The effect of tolterodine on the pharmacokinetics and pharmacodynamics of a combination oral contraceptive containing ethinyl estradiol and levonorgestrel.

PubMed

Olsson, B; Landgren, B M

2001-11-01

Tolterodine is an antimuscarinic agent for the treatment of overactive bladder, a chronic condition that is particularly common in women. Given the prevalence pattern of overactive bladder and the widespread use of oral contraception, circumstances are likely to arise in which physicians may wish to prescribe tolterodine for patients already taking oral contraceptives. Based on a search of MEDLINE from 1990 to 2001, there have been no studies of whether concomitant use of these agents entails a risk of drug-drug interaction or conception. This study investigated the effects of tolterodine on the pharmacokinetics and pharmacodynamics of a low-dose combination oral contraceptive (ethinyl estradiol 30 microg/levonorgestrel 150 microg). This was an open-label, randomized, 2-period crossover study in healthy women. Oral contraception was given for 21 days either alone or in combination with oral tolterodine 2 mg BID (on days 1-14) over two 28-day contraceptive cycles. Pharmacokinetic assessments were performed on day 14 based on plasma levels of ethinyl estradiol and levonorgestrel up to 24 hours after dosing and serum tolterodine levels at 1 to 3 hours after dosing. The potential for pharmacodynamic interaction was assessed in terms of the risk of failure of suppression of ovulation based on serum levels of estradiol and progesterone measured throughout each cycle. Twenty-four healthy women (age, 23-41 years [mean, 30 years]; height, 155-178 cm [mean, 167 cm]; body weight, 51-75 kg [mean, 64 kg]) participated in the study. There was no evidence of a pharmacokinetic interaction between tolterodine and the steroid hormones in the oral contraceptive used, nor did the oral contraceptive show any relevant pharmacokinetic interaction with tolterodine. Serum levels of estradiol and progesterone indicated suppression of ovulation in both treatment periods. In this selected population. coadministration of tolterodine did not affect the contraceptive efficacy of a low-dose

Oral contraceptives in polycystic ovary syndrome.

PubMed

Helvaci, N; Yildiz, B O

2014-09-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder of women of reproductive age and combined oral contraceptives (OCs) are often the first-line treatment of the syndrome by improving hyperandrogenism and regulating menstrual cycles. Oral contraceptives have some cardiovascular and metabolic effects that varies among different formulations depending upon the dose and type of the both estrogen and progestin components. These cardiometabolic effects of OCs raise some concerns about their long-term use in PCOS, but available data suggest that the benefits outweigh the risks. More studies are needed to clarify the safety of long-term use of OCs in PCOS.

Efficacy and safety of a low-dose monophasic combination oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol (Alesse). North american Levonorgestrel Study Group (NALSG).

PubMed

Archer, D F; Maheux, R; DelConte, A; O'Brien, F B

1999-11-01

The efficacy and safety of a low-dose 21-day combination oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol were evaluated in an open-label, multicenter trial. A total of 1708 subjects with regular menstrual cycles (27,011 cycles) were evaluated. The oral contraceptive was administered once a day for 21 days, followed by 7 days of placebo for a complete cycle. During 26,554 cycles evaluated for efficacy, 18 pregnancies occurred (Pearl index of 0.88); 6 of these events were attributable to subject noncompliance. After 30 cycles of exposure the cumulative rate of withdrawal as a result of accidental pregnancy was 1.9%. Breakthrough bleeding (with or without spotting) occurred in 12.9% of the cycles and spotting alone occurred in 10.1% of the cycles. The 2 most common adverse events cited as reasons for discontinuation were headache (2% of subjects) and metrorrhagia (2%). One serious event led to withdrawal of a subject. Overall, the results of this study demonstrate that the monophasic regimen of 100 microg levonorgestrel and 20 microg ethinyl estradiol offers effective contraception, acceptable cycle control, and a good tolerability profile.

Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive.

PubMed

Ayoub, R; Page, S T; Swerdloff, R S; Liu, P Y; Amory, J K; Leung, A; Hull, L; Blithe, D; Christy, A; Chao, J H; Bremner, W J; Wang, C

2017-03-01

Dimethandrolone (DMA, 7α,11β-dimethyl-19-nortestosterone) has both androgenic and progestational activities, ideal properties for a male hormonal contraceptive. In vivo, dimethandrolone undecanoate (DMAU) is hydrolyzed to DMA. We showed previously that single oral doses of DMAU powder in capsule taken with food are well tolerated and effective at suppressing both LH and testosterone (T), but absorption was low. We compared the pharmacokinetics and pharmacodynamics of two new formulations of DMAU, in castor oil and in self-emulsifying drug delivery systems (SEDDS), with the previously tested powder formulation. DMAU was dosed orally in healthy adult male volunteers at two academic medical centers. For each formulation tested in this double-blind, placebo-controlled study, 10 men received single, escalating, oral doses of DMAU (100, 200, and 400 mg) and two subjects received placebo. All doses were evaluated for both fasting and with a high fat meal. All three formulations were well tolerated without clinically significant changes in vital signs, blood counts, or serum chemistries. For all formulations, DMA and DMAU showed higher maximum (p < 0.007) and average concentrations (p < 0.002) at the 400 mg dose, compared with the 200 mg dose. The powder formulation resulted in a lower conversion of DMAU to DMA (p = 0.027) compared with both castor oil and SEDDS formulations. DMAU in SEDDS given fasting resulted in higher serum DMA and DMAU concentrations compared to the other two formulations. Serum LH and sex hormone concentrations were suppressed by all formulations of 200 and 400 mg DMAU when administered with food, but only the SEDDS formulation was effectively suppressed serum T when given fasting. We conclude that while all three formulations of oral DMAU are effective and well tolerated when administered with food, DMAU in oil and SEDDS increased conversion to DMA, and SEDDS may have some effectiveness when given fasting. These properties might be

Effect of a Low-Dose Contraceptive Patch on Efficacy, Bleeding Pattern, and Safety

PubMed Central

Wiegratz, Inka; Bassol, Susana; Weisberg, Edith; Mellinger, Uwe

2014-01-01

This Phase III, uncontrolled, open-label, multicenter study was conducted to investigate the contraceptive efficacy, bleeding pattern, and cycle control of a novel once-a-week contraceptive patch, delivering low-dose ethinyl estradiol (EE) and gestodene (GSD) at the same systemic exposure seen after oral administration of a combined oral contraceptive containing 0.02 mg EE/0.06 mg GSD. Participants were women aged 18 to 35 years, all of whom received the EE/GSD patch for 13 cycles each of 21 treatment days (one patch per week for 3 weeks) followed by a 7-day, patch-free interval. The primary efficacy variable was the occurrence of unintended pregnancies during the study period as assessed by life table analysis and the Pearl Index. Secondary efficacy variables were days with bleeding during four 90-day reference periods and during 1 treatment year, bleeding pattern, and cycle control. The Kaplan-Meier probability of contraceptive protection after 364 treatment days was 98.8% and the adjusted Pearl Index was 0.81. The percentage of participants with intracyclic bleeding/spotting decreased over time, from 11.4% to 6.8% in cycles 1 and 12, respectively. Almost all participants (range: 90.8%-97.6%) experienced withdrawal bleeding across the study period. Compliance was very high (mean: 97.9%; median: 100%). The most frequent adverse events were headache (9.5%) and application site reaction (8.5%); no clinically significant safety concerns were observed. Results suggest the EE/GSD patch is highly effective in preventing pregnancy. Menstrual bleeding pattern was favorable and within the ranges expected of a healthy female population. The patch was well tolerated and treatment compliance was high. PMID:24784719

Peripheral arterial disease in a female using high-dose combined oral contraceptive pills.

PubMed

Pallavee, P; Samal, Sunita; Samal, Rupal

2013-01-01

The association between oral contraceptive (OC) pills and vascular diseases is well-known, although, the present generation of pills is considered to be relatively safer in this regard. Hormonal treatment for severe abnormal uterine bleeding is usually considered after ruling out malignancy, when such bleeding is resistant to all other forms of treatment. We report a case of severe peripheral arterial disease in a female, who had been on high-dose OC pills for an extended period of time for severe uterine bleeding.

Risk of venous thromboembolism from use of oral contraceptives containing different progestogens and oestrogen doses: Danish cohort study, 2001-9

PubMed Central

Nielsen, Lars Hougaard; Skovlund, Charlotte Wessel; Skjeldestad, Finn Egil; Løkkegaard, Ellen

2011-01-01

Objective To assess the risk of venous thromboembolism from use of combined oral contraceptives according to progestogen type and oestrogen dose. Design National historical registry based cohort study. Setting Four registries in Denmark. Participants Non-pregnant Danish women aged 15-49 with no history of thrombotic disease and followed from January 2001 to December 2009. Main outcome measures Relative and absolute risks of first time venous thromboembolism. Results Within 8 010 290 women years of observation, 4307 first ever venous thromboembolic events were recorded and 4246 included, among which 2847 (67%) events were confirmed as certain. Compared with non-users of hormonal contraception, the relative risk of confirmed venous thromboembolism in users of oral contraceptives containing 30-40 µg ethinylestradiol with levonorgestrel was 2.9 (95% confidence interval 2.2 to 3.8), with desogestrel was 6.6 (5.6 to 7.8), with gestodene was 6.2 (5.6 to 7.0), and with drospirenone was 6.4 (5.4 to 7.5). With users of oral contraceptives with levonorgestrel as reference and after adjusting for length of use, the rate ratio of confirmed venous thromboembolism for users of oral contraceptives with desogestrel was 2.2 (1.7 to 3.0), with gestodene was 2.1 (1.6 to 2.8), and with drospirenone was 2.1 (1.6 to 2.8). The risk of confirmed venous thromboembolism was not increased with use of progestogen only pills or hormone releasing intrauterine devices. If oral contraceptives with desogestrel, gestodene, or drospirenone are anticipated to increase the risk of venous thromboembolism sixfold and those with levonorgestrel threefold, and the absolute risk of venous thromboembolism in current users of the former group is on average 10 per 10 000 women years, then 2000 women would need to shift from using oral contraceptives with desogestrel, gestodene, or drospirenone to those with levonorgestrel to prevent one event of venous thromboembolism in one year. Conclusion After

Randomized comparison of bleeding patterns in women using a combined contraceptive vaginal ring or a low-dose combined oral contraceptive on a menstrually signaled regimen.

PubMed

Weisberg, Edith; Merki-Feld, Gabriele S; McGeechan, Kevin; Fraser, Ian S

2015-02-01

To compare bleeding patterns for 12 months continuous use of a contraceptive ring [contraceptive vaginal ring (CVR)] and pill [combined oral contraceptive (COC)] on a menstrually signaled regimen and the effectiveness of 4 days "treatment withdrawal" to stop bleeding. Women, 66 to each group, were randomized to continuous use of a CVR (15 mcg ethinyl estradiol/150 mcg etonogestrel) or a low-dose pill (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for 360 days on a menstrually signaled regimen. Bleeding/spotting days, daily use of ring or pill, was recorded. Endpoint was the total number of bleeding/spotting days for each method over four 90-day reference periods (RP) plus the analysis of bleeding patterns using modified World Health Organization criteria. There was a reduction in the mean (±S.D.) number of bleeding/spotting days from RP1 (CVR 14.2±10; pill 16.6±10.9) to RP4 (CVR 8.8±9.6; pill 8.8±9.1). Fifteen percent of CVR and 4% COC users experienced amenorrhea or infrequent bleeding throughout the study. Amenorrhea increased over time (RP1 vs. RP4: CVR 10% vs. 21% and COC 2% vs. 30%). Compliance with the menstrually signaled regimen was poor. Ceasing hormones for 4 days stopped a bleeding episode within 5 days in the majority of episodes and many stopped spontaneously. Bleeding patterns with continuous use of the CVR and COC are similar and improve over 1 year of use. The unpredictability, but short duration, of bleeding episodes should be stressed during counseling. This information for clinicians and women about breakthrough bleeding patterns with use of a CVR or combined pill over 12 months using a menstrually signaled regimen will give women an indication of what to expect with continuous use. Copyright © 2015 Elsevier Inc. All rights reserved.

[Oral contraception].

PubMed

Montloin, A

1990-11-01

This brief discussion of the different types of oral contraceptives (OCs) makes abundant use of flow charts, tables, and diagrams to present information and stress specific points. The work begins by defining the different hypothalamic, pituitary, and ovarian hormones and diagramming and describing the menstrual cycle. A discussion of combined OCs defines and diagrams monophasic, biphasic, and triphasic pills, distinguishes between different dose levels, and describes the mechanisms of action of OCs. Sequential pills and their mechanism of action are briefly discussed. The discussion of OCs containing progestins distinguishes between low does pills and high dose pills and describes the use of injectable progestins. A table then lists the dose-dependent side effects of estrogens and progestins. Simple instructions are provided for administering pills beginning on the 1st cycle day and for actions to take in the event a pill is forgotten. A flow chart taking into account age and presence or absence of vascular and gynecologic risk factors indicates which type of OC should be selected. Some advantages of OCs are identified, including maximum effectiveness and prevention of benign breast disease and perhaps of some type of rheumatoid arthritis. Another flow chart, on patient monitoring, identifies the contraindications that should be ruled out before OCs are prescribed and the routine follow-up examinations required for safe use. Other charts list absolute and relative contraindications and possible drug interferences.

Rationale for eliminating the hormone-free interval in modern oral contraceptives.

PubMed

London, Andrew; Jensen, Jeffrey T

2016-07-01

Although most low-dose combined oral contraceptives (COCs) include 7-day hormone-free intervals (HFIs), these COCs could incompletely suppress ovarian activity. To review the impact of HFIs on ovarian suppression and tolerability, and evaluate the utility of COCs without traditional 7-day HFIs. PubMed was searched for clinical studies published in English between January 1980 and April 2015 on the impact of HFIs and HFI modifications in COCs. Articles assessing contraceptive efficacy or tolerability as the primary focus were included. Abstracts of 319 articles were screened. Analysis of the 161 articles selected revealed that suppression of ovarian activity with low-dose COCs with 7-day HFIs is suboptimal. Loss of ovarian suppression during 7-day HFIs is commonly associated with follicular development, and most dominant follicles appear during this period. By contrast, increased ovarian suppression was noted in regimens that shortened or eliminated the HFI, or that substituted low-dose ethinyl estradiol for the HFI. Extended regimens with modified HFIs may provide greater ovarian suppression with the potential for increased contraceptive effectiveness. Additional research is needed to evaluate whether COC regimens that include 10μg ethinyl estradiol instead of an HFI may improve tolerability. Copyright © 2016 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Oral contraceptives containing drospirenone for premenstrual syndrome.

