracycline-based adjuvant chemotherapy.

PubMed

Bourdeanu, Laura; Frankel, Paul; Yu, Wai; Hendrix, Gregory; Pal, Sumanta; Badr, Lina; Somlo, George; Luu, Thehang

2012-01-01

Chemotherapy-induced nausea and vomiting (CINV) remain among the most frequently reported distressing side effects associated with anthracycline-based chemotherapy despite significant advances in antiemetic management. The main risk factor for severity of CINV is the emetogenic potential of the chemotherapeutic agents. However, patient-related risk factors have been identified, including genetic makeup. Although studies have noted that ethnicity influences nausea and vomiting in other contexts, there is a paucity of research regarding the impact of ethnicity on CINV. This study was undertaken to evaluate whether Asian women receiving anthracycline-based chemotherapy experience more CINV than non-Asians. A retrospective, comparative, correlational chart review was performed to abstract the relevant variables. Data from a convenience sample of 358 women with breast cancer who received chemotherapy with doxorubicin between 2004 and 2008 at City of Hope in Duarte, California, were evaluated. The sample consisted of Caucasians (45%), Hispanics (27.7%), Asians (19.8%), and African Americans (7.5%). The results indicate that Asian women with breast cancer undergoing anthracycline-based chemotherapy experienced statistically significantly more clinically important CINV than their non-Asian counterparts. The data were collected retrospectively, with a certain population distribution at a specific time. This study provides interesting preliminary evidence that Asian ethnicity plays a role in the development of severe CINV. When managing chemotherapy toxicities in women with breast cancer, health-care providers should tailor therapy to individual risk profiles. Specifically, consideration of antiemetic therapy should accommodate patient characteristics, such as Asian descent. Copyright © 2012 Elsevier Inc. All rights reserved.

Women who receive continuous support during labour have reduced risk of caesarean, instrumental delivery or need for analgesia compared to usual care.

PubMed

McDonald, Susan

2013-04-01

Models of care supporting continuous support during labour were shown to be more likely to result in a spontaneous vaginal birth. Women receiving continuous support required less analgesia and were less likely to report negative feelings about the birth experience. Women receiving continuous support experienced shorter labours and their babies were less likely to have low 5-min Agpar scores. Therefore, such models of care should be considered for more extensive implementation in clinical practice settings.

OBSTETRIC-GYNECOLOGICAL STUDY ON WOMEN RECEIVING IRRADIATION IN SMALL DOSES ON THE LOWER ABDOMEN

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kurata, A.

1961-06-01

The effects of diagnostic x-ray exposure on reproductive function and on the offspring were investigated in 105 women in comparison with 131 control women who had not received abdominal radiation. The estimated radiation dose applied to the ovaries in hysterosalpingography was 200 to 550 mr (average 400 mr) and in fetal roentgenography about 560 mr. The irradiated women reported a shorter duration and less amount of menstruation after as compared with before irradiation but menstruation parameters were similar in the irradiated and control groups. The average age at menopause was the same in the 2 groups. Pregnancy rate increased markedlymore » after salpingography; it rose to 46% in women who had been infertile before this procedure. The frequency of spontaneous abortion was higher before irradiation (13.2%) than after (8.2%), whereas the frequency of stillbirths was the same in both instances. Although the sample was too small for definite conclusions, irradiation appeared to have no influence on the offspring with respect to sex ratio, weight at birth, and incidence of postnatal death. No malformed infants were born to the irradiated mothers. It was concluded that diagnostic x radiation at the doses employed have no significant effect on gonadal function or on the first generation offspring. (H.H.D.)« less

The effect of inflatable obstetric belts in nulliparous pregnant women receiving patient-controlled epidural analgesia during the second stage of labor.

PubMed

Kim, Jong-Woon; Kim, Yoon Ha; Cho, Hye Yon; Shin, Hee-Young; Shin, Jong Chul; Choi, Sea Kyung; Lee, Keun-Young; Song, Ji-Eun; Lee, Pil-Ryang

2013-11-01

The aim of this study was to evaluate the effect of inflatable obstetric belts on uterine fundal pressure in the management of the second stage of labor. Between July 2009 and December 2010, 188 nulliparous women with a singleton pregnancy at term were enrolled and only one dropped. The participants were randomized to receive either standard care (control group, n = 91) or uterine fundal pressure by the Labor Assister (Baidy M-520/Curexo, Inc., Seoul, Korea; active group, n = 97) during the second stage of labor in addition to standard care. The Labor Assister is an inflatable obstetric belt that is synchronized to apply constant fundal pressure during a uterine contraction. The primary endpoint was duration of the second stage of labor in women who delivered vaginally (control, n = 80 versus active, n = 93). It was not analyzed in women who delivered by cesarean section (n = 14) and delivered precipitously (n = 1). The secondary outcomes are perinatal outcomes and perineal laceration. Participants received patient-controlled epidural analgesia. The 93 women in the active group spent less time in the second stage of labor when compared to the 80 women in the control group (46.51 ± 28.01 min versus 75.02 ± 37.48 min, p < 0.001). There was no significant difference in perinatal outcomes and perineal laceration between the two groups. The uterine fundal pressure exerted by the inflatable obstetric belt reduces the duration of the second stage of labor without complications in nulliparous women who receive patient-controlled epidural analgesia.

Intent to Receive an HPV Vaccine among University Men and Women and Implications for Vaccine Administration

ERIC Educational Resources Information Center

Jones, Melissa; Cook, Robert

2008-01-01

Objective and Participants: In 2006, the authors examined intention to receive an HPV vaccine among 340 college students. Methods: A total of 138 men and 202 women completed questionnaires. The authors measured intention by asking participants how likely they would be to accept an HPV vaccine that prevented against (1) all HPV, (2) cervical cancer…

Analysis of pregnancy and infant health outcomes among women in the National Smallpox Vaccine in Pregnancy Registry who received Anthrax Vaccine Adsorbed.

PubMed

Conlin, Ava Marie S; Bukowinski, Anna T; Gumbs, Gia R

2015-08-26

The National Smallpox Vaccine in Pregnancy Registry (NSVIPR) actively follows women inadvertently vaccinated with smallpox vaccine during or shortly before pregnancy to evaluate their reproductive health outcomes. Approximately 65% of NSVIPR participants also inadvertently received Anthrax Vaccine Adsorbed (AVA) while pregnant, providing a ready opportunity to evaluate pregnancy and infant health outcomes among these women. AVA-exposed pregnancies were ascertained using NSVIPR and electronic healthcare data. Rates of pregnancy loss and infant health outcomes, including major birth defects, were compared between AVA-exposed and AVA-unexposed pregnancies. Analyses included AVA-exposed and AVA-unexposed pregnant women who also received smallpox vaccine 28 days prior to or during pregnancy. Rates of adverse outcomes among the AVA-exposed group were similar to or lower than expected when compared with published reference rates and the AVA-unexposed population. The findings provide reassurance of the safety of AVA when inadvertently received by a relatively young and healthy population during pregnancy. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial.

PubMed

Tripathy, Debu; Im, Seock-Ah; Colleoni, Marco; Franke, Fabio; Bardia, Aditya; Harbeck, Nadia; Hurvitz, Sara A; Chow, Louis; Sohn, Joohyuk; Lee, Keun Seok; Campos-Gomez, Saul; Villanueva Vazquez, Rafael; Jung, Kyung Hae; Babu, K Govind; Wheatley-Price, Paul; De Laurentiis, Michelino; Im, Young-Hyuck; Kuemmel, Sherko; El-Saghir, Nagi; Liu, Mei-Ching; Carlson, Gary; Hughes, Gareth; Diaz-Padilla, Ivan; Germa, Caroline; Hirawat, Samit; Lu, Yen-Shen

2018-05-24

In MONALEESA-2, ribociclib plus letrozole showed improved progression-free survival compared with letrozole alone as first-line treatment for postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, advanced breast cancer. MONALEESA-7 aimed to assess the efficacy and safety of ribociclib plus endocrine therapy in premenopausal women with advanced, HR-positive breast cancer. This phase 3, randomised, double-blind, placebo-controlled trial was done at 188 centres in 30 countries. Eligible patients were premenopausal women aged 18-59 years who had histologically or cytologically confirmed HR-positive, HER2-negative, advanced breast cancer; an Eastern Cooperative Oncology Group performance status of 0 or 1; measurable disease as per Response Evaluation Criteria in Solid Tumors version 1.1 criteria, or at least one predominantly lytic bone lesion; and had not received previous treatment with cyclin-dependent kinases 4 and 6 inhibitors. Endocrine therapy and chemotherapy in the adjuvant or neoadjuvant setting was permitted, as was up to one line of chemotherapy for advanced disease. Patients were randomly assigned (1:1) via interactive response technology to receive oral ribociclib (600 mg/day on a 3-weeks-on, 1-week-off schedule) or matching placebo with either oral tamoxifen (20 mg daily) or a non-steroidal aromatase inhibitor (letrozole 2·5 mg or anastrozole 1 mg, both oral, daily), all with goserelin (3·6 mg administered subcutaneously on day 1 of every 28-day cycle). Patients and investigators were masked to treatment assignment. Efficacy analyses were by intention to treat, and safety was assessed in all patients who received at least one dose of any study treatment. The primary endpoint was investigator-assessed progression-free survival. MONALEESA-7 is registered with ClinicalTrials.gov, NCT02278120 and is ongoing, but no longer enrolling patients. Between Dec 17, 2014, and Aug 1, 2016, 672 patients were randomly assigned: 335 to the

The relationship between women's experiences of mistreatment at facilities during childbirth, types of support received and person providing the support in Lucknow, India.

PubMed

Diamond-Smith, Nadia; Sudhinaraset, May; Melo, Jason; Murthy, Nirmala

2016-09-01

a growing body of literature has highlighted the prevalence of mistreatment that women experience around the globe during childbirth, including verbal and physical abuse, neglect, lack of support, and disrespect. Much of this has been qualitative. Research around the world suggests that support during childbirth can improve health outcomes and behaviours, and improve experiences. Support can be instrumental, informational, or emotional, and can be provided by a variety of people including family (husbands, mothers) or health providers of various professional levels. This study explores women's reported experiences of mistreatment during childbirth quantitatively, and how these varied by specific types of support available and provided by specific individuals. participants were women age 16-30 who had delivered infants in a health facility in the previous five years and were living in slums of Lucknow India. Data were collected on their experiences of mistreatment, the types of support they received, and who provided that support. women who reported lack of support were more likely to report mistreatment. Lack of support in regards to discussions with providers and provider information were most strongly associated with a higher mistreatment score. Women who received any type of support from their husband or a health worker were significantly more likely to report lower mistreatment scores. Receiving informational support from a mother/mother-in-law or emotional support from a health worker was also associated with lower mistreatment scores. However, receiving emotional support from a friend/neighbour/other family member was associated with a higher mistreatment score. women rely on different people to provide different types of support during childbirth in this setting. Some of these individuals provide specific types of support that ultimately improve a woman's overall experience of her childbirth. Interventions aiming to reduce mistreatment to women during

Preparation and characterization of letrozole-loaded poly(d,l-lactide) nanoparticles for drug delivery in breast cancer therapy.

PubMed

Alemrayat, Bayan; Elhissi, Abdelbary; Younes, Husam M

2018-04-05

Letrozole (LTZ), an aromatase inhibitor used for the treatment of hormonally-positive breast cancer in postmenopausal women, has poor water solubility, rapid metabolism, and a range of side effects. In this study, polymer-based nanoparticles (NPs) incorporating the drug have been designed and characterized, aimed to control the release, potentially maximize the therapeutic efficiency, and minimize the side effects of the drug. LTZ was incorporated into poly(d,l-lactide) (PDLLA) NPs by employing the emulsion-solvent evaporation technique using a range of drug concentrations. Loaded drug and drug-polymer interactions were studied using X-ray diffraction and NPs morphology was evaluated using scanning electron microscopy (SEM). Particle size distribution (PSD) and zeta potential of the NPs were analyzed using dynamic light scattering (DLS) and laser Doppler velocimetry (LDV), respectively. Drug content and release profile studies were carried out and determined using ultra performance liquid chromatography (UPLC). The yield of LTZ-PDLLA NPs reached as high as 85%. The NPs were spherical and smooth, regardless of LTZ concentration in the formulation. However, particle size increased from 241.6 ± 1.2 to 348.7 ± 6.1 nm upon increasing LTZ concentration from 0 to 30% w/w, with entrapment efficiencies reaching up to 96.8%. Drug release from the polymeric matrix was best described by Higuchi model with a predominant diffusion-based mechanism. More than 15, 46, and 86% of LTZ was released in a controlled fashion over 30 d from the 10, 20, and 30% LTZ-PDLLA NPs, respectively. Overall, LTZ-PDLLA NPs were designed with appropriate size and surface charge, high drug loading, superior entrapment efficiency, and prolonged release profile.

Cost utility and budget impact of third-generation aromatase inhibitors for advanced breast cancer: a literature-based model analysis of costs in the Italian National Health Service.

PubMed

Marchetti, Monia; Caruggi, Mauro; Colombo, Giorgio

2004-09-01

Third-generation aromatase inhibitors are effective alternatives to tamoxifen in patients with advanced breast cancer. However, their acquisition costs might burden fixed-budget health care systems. This study is a decision analysis of the clinical and economic consequences of alternative first-line hormone therapies for postmenopausal women with estrogen receptor-positive metastatic breast cancer in a real-life Italian health care setting. A Markov model was developed to describe disease evolution according to data from previously published, randomized clinical trials. The costs incurred by a local community hospital in the Italian National Health Service were considered (year-2003 values). Clinical data were taken from previously published trials. A 3% discount rate was applied to both resources and life-years gained. Based on model estimates, mean survival times with the third-generation aromatase inhibitors anastrozole and letrozole were 30.72 and 30.64 months, respectively, as opposed to 27.28 months with tamoxifen. Mean survival times after adjustment for quality of life were 18.84 and 18.78 months with anastrozole and letrozole, respectively, and 16.14 months with tamoxifen. Baseline analysis produced incremental cost-effectiveness ratios per quality-adjusted life-year gained of 10,795 Euro (95% CI, 7737 Euro-12,899 Euro) and 16,886 Euro (95% CI, 9117 Euro-15,465 Euro) for anastrozole and letrozole, respectively, compared with tamoxifen. The observed difference between the 2 cost-utility ratios may have been mainly due to the higher acquisition costs of letrozole compared with anastrozole. Despite similar incremental cost-effectiveness ratios, anastrozole and letrozole might increase the budget for advanced breast cancer care by 12% and 18%, respectively, based on the year-2003 Italian market prices of the 2 drugs. In this cost-effectiveness analysis using previously published clinical data and year-2003 cost data from a community hospital in the Italian

The Development of a Mindfulness-Based Music Therapy (MBMT) Program for Women Receiving Adjuvant Chemotherapy for Breast Cancer

PubMed Central

Lesiuk, Teresa

2016-01-01

Problems with attention and symptom distress are common clinical features reported by women who receive adjuvant chemotherapy for breast cancer. Mindfulness practice significantly improves attention and mindfulness programs significantly reduce symptom distress in patients with cancer, and, more specifically, in women with breast cancer. Recently, a pilot investigation of a music therapy program, built on core attitudes of mindfulness practice, reported significant benefits of enhanced attention and decreased negative mood and fatigue in women with breast cancer. This paper delineates the design and development of the mindfulness-based music therapy (MBMT) program implemented in that pilot study and includes clients’ narrative journal responses. Conclusions and recommendations, including recommendation for further exploration of the function of music in mindfulness practice are provided. PMID:27517966

Letrozole, an aromatase inhibitor, reduces post-peak age-related regression of rooster reproductive performance.

PubMed

Ali, Emad Abdulgabbar; Zhandi, Mahdi; Towhidi, Armin; Zaghari, Mojtaba; Ansari, Mahdi; Najafi, Mojtaba; Deldar, Hamid

2017-08-01

This study was designed to evaluate orally administrated Letrozole (Lz) on reproductive performance, plasma testosterone and estradiol concentrations and relative abundance of mRNA of GnRH, FSH and LH in roosters. Ross 308 roosters (n=32) that were 40-weeks of age were individually housed and received a basal standard diet supplemented different amounts of capsulated Lz [0 (Lz-0), 0.5 (Lz-0.5), 1 (Lz-1) or 1.5 (Lz-1.5), mg Lz/bird/day] for 12 weeks. Sperm quality variables and plasma testosterone and estradiol concentrations were assessed from the first to the tenth week of the treatment period. Semen samples from the 11th to 12th week were used for artificial insemination and eggs were collected and allotted to assess fertility and hatchability rates. Relative abundance of hypothalamic and pituitary GnRH, LH and FSH mRNA was evaluated at the end of 12th week. The results indicated that total and forward sperm motility as well as egg hatchability rate were greater in the Lz-0.5 group. Greater sperm concentrations, ejaculate volume, sperm plasma membrane integrity, testis index and fertility rates were recorded for both Lz-0.5 and Lz-1 groups compared with the Lz-0 group (P<0.05). Body weight, percentage of sperm abnormalities, and sperm plasma membrane functionality were not affected by treatment. Testosterone and estradiol concentrations were negatively related with greater testosterone concentrations in the Lz-1.5 group which had lesser estradiol concentrations. Relative mRNA transcript abundance for GnRH, LH and FSH was Lz dose responsive being greater in the treated groups; however, this trend plateaued for GnRH and for the relative abundance of both LH and FSH mRNA was less in the Lz-1.5 group than the other treatment groups. It is concluded that Lz may be an effective treatment to improve age related post-peak reproductive performance of roosters. Copyright © 2017 Elsevier B.V. All rights reserved.

Neutropenia in HIV-Infected Kenyan Women Receiving Triple Antiretroviral Prophylaxis to Prevent Mother-to-Child HIV Transmission Is Not Associated with Serious Clinical Sequelae.

PubMed

Iuliano, A Danielle; Weidle, Paul J; Brooks, John T; Masaba, Rose; Girde, Sonali; Ndivo, Richard; Ogindo, Paul; Omolo, Paul; Zeh, Clement; Thomas, Timothy K

2015-01-01

Absolute neutrophil counts (ANCs) are lower in East African adults. To assess the impact of lower ANCs, we reviewed data from HIV-infected Kenyan women receiving antiretroviral therapy antepartum and postpartum. The Kisumu Breastfeeding Study (KiBS) participants received an antiretroviral regimen from 34 weeks' gestation through 6 months postpartum. Measured ANCs and subsequent illnesses were reviewed. Adverse events (AEs) potentially attributable to neutropenia were identified, and ANCs were graded using the 2004 Division of AIDS table for Grading the Severity of AEs. Among 478 women with ≥1 postpartum ANC measured, 298 (62.1%) women met criteria for an AE (<1.3 × 10(9) cells/L). Of those, 38 (12.5%) women experienced a nonlife-threatening illness potentially attributable to neutropenia. More than half of KiBS women met criteria for neutropenia. The mild clinical experience of most participants with low ANCs supports that these values might be typical for this population and may not result in adverse clinical sequelae. © The Author(s) 2013.

Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases.