PubMed

Lopez, Laureen M; Kaptein, Adrian A; Helmerhorst, Frans M

2012-02-15

Premenstrual syndrome (PMS) is a common problem. Premenstrual dysphoric disorder (PMDD) is a severe form of premenstrual syndrome. Combined oral contraceptives, which provide both progestin and estrogen, have been examined for their ability to relieve premenstrual symptoms. An oral contraceptive containing drospirenone and a low estrogen dose has been approved for treating PMDD in women who choose oral contraceptives for contraception. To review all randomized controlled trials comparing a combined oral contraceptive containing drospirenone to a placebo or another combined oral contraceptive for effect on premenstrual symptoms. We searched for studies of drospirenone and premenstrual syndrome in the following databases: Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library), MEDLINE, and POPLINE (20 Dec 2011); EMBASE, LILACS, PsycINFO, ClinicalTrials.gov, and the International Clinical Trials Registry Platform (ICTRP) of the World Health Organization (02 Mar 2011). We also examined references lists of relevant articles and wrote to known investigators to find other trials. We included randomized controlled trials in any language that compared a combined oral contraceptive (COC) containing drospirenone with a placebo or with another COC for effect on premenstrual symptoms. The primary outcome included affective and physical premenstrual symptoms that were prospectively recorded. Adverse events related to combined oral contraceptive use were examined. Two review authors independently extracted data and assessed study quality. For continuous variables, the mean difference (MD) was computed with 95% confidence interval (CI). For dichotomous outcomes, the Peto odds ratio (OR) with 95% CI was calculated. We included five trials with a total of 1920 women. Two placebo-controlled trials of women with PMDD showed less severe premenstrual symptoms after three months with drospirenone 3 mg plus ethinyl estradiol 20 μg than with placebo (MD -7.92; 95

Adolescents and oral contraceptives.

PubMed

Sanfilippo, J S

1991-01-01

Oral contraceptive (OC) options for adolescents are provides. Clarification for those desiring a birth control method is necessary and the benefits of decreased acne and dysmenorrhea with low dose OCs should be stressed along with the importance of compliance. A community effort is suggested to communicate the sexual and contraceptive alternatives, including abstinence and outercourse (sexual stimulation to orgasm without intercourse). Attention is given to concerns associated with teenage sexual activity, prevention of adolescent pregnancy, contraceptive options for the adolescent patient, adolescent attitudes toward birth control OCs, management of the adolescent OC user, manipulation of steroid components of OCs to respond to adolescent concerns, and other hormonal contraceptive options such as minipills or abstinence. The text is supplemented with tables: the % of US women by single years of age for 1971, 1976, 1979, and 1982; comparative pregnancy and abortion rates for the US and 5 other countries; federal cost for teen childbearing; adolescent nonhormonal contraceptive methods (advantages, disadvantages, and retail cost); checklist to identify those at risk for noncompliance with OCs; hormonal side effects of OCs; risks from OCs to adolescents; and benefits of OCs. Concern about adolescent pregnancy dates back to Aristotle. A modern profile shows girls form single-parent families are sexually active at an earlier age, adolescent mothers produce offspring who repeat the cycle, victims of sexual abuse are more likely to be sexually active, and teenagers in foster care are 4 times more likely to be sexually active and 8 times more likely to become pregnant. Prevention involves a multifaceted approach. OCs are the most appropriate contraceptive choice for adolescents. Frequency of intercourse is closely associated with OC use after approximately 15 months of unprotected sexual activity. At risk for noncompliance variables are scales of personality development

Two low-dose levonorgestrel intrauterine contraceptive systems: a randomized controlled trial.

PubMed

Nelson, Anita; Apter, Dan; Hauck, Brian; Schmelter, Thomas; Rybowski, Sarah; Rosen, Kimberly; Gemzell-Danielsson, Kristina

2013-12-01

To evaluate the efficacy and safety of two low-dose levonorgestrel intrauterine contraceptive systems. Nulliparous and parous women aged 18-35 years with regular menstrual cycles (21-35 days) requesting contraception were randomized to 3 years of treatment with one of two levonorgestrel intrauterine contraceptive systems: 13.5 mg total content or 19.5 mg total content. The primary outcome was the pregnancy rate, calculated as the Pearl Index. Overall, 1,432 and 1,452 women in the 13.5 mg intrauterine contraceptive system and 19.5 mg intrauterine contraceptive system groups, respectively, had a placement attempted and were included in the full analysis set to evaluate efficacy and safety. Mean (standard deviation) age was 27.1 (4.8) years; 39.2% were nulliparous. Over the 3-year study period, 0.33 pregnancies per 100 women-years (95% confidence interval [CI] 0.16-0.60) were observed with the 13.5 mg intrauterine contraceptive system compared with 0.31 per 100 women-years (95% CI 0.15-0.57) with the 19.5 mg intrauterine contraceptive system. Kaplan-Meier estimates for that period were 0.009 and 0.010, respectively. At least partial expulsions occurred in 4.56% and 3.58% and discontinuation rates resulting from a reported adverse event occurred in 21.9% and 19.1%, respectively. Ten of the 20 pregnancies were ectopic. Serious adverse events included six cases of pelvic inflammatory disease and one partial uterine perforation. Both lower-dose levonorgestrel intrauterine contraceptive systems were highly effective for 3 years of use and generally well tolerated. ClinicalTrials.gov, www.clinicaltrials.gov, NCT00528112. : I.

Effect of exenatide on the pharmacokinetics of a combination oral contraceptive in healthy women: an open-label, randomised, crossover trial

PubMed Central

2012-01-01

Background Consistent with its effect on gastric emptying, exenatide, an injectable treatment for type 2 diabetes, may slow the absorption rate of concomitantly administered oral drugs resulting in a decrease in maximum concentration (Cmax). This study evaluated the drug interaction potential of exenatide when administered adjunctively with oral contraceptives, given their potential concomitant use. Methods This trial evaluated the effect of exenatide co-administration on single- and multiple-dose pharmacokinetics of a combination oral contraceptive (ethinyl estradiol [EE] 30 μg, levonorgestrel [LV] 150 μg [Microgynon 30®]). Thirty-two healthy female subjects participated in an open-label, randomised, crossover trial with 3 treatment periods (oral contraceptive alone, 1 hour before exenatide, 30 minutes after exenatide). Subjects received a single dose of oral contraceptive on Day 8 of each period and QD doses on Days 10 through 28. During treatment periods of concomitant usage, exenatide was administered subcutaneously prior to morning and evening meals at 5 μg BID from Days 1 through 4 and at 10 μg BID from Days 5 through 22. Single- (Day 8) and multiple-dose (Day 22) pharmacokinetic profiles were assessed for each treatment period. Results Exenatide did not alter the bioavailability nor decrease daily trough concentrations for either oral contraceptive component. No substantive changes in oral contraceptive pharmacokinetics occurred when oral contraceptive was administered 1 hour before exenatide. Single-dose oral contraceptive administration 30 minutes after exenatide resulted in mean (90% CI) Cmax reductions of 46% (42-51%) and 41% (35-47%) for EE and LV, respectively. Repeated daily oral contraceptive administration 30 minutes after exenatide resulted in Cmax reductions of 45% (40-50%) and 27% (21-33%) for EE and LV, respectively. Peak oral contraceptive concentrations were delayed approximately 3 to 4 hours. Mild-to-moderate nausea and vomiting were the

Cost-effectiveness analysis of a low-dose contraceptive levonorgestrel intrauterine system in Sweden.

PubMed

Henry, Nathaniel; Hawes, Charlie; Lowin, Julia; Lekander, Ingrid; Filonenko, Anna; Kallner, Helena K

2015-08-01

To evaluate the cost-effectiveness of a novel intrauterine system, levonorgestrel intrauterine system 13.5 mg vs. oral contraception, in women at risk of unintended pregnancy. Cost-effectiveness model using efficacy and discontinuation data from published articles. Societal perspective including direct and indirect costs. Women at risk of unintended pregnancy using reversible contraception. An economic analysis was conducted by modeling the different health states of women using contraception over a 3-year period. Typical use efficacy rates from published articles were used to determine unintended pregnancy events. Discontinuation rates were used to account for method switching. Cost-effectiveness was evaluated in terms of the incremental cost per unintended pregnancy avoided. In addition, the incremental cost per quality-adjusted life-year was calculated. Levonorgestrel intrauterine system 13.5 mg generated costs savings of € 311,000 in a cohort of 1000 women aged 15-44 years. In addition, there were fewer unintended pregnancies (55 vs. 294) compared with women using oral contraception. Levonorgestrel intrauterine system 13.5 mg is a cost-effective method when compared with oral contraception. A shift in contraceptive use from oral contraception to long-acting reversible contraception methods could result in fewer unintended pregnancies, quality-adjusted life-year gains, as well as cost savings. © 2015 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).

A primer on the hormone-free interval for combined oral contraceptives.

PubMed

Hauck, Brian A; Brown, Vivien

2015-01-01

The dosing, schedules, and other aspects of combined oral contraceptive (COC) design have evolved in recent years to address a variety of issues including short- and long-term safety, bleeding profiles, and contraceptive efficacy. In particular, several newer formulations have altered the length of the hormone-free interval (HFI), in order to minimize two key undesired effects that occur during this time: hormone-withdrawal-associated symptoms (HWaS) and follicular development. This primer reviews our current understanding of the key biological processes that occur during the HFI and how this understanding has led to changes in the dosing and schedule of newer COC formulations. In brief, HWaS are common, underappreciated, and a likely contributor to COC discontinuation; because of this, shortening the HFI and/or supplementing with estrogen during the progestin-free interval may provide relief from these symptoms and improve adherence. A short HFI (with or without estrogen supplementation) may also help maintain effective follicular suppression and contraceptive efficacy, even when the overall dose of estrogen throughout the cycle is low. Taken together, the available data about HWaS and follicular activity during the HFI support the rationale for recent COC designs that use a low estrogen dose and a short HFI. The availability of a variety of COC regimens gives physicians a range of choices when selecting the most appropriate COC for each woman's particular priorities and needs.

[The influence of low-dose oral contraceptive pill on clinical and metabolic parameters in young women with polycystic ovary syndrome].

PubMed

Banaszewska, Beata; Spaczyński, Robert Z; Ozegowska, Katarzyna; Pawelczyk, Leszek

2011-06-01

Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism, oligo/anovulation and is associated with risk factors for cardiovascular diseases, such as insulin resistance and central adiposity. The aim of the study was to evaluation of influence of the oral contraceptive pill on the endocrinologic and metabolic parameters in women with PCOS. Forty nine PCOS women (aged 23,9 +/- 3,5 [mean +/- SD]) without any other diseases were included into the study. Oral contraceptives (0,02 mg ethynylestradiol + 0,15 mg desogestrel) were administered for 6 months. Hormonal and biochemical analyses were performed with specific assays at the beginning and after 6 month-therapy BMI, insulin sensitivity index (ISI) and QUICKI were calculated. Statistical analysis was performed using Wilcoxon test. All patients completed 6-month therapy and no severe side effects were reported during the study. A significant reduction in testosterone (T) concentrations was observed (p<0.005). We recorded a significant increase in lipid concentrations. The administration of oral contraceptives in our study group caused decrease in the testosterone level but negative effect on total cholesterol and triglycerides level was observed.

Estimating systemic exposure to ethinyl estradiol from an oral contraceptive.

PubMed

Westhoff, Carolyn L; Pike, Malcolm C; Tang, Rosalind; DiNapoli, Marianne N; Sull, Monica; Cremers, Serge

2015-05-01

This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive with steady-state values and to assess whether any simpler measures could provide an adequate proxy of the "gold standard" 24-hour steady-state area under the curve (AUC) value. Identification of a simple, less expensive measure of systemic ethinyl estradiol exposure would be useful for larger studies that are designed to assess the relationship between an individual's ethinyl estradiol exposure and side-effects. We collected 13 samples over 24 hours for pharmacokinetic analysis on days 1 and 21 of the first cycle of a monophasic oral contraceptive that contained 30 μg ethinyl estradiol and 150 μg levonorgestrel in 17 nonobese healthy white women. We also conducted an abbreviated single-dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of a full 13-sample steady-state pharmacokinetic analysis with results that had been calculated with the use of fewer samples (9 or 5) and after the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. The AUC, maximum, and 24-hour values were similar after the 2 single oral contraceptive doses (AUC; r=0.92). The steady-state 13-sample 24-hour AUC value was correlated highly with the average 9-sample AUC value after the 2 single doses (r=0.81; P=.0002). This correlation remained the same if the number of single-dose samples was reduced to 4, taken at time 1, 2.5, 4, and 24 hours. The 24-hour value at steady-state was correlated highly with the 24-hour steady-state AUC value (r=0.92; P<.0001). The average of the 24-hour values after the 2 single doses was also correlated quite highly with the steady-state AUC value (r=0.72; P=.0026). Limited blood sampling, including results from 2 single doses, gave highly

Combined Oral Contraceptive Pills: Profile of Acceptors in a Tertiary Hospital in South-South Nigeria.

PubMed

Abasiattai, A M; Utuk, M N; Ojeh, S O; Eyo, U E

2011-01-01

BACKGROUND: Combined oral contraceptive pills were the first contraceptive method to provide sexual freedom of choice for women through reliable, personal and private control of fertility. They are the most widely used hormonal contraceptives and also the most popular non-surgical method of contraception. OBJECTIVE: To review the profile of acceptors of combined oral contraceptive pills at the University of Uyo Teaching Hospital, Uyo. METHODOLOGY: An 8 year review of all clients that accepted combined oral contraceptive pills in the family planning clinic. RESULTS: There were 1,146 new contraceptive acceptors during the period of study out of which 309 (27.9%) accepted the pills. Majority of the clients were between 20 and 29 years of age (54.0%), were multiparous (72.8%), Christians (99.7%) and 61.2% had tertiary level education. Two hundred and fifty-five women (82.5%) desired to use combined oral contraceptive pills to space births while 7.8% wanted to limit child bearing. There was a high discontinuation rate among the women (45.0%) and out of these 87.9% of the clients changed to other contraceptive methods. All the clients commenced their pills within seven days of menstruation and only the low dose monophasic preparations were available in the family planning unit and thus were given to the clients. CONCLUSION: Women who accept to initiate combined oral contraceptive pills in our center are young, well educated, multiparous women who want to space their pregnancies. However, due to the high discontinuation rate among the clients, there is need for further studies evaluating reasons for the high discontinuation rate, exploring interactions between clients and providers' and also providers' attitude towards combined pills in our environment.

Oral contraceptives and neuroactive steroids.

PubMed

Rapkin, Andrea J; Biggio, Giovanni; Concas, Alessandra

2006-08-01

A deregulation in the peripheral and brain concentrations of neuroactive steroids has been found in certain pathological conditions characterized by emotional or affective disturbances, including major depression and anxiety disorders. In this article we summarize data pertaining to the modulatory effects of oral contraceptive treatment on neuroactive steroids in women and rats. Given that the neuroactive steroids concentrations are reduced by oral contraceptives, together with the evidence that a subset of women taking oral contraceptives experience negative mood symptoms, we propose the use of this pharmacological treatment as a putative model to study the role of neuroactive steroids in the etiopathology of mood disorders. Moreover, since neuroactive steroids are potent modulators of GABA(A) receptor function and plasticity, the treatment with oral contraceptives might also represent a useful experimental model to further investigate the physiological role of these steroids in the modulation of GABAergic transmission.

ESTIMATING SYSTEMIC EXPOSURE TO ETHINYL ESTRADIOL FROM AN ORAL CONTRACEPTIVE

PubMed Central

WESTHOFF, Carolyn L.; PIKE, Malcolm C.; TANG, Rosalind; DINAPOLI, Marianne N.; SULL, Monica; CREMERS, Serge

2015-01-01

Objectives This study was conducted to compare single-dose pharmacokinetics of ethinyl estradiol in an oral contraceptive to steady-state values, and to assess whether any simpler measures could provide an adequate proxy of the ‘gold standard’ 24-hour steady-state area-under-the-curve. Identifying a simple, less expensive, measure of systemic ethinyl estradiol exposure would be useful for larger studies designed to assess the relationship between an individual’s ethinyl estradiol exposure and her side effects. Study Design We conducted a 13 samples over 24 hours pharmacokinetic analysis on day 1 and day 21 of the first cycle of a monophasic oral contraceptive containing 30 mcg ethinyl estradiol and 150 mcg levonorgestrel in 17 non-obese healthy white women. We also conducted an abbreviated single dose 9-sample pharmacokinetic analysis after a month washout. Ethinyl estradiol was measured by liquid chromatography-tandem mass spectrometry. We compared results of full 13-sample steady-state pharmacokinetic analysis with results calculated using fewer samples (9 or 5) and following the single doses. We calculated Pearson correlation coefficients to evaluate the relationships between these estimates of systemic ethinyl estradiol exposure. Results The area-under-the-curve, maximum (Cmax), and 24-hour (C24) values were similar following the two single oral contraceptive doses (area-under-the-curve, r = 0.92). The steady-state 13-sample 24-hour area-under-the-curve was highly correlated with the average 9-sample area-under-the-curve after the two single doses (r = 0.81, p = 0.0002). This correlation remained the same if the number of samples was reduced to 4, taken at time 1, 2.5, 4 and 24 hours. The C24 at steady-state was highly correlated with the 24-hour steady-state area-under-the-curve (r = 0.92, p < 0.0001). The average of the C24 values following the two single doses was also quite highly correlated with the steady-state area-under-the-curve (r = 0.72, p = 0

A study on utilization of oral contraceptives in the City of Zagreb (2008-2010).

PubMed

Zelić-Kerep, Ana; Stimac, Danijela; Ozić, Sanja; Zivković, Kresimir; Zivković, Nikica

2014-06-01

Main aim of this study is to quantify and analyze the utilization and utilization trends of oral hormonal contraceptives in the City of Zagreb, 2008-2010, and to propose potential interventions, if necessary. Data gathered from Zagreb pharmacies were assessed by Anatomical Therapeutic Chemical Classification of drugs and Daily Defined Dose methodology. An alarming decrease in total utilization of hormonal contraceptives by 76% from 2008-2009 was found as the main result of this study. A major decrease by 95.5% in utilization of G03AB04 subgroup, sequential combined oral contraceptives, was noted in the year 2009. The subgroup G03AC0, progesterone-only pill group, showed a stable trend, and it became the most utilized subgroup in 2010, due to the decrease in utilization of both fixed and sequential combined oral contraceptives. Utilization of oral contraceptives in Croatia is not regulated adequately, since such dynamics in utilization can occur unnoticed. Measures need to take place in order to improve this situation. Proposed measures include organized farmacovigilance, prescription based on guidelines, and strict screening for risk factors in women seeking oral contraception. More research is required in Croatia to understand the pattern of utilization of hormonal contraceptives and to find the true cause of decrease in utilization of oral contraceptives.

Mothers' attitude to the use of a combined oral contraceptive pill by their daughters for menstrual disorders or contraception.

PubMed

Yiu, K W; Chan, S Sc; Chung, T Kh

2017-04-01

Mothers' attitude may affect use of combined oral contraceptive pills by their daughters. We explored Chinese mothers' knowledge of and attitudes towards the use of combined oral contraceptive pills by their daughters for menstrual disorders or contraception, and evaluate the factors affecting their attitude. This survey was conducted from October 2012 to March 2013, and recruited Chinese women who attended a gynaecology clinic or accompanied their daughter to a gynaecology clinic, and who had one or more daughters aged 10 to 18 years. They completed a 41-item questionnaire to assess their knowledge of and attitude towards use of the combined oral contraceptive pills by their daughters. The demographic data of the mothers and their personal experience in using the pills were also collected. A total of 300 women with a mean age of 45.2 (standard deviation, 5.0) years completed the questionnaire. Only 58.3% of women reported that they had knowledge about the combined oral contraceptive pills; among them, a majority (63.3%) reported that their source of knowledge came from medical professionals. Of a total possible score of 22, their mean knowledge score for risk, side-effects, benefits, and contra-indications to use of combined oral contraceptive pills was only 5.0 (standard deviation, 4.7). If the medical recommendation to use an oral contraceptive was to manage their daughter's dysmenorrhoea, menorrhagia, acne, or contraception needs, 32.0%, 39.3%, 21.0% and 29.7%, respectively would accept this advice. Women who were an ever-user of combined oral contraceptive pills or who were more knowledgeable about combined oral contraceptives had a higher acceptance rate. Chinese women had a low acceptance level of using combined oral contraceptive pills as a legitimate treatment for their daughters. This was associated with lack of knowledge or a high degree of uncertainty about their risks and benefits. It is important that health caregivers provide up-to-date information

Comparing the effects of the second-and third-generation oral contraceptives on sexual functioning

PubMed Central

Shahnazi, Mahnaz; Bayatipayan, Somaye; Khalili, Azizeh Farshbaf; Kochaksaraei, Fatemeh Ranjbar; Jafarabadi, Mohammad Asghari; Banoi, Kamala Gaza; Nahaee, Jila

2015-01-01

Background: The aim of this study was to compare the effects of the second- and third-generation oral contraceptives on women's reproductive sexual function. Materials and Methods: This randomized, double-blind, placebo-controlled clinical trial was conducted on 82 married women of reproductive age in Tehran. Samples were randomized into the groups receiving second- and third-generation oral contraceptive pills. Female Sexual Function Index (FSFI) tool was used before the intervention and 2 and 4 months after the intervention. Data analysis was carried out using analysis of variance (ANOVA) within repeated measures and P < 0.05 were considered significant. Results: There was a statistically significant difference in the positive and negative moods between the experimental and control groups before the intervention in the second and fourth months. The second-generation pills caused a decrease in sexual function in the second month and an increase in sexual function in the fourth month, but the third-generation pills led to an increase in sexual function in the second and fourth months. The increase in sexual function that resulted from using the third-generation pills was significantly higher than that resulted on using the second-generation pills. Conclusions: According to the results of this study, sexual functioning decreased in the second month of using the second-generation pills and sexual performance was significantly more on using the third-generation pills compared to second-generation pills. The most common type of oral contraceptive used in Iran is the second-generation oral contraceptive LD™ (low-dose estrogen), which is freely distributed in health centers. Therefore, it is necessary for women who wish to use these contraceptive methods to be educated and consulted before they start using them. The third-generation contraceptive pills can be recommended to women who wish to use oral contraceptives. PMID:25709690

Comparing the effects of the second-and third-generation oral contraceptives on sexual functioning.

PubMed

Shahnazi, Mahnaz; Bayatipayan, Somaye; Khalili, Azizeh Farshbaf; Kochaksaraei, Fatemeh Ranjbar; Jafarabadi, Mohammad Asghari; Banoi, Kamala Gaza; Nahaee, Jila

2015-01-01

The aim of this study was to compare the effects of the second- and third-generation oral contraceptives on women's reproductive sexual function. This randomized, double-blind, placebo-controlled clinical trial was conducted on 82 married women of reproductive age in Tehran. Samples were randomized into the groups receiving second- and third-generation oral contraceptive pills. Female Sexual Function Index (FSFI) tool was used before the intervention and 2 and 4 months after the intervention. Data analysis was carried out using analysis of variance (ANOVA) within repeated measures and P < 0.05 were considered significant. There was a statistically significant difference in the positive and negative moods between the experimental and control groups before the intervention in the second and fourth months. The second-generation pills caused a decrease in sexual function in the second month and an increase in sexual function in the fourth month, but the third-generation pills led to an increase in sexual function in the second and fourth months. The increase in sexual function that resulted from using the third-generation pills was significantly higher than that resulted on using the second-generation pills. According to the results of this study, sexual functioning decreased in the second month of using the second-generation pills and sexual performance was significantly more on using the third-generation pills compared to second-generation pills. The most common type of oral contraceptive used in Iran is the second-generation oral contraceptive LD™ (low-dose estrogen), which is freely distributed in health centers. Therefore, it is necessary for women who wish to use these contraceptive methods to be educated and consulted before they start using them. The third-generation contraceptive pills can be recommended to women who wish to use oral contraceptives.

Low-dose combined oral contraceptive use is associated with lower bone mineral content variation in adolescents over a 1-year period.

PubMed

Biason, Talita Poli; Goldberg, Tamara Beres Lederer; Kurokawa, Cilmery Suemi; Moretto, Maria Regina; Teixeira, Altamir Santos; Nunes, Hélio Rubens de Carvalho

2015-04-03

Low-dose combined oral contraceptives (COCs) can interfere with bone mass acquisition during adolescence. This study aimed to evaluate bone mineral density (BMD) and bone mineral content (BMC) in female adolescents taking a standard low-dose COC (ethinylestradiol 20 μg/desogestrel 150 μg) over a 1-year period and to compare their data with those of healthy adolescents from the same age group not taking COCs. This was a non-randomized parallel-control study with a 1-year follow-up. Sixty-seven adolescents aged from 12 to 19 years, divided into COC users (n = 41) taking 20 μg ethinylestradiol/150 μg desogestrel and COC non-user controls (n = 26), were evaluated by bone densitometry examinations at baseline and after 12 months. Comparisons between the groups at the study onset were performed using the Mann-Whitney test with the significance level fixed at 5% or p < 0.05. Comparisons between the groups at the study onset and after 12 months were based on variations in the median percentages for bone mass variables. The COC users presented with low bone mass acquisition in the lumbar spine, and had BMD and BMC median variations of 2.07% and +1.57%, respectively, between the measurements at baseline and 12 months. The control group had median variations of +12.16% and +16.84% for BMD and BMC, respectively, over the same period. The total body BMD and BMC showed similar evolutions during the study in both groups. Statistical significance (p < 0.05) was seen for the BMC percentage variation between COC users and non-users. Use of a low-dose COC (ethinylestradiol 20 μg/desogestrel 150 μg) was associated with lower bone mass acquisition in adolescents during the study period. Registry Number, RBR-5h9b3c.

Unscheduled bleeding with continuous oral contraceptive pills: a comparison of progestin dose.

PubMed

Kaneshiro, Bliss; Edelman, Alison; Carlson, Nichole E; Nichols, Mark; Jensen, Jeffrey

2012-07-01

Although the use of continuous oral contraceptive pills (OCPs) eliminates scheduled uterine bleeding, unscheduled bleeding is common. The objective of this study was to determine whether progestin dose influences bleeding with use of continuous OCPs. This was a secondary data analysis of two other studies of continuous OCPs. Women were eligible if they were switching from a cyclic hormonal contraceptive to a continuous OCP. Women took a 20-mcg ethinyl estradiol (EE)/100-mcg levonorgestrel (LNG) pill or a 20-mcg EE/90-mcg LNG pill for 112 days. The number of bleeding/spotting days was compared between groups using a t test. Sample size was adequate to detect a difference of 8 days of bleeding/spotting over the 112 day study period (β=0.80, α=0.05). Sixty-six subjects were enrolled, 33 in each group. There were no differences in baseline characteristic, missed OCPs or side effects. There were no differences in the mean number of bleeding/spotting days in the first 84 days of the study (90 mcg LNG mean 20.8 (SE 3.6) days versus 100 mcg LNG 17.8 (SE 2.3) days, p=.48), nor was there a difference in the time to amenorrhea (p=.35). Our results do not support the use of one LNG dose over another to decrease the amount of unscheduled bleeding women experience when initiating a continuous OCP. Copyright © 2012 Elsevier Inc. All rights reserved.

Side and site of deep vein thrombosis in women using oral contraceptives.

PubMed

Kierkegaard, A

1985-01-01

The anatomy of the thrombus in acute deep vein thrombosis (DVT) in women using oral contraceptives was studied in 277 reports on DVT received by the Swedish Adverse Drug Reaction Advisory Committee (SADRAC). The study revealed a similarity between the anatomy of DVT in women on oral contraceptives and that of DVT in pregnant women, suggesting a pharmacologic influence of the hormones in the pill on the pathogenesis of DVT in women on oral contraceptives. The anatomy of DVT in women on low-estrogen pills was identical with that of DVT in women on high-estrogen pills, suggesting an identical pharmacologic influence of the two types of pill on the pathogenesis of DVT in women on oral contraceptives.

Basal and meal-stimulated ghrelin, PYY, CCK levels and satiety in lean women with polycystic ovary syndrome: effect of low-dose oral contraceptive.

PubMed

Arusoglu, Gulcan; Koksal, Gulden; Cinar, Nese; Tapan, Serkan; Aksoy, Duygu Yazgan; Yildiz, Bulent O

2013-11-01

Ghrelin is an orexigenic peptide that stimulates food intake, whereas peptide YY (PYY) and cholecystokinin (CCK) are anorexigenic gut hormones. Patients with polycystic ovary syndrome (PCOS) appear to have alterations in appetite regulation. We aimed to determine whether fasting or meal-stimulated ghrelin, PYY, CCK, and satiety responses are different between lean PCOS patients and healthy women. We also aimed to assess the potential effect of oral contraceptive use on these hormones and satiety response. We conducted a prospective observational study in a university practice. Eighteen lean PCOS patients and 18 healthy control women matched for age and body mass index underwent measurements of circulating ghrelin, PYY, CCK, and satiety index (SI) before and after a standardized mixed meal at 0, 15, 30, 45, 60, 90, 120, and 180 minutes. For PCOS patients who were treated with ethinyl estradiol 30 μg/drospirenone 3 mg for 3 months, measurements were repeated. We measured ghrelin, PYY, and CCK levels and SI. At baseline, fasting ghrelin, PYY, CCK, and SI values in PCOS patients were not different from controls. Meal-stimulated PYY, CCK, and SI were also not different between the groups, whereas PCOS patients had significantly lower meal-stimulated ghrelin levels compared to controls (P = .04). Ghrelin, PYY, CCK, and SI did not show a significant change after treatment with ethinyl estradiol/drospirenone for 3 months. Basal and stimulated hunger and satiety hormones in lean PCOS patients are not different from lean healthy women, except for a lower meal-stimulated ghrelin response. Short-term use of a low-dose oral contraceptive does not have an effect on appetite regulation of PCOS.