PubMed

Turner, N C; Finn, R S; Martin, M; Im, S-A; DeMichele, A; Ettl, J; Diéras, V; Moulder, S; Lipatov, O; Colleoni, M; Cristofanilli, M; Lu, D R; Mori, A; Giorgetti, C; Iyer, S; Bartlett, C Huang; Gelmon, K A

2018-03-01

This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases. Pre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N = 521) and postmenopausal women untreated for ABC (PALOMA-2; N = 666) were randomized 2 : 1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression-free survival (PFS), safety, and patient-reported quality of life (QoL) were evaluated by prior treatment and visceral involvement. Visceral metastases incidence was higher in patients with prior resistance to ET (58.3%, PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In patients with prior resistance to ET and visceral metastases, median PFS (mPFS) was 9.2 months with palbociclib plus fulvestrant versus 3.4 months with placebo plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35-0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In patients with nonvisceral metastases, mPFS was 16.6 versus 7.3 months, HR 0.53; 95% CI 0.36-0.77. In patients with visceral disease and naive to ET in the advanced disease setting, mPFS was 19.3 months with palbociclib plus letrozole versus 12.9 months with placebo plus letrozole (HR 0.63; 95% CI 0.47-0.85); ORR was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not reached with palbociclib plus letrozole versus 16.8 months with placebo plus letrozole (HR 0.50; 95% CI 0.36-0.70). In patients with prior resistance to ET with visceral metastases, palbociclib plus fulvestrant significantly delayed deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported QoL was maintained with palbociclib plus letrozole in patients naive to endocrine-based therapy for ABC. Palbociclib plus ET prolonged mPFS in

Clinical considerations of the role of palbociclib in the management of advanced breast cancer patients with and without visceral metastases

PubMed Central

Turner, N C; Finn, R S; Martin, M; Im, S -A; DeMichele, A; Ettl, J; Diéras, V; Moulder, S; Lipatov, O; Colleoni, M; Cristofanilli, M; Lu, D R; Mori, A; Giorgetti, C; Iyer, S; Bartlett, C Huang; Gelmon, K A

2018-01-01

Abstract Background This report assesses the efficacy and safety of palbociclib plus endocrine therapy (ET) in women with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer (ABC) with or without visceral metastases. Patients and methods Pre- and postmenopausal women with disease progression following prior ET (PALOMA-3; N = 521) and postmenopausal women untreated for ABC (PALOMA-2; N = 666) were randomized 2 : 1 to ET (fulvestrant or letrozole, respectively) plus palbociclib or placebo. Progression-free survival (PFS), safety, and patient-reported quality of life (QoL) were evaluated by prior treatment and visceral involvement. Results Visceral metastases incidence was higher in patients with prior resistance to ET (58.3%, PALOMA-3) than in patients naive to ET in the ABC setting (48.6%, PALOMA-2). In patients with prior resistance to ET and visceral metastases, median PFS (mPFS) was 9.2 months with palbociclib plus fulvestrant versus 3.4 months with placebo plus fulvestrant [hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35–0.61], and objective response rate (ORR) was 28.0% versus 6.7%, respectively. In patients with nonvisceral metastases, mPFS was 16.6 versus 7.3 months, HR 0.53; 95% CI 0.36–0.77. In patients with visceral disease and naive to ET in the advanced disease setting, mPFS was 19.3 months with palbociclib plus letrozole versus 12.9 months with placebo plus letrozole (HR 0.63; 95% CI 0.47–0.85); ORR was 55.1% versus 40.0%; in patients with nonvisceral disease, mPFS was not reached with palbociclib plus letrozole versus 16.8 months with placebo plus letrozole (HR 0.50; 95% CI 0.36–0.70). In patients with prior resistance to ET with visceral metastases, palbociclib plus fulvestrant significantly delayed deterioration of QoL versus placebo plus fulvestrant, whereas patient-reported QoL was maintained with palbociclib plus letrozole in patients naive to endocrine

Using Videoconferencing Technology to Provide Breastfeeding Support to Low-Income Women: Connecting Hospital-Based Lactation Consultants with Clients Receiving Care at a Community Health Center.

PubMed

Friesen, Carol A; Hormuth, Laura J; Petersen, Devan; Babbitt, Tina

2015-11-01

The Tele-Lactation Pilot Project (TLPP), 1 of 13 community-based breastfeeding projects implemented in Indiana in 2013 using Centers for Disease Control and Prevention grant funds, explored the feasibility of using videoconferencing technology to provide breastfeeding education and support to low-income women by a centrally located International Board Certified Lactation Consultant (IBCLC). The IBCLC was housed at the Breastfeeding Center at the hospital where the women would deliver; the women receiving the education and support were located at an inner-city community health center (CHC) where they received their primary care. The videoconferencing sessions were juxtaposed with the women's regularly scheduled prenatal and postnatal visits at the CHC. After delivery, the lactation consultant visited the mother and infant in person at the hospital to offer additional support. Overall, 35 mothers were served by the TLPP during the 9-month project period. A total of 134 visits (30-45 minutes each) were conducted (3.8 sessions per woman). At the conclusion of the project, interviews with key participants indicated that the tele-lactation videoconferencing sessions were easy to implement, allowed the IBCLC to reach a wider client base, and allowed the women to receive expert support that they might not have otherwise received. Comments indicated that, in addition to providing education and increasing the women's confidence, the tele-lactation sessions appeared to have decreased the mothers' anxiety about the birthing process and the hospital experience. The TLPP demonstrated that incorporating videoconferencing technology into routine care can help foster collaboration among health care providers and provide mothers with continuous, easily accessible breastfeeding education and support. © The Author(s) 2015.

Midwives and pregnant women talk about alcohol: what advice do we give and what do they receive?

PubMed

Jones, Sandra C; Telenta, Joanne; Shorten, Allison; Johnson, Keryn

2011-08-01

the Australian National Health and Medical Research Council (NHMRC) recently revised its guidelines for alcohol consumption during pregnancy and breast feeding, moving from a recommendation of minimising intake to one of abstinence. Women are potentially exposed to a variety of messages about alcohol and pregnancy, including from the media and social contacts, and are likely to see midwives as the source of expert advice in understanding these contradictory messages. to explore the advice that midwives believe they give to pregnant women about alcohol consumption, and the advice that pregnant women believe they receive; the knowledge and attitudes of both groups regarding alcohol consumption and the consistency with the NHMRC guidelines; and the receptivity and comfort of both groups in discussing alcohol consumption in the context of antenatal appointments. individual semi-structured interviews with midwives and pregnant women. face-to-face interviews with midwives and telephone interviews with pregnant women were conducted in two regional areas of New South Wales in 2008-2009. 12 midwives and 12 pregnant women. midwives and pregnant women consistently agreed that conversations about alcohol are generally limited to brief screening questions at the first visit, and the risks are not discussed or explained (except for high-risk women). both groups expressed comfort with the idea of discussing alcohol consumption, but lacked knowledge of the risk and recommendation, and it appears that this opportunity to provide women with information is under-utilised. there is a need to provide midwives with accurate information about the risks of alcohol consumption during pregnancy and effective communication tools to encourage them to discuss the risks and recommendations with their patients. Copyright © 2010 Elsevier Ltd. All rights reserved.

Palbociclib has no clinically relevant effect on the QTc interval in patients with advanced breast cancer.

PubMed

Durairaj, Chandrasekar; Ruiz-Garcia, Ana; Gauthier, Eric R; Huang, Xin; Lu, Dongrui R; Hoffman, Justin T; Finn, Richard S; Joy, Anil A; Ettl, Johannes; Rugo, Hope S; Zheng, Jenny; Wilner, Keith D; Wang, Diane D

2018-03-01

The aim of this study was to assess the potential effects of palbociclib in combination with letrozole on QTc. PALOMA-2, a phase 3, randomized, double-blind, placebo-controlled trial, compared palbociclib plus letrozole with placebo plus letrozole in postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. The study included a QTc evaluation substudy carried out as a definitive QT interval prolongation assessment for palbociclib. Time-matched triplicate ECGs were performed at 0, 2, 4, 6, and 8 h at baseline (Day 0) and on Cycle 1 Day 14. Additional ECGs were collected from all patients for safety monitoring. The QT interval was corrected for heart rate using Fridericia's correction (QTcF), Bazett's correction (QTcB), and a study-specific correction factor (QTcS). In total, 666 patients were randomized 2 : 1 to palbociclib plus letrozole or placebo plus letrozole. Of these, 125 patients were enrolled in the QTc evaluation substudy. No patients in the palbociclib plus letrozole arm of the substudy (N=77) had a maximum postbaseline QTcS or QTcF value of ≥ 480 ms, or a maximum increase from clock time-matched baseline for QTcS or QTcF values of ≥ 60 ms. The upper bounds of the one-sided 95% confidence interval for the mean change from time-matched baseline for QTcS, QTcF, and QTcB at all time points and at steady-state Cmax following repeated administration of 125 mg palbociclib were less than 10 ms. Palbociclib, when administered with letrozole at the recommended therapeutic dosing regimen, did not prolong the QT interval to a clinically relevant extent.

Changes in microscopic analysis of the urinary sediment in postmenopausal women who receive vaginal conjugated oestrogens

PubMed Central

Cruz-Ramírez, Miriam Elizabeth; Sulvarán-Victoria, Diana

2017-01-01

Introduction Microscopic haematuria is common in adults and it has been reported in 13% of postmenopausal women. Objective To evaluate the changes in urinary sediment after the use of vaginal conjugated oestrogens. Material and methods Postmenopausal women with vaginal dryness were studied. In all them a urinalysis was done, looking for density, pH, and the presence of leukocytes and erythrocytes. In order to be included in the study, all of the women had to have microscopic haematuria, considered as the presence of 3 or more erythrocytes in the urinary sediment. All received vaginally 1 g of conjugated equine oestrogens cream 3 times per week for one month, moment in which a new urinalysis was carried out and the same parameters were evaluated. Results Twenty-four women were studied. The median age was 62 years (40-83), and the time since menopause was 144 months (24-336). When comparing the values between baseline and end of treatment urinalyses, no significant differences in pH and urinary density were found. The number of leukocytes significantly decreased after treatment (3.0 [1-6] vs. 1.0 [1-6], p < 0.026), and the erythrocytes number decreased (4.5 [3-12] vs. 0.0 [0-2], p < 0.001). Conclusion In postmenopausal women with microscopic haematuria and vaginal dryness, it is worth considering administration of local oestrogen for one month, and after repeat the urine exam, before deciding to begin the microscopic haematuria study protocol. PMID:29507575

Hormone therapy for breast cancer

MedlinePlus

... a similar way are used to treat advanced cancer that has spread: Toremifene (Fareston) Fulvestrant (Faslodex) ... no longer make estrogen. Premenopausal women can take AIs if they ... Anastrozole (Arimidex) Letrozole (Femara) Exemestane (Aromasin)

Improving 24-Month Abstinence and Employment Outcomes for Substance-Dependent Women Receiving Temporary Assistance for Needy Families With Intensive Case Management

PubMed Central

Neighbors, Charles J.; Kuerbis, Alexis; Riordan, Annette; Blanchard, Kimberly A.; McVeigh, Katharine H.; Morgan, Thomas J.; McCrady, Barbara

2009-01-01

Objective. We examined abstinence rates among substance-dependent women receiving Temporary Assistance for Needy Families (TANF) in intensive case management (ICM) over 24 months and whether ICM yielded significantly better employment outcomes compared with a screen-and-refer program (i.e., usual care). Methods. Substance-dependent (n = 302) and non–substance dependent (n = 150) TANF applicants in Essex County, New Jersey, were recruited. We randomly assigned substance-dependent women to ICM or usual care. We interviewed all women at 3, 9, 15, and 24 months. Results. Abstinence rates were higher for the ICM group than for the usual care group through 24 months of follow-up (odds ratio [OR] = 2.11; 95% confidence interval [CI] = 1.36, 3.29). A statistically significant interaction between time and group on number of days employed indicated that the rate of improvement over time in employment was greater for the ICM group than for the usual care group (incidence rate ratio = 1.03; 95% CI = 1.02, 1.04). Additionally, there were greater odds of being employed full time for those in the ICM group (OR = 1.68; 95% CI = 1.12, 2.51). Conclusions. ICM is a promising intervention for managing substance dependence among women receiving TANF and for improving employment rates among this vulnerable population. PMID:19059855

In vitro fertilisation for unexplained subfertility.

PubMed

Pandian, Zabeena; Gibreel, Ahmed; Bhattacharya, Siladitya

2015-11-19

women pretreated with IUI + clomiphene, a higher live birth rate was reported among those who underwent IVF than those given IUI + gonadotropins (OR 3.90, 95% CI 2.32 to 6.57, one RCT, 280 women, moderate-quality evidence).There was no conclusive evidence of a difference in live birth rates between IVF and IUI + CC in treatment-naive women (OR 2.51, 95% CI 0.96 to 6.55, one RCT, 103 women, low quality evidence).In treatment-naive women, there was no evidence of a difference in rates of multiple pregnancy between women who underwent IVF and those who received IUI + gonadotropins (OR 0.79, 95% CI 0.45 to 1.39, four RCTs, 745 women, I(2) = 0%, moderate quality evidence). There was no evidence of a difference in MPRs between women who underwent IVF compared with those given IUI + CC (OR 1.02, 95% CI 0.20 to 5.31, one RCT, 103 women, low-quality evidence).There was no evidence of a difference in ovarian hyperstimulation syndrome rate between treatment-naive women who underwent IVF and those given IUI + gonadotropins (OR 1.23, 95% CI 0.36 to 4.14, two RCTs, 221 women, low quality evidence). There was no evidence of a difference in OHSS rates between groups receiving IVF versus those receiving IUI + CC (OR 1.02, 95% CI 0.20 to 5.31, one RCT, 103 women, low-quality evidence).In treatment naive women, there was no evidence of a difference in miscarriage rates between IVF and IUI + CC (OR 1.16, 95% CI 0.44 to 3.02, one RCT, 103 women, low-quality evidence), nor between women treated with IVF versus those receiving IUI+ gonadotropins (OR 1.16, 95% CI 0.44 to 3.02, one RCT, 103 women).No studies compared IVF with IUI + letrozole.The quality of the evidence ranged from very low to moderate. The main limitation was serious imprecision resulting from small study numbers and low event rates. IVF may be associated with higher live birth rates than expectant management, but there is insufficient evidence to draw firm conclusions. IVF may also be associated with higher live birth rates

Good practices according to WHO's recommendation for normal labor and birth and women's assessment of the care received: the "birth in Brazil" national research study, 2011/2012.

PubMed

Baldisserotto, Marcia Leonardi; Theme Filha, Mariza Miranda; da Gama, Silvana Granado Nogueira

2016-10-17

The World Health Organization recommends good practices for the conduct of uncomplicated labor and birth, with the aim of improving the quality of and assessment by women of childbirth care. The aim of this study was to evaluate the association between adoption of good practices according to WHO's recommendation for normal labor and birth and assessment by women of the care received. Birth in Brazil is a national hospital-based study with countrywide representation consisting of 23,894 mothers and their newborns, conducted between February 2011 and October 2012. The present study analysed a subsample of this national survey. Postpartum women classified as low risk during pregnancy who had experienced either spontaneous or induced labor were included in this study, totalling 4102 mothers. To estimate the association between assessment by women of the childbirth care received (dependent variable) and good practices according to WHO's recommendation during normal labor and birth (independent variables), a multinomial logistic regression analysis was used and crude and adjusted odds ratios calculated with their 95 % confidence intervals. The good practices associated with positive assessment of the care received by women during labor and birth included the partner's presence, privacy in the birthing place, time available to ask questions, clarity of information received, and empathic support from caregivers during labor and birth. Freedom of movement, free nutrition offered, choice of companions, nonpharmacological analgesia, skin-to-skin contact and breastfeeding in the childbirth room were not associated with the assessment by women of the care received. Our findings reveal the importance to mothers of their relationship with the team of caregivers during labor and birth. Therefore, caregiver teams must be qualified within a more humanistic vision of childbirth health care.

Intent to receive HPV vaccine and reasons for not vaccinating among unvaccinated adolescent and young women: findings from the 2006-2008 National Survey of Family Growth.

PubMed

Liddon, Nicole C; Hood, Julia E; Leichliter, Jami S

2012-03-30

HPV vaccine coverage for females has increased in the U.S., although challenges to achieving high coverage remain. HPV vaccine coverage continues to lag behind that of other routinely recommended adolescent vaccines and these gaps in coverage are widening. To inform strategies to improve uptake, we explore correlates of vaccine intention and describe reasons for refusing HPV vaccination among unvaccinated females in a nationally representative sample of adolescents and young adults during early stages of HPV vaccine availability. In 2007-2008, 1243 females aged 15-24 years were asked about HPV vaccination in the National Survey of Family Growth (NSFG). For unvaccinated women (n=955), we evaluated demographic and sexual behavior correlates of likelihood to receive the vaccine in the next 12 months in bivariate and multivariable analyses by age. Correlates to the main reasons for foregoing vaccination are described. A minority (42.5%) of unvaccinated respondents said they intended to receive HPV vaccine in the next 12 months: 37.6% of adolescents (15-19 years) and 42.0% of young adults (20-24 years). Sexually experienced women were more than twice as likely as non-sexually experienced women to intend to receive HPV vaccine (15-19 years: aOR=2.39, 95% CI=1.15, 4.94; 20-24 years: aOR=2.17, 95% CI=1.08, 4.33). Having health insurance was associated with being likely to receive HPV vaccine among adolescents. Hispanic young adults were more likely than non-Hispanic Whites to be likely to receive HPV vaccine. The belief of not being at risk for HPV and institutional barriers were the two most commonly cited reasons for foregoing vaccination.Among unvaccinated women who did not intend to get vaccinated, respondents who never had sex were more likely to report not being at risk as the main reason for not needing the vaccine compared to women with sexual experience (44.5 vs. 24.4%) but this finding was only marginally significant in our limited sample. In the first years

Ribociclib as First-Line Treatment for Metastatic Breast Cancer

Cancer.gov

A summary of interim results from a phase III trial testing ribociclib plus letrozole (Femara®) as a first-line treatment for postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer.

Increasing incidence of pregnancy among women receiving HIV care and treatment at a large urban facility in western Uganda.

PubMed

Kabami, Jane; Turyakira, Eleanor; Biraro, Sam; Bajunirwe, Francis

2014-12-06

Antiretroviral treatment restores physical functioning and may have an impact on fertility desires. Counseling is given to HIV positive women to create awareness and to provide information on pregnancy and delivery. The purpose of this study was to determine the incidence of pregnancy and factors that predict pregnancy among women of reproductive age receiving HIV care and treatment at a large urban center in western Uganda. We conducted a retrospective cohort study using routinely collected data at the Immune Suppression (ISS) Clinic of Mbarara Regional Referral Hospital located in Mbarara District, western Uganda collected between January 2006 and June 2010. Women aged 15 to 50 years were eligible for analysis. The primary outcome was incidence of pregnancy calculated as number of pregnancies per 1000 person years (PY). Data was analyzed by calendar year and year of enrolment and used survival analysis to determine the predictors of pregnancy. A total of 3144 women were included with a median follow up of 12.5 months. The overall incidence rate was 90.7 pregnancies per 1000 person years. Incidence increased from 29.8 pregnancies per 1000 PY in 2006 to 122 pregnancies per 1000 PY in 2010 (p < 0.001). Significant predictors for pregnancy were younger age (HR 10.96 95% CI 3.22-37.2), married (HR 2.09 95% CI 1.69-2.64) and single (HR 1.95 95% CI 1.34-2.84) compared to widowed or separated, primary education (HR 1.65 95% CI 1.02-2.66), not knowing the HIV status of the spouse (HR 1.46, 95%CI 1.13-1.93) compared to knowing. The use of family planning (HR 0.23 95% CI 0.18- 0.30) and an increase in CD4 count between baseline and most recent count were protective against pregnancy. ART use was not a significant predictor. Incidence of pregnancy among women receiving routine HIV care and treatment has increased and is almost comparable to that in the general population. Thus routine HIV care should integrate reproductive health needs for these women.

Intermittent Preventive Treatment of Malaria in Pregnancy with Mefloquine in HIV-Infected Women Receiving Cotrimoxazole Prophylaxis: A Multicenter Randomized Placebo-Controlled Trial

PubMed Central

Abdulla, Salim; Aponte, John J.; Bulo, Helder; Kabanywanyi, Abdunoor M.; Katana, Abraham; Maculuve, Sonia; Mayor, Alfredo; Nhacolo, Arsenio; Otieno, Kephas; Pahlavan, Golbahar; Rupérez, María; Sevene, Esperança; Slutsker, Laurence; Vala, Anifa; Williamsom, John; Menéndez, Clara

2014-01-01

Background Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs). Methods and Findings A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27–0.82]; p = 0.008), placental malaria (RR, 0.52 [95% CI 0.29–0.90]; p = 0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37–0.95]; p = 0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p = 0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14–3.33]; p = 0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis. Conclusions An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need

Intermittent preventive treatment of malaria in pregnancy with mefloquine in HIV-infected women receiving cotrimoxazole prophylaxis: a multicenter randomized placebo-controlled trial.

PubMed

González, Raquel; Desai, Meghna; Macete, Eusebio; Ouma, Peter; Kakolwa, Mwaka A; Abdulla, Salim; Aponte, John J; Bulo, Helder; Kabanywanyi, Abdunoor M; Katana, Abraham; Maculuve, Sonia; Mayor, Alfredo; Nhacolo, Arsenio; Otieno, Kephas; Pahlavan, Golbahar; Rupérez, María; Sevene, Esperança; Slutsker, Laurence; Vala, Anifa; Williamsom, John; Menéndez, Clara

2014-09-01

Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is recommended for malaria prevention in HIV-negative pregnant women, but it is contraindicated in HIV-infected women taking daily cotrimoxazole prophylaxis (CTXp) because of potential added risk of adverse effects associated with taking two antifolate drugs simultaneously. We studied the safety and efficacy of mefloquine (MQ) in women receiving CTXp and long-lasting insecticide treated nets (LLITNs). A total of 1,071 HIV-infected women from Kenya, Mozambique, and Tanzania were randomized to receive either three doses of IPTp-MQ (15 mg/kg) or placebo given at least one month apart; all received CTXp and a LLITN. IPTp-MQ was associated with reduced rates of maternal parasitemia (risk ratio [RR], 0.47 [95% CI 0.27-0.82]; p=0.008), placental malaria (RR, 0.52 [95% CI 0.29-0.90]; p=0.021), and reduced incidence of non-obstetric hospital admissions (RR, 0.59 [95% CI 0.37-0.95]; p=0.031) in the intention to treat (ITT) analysis. There were no differences in the prevalence of adverse pregnancy outcomes between groups. Drug tolerability was poorer in the MQ group compared to the control group (29.6% referred dizziness and 23.9% vomiting after the first IPTp-MQ administration). HIV viral load at delivery was higher in the MQ group compared to the control group (p=0.048) in the ATP analysis. The frequency of perinatal mother to child transmission of HIV was increased in women who received MQ (RR, 1.95 [95% CI 1.14-3.33]; p=0.015). The main limitation of the latter finding relates to the exploratory nature of this part of the analysis. An effective antimalarial added to CTXp and LLITNs in HIV-infected pregnant women can improve malaria prevention, as well as maternal health through reduction in hospital admissions. However, MQ was not well tolerated, limiting its potential for IPTp and indicating the need to find alternatives with better tolerability to reduce malaria in this

Treatment Services Received in the CASAWORKS for Families Program

ERIC Educational Resources Information Center

Mckay, James R.; Gutman, Marjorie; Mclellan, A. Thomas; Lynch, Kevin G.; Ketterlinus, Robert

2003-01-01

This article presents information on treatment services received by women participating in an initial multistate evaluation of CASAWORKS families. Results indicated most women received services to address medical, employment, basic needs, alcohol and drug, family, and psychiatric problems during the first six months of the program. The clients…

Aromatase inhibitor regulates let-7 expression and let-7f induced cell migration in endometrial cells from women with endometriosis

PubMed Central

Cho, SiHyun; Mutlu, Levent; Zhou, Yuping; Taylor, Hugh S.