Factors associated with the contraindicated use of oral contraceptives in Brazil

PubMed Central

Corrêa, Daniele Aparecida Silva; Felisbino-Mendes, Mariana Santos; Mendes, Mayara Santos; Malta, Deborah Carvalho; Velasquez-Melendez, Gustavo

2016-01-01

ABSTRACT OBJECTIVE To estimate the prevalence of the contraindicated use of oral contraceptives and the associated factors in Brazilian women. METHODS 20,454 women who answered the VIGITEL survey in 2008 also participated in this study, of which 3,985 reported using oral contraceptives. We defined the following conditions for the contraindicated use of contraceptives: hypertension; cardiovascular diseases such as heart attack, stroke/cerebrovascular accident; diabetes mellitus; being smoker and 35 years old or older. We estimated the prevalence and 95% confidence intervals of contraindicated use in users of oral contraceptives and the factors associated with contraindication by prevalence ratio and 95% confidence intervals. RESULTS In the total population, 21% (95%CI 19.7–21.9) of women showed some contraindication to the use of oral contraceptives, of which 11.7% (95%CI 10.6–13.7) belonged to the group of users of oral contraceptives. The most frequent contraindication in users of oral contraceptives was hypertension (9.1%). The largest proportion of women with at least one contraindication was aged between 45 and 49 years (45.8%) and with education level between zero and eight years (23.8%). The prevalence of contraindication to oral contraceptives was higher in women less educated (zero to eight years of study) (PR = 2.46; 95%CI 1.57–3.86; p < 0.05) and with age between 35-44 years (PR = 4.00; 95%CI 2.34–6.83) and 45-49 years (PR = 5.59; 95%CI 2.90–10.75). CONCLUSIONS Age greater than or equal to 35 and low education level were demographic and iniquity factors, respectively, in the contraindicated use of oral contraceptives. PMID:28099550

Pharmacists' counseling on oral contraceptives: A theory informed analysis.

PubMed

Amin, Mohamed E K; Chewning, Betty

2016-01-01

Providing correct and complete counseling on the use of oral contraceptives (OCs) is central to securing the autonomy of women in child-bearing age and is a powerful, proven tool of social change. Pharmacists in many developing countries such as Egypt are involved in dispensing and at times prescribing pharmaceuticals, including oral contraceptives that are readily available without a prescription. To predict Egyptian community pharmacists' counseling on oral contraceptives while utilizing a theoretical framework guided by the Theory of Planned Behavior (TPB). A cross-sectional, self-administered survey was completed by a random sample of community pharmacists in Alexandria, Egypt to determine their attitudes and behaviors regarding counseling on OCs. Multiple regression was used to predict self-reported counseling on oral contraceptives as a function of the TPB-related constructs and six other factors - "perceived importance of profit from dispensing OCs on pharmacy revenue," "number of hours worked," "age," "gender," "pharmacy practice degree" and "marital status" of the pharmacist. Of the 181 pharmacists invited to complete the survey, 168 (93%) participated. Pharmacists indicated they talked to a slightly higher proportion of women about the importance of taking OCs at the same time daily than about topics such as which day to start taking OCs, side effects and what to do when a dose of OCs was missed. Pharmacists' reported counseling on oral contraceptives was positively associated with their perception that women welcomed pharmacist initiated OC counseling (β = 0.315, P < 0.001), perceived adequacy of time available to counsel women on OCs (β = 0.290, P = 0.003) and the perceived number of women who asked for their help in selecting an OC without providing a prescription in the past week (β = 0.160, P = 0.018). Pharmacists reported that women's welcoming pharmacists initiating OC counseling was associated with the pharmacists' reported percent

A randomized controlled trial of subantimicrobial-dose doxycycline to prevent unscheduled bleeding with continuous oral contraceptive pill use.

PubMed

Kaneshiro, Bliss; Edelman, Alison; Carlson, Nichole E; Nichols, Mark; Forbes, Marci Messerle; Jensen, Jeffrey

2012-04-01

Unscheduled bleeding is the main side effect of continuous oral contraceptive pills (OCPs) and has been correlated with the up-regulation of matrix metalloprotineases (MMPs). The study objective was to determine if prophylactic administration of doxycycline (an MMP inhibitor at low subantimicrobial doses) would prevent unscheduled bleeding during the initiation of a continuous OCP. Subjects using cyclic hormonal contraceptives (combined OCPs, patch or ring) without unscheduled bleeding were switched to continuous OCPs (20 mcg ethinyl estradiol/100 mcg levonorgestrel). They were randomized to receive daily doxycycline [sustained-release subantimicrobial dose (40 mg daily)] or placebo for the first 84 days and then observed for an additional 28 days on the continuous OCP alone. The number of bleeding/spotting days and the time in days it took to achieve amenorrhea were compared using a t test. Sixty-five subjects were randomized. Although the use of doxycycline did not significantly decrease the number of mean bleeding/spotting days in the first 84 days of the study [doxycycline 14.75 (SE 2.30), placebo 17.78 (2.31), p=.36], women who received doxycycline had a significantly earlier onset of amenorrhea [mean last day of bleeding/spotting doxycycline 61.7 (7.7), placebo 85.2 (6.7), p=.03]. The coadministration of subantimicrobial-dose doxycycline during initiation of continuous OCPs results in a significant reduction in the length of time needed to achieve amenorrhea. Copyright © 2012 Elsevier Inc. All rights reserved.

A randomized controlled trial of subantimicrobial-dose doxycycline to prevent unscheduled bleeding with continuous oral contraceptive pill use☆

PubMed Central

Kaneshiro, Bliss; Edelman, Alison; Carlson, Nichole E.; Nichols, Mark; Forbes, Marci Messerle; Jensen, Jeffrey

2016-01-01

Background Unscheduled bleeding is the main side effect of continuous oral contraceptive pills (OCPs) and has been correlated with the up-regulation of matrix metalloprotineases (MMPs). The study objective was to determine if prophylactic administration of doxycycline (an MMP inhibitor at low subantimicrobial doses) would prevent unscheduled bleeding during the initiation of a continuous OCP. Study Design Subjects using cyclic hormonal contraceptives (combined OCPs, patch or ring) without unscheduled bleeding were switched to continuous OCPs (20 mcg ethinyl estradiol/100 mcg levonorgestrel). They were randomized to receive daily doxycycline [sustained-release subantimicrobial dose (40 mg daily)] or placebo for the first 84 days and then observed for an additional 28 days on the continuous OCP alone. The number of bleeding/spotting days and the time in days it took to achieve amenorrhea were compared using a t test. Results Sixty-five subjects were randomized. Although the use of doxycycline did not significantly decrease the number of mean bleeding/spotting days in the first 84 days of the study [doxycycline 14.75 (SE 2.30), placebo 17.78 (2.31), p=.36], women who received doxycycline had a significantly earlier onset of amenorrhea [mean last day of bleeding/spotting doxycycline 61.7 (7.7), placebo 85.2 (6.7), p=.03]. Conclusion The coadministration of subantimicrobial-dose doxycycline during initiation of continuous OCPs results in a significant reduction in the length of time needed to achieve amenorrhea. PMID:22067758

The combined use of oral medroxyprogesterone acetate and methyltestosterone in a male contraceptive trial programme.

PubMed

Bain, J; Rachlis, V; Robert, E; Khait, Z

1980-04-01

A male contraceptive trial was undertaken in 23 men using a combination of oral medroxyprogesterone acetate (MPA) and oral methyltestosterone (MeT). The men were divided into four groups according to varying drug dosages and were followed for 15 months (control - 3 months, treatment - 6 months, follow-up - 6 months). The parameters assessed included sperm count and motility, serum gonadotropins and sex steroids, and several biochemical and hematological tests. A questionnaire dealing with side-effects and changes in sexual function was administered intermittently. Although sperm count was suppressed (most dramatically at the highest drug doses, MPA 20mg,MeT 20mg), it was not suppressed to infertile levels. Sperm motility was unaltered; LH was modestly suppressed, FSH was not suppressed; testosterone was suppressed even at low doses; dihydrotestosterone responses were inconsistent. No significant biochemical abnormalities or side-effects occurred although some men experienced mild transient acne, gynecomastia and decreased testicular size. We conclude that in the doses used in this trial, the combination of MPA and MeT is not effective for male contraceptive, purposes and that higher doses may induce severe and undesirable side-effects.

Oral contraception in the former Czech and Slovak Federal Republic: attitudes and use.

PubMed

Ketting, E; Visser, A P; Uzel, R; Lehert, P

1993-06-01

This paper presents and discusses data on oral contraception from a national representative survey (n = 1072) on knowledge, attitudes and practice with regard to contraceptive use in the Czech and Slovak Federal Republic (CSFR). Only 7% of the women at risk of unplanned pregnancy used the pill. The low rate of use seems to be due to the general negative image of oral contraception, reinforced by the experiences of past users and opinions expressed by relative, friends, doctors, and the media. In particular, perceived psychological disadvantages have an important bearing on the decision not to use the method, whereas perceived advantages have hardly any impact. It is likely that this negative image is closely linked with the types of oral contraceptives that have been available in the country and also with the limited choice. Second- and third-generation oral contraceptives have only very recently become available. It is recommended that balanced information on the advantages and disadvantages of oral contraception be made available to doctors and to the general public on a large scale and through a variety of channels.

Use of and access to oral and injectable contraceptives in Brazil

PubMed Central

Farias, Mareni Rocha; Leite, Silvana Nair; Tavares, Noemia Urruth Leão; Oliveira, Maria Auxiliadora; Arrais, Paulo Sergio Dourado; Bertoldi, Andréa Dâmaso; Pizzol, Tatiane da Silva Dal; Luiza, Vera Lucia; Ramos, Luiz Roberto; Mengue, Sotero Serrate

2016-01-01

contraceptives from SUS. Monophasic combined oral contraceptives were the most frequently reported (71.6%) and low-level levonorgestrel + ethinylestradiol combination accounted for 38.7% of them. The most frequently reported medicines are included in the Relação Nacional de Medicamentos Essenciais (RENAME – National List of Essential Medicines. CONCLUSIONS Most women aged 15 to 49 who reported using contraceptives had access to the medicine and use monophasic combined oral contraceptives of appropriate efficiency and safety purchased by direct payment, mainly from retail pharmacies. PMID:27982384

Oral contraceptives and benign breast disease.

PubMed

Hislop, T G; Threlfall, W J

1984-08-01

In 1980 a questionnaire was mailed to 726 nurses who had previously entered a study of breast disease in the late 1940s and 1950s; 665 responded. Between the ages of 30 to 49 years, 137 reported detecting their first signs of benign breast disease and 76 reported receiving their first biopsy for these signs. Long-term oral contraceptive usage reduced the risk of developing signs of benign breast disease and the risk of biopsy for these signs. The potential bias due to the effect of prior benign breast disease on the prescribing practices for oral contraceptives was minimized by considering oral contraceptive usage prior to detecting the first signs of benign breast disease.

Efficacy and safety of an ascending-dose, extended-regimen levonorgestrel/ethinyl estradiol combined oral contraceptive.

PubMed

Portman, David J; Kaunitz, Andrew M; Howard, Brandon; Weiss, Herman; Hsieh, Jennifer; Ricciotti, Nancy

2014-04-01

To evaluate the efficacy and safety of an ascending-dose, extended-regimen (ADER) combined oral contraceptive consisting of levonorgestrel (LNG) 150 mcg/ethinyl estradiol (EE) 20 mcg for 42 days, LNG 150 mcg/EE 25 mcg for 21 days, LNG 150 mcg/EE 30 mcg for 21 days and EE 10 mcg for 7 days. This was a multicenter, open-label, phase 3, single-arm study. Sexually active women aged 18-40 years were enrolled and received ADER for up to 1 year (4 consecutive 91-day cycles). Participants kept diaries to record adherence, bleeding/spotting and other contraceptive use. Efficacy was measured using the Pearl Index and the life-table method; safety and tolerability were assessed through reported adverse events (AEs). A total of 3701 women were enrolled and 2144 completed the study. The Pearl Index was 3.19 [95% confidence interval (CI), 2.49-4.03], based on 70 pregnancies that occurred after ADER initiation and ≤ 7 days after the last LNG/EE or EE-only pill in women aged 18-35 years, excluding cycles in which another contraceptive method was used. Life-table pregnancy rate was 2.82% (95% CI, 2.23%-3.57%) for all users aged 18-35 years. Unscheduled bleeding/spotting decreased with increasing EE doses within each cycle and decreased after cycle 1. No unexpected AEs or changes in laboratory parameters were reported. This study demonstrated that ADER effectively prevented pregnancy with a favorable safety and tolerability profile. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Metabolic and cardiovascular impact of oral contraceptives in polycystic ovary syndrome.

PubMed

Soares, G M; Vieira, C S; de Paula Martins, W; Dos Reis, R M; de Sá, M F S; Ferriani, R A

2009-01-01

Chronic anovulation, polycystic ovarian morphology and hyperandrogenism are the diagnostic criteria for polycystic ovary syndrome (PCOS). Metabolic disturbances are more common in PCOS women who are prone to develop metabolic syndrome and to present higher levels of some cardiovascular disease risk marker. Oral contraceptives are widely used in PCOS, but conflicting data have been reported regarding their impact on carbohydrate and lipid metabolism on PCOS women. This paper presents a critical evaluation of combined oral contraceptives (COCs) metabolic effect - carbohydrate metabolism and insulin sensitivity, lipid metabolism, haemostasis, body weight, arterial pressure and cardiovascular impact - on PCOS women. Because of the paucity of data on the impact of COCs on cardiovascular and metabolic parameters in PCOS patients, most of there commendations are based on studies involving ovulatory women. The use of low-dose COCs is preferable in PCOS, especially among patients with glucose intolerance, insulin resistance and uncomplicated diabetes mellitus. Although reported as a side effect of COCs, marked weight gain has not been confirmed among users. However, when arterial hypertension or elevated risk for thromboembolism is present, progestogen-only hormonal contraceptives should be used instead of COCs. Regarding dyslipidaemia, COCs reduce low-density lipoprotein and total cholesterol and elevate high-density lipoprotein and triglycerides, and therefore are not recommended for women with high triglycerides levels. The choice of a COC, which alleviates the PCOS-induced hyperandrogenism without significant negative impact on cardiovascular risk, is one of the greatest challenges faced by gynaecologists nowadays.

A 1-year randomized study to evaluate the effects of a dose reduction in oral contraceptives on lipids and carbohydrate metabolism: 20 microg ethinyl estradiol combined with 100 microg levonorgestrel.

PubMed

Skouby, Sven O; Endrikat, Jan; Düsterberg, Bernd; Schmidt, Werner; Gerlinger, Christoph; Wessel, Jens; Goldstein, Henri; Jespersen, Joergen

2005-02-01

To evaluate the impact on lipid and carbohydrate variables of a combined one-third ethinyl estradiol (EE)/levonorgestrel (LNG) dose reduction in oral contraceptives. In an open-label, randomized study, a dose-reduced oral contraceptive containing 20 microg EE and 100 microg LNG (20 EE/100 LNG) was compared with a reference preparation containing 30 microg EE and 150 microg LNG (30 EE/150 LNG). One-year data from 48 volunteers were obtained. We found a decrease of HDL2 cholesterol and increases of low-density lipoprotein cholesterol, very low-density lipoprotein cholesterol and total triglycerides in both treatment groups from baseline to the 13th treatment cycle. Although for four of six variables, the changes in the 20 EE group were lower compared with the 30 EE group, none of the differences between the two treatments were statistically significant. The median values for the fasting levels of insulin, C-peptide and free fatty acids slightly increased or remained unchanged while the fasting glucose levels slightly decreased after 13 treatment cycles. While the glucose area under the curve (AUC) (0-3 h) was similar in both groups during the OGTT, the insulin AUC(0-3 h) was less increased in the 20 EE/100 LNG group compared with the 30 EE/150 LNG group. None of the differences between the treatment groups for any of the carbohydrate metabolism variables were statistically significant at any time point. Both study treatments were safe and well tolerated by the volunteers. Similar effects on the lipid and carbohydrate profiles were found for both preparations. The balanced one-third EE dose reduction in this new oral contraceptive caused slightly lower, but insignificant, changes in the lipid and carbohydrate variables compared with the reference treatment.

Differences in Reporting Pearl Indices in the United States and Europe: Focus on a 91-Day Extended-Regimen Combined Oral Contraceptive with Low-Dose Ethinyl Estradiol Supplementation

PubMed Central

Abascal, Paloma Lobo; Luzar-Stiffler, Vesna; Giljanovic, Silvana; Howard, Brandon; Weiss, Herman; Trussell, James

2017-01-01

Background Regulatory agencies in the United States (US) and Europe differ in requirements for defining pregnancies after the last dose of oral contraceptive, sometimes resulting in discrepant Pearl Indices (PIs) for the same product despite identical clinical data. This brief report highlights one such example, a 91-day extended-regimen combined oral contraceptive (COC). Methods The US- and European-based PI methodologies were compared for a 91-day extended-regimen COC consisting of 84 days of active levonorgestrel/EE 150 μg/30 μg tablets, followed by 7 days of EE 10 μg tablets in place of placebo. Conclusions At the times of approval of the 91-day extended-regimen COC in the US and Europe, the requirements for defining ‘on-treatment’ pregnancies differed (14-day vs. 2-day rule, respectively). This difference resulted in a higher PI in the US- vs. European-based calculation (1.34 and 0.76, respectively). The differences in the PI should not be interpreted as the extended-regimen COC being less effective in preventing pregnancy in the US compared with Europe. PMID:26115381

Differences in reporting Pearl Indices in the United States and Europe: Focus on a 91-day extended-regimen combined oral contraceptive with low-dose ethinyl estradiol supplementation.

PubMed

Lobo Abascal, Paloma; Luzar-Stiffler, Vesna; Giljanovic, Silvana; Howard, Brandon; Weiss, Herman; Trussell, James

2016-01-01

Regulatory agencies in the United States (US) and Europe differ in requirements for defining pregnancies after the last dose of oral contraceptive, sometimes resulting in discrepant Pearl Indices (PIs) for the same product despite identical clinical data. This brief report highlights one such example, a 91-day extended-regimen combined oral contraceptive (COC). The US- and European-based PI methodologies were compared for a 91-day extended-regimen COC consisting of 84 days of active levonorgestrel/EE 150 μg/30 μg tablets, followed by seven days of EE 10 μg tablets in place of placebo. At the times of approval of the 91-day extended-regimen COC in the US and Europe, the requirements for defining 'on-treatment' pregnancies differed (14-day vs. 2-day rule, respectively). This difference resulted in a higher PI in the US- vs. European-based calculation (1.34 and 0.76, respectively). The differences in the PI should not be interpreted as the extended-regimen COC being less effective in preventing pregnancy in the US compared with Europe.

Potential public sector cost-savings from over-the-counter access to oral contraceptives.

PubMed

Foster, Diana G; Biggs, M Antonia; Phillips, Kathryn A; Grindlay, Kate; Grossman, Daniel

2015-05-01

This study estimates how making oral contraceptive pills (OCPs) available without a prescription may affect contraceptive use, unintended pregnancies and associated contraceptive and pregnancy costs among low-income women. Based on published figures, we estimate two scenarios [low over-the-counter (OTC) use and high OTC use] of the proportion of low-income women likely to switch to an OTC pill and predict adoption of OCPs according to the out-of-pocket costs per pill pack. We then estimate cost-savings of each scenario by comparing the total public sector cost of providing OCPs OTC and medical care for unintended pregnancy. Twenty-one percent of low-income women at risk for unintended pregnancy are very likely to use OCPs if they were available without a prescription. Women's use of OTC OCPs varies widely by the out-of-pocket pill pack cost. In a scenario assuming no out-of-pocket costs for the over-the counter pill, an additional 11-21% of low-income women will use the pill, resulting in a 20-36% decrease in the number of women using no method or a method less effective than the pill, and a 7-25% decrease in the number of unintended pregnancies, depending on the level of use and any effect on contraceptive failure rates. If out-of-pocket costs for such pills are low, OTC access could have a significant effect on use of effective contraceptives and unintended pregnancy. Public health plans may reduce expenditures on pregnancy and contraceptive healthcare services by covering oral contraceptives as an OTC product. Interest in OTC access to oral contraceptives is high. Removing the prescription barrier, particularly if pill packs are available at low or zero out-of-pocket cost, could increase the use of effective methods of contraception and reduce unintended pregnancy and healthcare costs for contraceptive and pregnancy care. Copyright © 2015 Elsevier Inc. All rights reserved.

A study of cycle control, side effects and client's satisfaction of a low dose combined contraceptive containing ethinylestradiol/drospirenone (24/4 regimen).

PubMed

Chaiyasit, Noppadol; Taneepanichskul, Surasak

2010-05-01

To study cycle control, side effects, and satisfaction of low dose 24-day combined contraceptive containing 20 microg of Ethinylestradiol and 3 mg of Drospirenone. This was an open label, non-comparative study. The healthy females from the family planning clinic at King Chulalongkorn Memorial Hospital were assigned to receive six cycles of combined oral contraceptive containing 20 microg of ethinylestradiol and 3 mg of drospirenone administered daily for 24 days followed by 4-day hormone-free interval. Data were collected on cycle control, side effects, and satisfaction. Data were analyzed using descriptive statistics for descriptive data and Paired t test for comparison. One hundred fifty four women were assigned the study medication, including one (0.64%) who did not start medication. In the second reference period, the occurrence of frequent and infrequent bleeding was low (2.1% and 4.9%). Only one woman (0.65%) discontinued medication because of irregular bleeding. There was no pregnancy reported during the present study. Overall, the study medication was well tolerated and five subjects (3.24%) discontinued study because of side effects. No serious side effects related to the study medication were reported. The majority of women (84.2%) were satisfied and very satisfied with the treatment and most (73.3%) would continue the medication if it were available. The low dose combined contraceptive containing Ethinylestradiol/Drospirenone (24/4 regimen) has acceptable cycle control and good tolerability.

Psychosexual well-being in women using oral contraceptives containing drospirenone.

PubMed

Nappi, Rossella E; Albani, Francesca; Tonani, Silvia; Santamaria, Valentina; Pisani, Carla; Terreno, Erica; Martini, Ellis; Polatti, Franco

2009-01-01

Considerable advances have been made in hormonal contraception in recent years, geared at maximizing compliance and minimizing discontinuation. In oral contraceptive (OC) formulations, the estrogenic component, generally ethinyl estradiol (EE), has been reduced significantly and newer progestins like dienogest and drospirenone (DRSP), compounds with different molecular structures, have been introduced; in addition, new regimens (extended, flexible, 24/4 formats instead of the standard 21/7 format) and innovative delivery systems (vaginal rings, transdermal patches, subcutaneous implants and intrauterine devices) are available. The multitude of choices allows hormonal contraception to be tailored to the individual woman in order to obtain non-contraceptive benefits, without significant side effects, and also a favorable risk/benefit profile for her general and reproductive health. Over the past few years, new OC formulations combining DRSP (3 mg), a unique progestin with both antimineralocorticoid and antiandrogenic activities, with estrogen (30 mcg or 20 mcg EE), in two regimens (24/4 and 21/7) of active pills in a 28-day cycle, have shown positive effects on water retention-related weight gain and physical, emotional and psychosexual well-being. It seems likely that the use of a low-dose, well-balanced OC and the shorter 4-day hormone-free interval may minimize the side effects that can impair quality of life and thus increase women's compliance with hormonal contraception therapy.

Effect of low zinc intake and oral contraceptive agents on nitrogen utilization and clinical findings in young women.

PubMed

Hess, F M; King, J C; Margen, S

1977-12-01

In a previous paper we reported that serum, urine and fecal zinc levels fell markedly in women taking a combination oral contraceptive agent (+OCA) and in women with normal menstrual cycles (-OCA) when they consumed a low-zinc diet (less than 0.2 mg/day) for 35 days. We evaluated other biochemical and clinical data in order to determine if depletion of accessible body zinc and/or physiologic adjustment to conserve body zinc stores had occurred. Neither low zinc intake nor oral contraceptive use appeared to influence nitrogen balance or body weight. Use of contraceptive drugs appeared to influence the response of blood parameters to zinc depletion. Serum transferrin and cholesterol declined significantly in the -OCA group, whereas alkaline phosphatase and gamma-globulin changed significantly in both groups. Clinical problems developed in all the subjects with serum zinc levels below 50 microgram/dl during the study; three of the six with serum zinc levels above 50 microgram/dl also complained of clinical symptoms. The results suggest that zinc deficiency through depletion of accessible body zinc stores developed during the 35-day study.

A prospective randomized trial comparing low-dose ethinyl estradiol and drospirenone 24/4 combined oral contraceptive vs. ethinyl estradiol and drospirenone 21/7 combined oral contraceptive in the treatment of hirsutism.

PubMed

Oner, Gokalp; Muderris, Iptisam Ipek

2011-11-01

A prospective randomized trial was conducted to compare the clinical efficacy of two oral contraceptives containing drospirenone in the treatment of hirsutism in women. Fifty women with moderate to severe hirsutism were recruited. Three women were lost to follow-up. Twenty-four patients received oral 0.03 mg ethinyl estradiol and 3 mg drospirenone 21/7 regimen (Group 1) for 6 months. Another group of 23 patients received oral 0.02 mg ethinyl estradiol and 3 mg drospirenone 24/4 regimen (Group 2) for 6 months. Hirsutism was assessed after 6 months using the Ferriman-Gallwey (F-G) scoring system. Hormonal levels after 6 months of both therapies were compared with baseline values and each other. An improvement in the F-G scores for hirsutism (mean±SD) was observed in Group 1 (17.3±5.2 to 8.7±2.5, p<.001) and in Group 2 (17.5±4.8 to 7.9±2.8, p<.001). Pre- and post-treatment hirsutism scores were comparable between the groups (p>.05). Total and free testosterone levels decreased significantly after the therapy in both groups. The sex hormone-binding globulin levels increased significantly in both groups during the 6-month period. The treatment of hirsutism with both combined oral contraceptives (COCs) containing drospirenone offered comparable effects and was well tolerated. Copyright © 2011 Elsevier Inc. All rights reserved.

Choosing the Right Oral Contraceptive Pill for Teens.

PubMed

Powell, Anne

2017-04-01

Oral contraceptive pills (OCPs) continue to be the most commonly used form of prescription contraceptives used by adolescents in the United States. With proper use, oral contraceptives provide safe and effective birth control. Broad categories of OCPs include progestin-only pills (POPs) and combined oral contraceptive pills (COCs). Certain types of progestins have more potent antiandrogenic properties and are more effective in treating acne, hirsutism, and polycystic ovary syndrome. This article reviews types of OCPs, discusses risks and benefits of OCPs, and provides guidance for how to choose the most beneficial and appropriate OCP for individual adolescent patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Adherence to oral contraception in women on Category X medications.

PubMed

Steinkellner, Amy; Chen, William; Denison, Shannon E

2010-10-01

Over 6% of women become pregnant when taking teratogenic medications, and contraceptive counseling appears to occur at suboptimal rates. Adherence to contraception is an important component in preventing unwanted pregnancy and has not been evaluated in this population. We undertook a pharmacy claims-based analysis to evaluate the degree to which women of childbearing age who receive Category X medications adhere to their oral contraception. We evaluated the prescription medication claims for over 6 million women, age 18-44 years, with prescription benefits administered by a pharmacy benefits manager. Women with 2 or more claims for a Category X medication and 2 or more claims for oral contraception were evaluated in further detail. Adherence to oral contraception was measured by analyzing pharmacy claims. Multivariable logistic regression was performed to identify factors associated with adherence. There were 146,758 women of childbearing age who received Category X medications, of which 26,136 also took oral contraceptive medication. Women who received Category X medications were prescribed oral contraception (18%) at rates similar to others of childbearing age (17%). Women prescribed both Category X and oral contraception demonstrated adherence similar to the overall population. Age, class of Category X medication, number of medications, prescriber's specialty, and ethnicity correlated with lower adherence rates. Despite added risk associated with unintended pregnancy, many women who receive Category X medications have refill patterns suggesting nonadherence to oral contraception. Compared with all women age 18-44 years, women receiving teratogenic medications do not have better adherence to oral contraception. Copyright © 2010 Elsevier Inc. All rights reserved.

Challenging oral contraception after weight loss by bariatric surgery.

PubMed

Merhi, Zaher O

2007-01-01

As surgical weight loss becomes more commonly performed in fertile women, adequate contraception is more frequently becoming an issue. The purpose of this article is to appraise the literature to ascertain whether the use of oral contraception is effective and adequate after bariatric surgery. The literature search revealed that the combination of lower oral contraception dosages and surgical gastrointestinal disturbances might place patients at higher risks of unintended pregnancy. Until clinical trials show its efficacy, physicians should use oral contraception with prudence after bariatric surgery. 2007 S. Karger AG, Basel

21 CFR 310.501 - Patient package inserts for oral contraceptives.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false Patient package inserts for oral contraceptives... Patient package inserts for oral contraceptives. (a) Requirement for a patient package insert. The safe and effective use of oral contraceptive drug products requires that patients be fully informed of the...

21 CFR 310.501 - Patient package inserts for oral contraceptives.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Patient package inserts for oral contraceptives... Patient package inserts for oral contraceptives. (a) Requirement for a patient package insert. The safe and effective use of oral contraceptive drug products requires that patients be fully informed of the...

21 CFR 310.501 - Patient package inserts for oral contraceptives.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Patient package inserts for oral contraceptives... Patient package inserts for oral contraceptives. (a) Requirement for a patient package insert. The safe and effective use of oral contraceptive drug products requires that patients be fully informed of the...

Effect of oral contraceptive agents on nutrients: II. Vitamins.

PubMed

Prasad, A S; Oberleas, D; Moghissi, K S; Stryker, J C; Lei, K Y

1975-04-01

Clinical, biochemical and nutritional data were collected from a large population of women using oral contraceptive agents. Higher incidence of abnormal clinical signs related to malnutrition were observed in the lower (B) as compared to the higher (A) socioeconomic groups, and also in the nonsupplemented groups as compared to the supplemented groups in the B subjects. As a rule the intake of oral contraceptive agent subjects of vitamin A, C, B6 and folic acid did not differ from that of the controls As expected, subjects from the supplemented groups had higher intake of vitamin A, C, B6, thiamin, riboflavin and folic acid, and A groups had higher intake of vitamin C, B6, riboflavin and folic acid. Increased plasma vitamin A and decreased carotene levels were observed in oral contraceptive agent users. In general oral contraceptive agents had little or no effect on plasma ascorbic acid. Urinary excretion of both thiamin and riboflavin in subjects using oral contraceptive agents were lower in A groups. Erythrocyte folate and plasma pyridoxal phosphate was decreased in A groups due to oral contraceptive agents. Subjects who took supplements had higher levels of plasma vitamin A, ascorbic acid and folate. But urinary thiamin and riboflavin were higher only in group A subjects who took supplements.