2018-01-01

Objectives To evaluate associations between aromatase inhibitor (AI) treatment and let-7 family microRNA expression in endometriosis. Design In vitro study using Ishikawa cells and human endometrial stromal cells (HESC) obtained from patients with endometriosis Setting University research center. Patients Women undergoing laparoscopic surgery for endometriosis Interventions HESCs and Ishikawa cells treated with various letrozol concentrations and transfected with a mimic of let-7 subtypes of interest Main Outcome Measures microRNAs let7a-f and aromatase expression were evaluated. Migration potential after transfection with a let-7f mimic were analyzed. Results After letrozole treatment for 48 hours, all let-7 subtypes showed a trend toward increased expression in a dose dependent manner in Ishikawa cells, and significant differences were found in let-7b and let-7f between controls and the 20 μmol/L treated groups. Further, let-7f showed significant differences between control and 1.0 μmol/L treatment group, a typical therapeutic level, in HESCs. Transfection of a let-7f mimic decreased aromatase expression in both Ishikawa cells and HESC, and led to a significant decrease in number of migrating cells in both cell types. Conclusions AI treatment significantly increased expression of let-7f in Ishikawa cells and HESCs from patient with endometriosis; increased lef-7f expression effectively reduced the migration of endometrial cells. Modulation of miRNAs involved in the pathogenesis of endometriosis may have therapeutic potential for endometriosis. PMID:27320036

Clinical outcome in women with HER2-positive de novo or recurring stage IV breast cancer receiving trastuzumab-based therapy.

PubMed

Rossi, Valentina; Nolè, Franco; Redana, Stefania; Adamoli, Laura; Martinello, Rossella; Aurilio, Gaetano; Verri, Elena; Sapino, Anna; Viale, Giuseppe; Aglietta, Massimo; Montemurro, Filippo

2014-02-01

Five to 10% of women with newly diagnosed breast cancer have synchronous metastases (de novo stage IV). A further 20% will develop metastases during follow-up (recurring stage IV). We compared the clinical outcomes of women with HER2-positive metastatic breast cancer (MBC) receiving first-line trastuzumab-based therapy according to type of metastatic presentation. Retrospective analysis of 331 MBC patients receiving first-line trastuzumab-based treatment. Response rates (RR) were compared by the chi-square test. Time-to progression (TTP) and overall survival (OS) curves were compared by the log-rank test. Cox-proportional hazards models were used to study predictors of PFS and OS, including the type of metastatic presentation. Seventy-seven patients (23%) had de novo stage IV disease. Forty-six of these patients underwent surgery of the primary ("de novo/surgery"). Response rates to first-line trastuzumab-based therapy and median progression-free survival did not differ in patients with "recurring", "de novo/surgery" and "de novo" without surgery ("de novo/no surgery) stage IV breast cancer. However, women with "de novo/surgery" stage IV breast cancer had the longest median OS (60 months), and those with "de novo/no surgery" stage IV breast cancer the shortest (26 months). For women with recurring metastatic breast cancer median OS was 40 months (overall log-rank test, p < 0.01). Multivariate analysis confirmed these findings. Our analysis shows that response rates and PFS to first-line trastuzumab-based therapy do not differ significantly between de novo and recurring stage IV, HER2 positive breast cancer. The observed difference in OS favoring women with de novo stage IV disease submitted to surgery of the primary tumor could be the result of a selection bias. Copyright © 2013 Elsevier Ltd. All rights reserved.

Shame and eating psychopathology in Portuguese women: Exploring the roles of self-judgment and fears of receiving compassion.

PubMed

Oliveira, Vanessa Raquel; Ferreira, Cláudia; Mendes, Ana Laura; Marta-Simões, Joana

2017-03-01

Shame has been for long associated with the development and maintenance of body image and eating-related difficulties. However, the mechanisms underlying this association remain unclear. Therefore, the current study sought to examine the mechanisms of self-judgment and fears of receiving compassion from others in the association between external shame and disordered eating, while controlling for body mass index (BMI). Participants in this study were 400 women from the general population, aged between 18 and 55 years old. Correlation analyses revealed significant and positive relationships between external shame, self-judgment, fears of receiving compassion from others and eating psychopathology. A path analysis confirmed that, when controlling for the effect of BMI, external shame has a direct effect on disordered eating severity, and also an indirect effect, mediated by higher levels of self-judgment and increased fears of receiving others' kindness and compassion. Results showed the plausibility of the tested model which explained 36% of the variance of disordered eating. These findings seem to support that women who perceive that others view them negatively tend to be defensive and engage in maladaptive emotion regulation strategies (such as harsh critical attitudes towards the self and being resistant to others' compassion), which may trigger maladaptive eating attitudes and behaviours. The current research appears to be an innovative study in the field of body image and eating-related psychopathology and seems to represent a new avenue for future research and for the development of intervention programs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Substance use among women receiving post-rape medical care, associated post-assault concerns and current substance abuse: Results from a national telephone household probability sample

PubMed Central

McCauley, Jenna L.; Kilpatrick, Dean G.; Walsh, Kate; Resnick, Heidi S.

2013-01-01

Objective To examine post-rape substance use, associated post rape medical and social concern variables, and past year substance abuse among women reporting having received medical care following a most recent or only lifetime incident of rape. Method Using a subsample of women who received post-rape medical care following a most recent or only rape incident (n=104) drawn from a national household probability sample of U.S. women, the current study described the extent of peritraumatic substance use, past year substance misuse behaviors, post-rape HIV and pregnancy concerns, and lifetime mental health service utilization as a function of substance use at time of incident. Results One-third (33%) of women seeking post-rape medical attention reported consuming alcohol or drugs at the time of their rape incident. Nearly one in four (24.7%) and one in seven (15%) women seeking medical attention following their most recent rape incident endorsed drug (marijuana, illicit, non-medical use of prescription drugs, or club drug) use or met substance abuse criteria, respectively, in the past year. One in twelve (8.4%) women reported at least monthly binge drinking in the past year. Approximately two-thirds of women reported seeking services for mental health needs in their lifetime. Post-rape concerns among women reporting peritraumatic substance use were not significantly different from those of women not reporting such use. Conclusions Substance use was reported by approximately one-third of women and past year substance abuse was common among those seeking post-rape medical care. Implications for service delivery, intervention implementation, and future research are discussed. PMID:23380490

Substance use among women receiving post-rape medical care, associated post-assault concerns and current substance abuse: results from a national telephone household probability sample.

PubMed

McCauley, Jenna L; Kilpatrick, Dean G; Walsh, Kate; Resnick, Heidi S

2013-04-01

To examine post-rape substance use, associated post rape medical and social concern variables, and past year substance abuse among women reporting having received medical care following a most recent or only lifetime incident of rape. Using a subsample of women who received post-rape medical care following a most recent or only rape incident (n=104) drawn from a national household probability sample of U.S. women, the current study described the extent of peritraumatic substance use, past year substance misuse behaviors, post-rape HIV and pregnancy concerns, and lifetime mental health service utilization as a function of substance use at time of incident. One-third (33%) of women seeking post-rape medical attention reported consuming alcohol or drugs at the time of their rape incident. Nearly one in four (24.7%) and one in seven (15%) women seeking medical attention following their most recent rape incident endorsed drug (marijuana, illicit, non-medical use of prescription drugs, or club drug) use or met substance abuse criteria, respectively, in the past year. One in twelve (8.4%) women reported at least monthly binge drinking in the past year. Approximately two-thirds of women reported seeking services for mental health needs in their lifetime. Post-rape concerns among women reporting peritraumatic substance use were not significantly different from those of women not reporting such use. Substance use was reported by approximately one-third of women and past year substance abuse was common among those seeking post-rape medical care. Implications for service delivery, intervention implementation, and future research are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

The role of nesfatin-1 expression in letrozole-induced polycystic ovaries in the rat.

PubMed

Xu, Yingqiao; Zhang, Hua; Li, Qingchun; Lao, Kaixue; Wang, Yanlin

2017-06-01

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder, generally exhibiting the characteristic features of hyperandrogenemia, insulin resistance (IR) and obesity. Nesfatin-1 is derived from the precursor nucleobindin2 (NUCB2), and plays an active role in energy balance, glucose metabolism and most likely gonadal function. In order to explore the role of nesfatin-1, we employed a rat model that uses letrozole to induce PCOS. The PCOS rats exhibited increased body weight, irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. The expression of both nesfatin-1 mRNA and protein in the ovarian tissues of PCOS group decreased significantly compared to the control group (p < 0.05). Nesfatin-1 expression in peripheral blood also decreased in the PCOS group, in contrast with the control group. Furthermore, we found that nesfatin-1 had a positive correlation with FSH, E 2 and P, whereas it had a negative correlation with LH, and total T (p < 0.05). When taken together, these data indicated that the decrease in nesfatin-1 may contribute to the mechanism governing PCOS, and might provide a new potential target for therapies aimed at treating PCOS.

Family planning utilization and factors associated among women receiving abortion services in health facilities of central zone towns of Tigray, Northern Ethiopia: a cross sectional Study.

PubMed

Hagos, Goshu; Tura, Gurmesa; Kahsay, Gizienesh; Haile, Kebede; Grum, Teklit; Araya, Tsige

2018-06-05

Abortion remains among the leading causes of maternal death worldwide. Post-abortion contraception is significantly effective in preventing unintended pregnancy and abortion if provided before women leave the health facilty. However, the status of post-abortion family planning (PAFP) utilization and the contributing factors are not well studied in Tigray region. So, we conduct study aimed on family planning utilization and factors associated with it among women receiving abortion services. A facility based cross-sectional study design was conducted among women receiving abortion services in central zone of Tigray from December 2015to February 2016 using a total of 416 sample size. Women who came for abortion services were selected using systematic random sampling technique.. The data were collected using a pre-tested interviewer administered questionnair. Data were coded and entered in to Epi info 7 and then exported to SPSS for analysis. Descriptive statisticslike frequencies and mean were computed to display the results. Both Bivariable and multivariable logistic regression was used in the analysis. Variables statistically significant at p < 0.05 in the bivariable analysis were checked in multivariable logistic regration to identify independently associated factors. Then variables which were significantly associated with post abortion family planning utilization at p-value < 0.05 in the multivariable analysis were declared as significantly associated factors. A total of 409 abortion clients were interviewed in this study with 98.3% of response rate. Majority 290 (70.9%) of study participants utilized contracepives after abortion. Type of health facility, the decision maker on timing of having child, knowledge that pregnancy can happen soon after abortion and husband's opposition towards contraceptives were significantly associated with Post-abortion family planning ustilization. About one-third of abortion women failed to receive contraceptive before

High progesterone levels during the luteal phase related to the use of an aromatase inhibitor in breast cancer patients.

PubMed

Alviggi, C; Marci, R; Vallone, R; Conforti, A; Di Rella, F; Strina, I; Picarelli, S; De Rosa, P; De Laurentiis, M; Yding Andersen, C; De Placido, G

2017-07-01

To evaluate the hormonal profile in three breast cancer patients who underwent controlled ovarian stimulation in the presence of the aromatase inhibitor letrozole. In IVF University referral center, a case series of three breast cancer patients who underwent controlled ovarian stimulation (COS) with recombinant FSH and letrozole were investigated. Ovulation was induced with hCG (case No. 1) or with GnRH agonist (case No. 2-3). The primary outcome of our study was the detection of progesterone levels in the luteal phase. Very high progesterone values (mean 186.6 ± 43.6 ng/mL) during the luteal phase were recorded in all three cases. High progesterone levels can be related to the use of letrozole independently of the most commonly used trigger regimen. Although progesterone has long been considered a protective factor against breast cancer, several studies have demonstrated that progesterone could expand a transformation-sensitive stem cell population in the mammary glands. The estrogen negative feedback effect on the hypothalamus-pituitary axis and the disruption of steroid biosynthesis and could represent an intriguing reason behind this phenomenon. Our results highlight the need to evaluate further the increase in progesterone levels in the luteal phase in women with breast cancer undergoing COS with letrozole.

Lower urinary tract symptoms and falls risk among older women receiving home support: a prospective cohort study

PubMed Central

2013-01-01

Background Although lower urinary tract symptoms have been associated with falls, few studies have been undertaken to understand this relationship in vulnerable community dwelling older adults. The purpose of this study was to describe the relationship over time of falls risk and lower urinary tract symptoms among community based older women receiving home support services. Methods A prospective cohort study which took place in an urban setting in western Canada. Participants were 100 older women receiving home care or residing in assisted living with home support services and were followed for six months. Demographic characteristics were collected at baseline, with the Timed Up and Go (TUG), International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms (ICIQ-FLUTS), and self-report of falls collected at baseline, 3 and 6 months. Descriptive statistics were used to summarize demographic data. Differences between the three visits were analyzed using the Friedman test with post hoc analysis and associations between variables by the Spearman Rank-Order Correlation Coefficient. Results One hundred women initially enrolled; 88 and 75 remained at three months and six months. Mean age = 84.3 years; 91% reported at least one urinary symptom at baseline and 35% reported falling in the six months prior to enrollment; 15.9% reported falling between the baseline and three months and 14.6% between three and six months. Mean TUG scores at each time point indicated falls risk (27.21, 29.18 and 27.76 seconds). Significant correlations between TUG and ICIQ-FLUTS (r = 0.33, p < .001; r = 0.39, p < .001) as well as TUG and overactive bladder scores (r = 0.25, p = .005; r = 0.28, p < .008) were found at baseline and three months, but not six months. Conclusions The association of lower urinary tract symptoms and falls risk in this group of vulnerable community dwelling older women at baseline and three months has potential

Lower urinary tract symptoms and falls risk among older women receiving home support: a prospective cohort study.

PubMed

Hunter, Kathleen F; Voaklander, Donald; Hsu, Zoe Y; Moore, Katherine N

2013-05-15

Although lower urinary tract symptoms have been associated with falls, few studies have been undertaken to understand this relationship in vulnerable community dwelling older adults. The purpose of this study was to describe the relationship over time of falls risk and lower urinary tract symptoms among community based older women receiving home support services. A prospective cohort study which took place in an urban setting in western Canada. Participants were 100 older women receiving home care or residing in assisted living with home support services and were followed for six months. Demographic characteristics were collected at baseline, with the Timed Up and Go (TUG), International Consultation on Incontinence Questionnaire Female Lower Urinary Tract Symptoms (ICIQ-FLUTS), and self-report of falls collected at baseline, 3 and 6 months. Descriptive statistics were used to summarize demographic data. Differences between the three visits were analyzed using the Friedman test with post hoc analysis and associations between variables by the Spearman Rank-Order Correlation Coefficient. One hundred women initially enrolled; 88 and 75 remained at three months and six months. Mean age = 84.3 years; 91% reported at least one urinary symptom at baseline and 35% reported falling in the six months prior to enrollment; 15.9% reported falling between the baseline and three months and 14.6% between three and six months. Mean TUG scores at each time point indicated falls risk (27.21, 29.18 and 27.76 seconds). Significant correlations between TUG and ICIQ-FLUTS (r = 0.33, p < .001; r = 0.39, p < .001) as well as TUG and overactive bladder scores (r = 0.25, p = .005; r = 0.28, p < .008) were found at baseline and three months, but not six months. The association of lower urinary tract symptoms and falls risk in this group of vulnerable community dwelling older women at baseline and three months has potential clinical relevance. Lack of correlation at

Patient actions and reactions after receiving negative results from expanded carrier screening

PubMed Central

Kraft, Stephanie A.; Schneider, Jennifer L.; Leo, Michael C.; Kauffman, Tia L.; Davis, James V.; Porter, Kathryn M.; McMullen, Carmit K.; Wilfond, Benjamin S.; Goddard, Katrina A.B.

2018-01-01

With the expansion of carrier screening to general preconception and prenatal patient populations, most patients will receive negative results, which we define as indicating <25% risk of having a child with a genetic condition. Because there is limited experience with expanded carrier screening, it is important to understand how receiving negative results affects patients, especially as providers, payers, and policymakers consider whether to offer it. In this mixed-methods study, we asked preconception patients enrolled in the NextGen study about their expectations and experiences receiving negative expanded carrier screening results. Participants completed surveys at study enrollment (n=110 women, 51 male partners), after receiving carrier results (n=100 women, 38 male partners), after receiving secondary findings (n=98 women, 36 male partners), and 6 months after receiving results (n=95 women, 28 male partners). We also interviewed a subset of participants 12–24 months after receiving results (n=24 women, 12 male partners). We found minimal negative emotional impact and privacy concerns, increased confidence in reproductive plans, and few changes to health behaviors, although some patients made health decisions based on misunderstandings of their results. These findings suggest that expanded carrier screening causes minimal psychosocial harms, but systems are needed to reduce the risk of misinterpreting results. PMID:29293279

Febrile Neutropenia Rates According to Body Mass Index and Dose Capping in Women Receiving Chemotherapy for Early Breast Cancer.

PubMed

Lote, H; Sharp, A; Redana, S; Papadimitraki, E; Capelan, M; Ring, A

2016-09-01

Studies suggest worse outcomes in obese women with breast cancer than in non-obese women. One potential reason may be that oncologists 'dose cap' adjuvant chemotherapy in obese patients in order to avoid excessive toxicity. Reductions from standard dosing may compromise survival outcomes in the curative setting. Here we describe the body mass index (BMI) distribution of patients in a non-trial population, the frequency with which oncologists dose cap and its effect on febrile neutropenia chemotherapy toxicity. In this non-randomised study, electronic patient records retrospectively identified patients with early breast cancer who initiated neoadjuvant or adjuvant chemotherapy at the Royal Marsden Hospital between 1 January and 31 December 2013. Baseline data included age, BMI, performance status, tumour characteristics, granulocyte colony-stimulating factor and comorbidities. Chemotherapy doses, rates of dose capping across BMI groups and rates of febrile neutropenia were reported. In total, 325 patients were eligible: 79 (24.5%) were obese (BMI ≥ 30), 109 (33.5%) were overweight (BMI ≥25 - <30) and 137 (42%) were normal bodyweight (BMI < 25). Sixteen patients (20.5%) in the obese group received dose-capped chemotherapy. Overall, 62 patients (19%) had an episode of febrile neutropenia. Obese patients receiving uncapped chemotherapy did not experience a significant difference in febrile neutropenia rates when compared with overweight or normal bodyweight groups (P = 0.5798). The febrile neutropenia rate in obese patients receiving capped chemotherapy was 6.5%, compared with 24% in obese patients receiving uncapped chemotherapy (P = 0.1216). In a non-trial population of obese patients, dose capping is frequently used. Obese patients receiving uncapped chemotherapy do not experience increased febrile neutropenia rates when compared with uncapped overweight or normal bodyweight patients. Furthermore, dose capping was associated with a trend towards lower

Vaginal dilator therapy for women receiving pelvic radiotherapy.

PubMed

Miles, Tracie; Johnson, Nick

2014-09-08

Vaginal dilation therapy is advocated after pelvic radiotherapy to prevent stenosis (abnormal narrowing of the vagina), but can be uncomfortable and psychologically distressing. To assess the benefits and harms of different types of vaginal dilation methods offered to women treated by pelvic radiotherapy for cancer. Searches included the Cochrane Central Register of Controlled Trials (CENTRAL 2013, Issue 5), MEDLINE (1950 to June week 2, 2013), EMBASE (1980 to 2013 week 24) and CINAHL (1982 to 2013). Comparative data of any type, which evaluated dilation or penetration of the vagina after pelvic radiotherapy treatment for cancer. Two review authors independently assessed whether potentially relevant studies met the inclusion criteria. We found no trials and therefore analysed no data. We identified no studies for inclusion in the original review or for this update. However, we felt that some studies that were excluded warranted discussion. These included one randomised trial (RCT), which showed no improvement in sexual scores associated with encouraging women to practise dilation therapy; a recent small RCT that did not show any advantage to dilation over vibration therapy during radiotherapy; two non-randomised comparative studies; and five correlation studies. One of these showed that objective measurements of vaginal elasticity and length were not linked to dilation during radiotherapy, but the study lacked power. One study showed that women who dilated tolerated a larger dilator, but the risk of objectivity and bias with historical controls was high. Another study showed that the vaginal measurements increased in length by a mean of 3 cm after dilation was introduced 6 to 10 weeks after radiotherapy, but there was no control group; another case series showed the opposite. Three recent studies showed less stenosis associated with prophylactic dilation after radiotherapy. One small case series suggested that dilation years after radiotherapy might restore the

Evaluation of treatment-effect heterogeneity using biomarkers measured on a continuous scale: subpopulation treatment effect pattern plot.

PubMed

Lazar, Ann A; Cole, Bernard F; Bonetti, Marco; Gelber, Richard D

2010-10-10

The discovery of biomarkers that predict treatment effectiveness has great potential for improving medical care, particularly in oncology. These biomarkers are increasingly reported on a continuous scale, allowing investigators to explore how treatment efficacy varies as the biomarker values continuously increase, as opposed to using arbitrary categories of expression levels resulting in a loss of information. In the age of biomarkers as continuous predictors (eg, expression level percentage rather than positive v negative), alternatives to such dichotomized analyses are needed. The purpose of this article is to provide an overview of an intuitive statistical approach-the subpopulation treatment effect pattern plot (STEPP)-for evaluating treatment-effect heterogeneity when a biomarker is measured on a continuous scale. STEPP graphically explores the patterns of treatment effect across overlapping intervals of the biomarker values. As an example, STEPP methodology is used to explore patterns of treatment effect for varying levels of the biomarker Ki-67 in the BIG (Breast International Group) 1-98 randomized clinical trial comparing letrozole with tamoxifen as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer. STEPP analyses showed patients with higher Ki-67 values who were assigned to receive tamoxifen had the poorest prognosis and may benefit most from letrozole.

"The support I need": women's experiences of social support after having received breast cancer diagnosis and awaiting surgery.

PubMed

Drageset, Sigrunn; Lindstrøm, Torill C; Giske, Tove; Underlid, Kjell

2012-01-01

Social support is associated with a better adjustment to breast cancer, whereas inadequate social support increases psychological distress. However, the period between diagnosis and surgery is particularly stressful, and few studies have addressed the significance of social support in this period. The purpose of this study was to describe women's individual experiences of social support after having received a breast cancer diagnosis and awaiting surgery. A qualitative descriptive design was used. Individual semistructured interviews were conducted the day before surgery with 21 women aged 41 to 73 years with newly diagnosed breast cancer at a Norwegian university hospital. Methods of qualitative meaning condensation analysis revealed 5 themes: available support, information and advice, care, having confidants, and balancing distance and closeness. Knowing that both family and healthcare professionals were available and caring gave a sense of security. Social support gave strength, although too much could be experienced as difficult and frightening. The women needed a balance between distance from and closeness to their social network. Both professional information and someone professional with whom to talk personally were essential. Social support is an important resource for women with breast cancer but can be a double-edged sword as the network's offered support can sometimes be a burden. Healthcare professionals could call each patient, encourage the patients to call if they want, and, if preferred, offer face-to-face consultations for women with breast cancer awaiting surgery. This contact should be a supportive, informative, and confidential available resource.

Switching to letrozole or exemestane improves hot flushes, mood and quality of life in tamoxifen intolerant women

PubMed Central

Thomas, R; Williams, M; Marshall, C; Walker, L

2008-01-01

We report an open-label, prospective, crossover study involving 184 post-menopausal women experiencing hot flushes on adjuvant tamoxifen (T). Six weeks after switching to an AI, the primary end point, hot flush score, improved by 47.3% (P<0.001) compared to those reported on T. The mean mood rating scale (MRS) score improved by 9.7% (P=0.01). The total mean combined FACT (b+es) score improved from 134.2 (95% CI ±2.96) to 143.5 (95% CI ±2.96 <0.001), and the endocrine subscale improved by 9.8% from 51.73 (95% CI ±1.38) to 57.34 (CI ±1.38, P<0.001). At 6 weeks, significantly more women chose to remain on an AI: 133 (72%), vs 40 (22%) (P<0.001) preferring T. At 3 months, 107 (58%) preferred to remain on an AI, 55(30%) on T, and 22 (12%) withdrew. The overall arthralgia rate at 3 months was 47% on AI and 30% on T (P=0.001). In all 182 (99%) women reported appreciating the opportunity to experience both drugs. These data suggest that if patients suffering significant adverse effects on T are given the opportunity to try an AI, this empowers them to prioritise relative side-effects, improving wellbeing in a significant proportion. These data also highlight the need for hospital follow-up in this intolerant cohort. PMID:18392053

Experience with and amount of postpartum maternity care: Comparing women who rated the care they received from the maternity care assistant as 'good' or 'less than good care'.

PubMed

Baas, C I; Wiegers, T A; de Cock, T P; Erwich, J J H M; Spelten, E R; Hutton, E K

2017-12-01

The postpartum period is an important time in the lives of new mothers, their children and their families. The aim of postpartum care is 'to detect health problems of mother and/or baby at an early stage, to encourage breastfeeding and to give families a good start' (Wiegers, 2006). The Netherlands maternity care system aims to enable every new family to receive postpartum care in their home by a maternity care assistant (MCA). In order to better understand this approach, in this study we focus on women who experienced the postpartum care by the MCA as 'less than good' care. Our research questions are; among postpartum women in the Netherlands, what is the uptake of MCA care and what factors are significantly associated with women's rating of care provided by the MCA. Design and setting This study uses data from the 'DELIVER study', a dynamic cohort study, which was set up to investigate the organization, accessibility and quality of primary midwifery care in the Netherlands. Participants In the DELIVER population 95.6% of the women indicated that they had received postpartum maternity care by an MCA in their home. We included the responses of 3170 women. To assess the factors that were significantly associated with reporting 'less than good (postpartum) care' by the MCA, a full cases backward logistic regression model was built using the multilevel approach in Generalized Linear Mixed Models. The mean rating of the postpartum care by the MCA was 8.8 (on a scale from 1-10), and 444 women (14%) rated the postpartum maternity care by the MCA as 'less than good care'. In the full cases multivariable analysis model, odds of reporting 'less than good care' by the MCA were significantly higher for women who were younger (women 25-35 years had an OR 1.32, CI 0.96-1.81 and women 35 years), multiparous (OR 1.27, CI 1.01-1.60) and had a higher level of education (women with a middle level had an OR 1.84,CI 1.22-2.79, and women with a high level of education had an OR 2

A randomized controlled trial to improve health among women receiving welfare in the US: the relationship between employment outcomes and the economic recession.

PubMed

Kneipp, Shawn M; Kairalla, John A; Sheely, Amanda L

2013-03-01

The high prevalence of health conditions among U.S. women receiving Temporary Assistance for Needy Families (TANF, or 'welfare') impedes the ability of many in this group to move from 'welfare-to-work', and the economic recession has likely exacerbated this problem. Despite this, few interventions have been developed to improve employment outcomes by addressing the health needs of women receiving TANF, and little is known about the impact of economic downturns on the employment trajectory of this group. Using data from a recent randomized controlled trial (RCT) that tested the efficacy of a public health nursing (PHN) intervention to address the chronic health condition needs of 432 American women receiving TANF, we examine the effect of the intervention and of recession exposure on employment. We further explore whether intervention effects were modified by select sociodemographic and health characteristics. Both marginal and more robust intervention effects were noted for employment-entry outcomes (any employment, p = 0.05 and time-to-employment, p = 0.01). There were significant effects for recession exposure on employment-entry (any employment, p = 0.002 and time-to-employment, p < 0.001). Neither the intervention nor recession exposure influenced longer-term employment outcomes (employment rate or maximum continuous employment). Intervention effects were not modified by age, education, prior TANF receipt, functional status, or recession exposure, suggesting the intervention was equally effective in improving employment-entry across a fairly heterogeneous group both before and after the recession onset. These findings advance our understanding of the health and employment dynamics among this group of disadvantaged women under variable macroeconomic conditions, and have implications for guiding health and TANF-related policy. Copyright © 2012 Elsevier Ltd. All rights reserved.

Patient actions and reactions after receiving negative results from expanded carrier screening.

PubMed

Kraft, S A; Schneider, J L; Leo, M C; Kauffman, T L; Davis, J V; Porter, K M; McMullen, C K; Wilfond, B S; Goddard, K A B

2018-05-01

With the expansion of carrier screening to general preconception and prenatal patient populations, most patients will receive negative results, which we define as indicating <25% risk of having a child with a genetic condition. Because there is limited experience with expanded carrier screening, it is important to understand how receiving negative results affects patients, especially as providers, payers, and policymakers consider whether to offer it. In this mixed-methods study, we asked preconception patients enrolled in the NextGen study about their expectations and experiences receiving negative expanded carrier screening results. Participants completed surveys at study enrollment (n = 110 women, 51 male partners), after receiving carrier results (n = 100 women, 38 male partners), after receiving secondary findings (n = 98 women, 36 male partners), and 6 months after receiving results (n = 95 women, 28 male partners). We also interviewed a subset of participants 12 to 24 months after receiving results (n = 24 women, 12 male partners). We found minimal negative emotional impact and privacy concerns, increased confidence in reproductive plans, and few changes to health behaviors, although some patients made health decisions based on misunderstandings of their results. These findings suggest that expanded carrier screening causes minimal psychosocial harms, but systems are needed to reduce the risk of misinterpreting results. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of tamoxifen and letrozole response in mammary preneoplasia of ER and aromatase overexpressing mice defines an immune-associated gene signature linked to tamoxifen resistance

PubMed Central

Dabydeen, Sarah A.; Kang, Keunsoo; Díaz-Cruz, Edgar S.; Alamri, Ahmad; Axelrod, Margaret L.; Bouker, Kerrie B.; Al-Kharboosh, Rawan; Clarke, Robert; Hennighausen, Lothar; Furth, Priscilla A.

2015-01-01

Response to breast cancer chemoprevention can depend upon host genetic makeup and initiating events leading up to preneoplasia. Increased expression of aromatase and estrogen receptor (ER) is found in conjunction with breast cancer. To investigate response or resistance to endocrine therapy, mice with targeted overexpression of Esr1 or CYP19A1 to mammary epithelial cells were employed, representing two direct pathophysiological interventions in estrogen pathway signaling. Both Esr1 and CYP19A1 overexpressing mice responded to letrozole with reduced hyperplastic alveolar nodule prevalence and decreased mammary epithelial cell proliferation. CYP19A1 overexpressing mice were tamoxifen sensitive but Esr1 overexpressing mice were tamoxifen resistant. Increased ER expression occurred with tamoxifen resistance but no consistent changes in progesterone receptor, pSTAT3, pSTAT5, cyclin D1 or cyclin E levels in association with response or resistance were found. RNA-sequencing (RNA-seq) was employed to seek a transcriptome predictive of tamoxifen resistance using these models and a second tamoxifen-resistant model, BRCA1 deficient/Trp53 haploinsufficient mice. Sixty-eight genes associated with immune system processing were upregulated in tamoxifen-resistant Esr1- and Brca1-deficient mice, whereas genes related to aromatic compound metabolic process were upregulated in tamoxifen-sensitive CYP19A1 mice. Interferon regulatory factor 7 was identified as a key transcription factor regulating these 68 immune processing genes. Two loci encoding novel transcripts with high homology to human immunoglobulin lambda-like polypeptide 1 were uniquely upregulated in the tamoxifen-resistant models. Letrozole proved to be a successful alternative to tamoxifen. Further study of transcriptional changes associated with tamoxifen resistance including immune-related genes could expand our mechanistic understanding and lead to biomarkers predictive of escape or response to endocrine therapies

A randomized controlled trial to improve health among women receiving welfare in the U.S.: the relationship between employment outcomes and the economic recession

PubMed Central

Kneipp, Shawn M.; Kairalla, John A.; Sheely, Amanda L.

2012-01-01

The high prevalence of health conditions among U.S. women receiving Temporary Assistance for Needy Families (TANF, or `welfare') impedes the ability of many in this group to move from `welfare-to-work', and the economic recession has likely exacerbated this problem. Despite this, few interventions have been developed to improve employment outcomes by addressing the health needs of women receiving TANF, and little is known about the impact of economic downturns on the employment trajectory of this group. Using data from a recent randomized controlled trial (RCT) that tested the efficacy of a public health nursing (PHN) intervention to address the chronic health condition needs of 432 American women receiving TANF, we examine the effect of the intervention and of recession exposure on employment. We further explore whether intervention effects were modified by select sociodemographic and health characteristics. Both marginal and more robust intervention effects were noted for employment-entry outcomes (any employment, p=0.05 and time-to-employment, p=0.01). There were significant effects for recession exposure on employment-entry (any employment, p=0.002 and time-to-employment, p<0.001). Neither the intervention nor recession exposure influenced longer-term employment outcomes (employment rate or maximum continuous employment). Intervention effects were not modified by age, education, prior TANF receipt, functional status, or recession exposure, suggesting the intervention was equally effective in improving employment-entry across a fairly heterogeneous group both before and after the recession onset. These findings advance our understanding of the health and employment dynamics among this group of disadvantaged women under variable macroeconomic conditions, and have implications for guiding health and TANF-related policy. PMID:22963921

Clinical review: Breast development in trans women receiving cross-sex hormones.

PubMed

Wierckx, Katrien; Gooren, Louis; T'Sjoen, Guy

2014-05-01

In trans women (male-to-female transsexual persons), cross-sex hormone therapy is administered to induce feminization. Breast development is an important part of feminization for most trans women. The aim of this study is to assess the effect of cross-sex hormone therapy on breast development in adult trans women. Additionally, we aimed to investigate the benefit or harm of administration of progestogens on breast development. A review of the literature in Embase, Medline, The Cochrane Library, PsycINFO databases, PubMed, and Web of Knowledge until January 2014. Effects of cross-sex hormone therapy and progestogens on breast development in trans women. Only few studies with low quality of evidence addressed these topics. The available evidence suggests that breast development is insufficient for the majority of trans women and that type and dosage of hormonal therapy seem not to have an important role on final breast size. Our knowledge concerning the natural history and effects of different cross-sex hormone therapies on breast development in trans women is extremely sparse and based on low quality of evidence. Current evidence does not provide evidence that progestogens enhance breast development in trans women. Neither do they prove the absence of such an effect. This prevents us from drawing any firm conclusion at this moment and demonstrates the need for further research to clarify these important clinical questions. © 2014 International Society for Sexual Medicine.

Febrile neutropaenia and chemotherapy discontinuation in women aged 70 years or older receiving adjuvant chemotherapy for early breast cancer.

PubMed

Adjogatse, D; Thanopoulou, E; Okines, A; Thillai, K; Tasker, F; Johnston, S R D; Harper-Wynne, C; Torrisi, E; Ring, A

2014-11-01

Low rates of adjuvant chemotherapy use are frequently reported in older women with early breast cancer. One of the reasons for this may be the risk of febrile neutropaenia or the perception that older patients will probably not complete the chemotherapy course prescribed. There are no data regarding these adverse outcomes in routine clinical practice. We identified 128 patients aged 70 years or over who received neoadjuvant or adjuvant chemotherapy for early breast cancer in seven UK cancer centres between 2006 and 2012. Data were collected regarding standard clinical and pathological variables and treatment toxicity and outcomes. Twenty-four patients (19%) had an episode of febrile neutropaenia. Overall, 27 patients (21%) did not complete their planned therapy. Chemotherapy discontinuation was more common in those patients with an episode of febrile neutropaenia (46% versus 16%, P = 0.004). Thirty patients (23%) were admitted with chemotherapy-related complications. There were no treatment-related deaths. The rates of febrile neutropaenia and treatment discontinuation are high in women aged 70 years or over receiving adjuvant chemotherapy for breast cancer. Close attention should be paid to the choice or regimen and the use of supportive therapies in this patient population. Copyright © 2014 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Angiogenic Factor Profiles in Pregnant Women With a History of Early-Onset Severe Preeclampsia Receiving Low-Molecular-Weight Heparin Prophylaxis.

PubMed

Lecarpentier, Edouard; Gris, Jean Christophe; Cochery-Nouvellon, Eva; Mercier, Erick; Touboul, Cyril; Thadhani, Ravi; Karumanchi, S Ananth; Haddad, Bassam

2018-01-01

To evaluate whether daily low-molecular-weight (LMW) heparin prophylaxis during pregnancy alters profile of circulating angiogenic factors that have been linked with the pathogenesis of preeclampsia and fetal growth restriction. This is a planned ancillary study of the Heparin-Preeclampsia trial, a randomized trial in pregnant women with a history of severe early-onset preeclampsia (less than 34 weeks of gestation). In the parent study, all women were treated with aspirin and then randomized to receive LMW heparin or aspirin alone. In this study, we measured serum levels of circulating angiogenic factors (soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin by immunoassay) at the following gestational windows: 10-13 6/7 weeks, 14-17 6/7 weeks, 18-21 6/7 weeks, 22-25 6/7 weeks, 26-29 6/7 weeks, 30-33 6/7 weeks, and 34-37 6/7 weeks. Samples were available from 185 patients: LMW heparin+aspirin (n=92) and aspirin alone (n=93). The two groups had comparable baseline characteristics and had similar adverse composite outcomes (35/92 [38.0%] compared with 36/93 [38.7%]; P=.92). There were no significant differences in serum levels of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin in the participants who received LMW heparin and aspirin compared with those who received aspirin alone regardless of gestational age period. Finally, women who developed an adverse composite outcome at less than 34 weeks of gestation demonstrated significant alterations in serum angiogenic profile as early as 10-13 6/7 weeks that was most dramatic 6-8 weeks preceding delivery. Prophylactic LMW heparin therapy when beginning from before 14 weeks of gestation with aspirin during pregnancy is not associated with an improved angiogenic profile. This may provide a molecular explanation for the lack of clinical benefit noted in recent trials. ClinicalTrials.gov, NCT00986765.

Targeting the receptor tyrosine kinase RET in combination with aromatase inhibitors in ER positive breast cancer xenografts.

PubMed

Andreucci, Elena; Francica, Paola; Fearns, Antony; Martin, Lesley-Ann; Chiarugi, Paola; Isacke, Clare M; Morandi, Andrea

2016-12-06

The majority of breast cancers are estrogen receptor positive (ER+). Blockade of estrogen biosynthesis by aromatase inhibitors (AIs) is the first-line endocrine therapy for post-menopausal women with ER+ breast cancers. However, AI resistance remains a major challenge. We have demonstrated previously that increased GDNF/RET signaling in ER+ breast cancers promotes AI resistance. Here we investigated the efficacy of different small molecule RET kinase inhibitors, sunitinib, cabozantinib, NVP-BBT594 and NVP-AST487, and the potential of combining a RET inhibitor with the AI letrozole in ER+ breast cancers. The most effective inhibitor identified, NVP-AST487, suppressed GDNF-stimulated RET downstream signaling and 3D tumor spheroid growth. Ovariectomized mice were inoculated with ER+ aromatase-overexpressing MCF7-AROM1 cells and treated with letrozole, NVP-AST487 or the two drugs in combination. Surprisingly, the three treatment regimens showed similar efficacy in impairing MCF7-AROM1 tumor growth in vivo. However in vitro, NVP-AST487 was superior to letrozole in inhibiting the GDNF-induced motility and tumor spheroid growth of MCF7-AROM1 cells and required in combination with letrozole to inhibit GDNF-induced motility in BT474-AROM3 aromatase expressing cells. These data indicate that inhibiting RET is as effective as the current therapeutic regimen of AI therapy but that a combination treatment may delay cancer cell dissemination and metastasis.

Influence of side-effects on early therapy persistence with letrozole in post-menopausal patients with early breast cancer: Results of the prospective EvAluate-TM study.

PubMed

Nabieva, N; Fehm, T; Häberle, L; de Waal, J; Rezai, M; Baier, B; Baake, G; Kolberg, H-C; Guggenberger, M; Warm, M; Harbeck, N; Wuerstlein, R; Deuker, J-U; Dall, P; Richter, B; Wachsmann, G; Brucker, C; Siebers, J W; Popovic, M; Kuhn, T; Wolf, C; Vollert, H-W; Breitbach, G-P; Janni, W; Landthaler, R; Kohls, A; Rezek, D; Noesselt, T; Fischer, G; Henschen, S; Praetz, T; Heyl, V; Kühn, T; Krauss, T; Thomssen, C; Hohn, A; Tesch, H; Mundhenke, C; Hein, A; Hack, C C; Schmidt, K; Belleville, E; Brucker, S Y; Kümmel, S; Beckmann, M W; Wallwiener, D; Hadji, P; Fasching, P A

2018-06-01

Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor-positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. Post-menopausal hormone receptor-positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90-3.42), sleep disorders (HR 1.95; 95% CI, 1.41-2.70) and other AEs (HR 2.03; 95% CI, 1.51-2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74-1.84). These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. CFEM345DDE19. Copyright © 2018 Elsevier Ltd. All rights reserved.