A randomized cross-over comparison of two low-dose oral contraceptives upon hormonal and metabolic serum parameters: II. Effects upon thyroid function, gastrin, STH, and glucose tolerance.

PubMed

Kuhl, H; Gahn, G; Romberg, G; Althoff, P H; Taubert, H D

1985-07-01

The effect of a low-dose triphasic oral contraceptive (OC) containing ethinyl estradiol and levonorgestrel (EE/NG) upon thyroid function and some other biochemical serum parameters was compared to that of a preparation containing EE and desogestrel (EE/DG). Blood samples were taken on Day 6, 11, 21, and 28 of a control cycle and of the third cycle of treatment with either the EE/NG or EE/DG preparation (11 volunteers each). After a washout period of 3 months, the contraceptives were changed in a cross-over fashion. Blood samples were again taken on Day 6, 11, 21, and 28 of the third washout cycle and the third treatment cycle. There was a significant increase (13%) in basal glucose level during treatment with both OC, but no change in glucose tolerance. Both the EE/NG and FE/DG preparation elevated serum T4 (40%), FT4 (15-22%), T3 (17-28%), and TBG (20%) significant, whereby the effect was more pronounced during the second treatment period after washing-out. The effective thyroxine ratio (ETR) was slightly (4%) but significantly increased. Contrary to this, the levels of FT3, reverse T3 (rT3), TSH, and gastrin were not altered. STH showed great individual fluctuations, but was significantly elevated by 50% during treatment with both OC. There was no effect of endogenous estradiol upon thyroid or other parameter, even though it was raised considerably in some women under OC. Although the increase in T4 and T3 is probably due to a rise in estrogen-induced TBG production, the data seem to indicate that there is a slight but effective stimulation of thyroid function during treatment with low-dose OC.

Suppression of ovarian activity with a low-dose 21/7-day regimen oral contraceptive containing ethinylestradiol 20 mcg/drospirenone 3 mg in Japanese and Caucasian women.

PubMed

Anzai, Yuzuru; Heger-Mahn, Doris; Schellschmidt, Ilka; Marr, Joachim

2012-07-01

Two studies assessed the effect of a low-estrogen-dose 21/7-day oral contraceptive containing ethinylestradiol and drospirenone (EE 20 mcg/drsp 3 mg) on ovarian activity in Japanese and Caucasian women. Study 1 was conducted in Japanese women (20-35 years), and Study 2 was conducted in Caucasian women (18-35 years). All women received EE 20 mcg/drsp 3 mg in a 21-day active pill regimen. The primary endpoint was the proportion of women with ovulation inhibition (Hoogland score <6; as assessed by transvaginal ultrasonography) during treatment cycle 2. Japanese (n=23) and Caucasian (n=30) women received two cycles of study treatment. During treatment cycle 2, ovulation was inhibited in 100% and 92.9% of Japanese and Caucasian women, respectively. EE 20 mcg/drsp 3 mg in a 21/7-day regimen provides comparable ovarian suppression in Japanese and Caucasian women, with normal ovarian function resuming shortly after treatment end in both populations. Copyright © 2012 Elsevier Inc. All rights reserved.

New approach for food allergy management using low-dose oral food challenges and low-dose oral immunotherapies.

PubMed

Yanagida, Noriyuki; Okada, Yu; Sato, Sakura; Ebisawa, Motohiro

2016-04-01

A number of studies have suggested that a large subset of children (approximately 70%) who react to unheated milk or egg can tolerate extensively heated forms of these foods. A diet that includes baked milk or egg is well tolerated and appears to accelerate the development of regular milk or egg tolerance when compared with strict avoidance. However, the indications for an oral food challenge (OFC) using baked products are limited for patients with high specific IgE values or large skin prick test diameters. Oral immunotherapies (OITs) are becoming increasingly popular for the management of food allergies. However, the reported efficacy of OIT is not satisfactory, given the high frequency of symptoms and requirement for long-term therapy. With food allergies, removing the need to eliminate a food that could be consumed in low doses could significantly improve quality of life. This review discusses the importance of an OFC and OIT that use low doses of causative foods as the target volumes. Utilizing an OFC or OIT with a low dose as the target volume could be a novel approach for accelerating the tolerance to causative foods. Copyright © 2015 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.

Pharmacists' knowledge and interest in developing counseling skills relating to oral contraceptives.

PubMed

Amin, Mohamed E K

2016-04-01

Possessing correct therapeutic information on oral contraceptives is an important prerequisite for the provision of sound advice to women who are using these products. This study examines Egyptian pharmacists' knowledge of pharmacotherapeutic aspects of oral contraceptives as well as interest in developing skills in providing counseling on oral contraceptive pills. Community pharmacies throughout Alexandria, Egypt. A cross-sectional survey was self-administered by a random sample of community pharmacists in Alexandria, Egypt. Five multiple choice questions likely to arise when counseling women on oral contraceptives were constructed. Questions covered compatibility with breastfeeding, precautions, health risks and managing missed pills of oral contraceptives. Using ordered logistic regression, a model was estimated to predict pharmacists' interest in developing skills in providing counseling on oral contraceptives. Pharmacists' aggregate scores for knowledge questions and pharmacists' interest in developing skills in providing counseling on oral contraceptive pills. Of the 181 approached pharmacists, 92 % participated. Twenty one pharmacists (13 %) did not know the correct answer to any question, 122 (73 %) answered one-two correctly, 23 (14 %) answered three-four correctly. No pharmacist answered all five questions correctly. For pharmacists' interest in developing skills in providing counseling on oral contraceptives, the percentage values for answers were: not interested at all (10.2 %), slightly interested (27.0 %), somewhat interested (23.4 %), interested (30.0 %) and extremely interested (9.6 %). Pharmacists' interest in developing skills in providing counseling on oral contraceptives was significantly associated with the number of women who requested advice from the pharmacists on oral contraceptives (OR 1.54, CI 1.24-1.91). In terms of the learning method of preference, percentage values for answers were: attending a workshop (4 %), online course (18

Short-term response of bone turnover to low-dose oral contraceptives in exercising women with hypothalamic amenorrhea.

PubMed

Vescovi, Jason D; VanHeest, Jaci L; De Souza, Mary Jane

2008-02-01

We examined the response of bone turnover markers and indices of energy status after 2 weeks of oral contraceptive (OC) therapy in premenopausal women with exercise-associated menstrual disturbances (EAMD). Six women with EAMD received one 28-day cycle of a triphasic OC containing 180-250 mcg norgestimate/25 mcg ethinyl estradiol (EAMD+OC) and six were controls (EAMD controls). Bone turnover markers amino-terminal propeptide of Type I procollagen and serum carboxy-terminal telopeptides of Type I collagen (PINP and SCTX-I) were assessed at baseline and after 2 weeks of OC therapy (EAMD+OC) or after a 30-day monitoring period (EAMD controls). Total triiodothyronine, resting energy expenditure (REE) and dietary intake were assessed as secondary end points. The absolute and percent changes from baseline in the primary and secondary outcomes were evaluated using an analysis of covariance, adjusting for baseline values of the corresponding outcome. Compared to EAMD controls, a significant change from baseline was observed in the EAMD+OC group for PINP (mean+/-SEM, 9.9+/-6.1 vs. -33.9+/-9.0 mcg/L; p=.005) and SCTX-I (-0.02+/-0.11 vs. -0.25+/-0.07 ng/mL; p=.017), but not osteoprotegerin (-0.53+/-0.22 vs. 0.20+/-0.44 pmol/L; p=.429) after 2 weeks (14.7+/-0.3 days) of OC therapy. Total triiodothyronine levels were elevated in the EAMD+OC group after therapy compared with EAMD controls (19.7+/-4.1 vs. -8.4+/-4.9 ng/dL; p=.002); however, no differences between groups were observed for the changes in REE or dietary intake. Our data demonstrate that 2 weeks of low-dose OC therapy rapidly reduced markers of bone resorption and formation, without any significant impact on energy status in women with EAMD.

Combined oral contraceptives: health benefits beyond contraception.

PubMed

Caserta, D; Ralli, E; Matteucci, E; Bordi, G; Mallozzi, M; Moscarini, M

2014-09-01

It has been recognized for over 50 years that combined oral contraceptives (COCs) are also capable of offering health benefits beyond contraception through the treatment and prevention of several gynaecological and medical disorders. During the last years a constant attention was given to the adverse effects of COCs, whereas their non-contraceptive benefits were underestimated. To date, most women are still unaware of the therapeutic uses of hormonal contraceptives, while on the contrary there is an extensive and constantly increasing of these non-contraceptive health benefits. This review summarizes the conditions of special interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts, endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone mineral density, benign breast disease and endometrial/ovarian and colorectal cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis, menstrual migraine and in perimenopause have also been treated for more comprehensive information. Using COCs specifically for non-contraceptive indications is still outside the product licence in the majority of cases. We strongly believe that these aspects are not of minor relevance and they deserve a special consideration by health providers and by the mass media, which have the main responsibility in the diffusion of scientific information. Thus, counseling and education are necessary to help women make well-informed health-care decisions and it is also crucial to increase awareness among general practitioners and gynaecologists.

Communication about Contraception and Knowledge of Oral Contraceptives amongst Norwegian High School Students.

ERIC Educational Resources Information Center

Hansen, Thomas; Skjeldestad, Finn Egil

2003-01-01

Examines communication about contraception and specific knowledge of oral contraceptives (OCs) in a sample of Norwegian high school students. More females than males discussed contraception at least monthly. Discussions were predominantly held with peers and not adults. Females were far more knowledgeable about OCs than males. The most significant…

Examining the role of oral contraceptive users as an experimental and/or control group in athletic performance studies.

PubMed

Elliott-Sale, Kirsty Jayne; Smith, Stephanie; Bacon, James; Clayton, David; McPhilimey, Martin; Goutianos, Georgios; Hampson, Jennifer; Sale, Craig

2013-09-01

This study was conducted to examine the effect of oral contraceptives on endogenous reproductive hormone levels in order to assess the suitability of oral contraceptive users as experimental and/or control groups in human performance studies. Ninety-five females who were taking a variety of oral contraceptives (2 types and 11 brands) were recruited. A single blood sample was analysed for endogenous concentrations of oestradiol and progesterone. There were significant differences (p<.05) in circulating oestradiol and progesterone as a result of oral contraceptive type and brand. Overall, oral contraceptive use resulted in low levels of oestradiol and progesterone and large variation in hormone concentration when multiple brands were analysed together. This study indicates that future studies should employ a single pill type and brand when using oral contraceptive users as either a control or experimental group and that comparison between oral contraceptive users as a control group and the early follicular phase of the menstrual cycle as an experimental group should be reconsidered. Copyright © 2013 Elsevier Inc. All rights reserved.

Progestin-Only Oral Contraceptives

MedlinePlus

... oral contraceptives are a very effective method of birth control, but they do not prevent the spread of ... on another day, use a backup method of birth control (such as a condom and/or a spermicide) ...

Progestin-only pills for contraception.

PubMed

Grimes, David A; Lopez, Laureen M; O'Brien, Paul A; Raymond, Elizabeth G

2010-01-20

The introduction of a new progestin-only oral contraceptive in Europe has renewed interest in this class of oral contraceptives. Unlike the more widely used combined oral contraceptives containing an estrogen plus progestin, these pills contain only a progestin (progestogen) and are taken without interruption. How these pills compare to others in their class or to combined oral contraceptives is not clear. This review examined randomized controlled trials of progestin-only pills for differences in efficacy, acceptability, and continuation rates. We searched the computerized databases MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), POPLINE, LILACS, and EMBASE for studies of progestin-only pills. We also searched for current trials via ClinicalTrials.gov and ICTRP. We included all randomized controlled trials in any language that included progestin-only pills for contraception. We incorporated any comparison with a progestin-only pill; this could include different doses, other progestin-only pills, combined oral contraceptives, or other contraceptives. The first author abstracted the data and entered the information into RevMan 5. Another author performed a second, independent data abstraction to verify the initial data entry. Because of disparate exposures, we were not able to combine studies in meta-analysis. Six trials met the inclusion criteria. In the trial comparing the desogestrel versus levonorgestrel progestin-only pill, desogestrel was not associated with a significantly lower risk of accidental pregnancy; the rate ratio was 0.27 (95% CI 0.06 to 1.19). However, the desogestrel progestin-only pill caused more bleeding problems, although this difference was not statistically significant. The trial comparing low-dose mifepristone versus a levonorgestrel progestin-only pill found similar pregnancy rates. In the trial comparing ethynodiol diacetate versus a combined oral contraceptive, irregular cycles occurred in all women assigned to the

Bleeding pattern and cycle control of a low-dose transdermal contraceptive patch compared with a combined oral contraceptive: a randomized study.

PubMed

Merz, M; Kroll, R; Lynen, R; Bangerter, K

2015-02-01

The aim of this study was to investigate the bleeding pattern and cycle control of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a combined oral contraceptive (COC) containing 0.02 mg EE and 0.1 mg levonorgestrel (LNG). In this phase III, randomized, controlled, double-blind, double-dummy, multicenter trial, healthy women aged 18-45 years (smokers aged 18-35 years) received either the EE/GSD patch and a placebo tablet (n=171), or a placebo patch and the COC (n=175) for seven 28-day cycles. Bleeding control was assessed in two 90-day reference periods. Mean number of bleeding/spotting days was comparable across treatment groups in both reference periods (p>.05). Mean number of bleeding/spotting episodes was also comparable in reference period 1; however, there were fewer bleeding/spotting episodes for COC in reference period 2 (3.4 versus 3.1; p=.01). Mean length of bleeding/spotting episodes was comparable across treatment groups for both reference periods (p>.05). Withdrawal bleeding occurred consistently in both groups over the entire treatment period, but its absence was more common in the COC group in cycles 4 and 6 of reference period 2 (p<.01). Intracyclic bleeding was comparable between groups. Bleeding pattern and cycle control with the EE/GSD patch was comparable to an EE/LNG-containing COC. The findings suggest that bleeding patterns with the EE/GSD patch are similar to an EE/LNG-containing COC, except for absence of withdrawal bleeding, which was less common in patch users. The EE/GSD patch may constitute an additional contraceptive option for women. Copyright © 2015 Elsevier Inc. All rights reserved.

Contraceptive use in the Nordic countries.