Exercise for women receiving adjuvant therapy for breast cancer.

PubMed

Furmaniak, Anna C; Menig, Matthias; Markes, Martina H

2016-09-21

A huge clinical research database on adjuvant cancer treatment has verified improvements in breast cancer outcomes such as recurrence and mortality rates. On the other hand, adjuvant and neoadjuvant therapy with chemotherapy and radiotherapy impacts on quality of life due to substantial short- and long-term side effects. A number of studies have evaluated the effect of exercise interventions on those side effects. This is an updated version of the original Cochrane review published in 2006. The original review identified some benefits of physical activity on physical fitness and the resulting capacity for performing activities of daily life. It also identified a lack of evidence for other outcomes, providing clear justification for an updated review. To assess the effect of aerobic or resistance exercise interventions during adjuvant treatment for breast cancer on treatment-related side effects such as physical deterioration, fatigue, diminished quality of life, depression, and cognitive dysfunction. We carried out an updated search in the Cochrane Breast Cancer Group Specialised Register (30 March 2015), the Cochrane Central Register of Controlled Trials (CENTRAL) (Issue 2, 2015), MEDLINE (1966 to 30 March 2015), and EMBASE (1966 to 30 March 2015). We did not update the original searches in CINAHL (1982 to 2004), SPORTDiscus (1975 to 2004), PsycINFO (1872 to 2003), SIGLE (1880 to 2004), and ProQuest Digital Dissertations (1861 to 2004). We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials on 30 March 2015. We screened references in relevant reviews and published clinical trials. We included randomised controlled trials that examined aerobic or resistance exercise or both in women undergoing adjuvant treatment for breast cancer. Published and unpublished trials were eligible. Two review authors independently performed data extraction, assessed trials, and graded the

Who receives a medical evaluation for infertility in the United States?

PubMed

Farland, Leslie V; Collier, Ai-Ris Y; Correia, Katharine F; Grodstein, Francine; Chavarro, Jorge E; Rich-Edwards, Janet; Missmer, Stacey A

2016-05-01

To investigate characteristics of receiving a medical evaluation for infertility among infertile women. Prospective cohort. Academic institution. A total of 7,422 women who reported incident infertility between 1989 and 2009 in the Nurses' Health Study II. None. Report of receiving a medical evaluation for infertility. Approximately 65% of women who reported infertility had a medical evaluation for infertility. Infertile women who were parous (relative risk [RR] = 0.81, 95% confidence interval [CI] 0.78-0.84), older, current smokers (RR = 0.89, 95% CI 0.83-0.96), or who had a higher body mass index (BMI) were less likely to report receiving a medical infertility evaluation. Infertile women who exercised frequently, took multivitamins (RR = 1.03, 95% CI 1.00-1.07), lived in states with comprehensive insurance coverage (RR = 1.09, 95% CI 1.00-1.19), had a high household income, or who had a recent physical examination (RR = 1.15, 95% CI 1.06-1.24) were more likely to report receiving a medical infertility evaluation. These findings highlight demographic, lifestyle, and access barriers to receiving medical infertility care. Historically, the discussion of barriers to infertility care has centered on financial access, geographic access, and socioeconomic status. Our findings build off literature by supporting previously reported associations and showcasing the importance of demographic and lifestyle factors in accessing care. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The lived experience of Jordanian women who received family support during labor.

PubMed

Khresheh, Reham; Barclay, Lesley

2010-01-01

Policies regarding childbirth in Jordan currently exclude attendance by a female relative to provide support. This study was done in order to describe the experience of a group of Jordanian women who had been afforded support from a female relative during a nursing research project. Semistructured interviews were conducted with 25 women at 6 weeks postpartum. All of the women had given birth at the main hospital in the southern region of Jordan. Women had positive experiences with their female relative support. Four themes were identified as common to the women involved: (1) increased sense of security, (2) provision of physical help, (3) communicating the woman's needs/wishes to her professional caregivers, and (4) emotional support and encouragement. The results show that the support of a female relative was helpful for this small group of Jordanian women experiencing their first labor and birth. Since the literature clearly shows that support in labor is appropriate and produces improved outcomes, public health practitioners in maternal and child health, along with hospitals, should emphasize this as a valuable resource for pregnant women. Non-Western or developing countries could benefit from more fully using evidence currently in the literature on a range of practices, including that of emotional and social support in labor.

Effects of Electro-Acupuncture on Ovarian P450arom, P450c17α and mRNA Expression Induced by Letrozole in PCOS Rats

PubMed Central

Wu, Huangan; Zhao, Jimeng; Cui, Yunhua; Liu, Huirong; Wu, Lingxiang; Shi, Yin; Zhu, Bing

2013-01-01

Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS). Abnormalities in enzymatic activity and the expression of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA) in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD) rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA) consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg−1 of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA) showed significantly decreased androgens (i.e., androstenedione and testosterone) with significantly increased estrogens (i.e., estrone, estradiol) and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive and

Effects of electro-acupuncture on ovarian P450arom, P450c17α and mRNA expression induced by letrozole in PCOS rats.

PubMed

Sun, Jie; Jin, Chunlan; Wu, Huangan; Zhao, Jimeng; Cui, Yunhua; Liu, Huirong; Wu, Lingxiang; Shi, Yin; Zhu, Bing

2013-01-01

Hyperandrogenism is a core factor in the series of reproductive and endocrine metabolic disorders involved in polycystic ovary syndrome (PCOS). Abnormalities in enzymatic activity and the expression of ovarian granular cell layer P450arom and theca cell P450c17α can lead to an atypical environment of local ovarian hormones, including excessive androgen levels. Rat models prepared with letrozole exhibit similar endocrine and histological changes to those that occur in human PCOS. We used such a model to study the role of electro-acupuncture (EA) in regulating ovarian P450arom and P450c17α enzymatic activity and mRNA expression in PCOS rats. Female Sprague Dawley (SD) rats aged 42 days were randomly divided into 3 groups (control, PCOS, and PCOS EA) consisting of 10 rats each. The PCOS and PCOS EA groups were administered a gavage of 1.0 mg/kg(-1) of letrozole solution once daily for 21 consecutive days. Beginning in the ninth week, the PCOS EA group was administered low-frequency EA treatment daily for 14 consecutive days. After the treatment, we obtained the following results. The estrous cycles were restored in 8 of the 10 rats in the PCOS EA group, and their ovarian morphologies and ultrastructures normalized. The peripheral blood measurements (with ELISA) showed significantly decreased androgens (i.e., androstenedione and testosterone) with significantly increased estrogens (i.e., estrone, estradiol) and increased P450arom with decreased P450C17α. Immunohistochemistry and Western blotting methods showed enhanced expression of ovarian granular cell layer P450arom as well as decreased expression of theca cell layer P450C17α. Fluorescence quantitative PCR methods showed enhanced expression of ovarian granular cell layer P450arom mRNA as well as decreased expression of theca cell layer P450C17α mRNA. These results may help explain the effects of electro-acupuncture in changing the local ovarian hyperandrogenic environment and improving reproductive and

Fertility preservation with ovarian stimulation and time to treatment in women with stage II-III breast cancer receiving neoadjuvant therapy.

PubMed

Chien, A Jo; Chambers, Julia; Mcauley, Fiona; Kaplan, Tessa; Letourneau, Joseph; Hwang, Jimmy; Kim, Mi-Ok; Melisko, Michelle E; Rugo, Hope S; Esserman, Laura J; Rosen, Mitchell P

2017-08-01

To determine whether fertility preservation with ovarian stimulation (OS) results in treatment delay in breast cancer (BC) patients receiving neoadjuvant therapy (NAT). This is a retrospective study of women screened for the prospective neoadjuvant ISPY2 trial at the University of California San Francisco. All patients were <43, had stage II-III BC, and received neoadjuvant therapy. Time to initiation of NAT was compared between women who underwent OS (STIM) and women who did not (control). Patient and tumor characteristics, as well as oncologic outcomes, were compared between STIM and control groups. 82 patients were included (34 STIM and 48 control). STIM patients were overall younger (mean = 35 vs. 36.9 years old, p = 0.06), and more likely to be childless (79.4 vs 31.2%, p < 0.0001) than controls. Mean time from diagnosis to initiation of NAT was 40 days, with no significant difference between STIM and control groups (mean 39.8 days vs 40.9 days, p = 0.75). Mean time from diagnosis to fertility consultation was 16.3 days. With median follow-up of 79 months, 16 (19.5%) patients have recurred or died from BC. Rates of pCR, recurrence, and death were similar in both groups. Six of 34 STIM patients have undergone embryo transfer, resulting in one patient with two live births. Fertility preservation with OS can be performed in the neoadjuvant setting without delay in initiation of systemic therapy and should be discussed with all early-stage BC patients of reproductive age.

Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation.

PubMed

Kamath, Mohan S; Maheshwari, Abha; Bhattacharya, Siladitya; Lor, Kar Yee; Gibreel, Ahmed

2017-11-02

Gonadotropins are the most commonly used medications for controlled ovarian stimulation in in vitro fertilisation (IVF). However, they are expensive and invasive, and are associated with the risk of ovarian hyperstimulation syndrome (OHSS). Recent calls for more patient-friendly regimens have led to growing interest in the use of clomiphene citrate (CC) and aromatase inhibitors with or without gonadotropins to reduce the burden of hormonal injections. It is currently unknown whether regimens using CC or aromatase inhibitors such as letrozole (Ltz) are as effective as gonadotropins alone. To determine the effectiveness and safety of regimens including oral induction medication (such as clomiphene citrate or letrozole) versus gonadotropin-only regimens for controlled ovarian stimulation in IVF or intracytoplasmic sperm injection (ICSI) treatment. We searched the following databases: Cochrane Gynaecology and Fertility Group Specialised Register (searched January 2017), the Cochrane Central Register of Controlled Trials (CENTRAL CRSO), MEDLINE (1946 to January 2017), Embase (1980 to January 2017), and reference lists of relevant articles. We also searched trials registries ClinicalTrials.gov (clinicaltrials.gov/) and the World Health Organization International Clinical Trials Registry Platform (www.who.int/trialsearch/Default.aspx). We handsearched relevant conference proceedings. We included randomized controlled trials (RCTs). The primary outcomes were live-birth rate (LBR) and OHSS. Three review authors independently assessed trial eligibility and risk of bias. We calculated risk ratios (RR) and Peto odds ratio (OR) with 95% confidence intervals (CIs) for dichotomous outcomes and mean differences (MD) for continuous outcomes. We analyzed the general population of women undergoing IVF treatment and (as a separate analysis) women identified as poor responders. We assessed the overall quality of the evidence using the GRADE approach. We included 27 studies in the

Exercise differentially affects metabolic functions and white adipose tissue in female letrozole- and dihydrotestosterone-induced mouse models of polycystic ovary syndrome.

PubMed

Marcondes, Rodrigo R; Maliqueo, Manuel; Fornes, Romina; Benrick, Anna; Hu, Min; Ivarsson, Niklas; Carlström, Mattias; Cushman, Samuel W; Stenkula, Karin G; Maciel, Gustavo A R; Stener-Victorin, Elisabet

2017-06-15

Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Who receives a medical evaluation for infertility in the United States?

PubMed Central

Farland, Leslie V; Collier, Ai-ris Y; Correia, Katharine F; Grodstein, Francine; Chavarro, Jorge E; Rich-Edwards, Janet; Missmer, Stacey A

2015-01-01

Objective To investigate characteristics of receiving a medical evaluation for infertility among infertile women Design Prospective Cohort Setting Academic Institution Patients Seven thousand four-hundred and twenty two women who reported incident infertility between 1989 and 2009 in the Nurses’ Health Study II. Intervention None Main Outcome Measures Report of receiving a medical evaluation for infertility Results Approximately 65% of women who reported infertility had a medical evaluation for infertility. Infertile women who were parous (RR:0.81, CI:0.78, 0.84), older (P-value, test for linear trend:<0.001), current smokers (RR:0.89, CI:0.83, 0.96), or who had a higher body mass index (BMI)(P-value: 0.01) were less likely to report receiving a medical infertility evaluation. Infertile women who exercised frequently (P-value: 0.04), took multivitamins (RR: 1.03, CI:1.00, 1.07), lived in states with comprehensive insurance coverage (RR:1.09, CI:1.00, 1.19), had a high household income (P-value: 0.05), or who had a recent physical exam (RR:1.15, CI:1.06, 1.24) were more likely to report receiving a medical infertility evaluation. Conclusions These findings highlight demographic, lifestyle, and access barriers to receiving medical infertility care. Historically, the discussion of barriers to infertility care has centered on financial access, geographic access, and socioeconomic status. Our findings build off previous literature by supporting previously reported associations and showcasing the importance of demographic and lifestyle factors in accessing care. PMID:26785253

Project WINGS (Women Initiating New Goals of Safety): A randomised controlled trial of a screening, brief intervention and referral to treatment (SBIRT) service to identify and address intimate partner violence victimisation among substance-using women receiving community supervision.

PubMed

Gilbert, Louisa; Shaw, Stacey A; Goddard-Eckrich, Dawn; Chang, Mingway; Rowe, Jessica; McCrimmon, Tara; Almonte, Maria; Goodwin, Sharun; Epperson, Matthew

2015-12-10

The high rate of intimate partner violence (IPV) victimisation found among substance-using women receiving community supervision underscores the need for effective IPV victimisation screening, brief intervention and referral to treatment services (SBIRT) for this population. This randomised controlled trial (RCT) aims to assess the feasibility, safety and efficacy of a single-session computerised self-paced IPV SBIRT (Computerised WINGS) in identifying IPV victimisation among women under community supervision and increasing access to IPV services, compared to the same IPV SBIRT service delivered by a case manager (Case Manager WINGS). This RCT was conducted with 191 substance-using women in probation and community court sites in New York City. No significant differences were found between Computerised and Case Manager WINGS arms on any outcomes. Both arms reported identical high rates of any physical, sexual or psychological IPV victimisation in the past year (77% for both arms) during the intervention. Both arms experienced significant increases from baseline to the 3-month follow-up in receipt of IPV services, social support, IPV self-efficacy and abstinence from drug use. Findings suggest that both modalities of WINGS show promise in identifying and addressing IPV victimisation among substance-using women receiving community supervision. Copyright © 2015 John Wiley & Sons, Ltd.

The effect of estradiol on granulosa cell responses to FSH in women with polycystic ovary syndrome.

PubMed

Homer, Michael V; Rosencrantz, Marcus A; Shayya, Rana F; Chang, R Jeffrey

2017-02-10

The influence of estradiol (E 2 ) on granulosa cell (GC) function has not been tested clinically in women with polycystic ovary syndrome (PCOS). The objective of this study is to determine if E 2 influences GC responses to FSH in women with PCOS. This is a two phase, single cohort study conducted over a 2-year period at a single academic center. Nine women with PCOS according to NIH criteria. In Phase 1, FSH stimulation of GC responses as measured by E 2 and Inhibin B (Inh B) were assessed before and at 5 and 6 weeks after GnRH agonist administration. In Phase 2, the same protocol was employed with the addition of an aromatase inhibitor (letrozole, LET) administered daily beginning at week 4 for 2 weeks. In Phase 1, recovery of FSH, E 2 and Inh B from ovarian suppression occurred at 5 and 6 weeks after GnRH agonist injection and preceded resumption of LH and androgen secretion. In Phase 2, hormone recovery after GnRH agonist was characterized by elevated FSH and suppressed E 2 levels whereas recovery of LH and androgen levels were unchanged. In Phase 1, FSH stimulated E 2 and Inh B responses were unaltered during recovery from ovarian suppression. In Phase 2, E 2 and Inh B fold changes after FSH were significantly reduced at weeks 5 (p < 0.04) and 6 (p < 0.01), respectively. In anovulatory women with PCOS, chronic, unopposed E 2 secretion may contribute, at least in part, to enhanced ovarian responsiveness to FSH. NCT02389088.

Women Nurturing Women: A Woman's Group Using Hypnotherapy.

ERIC Educational Resources Information Center

Forester-Miller, Holly

1999-01-01

Provides information regarding rationale, objectives, format, and insights from a women's psychotherapy group where self-hypnosis and working in trance were major components. The group was designed to promote emotional, psychological, and physiological healing, and to facilitate women in learning how to give and receive nurturing. Describes…

Barriers for Hispanic women in receiving the human papillomavirus vaccine: a nursing challenge.

PubMed

Wagner, Janelle

2009-12-01

Cervical cancer affects more Hispanic women than non-Hispanic women in the United States. A vaccination exists to aid in the prevention of cervical cancer; an estimated 70% of cases could be avoided with the human papillomavirus (HPV) vaccine. However, women of Hispanic descent have many access barriers. By identifying and addressing such barriers, nurses can play a significant role in educating Hispanic women about the benefits of vaccination before HPV exposure occurs. Theoretical integration with Leininger's Culture Care Theory of Diversity and Universality provides a framework to address cultural differences and awareness when educating Hispanic women about this health issue. Additional nursing research into effective communication and educational programs to help reach the Hispanic population continues to be a priority in this vulnerable community.

NEOCENT: a randomised feasibility and translational study comparing neoadjuvant endocrine therapy with chemotherapy in ER-rich postmenopausal primary breast cancer.

PubMed

Palmieri, C; Cleator, S; Kilburn, L S; Kim, S B; Ahn, S-H; Beresford, M; Gong, G; Mansi, J; Mallon, E; Reed, S; Mousa, K; Fallowfield, L; Cheang, M; Morden, J; Page, K; Guttery, D S; Rghebi, B; Primrose, L; Shaw, J A; Thompson, A M; Bliss, J M; Coombes, R C

2014-12-01

Neoadjuvant endocrine therapy is an alternative to chemotherapy for women with oestrogen receptor (ER)-positive early breast cancer (BC). We aimed to assess feasibility of recruiting patients to a study comparing chemotherapy versus endocrine therapy in postmenopausal women with ER-rich primary BC, and response as well as translational endpoints were assessed. Patients requiring neoadjuvant therapy were randomised to chemotherapy: 6 × 3-weekly cycles FE₁₀₀C or endocrine therapy: letrozole 2.5 mg, daily for 18-23 weeks. Primary endpoints were recruitment feasibility and tissue collection. Secondary endpoints included clinical, radiological and pathological response rates, quality of life and translational endpoints. 63/80 patients approached were eligible, of those 44 (70, 95% CI 57-81) were randomised. 12 (54.5, 95% CI 32.2-75.6) chemotherapy patients showed radiological objective response compared with 13 (59.1, 95% CI 36.4-79.3) letrozole patients. Compared with baseline, mean Ki-67 levels fell in both groups at days 2-4 and at surgery [fold change: 0.24 (95% CI 0.12-0.51) and 0.24; (95% CI 0.15-0.37), respectively]. Plasma total cfDNA levels rose from baseline to week 8 [fold change: chemotherapy 2.10 (95% CI 1.47-3.00), letrozole 1.47(95% CI 0.98-2.20)], and were maintained at surgery in the chemotherapy group [chemotherapy 2.63; 95% CI 1.56-4.41), letrozole 0.95 (95% CI 0.71-1.26)]. An increase in plasma let-7a miRNA was seen at surgery for patients with objective radiological response to chemotherapy. Recruitment and tissue collection endpoints were met; however, a larger trial was deemed unfeasible due to slow accrual. Both regimens were equally efficacious. Dynamic changes were seen in Ki-67 and circulating biomarkers in both groups with increases in cfDNA and let-7a miRNA persisting until surgery for chemotherapy patients.

Earnings Differences between Women and Men. Facts on Working Women.

ERIC Educational Resources Information Center

Women's Bureau (DOL), Washington, DC.

Although the gap between women's and men's wages differs slightly depending on how the gap is measured, no matter how they are measured, women's earnings are below those received by men in 97% of the occupations for which data are available. Since 1979, women's earnings have been climbing when compared with men's earnings, gaining steeply during…

Barriers to Receiving Long-acting Reversible Contraception in the Postpartum Period.

PubMed

Zerden, Matthew L; Tang, Jennifer H; Stuart, Gretchen S; Norton, Deborah R; Verbiest, Sarah B; Brody, Seth

2015-01-01

To assess why postpartum women who desired long-acting reversible contraception (LARC) did not receive it in the postpartum period and to assess which contraceptive methods they were using instead. This was a subgroup analysis of 324 women enrolled in a randomized, controlled trial to receive or not receive an educational LARC script during their postpartum hospitalization. Participants in this subgroup analysis stated that they were either using LARC (n = 114) or interested in using LARC (n = 210) during a follow-up survey completed after their scheduled 6-week postpartum visit. Modified Poisson regression analysis was used to assess for characteristics associated with using LARC by the time of the follow-up survey. Women who were interested in LARC but not using it were more likely to be multiparous (relative risk [RR], 1.59; 95% CI, 1.19-2.11) and to have missed their postpartum visit (RR, 25.88; 95% CI, 3.75-178.44) compared with those using LARC. Among the interested 210 who were not using LARC, the most common reasons provided for non-use were that they were told to come back for another insertion visit (45%), missed the postpartum visit (26%), and could not afford LARC (11%). The most common contraceptive methods used instead of LARC were barrier methods (42%) and abstinence (19%); 18% used no contraceptive method. Two-thirds (65%) of postpartum women who desired to use LARC did not receive it in the postpartum period and used less effective contraceptive methods. Increasing access to immediate postpartum LARC and eliminating two-visit protocols for LARC insertion may increase postpartum LARC use. As the Affordable Care Act moves toward full implementation, it is necessary to understand the barriers that prevent interested patients from receiving LARC. Copyright © 2015 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Treatment patterns and duration in post-menopausal women with HR+/HER2- metastatic breast cancer in the US: a retrospective chart review in community oncology practices (2004-2010).

PubMed

Macalalad, Alexander R; Hao, Yanni; Lin, Peggy L; Signorovitch, James E; Wu, Eric Q; Ohashi, Erika; Zhou, Zhou; Kelley, Caroline

2015-02-01

Clinical guidelines prefer endocrine therapy (ET) as initial treatment for post-menopausal women with hormone receptor positive (HR+)/human epidermal growth factor receptor 2 negative (HER2-) metastatic breast cancer (mBC). Chemotherapy (CT) should be reserved for patients who develop symptomatic visceral disease or have no clinical benefit after three sequential ET regimens. It is unclear if real-world clinical practice reflects these guidelines. To describe treatment patterns and treatment durations by lines of therapy for ET and CT among post-menopausal HR+/HER2- mBC patients. Charts were reviewed from a network of community-based oncology practices of eligible patients who had progressed after initiating adjuvant or first-line treatment for mBC between 1 January 2004 and 30 September 2010. Extracted chart data included demographics, treatment histories, and outcomes. Treatment duration was estimated using Kaplan-Meier estimators. A total of 144 patients were studied. Patients received a median of two lines of ET, and <10% had three or more lines of ET before receiving CT. From first line to second line, the median treatment duration was 11.6 to 4.9 months for ET overall; 13.8 to 10.5 months for anastrozole; 18.6 to 7.0 months for letrozole; and 5.1 to 2.9 months for fulvestrant. For CT, the median duration was 5.1 months in the first line and 3.7 months and below in subsequent lines. During the study period (1 January 2004 - 30 September 2012), most patients received <3 lines of ET before receiving CT. The drop in median duration of ET from first to second line suggests that single agent ETs might not be as effective beyond the first line. A key limitation of this study was the small sample size. In addition, more research is needed to further investigate the short treatment duration of fulvestrant across early lines of therapy (which could indicate lack of efficacy).

Identification and replication of prediction models for ovulation, pregnancy and live birth in infertile women with polycystic ovary syndrome.

PubMed

Kuang, Hongying; Jin, Susan; Hansen, Karl R; Diamond, Michael P; Coutifaris, Christos; Casson, Peter; Christman, Gregory; Alvero, Ruben; Huang, Hao; Bates, G Wright; Usadi, Rebecca; Lucidi, Scott; Baker, Valerie; Santoro, Nanette; Eisenberg, Esther; Legro, Richard S; Zhang, Heping

2015-09-01

Can we build and validate predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome (PCOS)? We were able to develop and validate a predictive model for pregnancy outcomes in women with PCOS using simple clinical and biochemical criteria particularly duration of attempting conception, which was the most consistent predictor among all considered factors for pregnancy outcomes. Predictive models for ovulation and pregnancy outcomes in infertile women with polycystic ovary syndrome have been reported, but such models require validation. This is a secondary analysis of the data from the Pregnancy in Polycystic Ovary Syndrome I and II (PPCOS-I and -II) trials. Both trials were double-blind, randomized clinical trials that included 626 and 750 infertile women with PCOS, respectively. PPCOS-I participants were randomized to either clomiphene citrate (CC), metformin, or their combination, and PPCOS-II participants to either letrozole or CC for up to five treatment cycles. Linear logistic regression models were fitted using treatment, BMI, and other published variables as predictors of ovulation, conception, clinical pregnancy, and live birth as the outcome one at a time. We first evaluated previously reported significant predictors, and then constructed new prediction models. Receiver operating characteristic (ROC) curves were constructed and the area under the curves (AUCs) was calculated to compare performance using different models and data. Chi-square tests were used to examine the goodness-of-fit and prediction power of logistic regression model. Predictive factors were similar between PPCOS-I and II, but the two participant samples differed statistically significantly but the differences were clinically minor on key baseline characteristics and hormone levels. Women in PPCOS-II had an overall more severe PCOS phenotype than women in PPCOS-I. The clinically minor but statistically significant differences may be due to the

Androgens in women with anorexia nervosa and normal-weight women with hypothalamic amenorrhea.

PubMed

Miller, K K; Lawson, E A; Mathur, V; Wexler, T L; Meenaghan, E; Misra, M; Herzog, D B; Klibanski, A

2007-04-01

Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/ or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. We conducted a cross-sectional study at a general clinical research center. A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with anorexia nervosa. Interventional studies are needed to confirm these findings and determine whether

Disclosure of HIV serostatus to male partner and use of modern contraceptives among women receiving HIV care services in Kampala, Uganda.

PubMed

Zalwango, Vivian W; Tweheyo, Raymond; Makumbi, Fredrick

2013-11-01

To investigate whether disclosure of HIV status is associated with use of modern contraceptives (MCs) among women attending HIV care services at an AIDS Information Center (AIC) in an urban setting in Uganda. In a cross-sectional study between March and April 2010, HIV-positive married women aged 15-49years who had received their HIV-positive serostatus results at least 4weeks previously were interviewed at the AIC, Kampala, Uganda. Female use of MCs was compared by HIV disclosure to male marital partners. Log-binomial regression models were used to obtain crude and adjusted prevalence risk ratios (PRRs) and corresponding 95% confidence intervals (CIs). Nearly three-quarters (72.6%) of the women had disclosed their HIV-positive status to their partner. Overall, use of MCs was reported by 41.0% of the participants. Use of only 1 MC method was similar between those disclosing (81.1%) and those not disclosing (84.3%), but use of dual methods tended to be higher among disclosers (14.4%) than among non-disclosers (10.8%). In adjusted analyses, MC use was 41.0% lower among disclosers than among non-disclosers (adjusted PRR, 0.59; 95% CI, 0.46-0.77). HIV serostatus disclosure was associated with lower use of MCs among HIV-positive women in Kampala, Uganda. © 2013.

Examining Progress and Equity in Information Received by Women Using a Modern Method in 25 Developing Countries.

PubMed

Jain, Anrudh K

2016-09-01

The information exchanged during a contraceptive visit is important because providers need to understand clients' reproductive intentions and clients need to receive adequate information about methods and possible method-related side effects and problems. Little is known about how information exchange has changed over time and how it might vary across countries or subgroups within a country. Demographic and Health Survey data from 25 developing countries were used to calculate the Method Information Index (MII), a Family Planning 2020 indicator that reflects some aspects of contraceptive information exchanged between providers and clients. For each country, the MII was calculated from each of two surveys about five years apart to examine change in the indicator over time. In addition, the MII was examined for all countries combined and by region. The average MII for all 25 countries increased from 34% at the earlier survey time to 39% at the later survey time; the index values of individual countries ranged from 19% to 64% at survey time 1 and from 13% to 65% at survey time 2. The MII increased over time in 15 countries and declined in 10. In analyses by contraceptive method type, the MII tended to be highest among implant users and lowest among women relying on sterilization. The index was generally higher among women living in urban areas than among those in rural areas, and tended to rise with increases in women's education and household wealth. On the basis of the MII, developing countries have room to improve information exchange between providers and clients. Such improvements would require concerted efforts by programs and donors.

Cost-effectiveness of dual-energy X-ray absorptiometry plus antiresorptive treatment in Australian women with breast cancer who receive aromatase inhibitors.

PubMed

Sowa, P Marcin; Downes, Martin J; Gordon, Louisa G

2017-03-01

Postmenopausal women with breast cancer on aromatase inhibitor (AI) treatment are at increased risk of bone mineral density loss, which may lead to minimal trauma fractures. We examined the cost-effectiveness of dual energy X-ray absorptiometry (DXA) with antiresorptive (AR) therapy compared with fracture risk assessment, lifestyle advice, and vitamin supplementation. We used a hypothetical Markov cohort model of lifetime duration for 60-year-old women with early stage breast cancer receiving AIs. The data to inform the model came from medical literature, epidemiological reports, and costing data sets. Two eligibility scenarios for AR therapy were considered: (A) osteoporosis and (B) osteopenia or osteoporosis. The main outcomes were incremental cost per quality-adjusted life years gained and cumulative fractures per 1000 women, calculated relative to the comparator. Key aspects of the model were explored in sensitivity analyses. Due to relatively low effectiveness gains, the outcomes were primarily driven by the costs. The incremental cost per quality-adjusted life year gained was A$47,556 and A$253,000 for scenarios A and B, respectively. The numbers of fractures avoided were 56 and 77 per 1000 women, respectively. The results were most sensitive to the initial probability of osteoporosis, baseline risk of fracture, and cohort starting age. Compared with risk assessment and lifestyle advice only, a DXA scan followed by an AR treatment is potentially cost-effective for women aged 60 and over undergoing AI therapy for early breast cancer. However, the number of fractures averted through this intervention is small.

MONARCH 2: Abemaciclib in Combination With Fulvestrant in Women With HR+/HER2- Advanced Breast Cancer Who Had Progressed While Receiving Endocrine Therapy.

PubMed

Sledge, George W; Toi, Masakazu; Neven, Patrick; Sohn, Joohyuk; Inoue, Kenichi; Pivot, Xavier; Burdaeva, Olga; Okera, Meena; Masuda, Norikazu; Kaufman, Peter A; Koh, Han; Grischke, Eva-Maria; Frenzel, Martin; Lin, Yong; Barriga, Susana; Smith, Ian C; Bourayou, Nawel; Llombart-Cussac, Antonio

2017-09-01

Purpose MONARCH 2 ( ClinicalTrials.gov identifier: NCT02107703) compared the efficacy and safety of abemaciclib, a selective cyclin-dependent kinase 4 and 6 inhibitor, plus fulvestrant with fulvestrant alone in patients with advanced breast cancer (ABC). Patients and Methods MONARCH 2 was a global, double-blind, phase III study of women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who had progressed while receiving neoadjuvant or adjuvant endocrine therapy (ET), ≤ 12 months from the end of adjuvant ET, or while receiving first-line ET for metastatic disease. Patients were randomly assigned 2:1 to receive abemaciclib or placebo (150 mg twice daily) on a continuous schedule and fulvestrant (500 mg, per label). The primary end point was investigator-assessed progression-free survival (PFS), and key secondary end points included overall survival, objective response rate (ORR), duration of response, clinical benefit rate, quality of life, and safety. Results Between August 2014 and December 2015, 669 patients were randomly assigned to receive abemaciclib plus fulvestrant (n = 446) or placebo plus fulvestrant (n = 223). Abemaciclib plus fulvestrant significantly extended PFS versus fulvestrant alone (median, 16.4 v 9.3 months; hazard ratio, 0.553; 95% CI, 0.449 to 0.681; P < .001). In patients with measurable disease, abemaciclib plus fulvestrant achieved an ORR of 48.1% (95% CI, 42.6% to 53.6%) compared with 21.3% (95% CI, 15.1% to 27.6%) in the control arm. The most common adverse events in the abemaciclib versus placebo arms were diarrhea (86.4% v 24.7%), neutropenia (46.0% v 4.0%), nausea (45.1% v 22.9%), and fatigue (39.9% v 26.9%). Conclusions Abemaciclib at 150 mg twice daily plus fulvestrant was effective, significantly improving PFS and ORR and demonstrating a tolerable safety profile in women with hormone receptor-positive and human epidermal growth factor receptor 2-negative ABC who progressed while receiving ET.

[Optimal Ovulation Induction in Polycystic Ovary Syndrome Resistant to Clomiphene Citrate or Letrozole.

PubMed

Chen, Ying; Zhang, Dan

2016-11-01

To investigate the optimal ovulation induction with the combination of combining letrozole(LE),clomiphene citrate (CC),and human menopausal gonadotropin (HMG) in polycystic ovary syndrome(PCOS) patients resistant to CC or LE. Two hundreds nine PCOS patients (209 cycles) resistant to CC or LE were randomly divided into three groups: CC+HMG group (59 cycles),LE+HMG group (72 cycles) and LE+CC group (78 cycles).The patients in LE+CC group unable to form the dominant follicle after 54 cycles were enrolled into LE+CC+HMG group.Maximum follicle diameter (MFD),endometrial thickness,number of follicles (diameter>1.4 cm),the level of serum estradiol (E2) were measured on the day of HMG administration.Also these results were observed and compared including the duration of treatment,dosage of HMG,number of ovulated follicles,clinical pregnancy rate,biochemical pregnancy rate,early abortion rate,twinning rate,and ectopic pregnancy rate. The ovulation rate was significantly lower in LE+CC group (30.77%) ( P <0.05),but similar in the other three groups.The number of >1.4 cm follicles and ovulated follicles,ovulation duration and E2 concentration in LE+CC group were also at a lower level ( P <0.05).The patients in LE+CC+HMG group showed higher E2 level and more HMG consumption ( P <0.05).There was no statistical difference in endometrial thickness,MFD,clinical pregnancy rate,biochemical pregnancy rate,early abortion rate and twinning rate among these groups ( P >0.05).No severe ovarian hyperstimulation syndrome (OHSS) or luteinized unruptured follicle (LUF) occurred. Combintion of LE with CC could achieve 1/3 ovulation induction in PCOS resistant to CC or LE alone.When both combined with HMG,the induction of ovulation could be significantly higher than LE+HMG and CC+HMG,while the risk of multiple pregnancy and OHSS was reduced.

Household food insecurity, maternal nutritional status, and infant feeding practices among HIV-infected Ugandan women receiving combination antiretroviral therapy

PubMed Central

YOUNG, Sera L.; PLENTY, Albert H. J.; LUWEDDE, Flavia A.; NATAMBA, Barnabas K.; NATUREEBA, Paul; ACHAN, Jane; MWESIGWA, Julia; RUEL, Theodore D.; ADES, Veronica; OSTERBAUER, Beth; CLARK, Tamara D.; DORSEY, Grant; CHARLEBOIS, Edwin D.; KAMYA, Moses; HAVLIR, Diane V.; COHAN, Deborah L.

2015-01-01

Objectives Household food insecurity may be a barrier to both optimal maternal nutritional status and infant feeding practices, but few studies have tested this relationship quantitatively, and never among HIV-infected individuals. We therefore explored if greater household food insecurity was associated with poorer maternal nutritional status, shorter duration of exclusive breastfeeding (EBF) and fewer animal-source complementary foods. Methods We assessed these outcomes among 180 HIV-infected pregnant and breastfeeding (BF) women receiving combination antiretroviral therapy in the PROMOTE trial (NCT00993031), a prospective, longitudinal cohort study in Tororo, Uganda. Results Household food insecurity was common; the prevalence of severe, moderate, and little to no household hunger was 7.3%, 40.5%, and 52.2%, respectively. Poor maternal nutritional status was common and women in households experiencing moderate to severe household hunger (MSHH) had statistically significantly lower BMIs at enrollment (21.3 vs 22.5, p<0.01) and prior to delivery (22.6 vs. 23.8, p<0.01). However, MSHH was not associated with maternal BMI or gestational weight gain in multivariate models. The prevalence (95% CI) of EBF at 6 months was 66.4% (59.0%-72.8%), and the proportion of women breastfeeding at 12 months was 80.0% (73.0%-85.3%).MSHH was not associated with EBF at 6 months or breastfeeding at 12 months. However, among those women still EBF at 4 months (81.0% of population), those experiencing MSHH were significantly more likely to cease EBF between 4 and 6 months (aHR: 2.52, 95% CI 1.03-6.19). Conclusions Interventions addressing household food insecurity, maternal malnutrition and suboptimal breastfeeding practices are urgently needed. PMID:24585398

“I have remained strong because of that food”: Acceptability and use of lipid-based nutrient supplements among pregnant HIV-infected Ugandan women receiving combination antiretroviral therapy

PubMed Central

Young, Sera; Natamba, Barnabas; Luwedde, Flavia; Nyafwono, Dorcas; Okia, Ben; Osterbauer, Beth; Natureeba, Paul; Johnson, Lynn; Michel, Chloe; Zheng, Amy; Robine, Marion; Achan, Jane; Charlebois, Edwin; Cohan, Deb; Havlir, Diane

2015-01-01

We evaluated the acceptability and use of macronutrient supplementation among HIV-infected pregnant Ugandan women receiving antiretroviral therapy in a clinical study (NCT 00993031). We first conducted formative research among 56 pregnant and lactating women to select a supplement regimen. Acceptability and use of the supplementation regimen [35 sachets of lipid-based nutrient supplements (LNS) and 4 or 6 kg of instant soy porridge for the household provided monthly] were evaluated among 87 pregnant women. Organoleptic assessments of LNS were favorable. Participants reported consuming LNS a mean of 6.1 days per week, and adherence to recommended consumption behaviors (e.g. frequency, quantity, not sharing) was >80%. Few women reported negative social consequences of supplementation. The majority of participants also consumed most of the porridge intended for the household. In sum, LNS was acceptable and used regularly. Larger studies to evaluate physical and psychosocial consequences of LNS during pregnancy among HIV-infected women are warranted. PMID:25416075

An Assessment of the Likelihood, Frequency, and Content of Verbal Communication Between Radiologists and Women Receiving Screening and Diagnostic Mammography

PubMed Central

Carney, Patricia A.; Kettler, Mark; Cook, Andrea J.; Geller, Berta M.; Karliner, Leah; Miglioretti, Diana L.; Bowles, Erin Aiello; Buist, Diana S.; Gallagher, Thomas H.; Elmore, Joann G.

2009-01-01

Rationale & Objective Research on communication between radiologists and women undergoing screening and diagnostic mammography is limited. We describe community radiologists’ communication practices with patients regarding screening and diagnostic mammogram results and factors associated with frequency of communication. Materials & Methods We received surveys from 257 radiologists (70% of those eligible) about the extent to which they talk to women as part of their healthcare visit for either screening or diagnostic mammograms, whether this occurs if the exam assessment is positive or negative, and how they use estimates of patient risk to convey information about an abnormal exam where the specific finding of cancer is not yet known. We also assessed characteristics of the radiologists to identify associations with more or less frequent communication at the time of the mammogram. Results Two hundred and forty-three radiologists provided complete data (95%). Very few (<6%) reported routinely communicating with women when screening mammograms were either normal or abnormal. Less than half (47%) routinely communicated with women when their diagnostic mammograms were normal, while 77% often or always communicated with women when their diagnostic exams were abnormal. For positive diagnostic exams, female radiologists were more likely to be frequent communicators compared to males (87.1% to 72.8%; p-value = 0.02) and those who spend 40-79% of their time in breast imaging (94.6%) were more likely to be frequent communicators compared to those who spend less time (67.2%-78.9%; p-value = 0.02). Most radiologists convey risk information using general rather than numeric statements (57.7% vs. 28.5%). Conclusions Radiologists are most likely to convey information about diagnostic mammographic findings when results are abnormal. Most radiologists convey risk information using general rather than numeric statements. PMID:19442539

Impact of Male and Female Weight, Smoking, and Intercourse Frequency on Live Birth in Women With Polycystic Ovary Syndrome

PubMed Central

Allshouse, Amanda A.; Casson, Peter R.; Coutifaris, Christos; Diamond, Michael P.; Christman, Gregory M.; Schlaff, William D.; Alvero, Ruben; Trussell, J. C.; Krawetz, Stephen A.; Santoro, Nanette; Eisenberg, Esther; Zhang, Heping; Legro, Richard S.

2015-01-01

Context: Obese men with normal semen parameters exhibit reduced fertility but few prospective data are available. Objective: This study aimed to determine the effect of male factors and body mass among the Pregnancy in Polycystic Ovary Syndrome II (PPCOS II) participants. Methods: This is a secondary analysis of the PPCOS II trial. A total of 750 infertile women with polycystic ovary syndrome (PCOS) were randomly assigned to up to receive five cycles of letrozole or clomiphene citrate. Females were 18–39-years-old and had a male partner with sperm concentration of at least 14 million/mL who consented to regular intercourse. Analysis was limited to couples with complete male partner information (n = 710). Results: Male body mass index (BMI) was higher in couples who failed to conceive (29.5 kg/m2 vs 28.2 kg/m2; P = .039) as well as those who did not achieve a live birth (29.5 kg/m2 vs 28.1 kg/m2; P = .047). At least one partner was obese in 548 couples (77.1%). A total of 261 couples were concordant for obesity (36.8%). After adjustment for female BMI, the association of male BMI with live birth was no longer significant (odds ratio [OR] = 0.85; 95 % confidence interval [CI], 0.68–1.05; P = .13). Couples in which both partners smoked had a lower chance of live birth vs nonsmokers (OR = 0.20; 95 % CI, 0.08–0.52; P = .02), whereas there was not a significant effect of female or male smoking alone. Live birth was more likely in couples with at least three sexual intercourse attempts over the previous 4 weeks (reported at baseline) as opposed to couples with lesser frequency (OR = 4.39; 95 % CI, 1.52–12. 4; P < .01). Conclusions: In this large cohort of obese women with PCOS, effect of male obesity was explained by female BMI. Lower chance of success was seen among couples where both partners smoked. Obesity and smoking are common among women with PCOS and their partners and contribute to a decrease in fertility treatment success. PMID:25856211

Longevity of Women Superintendents

ERIC Educational Resources Information Center

Sethna, Kim C.