PubMed

Lindh, Ingela; Skjeldestad, Finn E; Gemzell-Danielsson, Kristina; Heikinheimo, Oskari; Hognert, Helena; Milsom, Ian; Lidegaard, Øjvind

2017-01-01

The aim was to compare contraceptive use in the Nordic countries and to assess compliance with recommendations from the European Medicines Agency regarding the use of combined oral contraception containing low-dose estrogen and levonorgestrel, norethisterone or norgestimate. Data on hormonal contraceptive prescriptions and sales figures for copper intrauterine devices were obtained from national databases and manufacturers in Denmark, Finland, Iceland, Norway and Sweden in 2010-2013. Contraceptive use was highest in Denmark (42%) and Sweden (41%), followed by Finland (40%). Combined oral contraception was the most used method in all countries, with the highest use in Denmark (26%). The second most used method was the levonorgestrel-releasing intrauterine system, with the highest use in Finland (15%) and ≈10% in the other countries. Copper intrauterine devices (7%) and the progestin-only pill (7%) were most often used in Sweden. Combined oral contraception use decreased with increasing age and levonorgestrel-releasing intrauterine system and progestin-only pills use increased. The use of long-acting reversible methods of contraception (=levonorgestrel-releasing intrauterine system, copper intrauterine devices, and implants) increased with time and was highest in Sweden (20%) and Finland (18%). The highest use of European Medicines Agency recommended combined oral contraception was in Denmark, increasing from 13 to 50% between 2010 and 2013. In Finland, recommended combined oral contraception remained below 1%. Contraceptive use was highest in Denmark and Sweden, levonorgestrel-releasing intrauterine system use was highest in Finland and all long-acting methods were most common in Sweden. The use of combined oral contraception recommended by the European Medicines Agency was highest in Denmark. © 2016 Nordic Federation of Societies of Obstetrics and Gynecology.

A phase 1, multicentre, open-label study to evaluate ovarian follicular activity and hormone levels with an extended-regimen combined oral contraceptive with low-dose ethinyl estradiol supplementation.

PubMed

Kroll, Robin; Seidman, Larry; Ricciotti, Nancy; Howard, Brandon; Weiss, Herman

2015-01-01

To evaluate the effect on ovarian follicular activity of the 91-day extended-regimen combined oral contraceptive (COC), consisting of 84 days of levonorgestrel (LNG)/ethinylestradiol (EE) 150 μg/30 μg tablets plus seven days of EE 10 μg tablets in place of placebo. This was a phase 1, open-label study. Ovarian follicular activity was classified via the Hoogland and Skouby method. Safety and tolerability as well as return to ovulation were assessed. Of the 35 subjects included in the efficacy analysis, luteinized, unruptured follicles, or ovulation were detected in 0 of 35 cycles during the first 28-day interval; 1 of 35 cycles (2.9%) in the second 28-day interval; and 2 of 35 cycles (5.7%) in the final 35-day interval. The ovarian activity rate over the entire 91-day treatment period was 2.9%. There was a low incidence of treatment-emergent adverse events. Ovulation returned in most subjects (77.1%, 27/35) within 32 days following the last dose of COC. The 91-day extended-regimen COC with low-dose EE supplementation was found to be effective in suppressing ovarian activity and inhibiting ovulation and was well tolerated. Return to ovulation was rapid, occurring within approximately one month after discontinuation of COC.

Pharmacokinetic overview of ethinyl estradiol dose and bioavailability using two transdermal contraceptive systems and a standard combined oral contraceptive

PubMed Central

Hofmann, Birte; Reinecke, Isabel; Schuett, Barbara; Merz, Martin; Zurth, Christian

2014-01-01

), average steady-state serum concentration, and maximum steady-state serum concentration for EE was 2.0 – 2.7-fold higher for the EE/NGMN patch vs. the EE/GSD patch. The EE/GSD patch was well tolerated in both studies. Conclusions: Based on the 90% CI of the AUC ratio of oral treatment vs. patch application for unbound GSD and EE, the daily doses of GSD and EE released from the EE/GSD patch over the 7-day application period provided the same systemic exposure as those recorded after daily oral administration of a COC containing 0.02 mg EE and 0.06 mg GSD. The EE/GSD patch showed reduced EE exposure compared with the EE/NGMN patch. Together with its good tolerability, these properties support the EE/GSD patch as an effective and well-tolerated alternative to available transdermal and oral contraceptives. PMID:25295716

Oral contraceptives may alter the detection of emotions in facial expressions.

PubMed

Hamstra, Danielle A; De Rover, Mischa; De Rijk, Roel H; Van der Does, Willem

2014-11-01

A possible effect of oral contraceptives on emotion recognition was observed in the context of a clinical trial with a corticosteroid. Users of oral contraceptives detected significantly fewer facial expressions of sadness, anger and disgust than non-users. This was true for trial participants overall as well as for those randomized to placebo. Although it is uncertain whether this is an effect of oral contraceptives or a pre-existing difference, future studies on the effect of interventions should control for the effects of oral contraceptives on emotional and cognitive outcomes. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Bioavailability of the Yuzpe and levonorgestrel regimens of emergency contraception: vaginal vs. oral administration.

PubMed

Kives, Sari; Hahn, Philip M; White, Emily; Stanczyk, Frank Z; Reid, Robert L

2005-03-01

Separate crossover studies compared the bioavailability of oral vs. vaginal routes of administration for the Yuzpe (n=5) and levonorgestrel regimens (n=4) of emergency contraception. Twice the standard dose of the Yuzpe regimen (200 microg of ethinyl estradiol, 1000 microg of levonorgestrel) or the levonorgestrel regimen (1500 microg of levonorgestrel) was self-administered vaginally. One week later, each subject received orally the standard dose of the assigned medication. Serial blood samples were collected over 24 h and assayed for levonorgestrel and ethinyl estradiol (for the Yuzpe regimen only). Paired t tests were used to compare oral vs. vaginal administration for maximum concentration (Cmax), time to maximum concentration (Tmax) and area under the curve over 24 h (AUC0-24). Relative bioavailability (vaginal/oral) was derived from AUC0-24. Vaginal administration of double the standard dose of the Yuzpe regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=14.6 ng/mL, p=.038) and a later Tmax (5.9 vs. 2.0 h, p=.066) for levonorgestrel, compared to oral administration. Corresponding ethinyl estradiol concentrations were higher (786 vs. 391 pg/mL, p=.039) and peaked later (4.0 vs. 1.9 hr, p=.154) with vaginal administration. Relative bioavailabilities for levonorgestrel and ethinyl estradiol were 58% and 175%, respectively. Similarly, vaginal administration of the levonorgestrel regimen resulted in a lower Cmax (vaginal=5.4 vs. oral=15.2 ng/mL, p=.006) and a later Tmax (7.4 vs. 1.3 h, p=.037) for levonorgestel, compared to oral administration. The relative bioavailability was 62%. Our preliminary data suggest that vaginal administration of these emergency contraception regimens appears to require at least three times the standard oral dose to achieve equivalent systemic levonorgestrel concentrations.

Decreased maximal aerobic capacity with use of a triphasic oral contraceptive in highly active women: a randomised controlled trial

PubMed Central

Lebrun, C; Petit, M; McKenzie, D; Taunton, J; Prior, J

2003-01-01

Background: Oral contraceptives are commonly used by women athletes. However, their effect on athletic performance is unclear. Objectives: To examine the effects of a moderate dose, triphasic oral contraceptive on measures of athletic performance in highly trained women athletes. Methods: This is a double blind, placebo controlled trial in 14 women with ovulatory menstrual cycles and maximal aerobic capacity (VO2MAX) ≥50 ml/kg/min. Four measures of athletic performance were tested: VO2MAX, anaerobic capacity (anaerobic speed test), aerobic endurance (time to fatigue at 90% of VO2MAX), and isokinetic strength (Cybex II dynamometer). Height, weight, and six skinfold measurements were also recorded. All these observational tests were completed during both the follicular and mid-luteal phases of an ovulatory menstrual cycle. Cycle phases were confirmed by assaying plasma oestradiol and progesterone. Participants were subsequently randomly assigned to either a tricyclic oral contraceptive or placebo and retested in identical fashion (oral contraceptive phase). Results: Absolute and relative changes in VO2MAX from follicular to oral contraceptive phase decreased in the oral contraceptive group by 4.7%, whereas the placebo group showed a slight increase (+1.5%) over the same time period. Two of the women taking oral contraceptive had decreases of 4 and 9 ml/kg/min. In contrast, most women in the placebo group improved or maintained VO2MAX. There was also a significant increase in the sum of skinfolds in women taking oral contraceptive compared with those taking placebo (p<0.01). There were no significant changes in other physiological variables (maximum ventilation, heart rate, respiratory exchange ratio, packed cell volume) or measures of performance (anaerobic speed test, aerobic endurance, isokinetic strength) as a function of oral contraceptive treatment. Conclusions: The decrease in VO2MAX that occurs when oral contraceptive is taken may influence elite sporting

Update on oral contraception.

PubMed

Rabe, T; Runnebaum, B

1993-04-01

Oral contraceptives (OCs) were first introduced more than 30 years ago. OC manufacturers have reduced the dosage of synthetic estrogens (e.g., ethinyl estradiol, 100-150 mcg to 20-35 mcg) and progestins to limit their metabolic effects on lipoproteins, carbohydrates, and hemostasis. In addition to protection from pregnancy, OC benefits include lower incidence of painful periods, excessive bleeding, and iron deficiency anemia; reduction of ovarian cysts, benign breast tumors, and pelvic inflammatory disease; and protection against endometrial and ovarian cancers. The risk of a cardiovascular event (myocardial infarction, cerebrovascular events, venous thromboembolism, and deep vein thrombophlebitis) in OC users is 1-2/100,000 women years. Cardiovascular risk factors include smoking, hypertension, lipid disorders, severe obesity, diabetes mellitus, and cardiovascular events in first degree relatives before age 40. Thus, women with any of these risk factors should not use OCs. OCs do not increase the risk of breast cancer in women less than 59 years old. They may increase this risk if used over a long duration before the first fullterm pregnancy. OCs may cause a modest increase in cervical neoplasia. Low-dose OCs have a small effect on lipid metabolism. OCs increase serum triglycerides 30-50%. OCs increase insulin secretion and hyperinsulinemia increases the cardiovascular risk. Practitioners should evaluate clients before prescribing OCs. They should not prescribe OCs to women with hypertension, diabetes mellitus, lipid disorders, gynecological cancers, and previous cardiovascular disorders. Practitioners should tell clients that smoking is a leading risk factor and about OC's side effects (e.g., menstrual disturbances). The physical exam should include a cervical PAP smear, gynecological exam of the uterus and the ovaries, and a breast exam. Practitioners should test cholesterol and triglycerides before and during OC use. Premenopausal healthy women with no risk

Treatment of acne using a 3-milligram drospirenone/20-microgram ethinyl estradiol oral contraceptive administered in a 24/4 regimen: a randomized controlled trial.

PubMed

Maloney, J Michael; Dietze, Peter; Watson, David; Niknian, Minoo; Lee-Rugh, Sooji; Sampson-Landers, Carole; Korner, Paul

2008-10-01

To assess the efficacy of the combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol (3-mg drospirenone/20-microgram ethinyl estradiol) administered as 24 consecutive days of active treatment after a 4-day hormone-free interval (24/4 regimen) compared with placebo for the treatment of moderate acne vulgaris. Healthy females aged 14-45 years with moderate acne were randomized in this double-blind study to 3-mg drospirenone/20-microgram ethinyl estradiol (n=270) or placebo (n=268) for six cycles of 28 days. The primary outcome measures of acne lesion counts and Investigator Static Global Assessment scale ratings were assessed at baseline and during cycles 1, 3, and 6. The percentage reduction from baseline to endpoint for total lesions is 46.3% for 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 combination oral contraceptive group and 30.6% for placebo group (P<.001). The likelihood of participants in the 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen group having "clear" or "almost clear" skin as rated by the investigators at endpoint was about threefold (odds ratio 3.13, 95% confidence interval 1.69-5.81; P=.001) greater than in the placebo group. The 3-mg drospirenone/20-microgram ethinyl estradiol 24/4 regimen was well tolerated. The low-dose combined oral contraceptive containing 3-mg drospirenone/20-microgram ethinyl estradiol administered in a 24/4 regimen significantly reduced acne lesion counts more effectively than placebo and demonstrated greater improvement in the Investigator Static Global Assessment rating of acne. The safety profile was consistent with low-dose combined oral contraceptive use.

[Cholestatic icterus due to oral contraceptives].

PubMed

Pestel, M; Lambert, C; Jeanmougin, M

1973-03-01

A case report of cholestatic jaundice in a 25 year old woman, who had had jaundice at age 4 years, and had taken Stediril (a combined oral contraceptive) for 1 month, implicates either the pill or a possibly hereditary hyperlipidemia. The jaundice developed in 2 weeks with vomiting, epigastric pain, anorexia, then discolored urine and feces, and intense pruritus. On hospitalization the patient had moderate bilirubinemia (56 mg/1), low alkaline phosphatase (13 U.K.) and slightly high serum glutamate pyruvate transaminase (270 U.W.). There were elevated serum cholesterol (3 gm/1), triglycerides (2.05 gm/1), total lipids (10.6 gm/1), and a definitely increased pre-beta lipoprotein, suggesting hyperlipidemia type IV (Frederickson classification). Liver biopsy showed fibrosis of the portal spaces lymphocytic infiltration, canalicular and intrahepatocytic thrombi. On laparoscopy the liver had a regular lower border, normal volume color and surface. Albumin, prothrombin and flocculation tests were normal. The patient's jaundice lasted about 1 month, then liver function slowly improved, although pruritus remained intense. Probably this jaundice was due to oral contraceptives, in a patient predisposed either by jaundice in childhood or endogenous hyperlipidemia.

Risk of thromboembolism in women taking ethinylestradiol/drospirenone and other oral contraceptives.

PubMed

Seeger, John D; Loughlin, Jeanne; Eng, P Mona; Clifford, C Robin; Cutone, Jennifer; Walker, Alexander M

2007-09-01

The oral contraceptive ethinylestradiol 0.03 mg/drospirenone 3 mg contains a progestin component that differs from other oral contraceptives. Case reports and prescription event monitoring suggested that ethinylestradiol/drospirenone might be associated with an elevated risk of thromboembolism. We sought to estimate the association between ethinylestradiol/drospirenone and risk of thromboembolism relative to the association among other oral contraceptives. We identified ethinylestradiol/drospirenone initiators and a twofold larger group of other oral contraceptive initiators between June 2001 and June 2004 within a U.S. health insurer database. The comparison group was selected to have demographic and health care characteristics preceding oral contraceptive initiation that were similar to ethinylestradiol/drospirenone initiators. Thromboembolism during the follow-up of the cohorts was identified through claims for medical services, and only medical record-confirmed cases were included in analyses. The primary (as-matched) analysis used proportional hazards regression, whereas a secondary (as-treated) analysis accounted for changes in oral contraceptives during follow-up using Poisson regression. The 22,429 ethinylestradiol/drospirenone initiators and 44,858 other oral contraceptive initiators were followed for an average of 7.6 months, and there were 18 cases of thromboembolism in ethinylestradiol/drospirenone initiators and 39 in the comparators (rate ratio 0.9, 95% confidence interval 0.5-1.6). More than 9,000 women would need to be prescribed oral contraceptives to observe a difference of one case of thromboembolism. Results of the as-treated analysis were similar to those of the as-matched analysis. Ethinylestradiol/drospirenone initiators and initiators of other oral contraceptives are similarly likely to experience thromboembolism. II.