2014-01-01

Public schools are facing a leadership crisis regarding the lack of women superintendents in the United States. Although, historically, women have dominated the positions of classroom teachers and outnumbered men in receiving administrative leadership certificates, there is a disproportion in the number of men and women superintendents leading the…

Methadone adverse reaction presenting with large increase in plasma methadone binding: a case series

PubMed Central

2011-01-01

Introduction The use of methadone as an analgesic is on the increase, but it is widely recognized that the goal of predictable and reproducible dosing is confounded by considerable variability in methadone pharmacokinetics, and unpredictable side effects that include sedation, respiratory depression and cardiac arrhythmias. The mechanisms underlying these unpredictable effects are frequently unclear. Here, to the best of our knowledge we present the first report of an association between accidental methadone overexposure and increased plasma protein binding, a new potential mechanism for drug interactions with methadone. Case presentation We describe here the cases of two patients who experienced markedly different responses to the same dose of methadone during co-administration of letrozole. Both patients were post-menopausal Caucasian women who were among healthy volunteers participating in a clinical trial. Under the trial protocol both patients received 6 mg of intravenous methadone before and then after taking letrozole for seven days. One woman (aged 59) experienced symptoms consistent with opiate overexposure after the second dose of methadone that were reversed by naloxone, while the other (aged 49) did not. To understand the etiology of this event, we measured methadone pharmacokinetics in both patients. In our affected patient only, a fourfold to eightfold increase in methadone plasma concentrations after letrozole treatment was observed. Detailed pharmacokinetic analysis indicated no change in metabolism or renal elimination in our patient, but the percentage of unbound methadone in the plasma decreased 3.7-fold. As a result, the volume of distribution of methadone decreased approximately fourfold. The increased plasma binding in our affected patient was consistent with observed increases in plasma protein concentrations. Conclusions The marked increase in the total plasma methadone concentration observed in our patient, and the enhanced pharmacodynamic

Conditioned Emotional Distress in Women Receiving Chemotherapy for Breast Cancer.

ERIC Educational Resources Information Center

Jacobsen, Paul B.; And Others

1995-01-01

Investigated whether women undergoing outpatient chemotherapy for breast cancer can develop classically conditioned emotional distress. Patients' responses to a distinctive stimulus were assessed in a location not associated with chemotherapy administration. Results supported hypothesis that pairing a distinctive stimulus with chemotherapy would…

Vitamin D supplementation for women during pregnancy

PubMed Central

De-Regil, Luz Maria; Palacios, Cristina; Ansary, Ali; Kulier, Regina; Peña-Rosas, Juan Pablo

2013-01-01

Background Vitamin D deficiency or insufficiency is thought to be common among pregnant women. Vitamin D supplementation during pregnancy has been suggested as an intervention to protect against adverse gestational outcomes. Objectives To examine whether supplements with vitamin D alone or in combination with calcium or other vitamins and minerals given to women during pregnancy can safely improve maternal and neonatal outcomes. Search methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2011), the International Clinical Trials Registry Platform (ICTRP) (31 October 2011), the Networked Digital Library of Theses and Dissertations (28 October 2011) and also contacted relevant organisations (8 April 2011). Selection criteria Randomised and quasi-randomised trials with randomisation at either individual or cluster level, evaluating the effect of supplementation with vitamin D alone or in combination with other micronutrients for women during pregnancy. Data collection and analysis Two review authors independently i) assessed the eligibility of studies against the inclusion criteria ii) extracted data from included studies, and iii) assessed the risk of bias of the included studies. Data were checked for accuracy. Main results The search strategy identified 34 potentially eligible references. We included six trials assessing a total of 1023 women, excluded eight studies, and 10 studies are still ongoing. Five trials involving 623 women compared the effects of vitamin D alone versus no supplementation/placebo and one trial with 400 women compared the effects of vitamin D and calcium versus no supplementation. Only one trial with 400 women reported on pre-eclampsia: women who received 1200 IU vitamin D along with 375 mg of elemental calcium per day were as likely to develop pre-eclampsia as women who received no supplementation (average risk ratio (RR) 0.67; 95% confidence interval (CI) 0.33 to 1.35). Data from four trials

Comparison of estradiol and progesterone priming/antagonist/letrozole and microdose flare-up protocols for poor responders undergoing intracytoplasmic sperm injection.

PubMed

Yucel, Oguz; Ekin, Murat; Cengiz, Hüseyin; Zebitay, Ali Galip; Yalcinkaya, Sener; Karahuseyinoglu, Sercin

2014-09-01

To compare the effect of the GnRH antagonist/letrozole/gonadotropin protocol with the microdose GnRH agonist flare-up protocol in poor ovarian responders for intracytoplasmic sperm injection. One hundred twenty-one consecutive patients suspected of having or with a history of poor ovarian response between January 2009 and June 2010, who were undergoing ICSI were enrolled. The microdose flareup (MF) protocol was used in 79 patients and the estradiol + progesterone/letrozole + gonadotropin and GnRH antagonist (EP/ALG) protocol was used in 42 patients. Age of the patients, duration of infertility, basal FSH, the total gonadotropin consumption, duration of stimulation, E2 level on the day of hCG administration, the number of embryo transferred, the fertilization rate, implantation rate, clinical pregnancy rate and the live birth rate were not statistically different (p > 0.05). Only the number of oocytes retrieved was significantly higher in the EP/LGA group (1.7 ± 0.7 versus 2.6 ± 0.6). The EP/LGA protocol has no significant improvement against the microdose flare-up protocol in poor responder patients.

A comparison of depression and anxiety symptom trajectories between women who had an abortion and women denied one

PubMed Central

Foster, Diana G.; Steinberg, Julia R.; Roberts, Sarah C.M.; Neuhaus, John; Biggs, M. Antonia

2016-01-01

Background This study prospectively assesses the mental health outcomes among women seeking abortions, by comparing women having later abortions to women denied abortions, up to two years post-abortion seeking. Methods We present the first two years of a 5-year telephone interview study that is following 956 women who sought an abortion from 30 facilities throughout the U.S. We use adjusted linear mixed effects regression analyses to assess whether symptoms of depression and anxiety, as measured by the BSI-short form and Prime-MD, differ over time among women denied an abortion due to advanced gestational age, compared to women who received abortions. Results Baseline predicted mean depressive symptom scores for women denied abortion (3.07) were similar to women receiving an abortion just below the gestational limit (2.86). Depressive symptoms declined over time with no difference between groups. Initial predicted mean anxiety symptoms were higher among women denied care (2.59) than among women who had an abortion just below the gestational limit (1.91). Anxiety levels in the two groups declined and converged after one year. Conclusions Women who received an abortion had similar or lower levels of depression and anxiety than women denied an abortion. Our findings do not support the notion that abortion is a cause of mental health problems. PMID:25628123

A comparison of depression and anxiety symptom trajectories between women who had an abortion and women denied one.

PubMed

Foster, D G; Steinberg, J R; Roberts, S C M; Neuhaus, J; Biggs, M A

2015-07-01

This study prospectively assesses the mental health outcomes among women seeking abortions, by comparing women having later abortions with women denied abortions, up to 2 years post-abortion seeking. We present the first 2 years of a 5-year telephone interview study that is following 956 women who sought an abortion from 30 facilities throughout the USA. We use adjusted linear mixed-effects regression analyses to assess whether symptoms of depression and anxiety, as measured by the Brief Symptom Inventory-short form and the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire, differ over time among women denied an abortion due to advanced gestational age, compared with women who received abortions. Baseline predicted mean depressive symptom scores for women denied abortion (3.07) were similar to women receiving an abortion just below the gestational limit (2.86). Depressive symptoms declined over time, with no difference between groups. Initial predicted mean anxiety symptoms were higher among women denied care (2.59) than among women who had an abortion just below the gestational limit (1.91). Anxiety levels in the two groups declined and converged after 1 year. Women who received an abortion had similar or lower levels of depression and anxiety than women denied an abortion. Our findings do not support the notion that abortion is a cause of mental health problems.

Androgens in Women with Anorexia Nervosa and Normal-Weight Women with Hypothalamic Amenorrhea

PubMed Central

Miller, K. K.; Lawson, E. A.; Mathur, V.; Wexler, T. L.; Meenaghan, E.; Misra, M.; Herzog, D. B.; Klibanski, A.

2011-01-01

Context Anorexia nervosa and normal-weight hypothalamic amenorrhea are characterized by hypogonadism and hypercortisolemia. However, it is not known whether these endocrine abnormalities result in reductions in adrenal and/or ovarian androgens or androgen precursors in such women, nor is it known whether relative androgen deficiency contributes to abnormalities in bone density and body composition in this population. Objective Our objective was to determine whether endogenous androgen and dehydroepiandrosterone sulfate (DHEAS) levels: 1) are reduced in women with anorexia nervosa and normal-weight hypothalamic amenorrhea, 2) are reduced further by oral contraceptives in women with anorexia nervosa, and 3) are predictors of weight, body composition, or bone density in such women. Design and Setting We conducted a cross-sectional study at a general clinical research center. Study Participants A total of 217 women were studied: 137 women with anorexia nervosa not receiving oral contraceptives, 32 women with anorexia nervosa receiving oral contraceptives, 21 normal-weight women with hypothalamic amenorrhea, and 27 healthy eumenorrheic controls. Main Outcome Measures Testosterone, free testosterone, DHEAS, bone density, fat-free mass, and fat mass were assessed. Results Endogenous total and free testosterone, but not DHEAS, were lower in women with anorexia nervosa than in controls. More marked reductions in both free testosterone and DHEAS were observed in women with anorexia nervosa receiving oral contraceptives. In contrast, normal-weight women with hypothalamic amenorrhea had normal androgen and DHEAS levels. Lower free testosterone, total testosterone, and DHEAS levels predicted lower bone density at most skeletal sites measured, and free testosterone was positively associated with fat-free mass. Conclusions Androgen levels are low, appear to be even further reduced by oral contraceptive use, and are predictors of bone density and fat-free mass in women with

Investigating determinants for patient satisfaction in women receiving epidural analgesia for labour pain: a retrospective cohort study.

PubMed

Tan, Daryl Jian An; Sultana, Rehena; Han, Nian Lin Reena; Sia, Alex Tiong Heng; Sng, Ban Leong

2018-05-09

Epidural analgesia is a popular choice for labour pain relief. Patient satisfaction is an important patient-centric outcome because it can significantly influence both mother and child. However, there is limited evidence in the correlations between clinical determinants and patient satisfaction. We aim to investigate clinical covariates that are associated with low patient satisfaction in parturients receiving labour neuraxial analgesia. After institutional ethics approval was obtained, we conducted a retrospective cohort study using electronic and corresponding hardcopy records from 10,170 parturients receiving neuraxial analgesia between the periods of January 2012 to December 2013 in KK Women's and Children's Hospital in Singapore. Demographic, obstetric and anesthetic data were collected. The patient satisfaction scores on the neuraxial labour analgesia was reported by the parturient at 24 to 48 h post-delivery during the post-epidural round conducted by the resident and pain nurse. Parturients were stratified into one of three categories based on their satisfaction scores. Ordinal logistic regression models were used to identify potential covariates of patient dissatisfaction. 10,146 parturients were included into the study, of which 3230 (31.8%) were 'not satisfied', 3646 (35.9%) were 'satisfied', and 3270 (32.2%) were 'very satisfied'. Multivariable ordinal logistic regression analysis showed that instrument-assisted vaginal delivery (p = 0.0007), higher post-epidural pain score (p = 0.0016), receiving epidural catheter resiting (p <  0.0001), receiving neuraxial analgesia at a more advanced cervical dilation (p = 0.0443), multiparity (p = 0.0039), and post-procedure complications headache (p = 0.0006), backache (p <  0.0001), urinary retention (p = 0.0002) and neural deficit (p = 0.0297) were associated with patient dissatisfaction. Chinese, compared with other ethnicities (p = 0.0104), were more likely to be

Receipt of mammography among women with intellectual disabilities: medical record data indicate substantial disparities for African American women.

PubMed

Parish, Susan L; Swaine, Jamie G; Son, Esther; Luken, Karen

2013-01-01

Little information exists on the receipt of mammography by African American women with intellectual disabilities. Given the high rates of mortality from breast cancer among African American women and low screening rates among women with intellectual disabilities, it is important to understand the health screening behavior of this population. We compared rates of mammography receipt among African American and White women with intellectual disabilities (n = 92) living in community settings in one Southeastern state in the United States. Data were collected from women's medical records or abstraction forms obtained from medical practices. Multivariate logistic regressions were modeled for receipt of mammography in one year, one of two years, or both study years (2008- 2009). Covariates included the women's age, living arrangement, severity of impairment, and urban/rural residence location. In 2009, 29% of African American women and 59% of White women in the sample received mammograms. Similar disparities were found for receipt of mammography in either 2008 or 2009 and both 2008 and 2009. These disparities persisted after inclusion of model covariates. White women with intellectual disabilities received mammograms at adjusted rates that were nearly three to five times higher than African American women. African American women with intellectual disabilities receive mammography at significantly lower rates than White women with intellectual disabilities. Assertive measures to improve the screening rates for African American women with intellectual disabilities are urgently needed. Copyright © 2013 Elsevier Inc. All rights reserved.

Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women

PubMed Central

Money, Deborah M.; Wagner, Emily C.; Maan, Evelyn J.; Chaworth-Musters, Tessa; Gadawski, Izabelle; van Schalkwyk, Julie E.; Forbes, John C.; Burdge, David R.; Albert, Arianne Y. K.; Lohn, Zoe; Côté, Hélène C. F.

2015-01-01

Introduction Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period. Methods This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30–40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR. Results Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001). Conclusions In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is

Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women.

PubMed

Money, Deborah M; Wagner, Emily C; Maan, Evelyn J; Chaworth-Musters, Tessa; Gadawski, Izabelle; van Schalkwyk, Julie E; Forbes, John C; Burdge, David R; Albert, Arianne Y K; Lohn, Zoe; Côté, Hélène C F

2015-01-01

Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period. This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30-40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR. Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001). In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is another step toward optimizing the safety

An exploration of the socio-economic profile of women and costs of receiving abortion services at public health facilities of Madhya Pradesh, India.

PubMed

Banerjee, Sushanta K; Kumar, Rakesh; Warvadekar, Janardan; Manning, Vinoj; Andersen, Kathryn Louise

2017-03-21

Maternal mortality, which primarily burdens developing countries, reflects the greatest health divide between rich and poor. This is especially pronounced for access to safe abortion services which alone avert 1 of every 10 maternal deaths in India. Primarily due to confidentiality concerns, poor women in India prefer private services which are often offered by untrained providers and may be expensive. In 2006 the state government of Madhya Pradesh (population 73 million) began a concerted effort to ensure access to safe abortion services at public health facilities to both rural and urban poor women. This study aims to understand the socio-economic profile of women seeking abortion services in public health facilities across this state and out of pocket cost accessing abortion services. In particular, we examine the level of access that poor women have to safe abortion services in Madhya Pradesh. This study consisted of a cross-sectional client follow-up design. A total of 19 facilities were selected using two-stage random sampling and 1036 women presenting to chosen facilities with abortion and post-abortion complications were interviewed between May and December 2014. A structured data collection tool was developed. A composite wealth index computed using principal component analysis derived weights from consumer durables and asset holding and classified women into three categories, poor, moderate, and rich. Findings highlight that overall 57% of women who received abortion care at public health facilities were poor, followed by 21% moderate and 22% rich. More poor women sought care at primary level facilities (58%) than secondary level facilities and among women presenting for postabortion complications (67%) than induced abortion. Women reported spending no money to access abortion services as abortion services are free of cost at public facilities. However, poor women spend INR 64 (1 USD) while visiting primary level facilities and INR 256 (USD 4) while

Which female cancer patients fail to receive fertility counseling before treatment in the state of Georgia?

PubMed

Chin, Helen B; Howards, Penelope P; Kramer, Michael R; Mertens, Ann C; Spencer, Jessica B

2016-12-01

To assess which characteristics are associated with failure to receive fertility counseling among a cohort of young women diagnosed with cancer. Population-based cohort study. Not applicable. A total of 1,282 cancer survivors, of whom 1,116 met the inclusion criteria for the analysis. None. The main outcome in this study was whether or not women reported receiving any information at the time of their cancer diagnosis on how cancer treatment might affect their ability to become pregnant. Forty percent of cancer survivors reported that they did not receive fertility counseling at the time of cancer diagnosis. Women were more likely to fail to receive counseling if they had only a high school education or less or if they had given birth. Cancer-related variables that were associated with a lack of counseling included not receiving chemotherapy as part of treatment and diagnosis with certain cancer types. Counseling about the risk of infertility and available fertility preservation options is important to cancer patients. Additionally, counseling can make women aware of other adverse reproductive outcomes, such as early menopause and its associated symptoms. Less-educated women and parous women are at particular risk of not getting fertility-related information. Programs that focus on training not just the oncologist, but also other health care providers involved with cancer care, to provide fertility counseling may help to expand access. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Symptom Clusters Change over Time in Women Receiving Adjuvant Chemotherapy for Breast Cancer

PubMed Central

Albusoul, Randa M.; Berger, Ann M.; Gay, Caryl L.; Janson, Susan L.; Lee, Kathryn A.

2017-01-01

Context Patients with breast cancer receiving chemotherapy (CTX) experience multiple concurrent symptoms, but little is known about how symptoms change during and after treatment. Knowledge of the identity and trajectory of symptom clusters (SCs) would enhance measurement and management. Objectives We aimed to identify SCs and their change over time from baseline to completion of breast cancer CTX. Methods SCs were identified and assessed for change in 219 women from Nebraska at four times: baseline, during cycles #3 and #4 of CTX, and one-month after finishing CTX. Ten symptoms were measured: two using the Hospital Anxiety and Depression Scale and eight using the Symptom Experience Scale. Exploratory factor analysis was conducted at each time point, then changes in SCs were evaluated at different times. Results Two SCs were identified before and after initiating CTX: Gastrointestinal (GI) and Treatment-related (Tr). The number and type of symptoms in each cluster differed over time. Clusters were dynamic during CTX with changes in the number and type of symptoms. Only one Tr SC, which consisted of fatigue, pain, and sleep disturbance, was identified after CTX completion. Conclusion SCs during CTX appear to be dynamic, changing over time from before until after CTX completion. Repeated assessments of SCs reveal symptoms that are present and when patients are most burdened and in need of additional support. PMID:28062343

They receive antenatal care in health facilities, yet do not deliver there: predictors of health facility delivery by women in rural Ghana.

PubMed

Boah, Michael; Mahama, Abraham B; Ayamga, Emmanuel A

2018-05-03

Research has shown that use of antenatal services by pregnant women and delivery in health facilities with skilled birth attendants contribute to better delivery outcomes. However, a gap exists in Ghana between the use of antenatal care provided by health facilities and delivery in health facilities with skilled birth attendants by pregnant women. This study sought to identify the predictors of health facility delivery by women in a rural district in Ghana. This was a cross-sectional study conducted in June 2016. Women who delivered in the past 6 months preceding the study were interviewed. Data on socio-demographic characteristics, use of antenatal care, place of delivery and reasons for home delivery were collected from study participants. Chi-square test and multiple logistic regression analysis were used to assess an association between women's socio-demographic and obstetric characteristics and place of delivery at 95% confidence interval. The study found that 98.8% of women received antenatal care services at least once during their recent pregnancy, and 67.9% attended antenatal care at least four times before delivery. However, 61.9% of the women delivered in a health facility with a skilled attendant. The frequently mentioned reason for home delivery was "unaware of onset of labour and delivery". The odds for delivery at a health facility were reduced among women with four living children [(AOR = 0.07, CI = 0.15-0.36, p = 0.001)], with no exposure to delivery care information [(AOR = 0.06, CI = 0.01-0.34, p = 0.002), who started their first ANC visit from the second trimester of pregnancy[(AOR = 0.003, CI = 0.01-0.15, p < 0.001)] and increased among women who made at least four ANC visits before delivery [(AOR = 17.53, CI = 6.89-44.61, p < 0.001)]. Findings from this study revealed a low rate of delivery at health facilities although visits to antenatal care sessions were high, an indication that there was the

Multi-Reservoir Phospholipid Shell Encapsulating Protamine Nanocapsules for Co-Delivery of Letrozole and Celecoxib in Breast Cancer Therapy.

PubMed

Elzoghby, Ahmed O; Mostafa, Shaimaa K; Helmy, Maged W; ElDemellawy, Maha A; Sheweita, Salah A

2017-09-01

In the current work, we propose a combined delivery nanoplatform for letrozole (LTZ) and celecoxib (CXB). Multi-reservoir nanocarriers were developed by enveloping protamine nanocapsules (PRM-NCs) within drug-phospholipid complex bilayer. Encapsulation of NCs within phospholipid bilayer was confirmed by both size increase from 109.7 to 179.8 nm and reduction of surface charge from +19.0 to +7.78 mV. The multi-compartmental core-shell structure enabled biphasic CXB release with initial fast release induced by complexation with phospholipid shell followed by prolonged release from oily core. Moreover, phospholipid coating provided protection for cationic PRM-NCs against interaction with RBCs and serum proteins enabling their systemic administration. Pharmacokinetic analysis demonstrated prolonged circulation and delayed clearance of both drugs after intravenous administration into rats. The superior anti-tumor efficacy of multi-reservoir NCs was manifested as powerful cytotoxicity against MCF-7 breast cancer cells and marked reduction in the mammary tumor volume in Ehrlich ascites bearing mice compared with free LTZ-CXB combination. Moreover, the NCs induced apoptotic caspase activation and marked inhibition of aromatase expression and angiogenic marker, VEGF as well as inhibition of both NFκB and TNFα. Multi-reservoir phospholipid shell coating PRM-NCs could serve as a promising nanocarrier for parenteral combined delivery of LTZ and CXB.

Letrozole induced low estrogen levels affected the expressions of duodenal and renal calcium-processing gene in laying hens.

PubMed

Li, Qiao; Zhao, Xingkai; Wang, Shujie; Zhou, Zhenlei

2018-01-01

Estrogen regulates the calcium homeostasis in hens, but the mechanisms involved are still unclear fully. In this study, we investigated whether letrozole (LZ) induced low estrogen levels affected the calcium absorption and transport in layers. In the duodenum, we observed a significant decrease of mRNA expressions of Calbindin-28k (CaBP-28k) and plasma membrane Ca 2+ -ATPase (PMCA 1b) while CaBP-28k protein expression was declined in birds with LZ treatment, and the mRNA levels of duodenal transient receptor potential vanilloid 6 (TRPV6) and Na + /Ca 2+ exchanger 1 (NCX1) were not affected. Interestingly, we observed the different changes in the kidney. The renal mRNA expressions of TRPV6 and NCX1 were unregulated while the PMCA1b was down-regulated in low estrogen layers, however, the CaBP-28k gene and protein expressions were no changed in the kidney. Furthermore, it showed that the duodenal estradiol receptor 2 (ESR2) transcripts rather than parathyroid hormone 1 receptor (PTH1R) and calcitonin receptor (CALCR) played key roles to down-regulate calcium transport in LZ-treated birds. In conclusion, CaBP-28k, PMCA 1b and ESR2 genes in the duodenum may be primary targets for estrogen regulation in order to control calcium homeostasis in hens. Copyright © 2017 Elsevier Inc. All rights reserved.

How group education impacts female factory workers' behavior and readiness to receive mammography and Pap smear.

PubMed

Seven, Memnun; Bahar, Mine; Akyüz, Aygül; Erdoğan, Hatice

2015-01-01

The workplace has been deemed a suitable location for educating many women at once about cancer screening. To determine how group education about early diagnostic methods for breast and cervical cancer effects women's behavior and readiness to receive mammography and Pap smear. This semi-interventional study was conducted at a textile factory in Istanbul, Turkey. Female workers (n= 125) were included in the study. A participant identification form and knowledge evaluation form developed for this study, along with the transtheoretical model, were used to collect data. A 45-min interactive group education was given to the participants. Upon contacting participants 3 months after group education, 15.4% (n = 11) stated that they had since received a mammogram and 9.8% (n = 7) a Pap smear. As suggested by the transtheoretical model, group education increased participants' readiness to receive cancer screening, along with their knowledge of breast and cervical cancer. Group education positively impacted women's knowledge of cancer and their readiness to receive mammography and Pap smear. Group education can potentially create awareness of cancer screening tests among women and improve their readiness to receive such tests.

Predictive validity of five cognitive skills tests among women receiving engineering training

NASA Astrophysics Data System (ADS)

Wittig, Michele Andrisin; Hennix Sasse, Sharon; Giacomi, Jean

This article addresses two sets of theoretical and practical issues related to increasing the percentage of women engineers. First, the measurement of women's aptitude for and changes in skills during engineering training was assessed. Five cognitive skills tests were administered in a one-group pretest-posttest design to 24 baccalaureate women enrolled in an eleven-month engineering training course. Significant increases in skills were shown on three of the five assessments. Scores on a mathematics anxiety scale and a measure of conservation of horizontality are also reported. Second, the relationship of academic and demographic information and cognitive skills to degree of success in the program is reported. Pretraining spatial visualization scores predicted posttraining GPA group membership. The results are compared and contrasted with those of studies of male undergraduates. Implications are drawn concerning the ways in which evaluations of such programs can contribute to our understanding of the changes in skills that occur with training in engineering and of the factors that predict success in such programs.

An interactional test of the reformulated helplessness theory of depression in women receiving clinical treatment for eating disorders.

PubMed

Rotenberg, Ken J; Costa, Paula; Trueman, Mark; Lattimore, Paul

2012-08-01

The study tested the Reformulated Helplessness model that individuals who show combined internal locus of control, high stability and high globality attributions for negative life events are prone to depression. Thirty-six women (M=29 years-8 months of age) receiving clinical treatment for eating disorders completed: the Attribution Style Questionnaire, the Beck Depression Inventory, and the Stirling Eating Disorder Scales. An HRA yielded a three-way interaction among the attributional dimensions on depressive symptoms. Plotting of the slopes showed that the attribution of negative life events to the combination of internal locus of control, high stability, and a high globality, was associated with the optimal level of depressive symptoms. The findings supported the Reformulated Helplessness as a model of depression. Copyright © 2012 Elsevier Ltd. All rights reserved.

Central leptin resistance and hypothalamic inflammation are involved in letrozole-induced polycystic ovary syndrome rats.

PubMed

Lian, Yuling; Zhao, Fangui; Wang, Wenjun

2016-08-05

Accumulating evidence indicates that leptin acts as an important mediator in energy homeostasis and reproduction. Since dysfunction of reproduction and metabolism are major characteristics of polycystic ovarian syndrome (PCOS), the role of leptin in pathogenesis of PCOS needs further research. Many studies have shown that central leptin resistance existed in obesity rats through leptin intracerebroventricular (icv) injection; however, central leptin resistance in PCOS rats has not been reported. This study aimed to investigate whether there was a state of central leptin resistance in PCOS rats, as well as explore the possible association of hypothalamic inflammation with central leptin resistance. First, letrozole was used to induce the PCOS model, 24 h food intake, 24 h body weight changes and the expression of p-STAT3 were determined following leptin or artificial cerebrospinal fluid (aCSF) icv injection in rats. Second, we further evaluated the expressions of IL-1β, IL-6, TNF-α, p-IKKβ, NF-κB, p-NF-κB, IκBα, p-IκBα and SOCS3 in hypothalamus. The results showed that 24 h food intake and body weight were decreased, while the expression of p-STAT3 was increased in control group rats following leptin icv injection compared with aCSF icv injection; however, both of them showed no significant difference in PCOS rats. Furthermore, inflammatory markers were upregulated in the hypothalami of PCOS rats. Taken together, our data indicated that there was a state of chronic low-grade inflammation in hypothalamus which might be the possible mechanism for central leptin resistance in PCOS rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Association between insulin resistance and preeclampsia in obese non-diabetic women receiving metformin.

PubMed

Balani, Jyoti; Hyer, Steve; Syngelaki, Argyro; Akolekar, Ranjit; Nicolaides, Kypros H; Johnson, Antoinette; Shehata, Hassan

2017-12-01

To examine whether the reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is mediated by changes in insulin resistance. This was a secondary analysis of obese pregnant women in a randomised trial (MOP trial). Fasting plasma glucose and insulin were measured in 384 of the 400 women who participated in the MOP trial. Homeostasis model assessment of insulin resistance (HOMA-IR) was compared in the metformin and placebo groups and in those that developed preeclampsia versus those that did not develop preeclampsia. At 28 weeks, median HOMA-IR was significantly lower in the metformin group. Logistic regression analysis demonstrated that there was a significant contribution in the prediction of preeclampsia from maternal history of chronic hypertension and gestational weight gain, but not HOMA-IR either at randomisation ( p  = 0.514) or at 28 weeks ( p  = 0.643). Reduced incidence of preeclampsia in non-diabetic obese pregnant women treated with metformin is unlikely to be due to changes in insulin resistance.

Sex education attitudes and outcomes among North American women.

PubMed

Williams, Monnica T; Bonner, Laura

2006-01-01

Attitudes and outcomes of sex education received by North American women are examined via an Internet survey (N = 1,400). Mean age was 19.5, with 24% reporting one or more unplanned pregnancies. Women were more satisfied with sex education from informal sources than from parents, schools, and physicians. Those receiving sex education from parents or schools reported fewer pregnancies and abortions. In school, women receiving a combination of contraceptive and abstinence education and those receiving primarily abstinence education were least likely to experience unplanned pregnancy. Religious identification was significantly related to unplanned pregnancy and type of sex education received from parents. These factors seem to play a significant role in reducing unplanned pregnancy and abortion.

Effect of travel distance and time to radiotherapy on likelihood of receiving mastectomy.

PubMed

Goyal, Sharad; Chandwani, Sheenu; Haffty, Bruce G; Demissie, Kitaw

2015-04-01

Breast-conserving surgery (BCS) followed by adjuvant radiation therapy (RT) is the standard of care for women with early-stage breast cancer as an alternative to mastectomy. The purpose of this study was to examine the relationship between receipt of mastectomy and travel distance and time to RT facility in New Jersey (NJ). Data were collected from a cohort of 634 NJ women diagnosed with early-stage breast cancer. In patients receiving RT, the precise RT facility was used, whereas in patients not receiving RT, surgeons were contacted to determine the location of RT referral. Travel distance and time to RT facility from the patients' residential address were modeled separately using multiple binomial regression to examine their association with choice of surgery while adjusting for clinical and sociodemographic factors. Overall, 58.5 % patients underwent BCS with median travel distance to the radiation facility of 4.8 miles (vs. 6.6 miles for mastectomy) and median travel time of 12.0 min (vs. 15.0 min for mastectomy). Patients residing > 9.2 miles compared with ≤ 9.2 miles from radiation facility were 44 % more likely to receive mastectomy. Additionally, patients requiring > 19 min compared with ≤ 19 min of travel time were 36 % more likely to receive mastectomy. These data found that travel distance and time from RT facility act as barriers to undergoing BCS in women with early-stage breast cancer. Despite being in an urban region, a significant number of women in NJ with early-stage breast cancer did not receive BCS.

Risk of high-grade cervical dysplasia and cervical cancer in women with systemic lupus erythematosus receiving immunosuppressive drugs.

PubMed

Feldman, C H; Liu, J; Feldman, S; Solomon, D H; Kim, S C

2017-06-01

Objective Prior studies suggest an increased risk of cervical cancer among women with systemic lupus erythematosus. However, the relationship with immunosuppressive drugs is not well studied in US nationwide cohorts. We compared the risk of high-grade cervical dysplasia and cervical cancer among women with systemic lupus erythematosus who started immunosuppressive drugs versus hydroxychloroquine. Methods We identified systemic lupus erythematosus patients initiating immunosuppressive drugs or hydroxychloroquine using claims data from two US commercial health plans and Medicaid (2000-2012). We used a validated claims-based algorithm to identify high-grade cervical dysplasia or cervical cancer. To account for potential confounders, including demographic factors, comorbidities, medication use, HPV vaccination status, and health care utilization, immunosuppressive drugs and hydroxychloroquine initiators were 1:1 matched on the propensity score. We used inverse variance-weighted, fixed effect models to pool hazard ratios from the propensity score-matched Medicaid and commercial cohorts. Results We included 2451 matched pairs of immunosuppressive drugs and hydroxychloroquine new users in the commercial cohort and 7690 matched pairs in Medicaid. In the commercial cohort, there were 14 cases of cervical dysplasia or cervical cancer among immunosuppressive drugs users and five cases among hydroxychloroquine users (hazard ratio 2.47, 95% CI 0.89-6.85, hydroxychloroquine = ref). In Medicaid, there were 46 cases among immunosuppressive drugs users and 29 cases in hydroxychloroquine users (hazard ratio 1.24, 95% CI 0.78-1.98, hydroxychloroquine = ref). The pooled hazard ratio of immunosuppressive drugs was 1.40 (95% CI 0.92-2.12). Conclusion Among women with systemic lupus erythematosus, immunosuppressive drugs may be associated with a greater, albeit not statistically significant, risk of high-grade cervical dysplasia and cervical cancer compared to patients receiving

Albanian women in physics

NASA Astrophysics Data System (ADS)

Deda, Antoneta; Alushllari, Mirela; Mico, Silvana

2015-12-01

In this report, presented at the 5th IUPAP International Conference on Women in Physics, we describe the status of women physicists in Albania and offer some statistical data illustrating the present situation. Undergraduate physics enrollment by girls is high and stable, more women are receiving financial support for doctoral studies, women are well represented in recent academic promotions, and recently women scientists have been appointed to several leadership positions. However, both women and men are challenged by the overall low levels of funding for research and by issues of availability and affordability of child care.

Women's views on reminder letters for screening mammography: Mixed methods study of women from 23 family health networks.

PubMed

Kaczorowski, Janusz; Karwalajtys, Tina; Lohfeld, Lynne; Laryea, Stephanie; Anderson, Kelly; Roder, Stefanie; Sebaldt, Rolf J

2009-06-01

To explore women's perspectives on the acceptability and content of reminder letters for screening mammography from their family physicians, as well as such letters' effect on screening intentions. Cross-sectional mailed survey followed by focus groups with a subgroup of respondents. Ontario. One family physician was randomly selected from each of 23 family health networks and primary care networks participating in a demonstration project to increase the delivery of preventive services. From the practice roster of each physician, up to 35 randomly selected women aged 50 to 69 years who were due or overdue for screening mammograms and who had received reminder letters from their family physicians within the past 6 months were surveyed. Recall of having received reminder letters and of their content, influence of the letters on decisions to have mammograms, and interest in receiving future reminder letters. Focus group interviews with survey respondents explored the survey findings in greater depth using a standardized interview guide. The response rate to the survey was 55.7% (384 of 689), and 45.1% (173 of 384) of responding women reported having mammograms in the past 6 months. Among women who recalled receiving letters and either making appointments for or having mammograms, 74.8% (122 of 163) indicated that the letters substantially influenced their decisions. Most respondents (77.1% [296 of 384]) indicated that they would like to continue to receive reminders, and 28.9% (111 of 384) indicated that they would like to receive additional information about mammograms. Participants in 2 focus groups (n = 3 and n = 5) indicated that they thought letters reflected a positive attitude of physicians toward mammography screening. They also commented that newly eligible women had different information needs than women who had had mammograms done in the past. Reminder letters were considered by participants to be useful and appeared to influence women's decisions to

Receiving a summary of the results of a trial: qualitative study of participants' views

PubMed Central

Dixon-Woods, Mary; Jackson, Clare; Windridge, Kate C; Kenyon, Sara

2006-01-01

Objective To explore trial participants' responses to receiving a summary of the results of a trial in pregnancy. Design Qualitative study with semistructured interviews. Participants 20 women who had when pregnant participated in the ORACLE trial of antibiotics for preterm labour and preterm rupture of the membranes and requested a copy of the trial results. Results Less than a fifth of women who participated in the ORACLE trial indicated that they wished to receive the trial results. Reactions to the leaflet summarising the trial results were generally positive or neutral, although some women had difficulty in understanding the leaflet, and there was evidence of possible negative implications for women who had adverse outcomes. Women requested the results because they were interested in being able to complete their own personal narrative. They wished to know to which arm of the trial they had been allocated and the implications for their own pregnancy, and they were disappointed with receiving a generic summary. Women's accounts indicated some confusion about the trial findings. Conclusions Recommendations that research participants be routinely provided with the results of studies have been made without the benefit of research to show the consequences of doing this or how it should best be managed. Caution is needed, as is more evaluation of how feedback of results should be handled, and assessment of the risks, benefits, and costs. PMID:16401631

Knowledge and Acceptability of Long-Acting Reversible Contraception Among Adolescent Women Receiving School-Based Primary Care Services.

PubMed

Hoopes, Andrea J; Ahrens, Kym R; Gilmore, Kelly; Cady, Janet; Haaland, Wren L; Amies Oelschlager, Anne-Marie; Prager, Sarah

2016-07-01

A key strategy to reduce unintended adolescent pregnancies is to expand access to long-acting reversible contraceptive (LARC) methods, including intrauterine devices and subdermal contraceptive implants. LARC services can be provided to adolescents in school-based health and other primary care settings, yet limited knowledge and negative attitudes about LARC methods may influence adolescents' utilization of these methods. This study aimed to evaluate correlates of knowledge and acceptability of LARC methods among adolescent women at a school-based health center (SBHC). In this cross-sectional study, female patients receiving care at 2 SBHCs in Seattle, Washington completed an electronic survey about sexual and reproductive health. Primary outcomes were (1) LARC knowledge as measured by percentage correct of 10 true-false questions and (2) LARC acceptability as measured by participants reporting either liking the idea of having an intrauterine device (IUD)/subdermal implant or currently using one. A total of 102 students diverse in race/ethnicity and socioeconomic backgrounds completed the survey (mean age 16.2 years, range 14.4-19.1 years). Approximately half reported a lifetime history of vaginal sex. Greater LARC knowledge was associated with white race (regression coefficient [coef] = 26.8; 95% CI 13.3-40.4; P < .001), history of vaginal intercourse (coef = 29.9; 95% CI 17.1-42.7; P < .001), and current/prior LARC use (coef = 22.8; 95% CI 6.5-40.0; P = .007). Older age was associated with lower IUD acceptability (odds ratio = 0.53, 95% CI 0.30-0.94; P = .029) while history of intercourse was associated with greater implant acceptability (odds ratio 5.66, 95% CI 1.46-22.0; P = .012). Adolescent women in this SBHC setting had variable knowledge and acceptability of LARC. A history of vaginal intercourse was the strongest predictor of LARC acceptability. Our findings suggest a need for LARC counseling and education strategies, particularly for young women from

Knowledge and Acceptability of Long-Acting Reversible Contraception Among Adolescent Women Receiving School-Based Primary Care Services

PubMed Central

Hoopes, Andrea J.; Ahrens, Kym R.; Gilmore, Kelly; Cady, Janet; Haaland, Wren L.; Amies Oelschlager, Anne-Marie; Prager, Sarah

2016-01-01

Background: A key strategy to reduce unintended adolescent pregnancies is to expand access to long-acting reversible contraceptive (LARC) methods, including intrauterine devices and subdermal contraceptive implants. LARC services can be provided to adolescents in school-based health and other primary care settings, yet limited knowledge and negative attitudes about LARC methods may influence adolescents’ utilization of these methods. This study aimed to evaluate correlates of knowledge and acceptability of LARC methods among adolescent women at a school-based health center (SBHC). Methods: In this cross-sectional study, female patients receiving care at 2 SBHCs in Seattle, Washington completed an electronic survey about sexual and reproductive health. Primary outcomes were (1) LARC knowledge as measured by percentage correct of 10 true-false questions and (2) LARC acceptability as measured by participants reporting either liking the idea of having an intrauterine device (IUD)/subdermal implant or currently using one. Results: A total of 102 students diverse in race/ethnicity and socioeconomic backgrounds completed the survey (mean age 16.2 years, range 14.4-19.1 years). Approximately half reported a lifetime history of vaginal sex. Greater LARC knowledge was associated with white race (regression coefficient [coef] = 26.8; 95% CI 13.3-40.4; P < .001), history of vaginal intercourse (coef = 29.9; 95% CI 17.1-42.7; P < .001), and current/prior LARC use (coef = 22.8; 95% CI 6.5-40.0; P = .007). Older age was associated with lower IUD acceptability (odds ratio = 0.53, 95% CI 0.30-0.94; P = .029) while history of intercourse was associated with greater implant acceptability (odds ratio 5.66, 95% CI 1.46-22.0; P = .012). Discussion: Adolescent women in this SBHC setting had variable knowledge and acceptability of LARC. A history of vaginal intercourse was the strongest predictor of LARC acceptability. Our findings suggest a need for LARC counseling and education

Women in Aerospace Awards

NASA Image and Video Library

2010-10-26

NASA Langley Aerospace Engineer Jill Lynette Hanna Prince receives the Women in Aerospace Achievement in Aerospace award from North Carolina State Professor Robert Tolson during the Women in Aerospace organization's annual awards ceremony and banquet held at the Ritz-Carlton Hotel in Arlington, VA on Tuesday, Oct. 26, 2010. Four current NASA leaders and one retiree were recognized for their work by Women in Aerospace. The event celebrates women's professional excellence in aerospace and honors women who have made outstanding contributions to the aerospace community. Photo Credit: (NASA/Bill Ingalls)

Women in Science Fellowships