Attitudes to current oral contraceptive use and future developments: the women's perspective.

PubMed

Fuchs, N; Prinz, H; Koch, U

1996-09-01

The study was planned to determine current trends in contraceptive usage and to examine the attitudes, needs and preferences of women with respect to oral contraceptives. Semi-structured interviews were carried out with women (n = 1201, aged 16-45 years) in Germany, the UK and France. The study revealed that oral contraceptives were the most popular method of contraception employed, followed by condoms, and that the majority of respondents were aged 16-19 years when they first used an oral contraceptive. An important finding of the study was that an oral contraceptive was first used only after having sexual intercourse for the first time (within 1 year), emphasizing the importance of effective contraceptive information and education for adolescents. Regarding non-contraceptive health benefits, protection from ovarian and endometrial cancer was perceived by respondents to be of the greatest importance; however, few women were spontaneously aware of this benefit. When given a number of different oral contraceptive intake options to assess, the established 'once daily for 21 consecutive days' option remained the most popular, although a 'once weekly' alternative was cited by many women. When asked about the preferred frequency of menstrual bleeding, there was a polarization between women favoring the normal monthly bleed and those wanting a 'no-bleed' regimen. Women are poorly informed about oral contraceptive use, and are largely unaware of the important long-term non-contraceptive benefits. Many women would prefer alternative pill intake options and a significant number would favor a 'no-bleed' regimen.

Family Planning for women unable to tolerate oral contraceptives.

PubMed

Spellacy, W N

1974-04-08

Should women with a family history of diabetes or myocardial infarcation, or women with abnormal blood glucose or cholesterol levels receive oral contraceptives? There is clear evidence that oral contraceptives can alter both carbohydrate and lipid metabolism in certain women. The lipid alteration is mainly an elevation of the circulating triglyceride levels, and only rarely is cholesterol content altered. It is also clear from extensive research during the past ten years that women who already have subclinical abnormalities, either in their triglyceride levels (family hyperlipoproteinemia) or glucose tolerance, are at great risk for the development of clinical disease while using oral contraceptives. Accordingly, all pharmaceutical firms are required by the Food and Drug Administration to instruct physicians about these problems through the package inserts and other means. Specifically, the physician should be alerted by the patient's history, and then he should use the laboratory to confirm any suspicion of abnormalities of carbohydrate or lipid metabolism. If there is any abnormal blood glucose or triglyceride value, the oral contraceptives should not be prescribed. There are other forms of contraception available for child spacing. Mechanical contraceptives will not aggravate a metabolic disorder. A useful substitute then would be an intrauterine device plus vaginal foam. When the woman has completed her family, she should be all means be offered surgical sterilization as a permanent family planning technique.

Risk of non-fatal venous thromboembolism in women using oral contraceptives containing drospirenone compared with women using oral contraceptives containing levonorgestrel: case-control study using United States claims data

PubMed Central

Hernandez, Rohini K

2011-01-01

Objective To compare the risk of non-fatal venous thromboembolism in women receiving oral contraceptives containing drospirenone with that in women receiving oral contraceptives containing levonorgestrel. Design Nested case-control and cohort study. Setting The study was based on information from PharMetrics, a United States based company that collects information on claims paid by managed care plans. Participants The study encompassed all women aged 15 to 44 years who received an oral contraceptive containing either drospirenone or levonorgestrel after 1 January 2002. Cases were women with current use of a study oral contraceptive and a diagnosis of venous thromboembolism in the absence of identifiable clinical risk factors (idiopathic venous thromboembolism). Up to four controls were matched to each case by age and calendar time. Main outcome measures Odds ratios comparing the risk of non-fatal venous thromboembolism in users of the two contraceptives; incidence rates and rate ratios of non-fatal venous thromboembolism for users of each of the study contraceptives. Results 186 newly diagnosed, idiopathic cases of venous thromboembolism were identified in the study population and matched with 681 controls. In the case-control analysis, the conditional odds ratio for venous thromboembolism comparing use of oral contraceptives containing drospirenone with use of those containing levonorgestrel was 2.3 (95% confidence interval 1.6 to 3.2). The incidence rates for venous thromboembolism in the study population were 30.8 (95% confidence interval 25.6 to 36.8) per 100 000 woman years among users of oral contraceptives containing drospirenone and 12.5 (9.61 to 15.9) per 100 000 woman years among users of oral contraceptives containing levonorgestrel. The age adjusted incidence rate ratio for venous thromboembolism for current use of oral contraceptives containing drospirenone compared with those containing levonorgestrel was 2.8 (2.1 to 3.8). Conclusions The risk of

Success with oral contraceptives: a pilot study.

PubMed

Gilliam, Melissa; Knight, Sara; McCarthy, Martin

2004-05-01

The objective of this pilot study was to examine the effectiveness of a postpartum educational intervention aimed at increasing compliance with oral contraception (OCs) and decreasing repeat pregnancies in young, African American women in the year following an unplanned pregnancy. In this longitudinal study, 43 young, pregnant women attending Prentice Ambulatory Care, Northwestern Hospital, were enrolled and 33 were randomized to receive an antepartum, multicomponent intervention consisting of counseling, a videotape about OCs and written material or resident-physician counseling (usual care). Questionnaire data were collected at enrollment, immediately following the intervention, at 6 weeks, 6 months and 12 months. At 1 year, 25 women remained in the study. More women in the intervention group were not pregnant and still using contraception, and were able to successfully switch contraceptive methods compared to women in the control group. There was no decrease in repeat pregnancy in the intervention group at 1 year compared to the control group. Our intervention resulted in a sustained increase in knowledge of OCs throughout the study period. However, more is needed to promote postpartum contraceptive compliance and decrease repeat pregnancies in young, low-income African Americans with unintended pregnancies.

Deep vein thrombosis and the oestrogen content in oral contraceptives. An epidemiological analysis.

PubMed

Kierkegaard, A

1985-01-01

Epidemiological studies have pointed to a correlation between the oestrogen content of oral contraceptives and the risk of deep vein thrombosis (DVT). The correlation has been strongest in studies which partially consisted of adverse drug reaction reports to the Swedish Adverse Drug Reaction Advisory Committee (SADRAC). The present study analyzes the epidemiological basis of the adverse drug reaction reports on DVT in women on oral contraceptives to SADRAC. It verifies the reported correlation between the oestrogen content of the pills and the risk of DVT but it also demonstrates that this correlation probably was secondary to differences in the diagnostic standard of DVT, to differences in reporting policies to SADRAC and to an age difference between women on low-oestrogen-pills and those on high-oestrogen pills and is thus due to bias. It is concluded that adverse drug reaction reporting on oral contraceptives has been very unreliable, for which reason it cannot support any epidemiological conclusion concerning the relative thrombogenicity of high-oestrogen pills compared with that of low-oestrogen pills.

Estrogen and Progestin (Oral Contraceptives)

MedlinePlus

... from entering. Oral contraceptives are a very effective method of birth control, but they do not prevent ... tell you whether you need to use another method of birth control during the first 7 to ...

Oral Contraceptives and Bone Health in Female Runners

DTIC Science & Technology

2006-10-01

activity. Previous cross-sectional research has shown that women with exercise - induced menstrual irregularities have a significantly higher...6. Cumming D.C. Exercise -associated amenorrhea , low BMD, and estrogen replacement therapy. Arch Intern Med. 156:2193-2195, 1996. 34 7. De...Science in Sports & Exercise . (i) Abstract from manuscript, “Randomized trial of the effect of oral contraceptives on bone mass and stress

Effects of menstrual cycle, oral contraception, and training on exercise-induced changes in circulating DHEA-sulphate and testosterone in young women.

PubMed

Enea, C; Boisseau, N; Ottavy, M; Mulliez, J; Millet, C; Ingrand, I; Diaz, V; Dugué, B

2009-06-01

The objective of this study was to ascertain the effects of menstrual cycle, oral contraception, and training status on the exercise-induced changes in circulating DHEA-sulphate and testosterone in young women. Twenty-eight healthy women were assigned to an untrained group (n = 16) or a trained group (n = 12) depending on their training background. The untrained group was composed of nine oral contraceptive users (OC+) and seven eumenorrheic women (OC-). The trained group was composed of OC+ subjects only. All the OC+ subjects were taking the same low-dose oral contraception. Three laboratory sessions were organised in a randomised order: a prolonged exercise test until exhaustion, a short-term exhaustive exercise test, and a control session. Blood specimens were collected before, during and after the exercise tests and at the same time of the day during the control session. Basal circulating testosterone was significantly lower in trained as compared to untrained subjects. In all subjects, the prolonged exhaustive exercise induced a significant increase in circulating DHEA-s and testosterone. The short-term exercise induced a significant increase in circulating DHEA-s in untrained eumenorrheic and in trained OC users only. Menstrual phases in OC- did not influence the responses. It was found that exhaustive physical exercise induced an increase in circulating DHEA-s and testosterone in young women. Oral contraception may limit short-term exercise-induced changes.

Endothelial function across an oral contraceptive cycle in women using levonorgestrel and ethinyl estradiol.

PubMed

Torgrimson, Britta N; Meendering, Jessica R; Kaplan, Paul F; Minson, Christopher T

2007-06-01

Oral contraceptive pills (OCPs) are a popular contraception method. Currently, lower-dose ethinyl estradiol formulations are most commonly prescribed, although they have been linked to increased arterial vascular risk. The aim of this study was to investigate endothelial function in healthy young women using lower-dose ethinyl estradiol OCPs. We examined flow-mediated, endothelium-dependent and nitroglycerin-mediated, endothelium-independent vasodilation of the brachial artery, comparing two doses of ethinyl estradiol/levonorgestrel OCPs in 15 healthy young women on two study days: once during the active phase and once during the placebo phase of an OCP cycle. Group low dose (LD) (n=7) active pills contained 150 microg levonorgestrel/30 microg ethinyl estradiol versus Group very low dose (VLD) (n=8) with 100 microg levonorgestrel/20 microg ethinyl estradiol. Endothelium-dependent vasodilation was lower during the active phase in Group VLD (5.33 +/- 1.77% vs. 7.23 +/- 2.60%; P=0.024). This phase difference was not observed in Group LD (8.00 +/- 0.970% vs. 7.61 +/- 1.07%; P=0.647). Endothelium-independent vasodilation did not differ between phases in either group. Finally, we measured endothelium-dependent vasodilation in two additional women who received 10 microg of unopposed ethinyl estradiol. Endothelium-dependent vasodilation was increased by unopposed ethinyl estradiol compared with the placebo phase (10.88 +/- 2.34% vs. 6.97 +/- 1.83%). These results suggest that levonorgestrel may antagonize the activity of ethinyl estradiol. Thus both the progestin type and estradiol dose need to be considered when assessing arterial vascular risk of OCP use in women.

Effect of a low dose combined oral contraceptive pill on the hormonal profile and cycle outcome following COS with a GnRH antagonist protocol in women over 35 years old.

PubMed

Bakas, Panagiotis; Hassiakos, Dimitrios; Grigoriadis, Charalampos; Vlahos, Nikolaos F; Liapis, Angelos; Creatsas, George

2014-11-01

This prospective study examines if pre-treatment with two different doses of an oral contraceptive pill (OCP) modifies significantly the hormonal profile and/or the IVF/ICSI outcome following COS with a GnRH antagonist protocol. Infertile patients were allocated to receive either OCP containing 0.03 mg of ethinylestradiol and 3 mg of drospirenone, or OCP containing 0.02 mg of ethinylestradiol and 3 mg of drospirenone prior to initiation of controlled ovarian stimulation (COS) with recombinant gonadotropins on a variable multi-dose antagonist protocol (Ganirelix), while the control group underwent COS without OCP pretreatment. Lower dose OCP was associated with recovery of FSH on day 3 instead of day 5, but the synchronization of the follicular cohort, the number of retrieved oocytes and the clinical pregnancy rate were similar to higher dose OCP.

Sex hormone-binding globulin and antithrombin III activity in women with oral ultra-low-dose estradiol.

PubMed

Matsui, Sumika; Yasui, Toshiyuki; Kasai, Kana; Keyama, Kaoru; Yoshida, Kanako; Kato, Takeshi; Uemura, Hirokazu; Kuwahara, Akira; Matsuzaki, Toshiya; Irahara, Minoru

2017-07-01

Oral oestrogen increases the risk of venous thromboembolism (VTE) and increases production of sex hormone-binding globulin (SHBG) in a dose-dependent manner. SHBG has been suggested to be involved in venous thromboembolism. We examined the effects of oral ultra-low-dose oestradiol on circulating levels of SHBG and coagulation parameters, and we compared the effects to those of transdermal oestradiol. Twenty women received oral oestradiol (500 μg) every day (oral ultra-low-dose group) and 20 women received a transdermal patch (50 μg) as a transdermal group. In addition, the women received dydrogesterone continuously (5 mg) except for women who underwent hysterectomy. Circulating SHBG, antithrombin III (ATIII) activity, d-dimer, thrombin-antithrombin complex and plasmin-α2 plasmin inhibitor complex were measured before and 3 months after the start of treatment. SHBG was significantly increased at 3 months in the oral ultra-low-dose group, but not in the transdermal group. However, percent changes in SHBG were not significantly different between the two groups. In both groups, ATIII was significantly decreased at 3 months. In conclusion, even ultra-low-dose oestradiol orally increases circulating SHBG level. However, the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. Impact statement Oral oestrogen replacement therapy increases production of SHBG which may be related to increase in VTE risk. However, the effect of oral ultra-low-dose oestradiol on SHBG has not been clarified. Even ultra-low-dose oestradiol orally increases circulating SHBG levels, but the magnitude of change in SHBG caused by oral ultra-low-dose oestradiol is small and is comparable to that caused by transdermal oestradiol. VTE risk in women receiving oral ultra-low-dose oestradiol may be comparable to that in women receiving transdermal oestradiol.

Oral contraceptive use and bone density in adolescent and young adult women

PubMed Central

Scholes, Delia; Ichikawa, Laura; LaCroix, Andrea Z.; Spangler, Leslie; Beasley, Jeannette M.; Reed, Susan; Ott, Susan M.

2009-01-01

Background Most of the millions of oral contraceptive (OC) users are under age 30 years and in the critical period for bone mass accrual. Study Design This cross-sectional study of 606 women aged 14–30 years examined both OC duration and estrogen dose and their association with bone mineral density (BMD) at the hip, spine, and whole-body (DEXA). Results Of 389 OC users and 217 nonusers enrolled, 50% were adolescents (14–18 years). Of OC users, 38% used “low-dose” OCs [<30 mcg ethinyl estradiol (EE)]. In adolescents, mean BMD differed by neither OC duration nor EE dose. However, 19–30 year-old women’s mean BMD was lower with longer OC use for spine and whole-body (p=0.004, p=0.02, respectively) and lowest for >12 months of low-dose OCs for the hip, spine and whole-body (p=0.02, 0.003 and 0.002, respectively). Conclusions Prolonged use of today’s OCs, particularly <30 mcg EE, may adversely impact young adult women’s bone density while ingesting these agents. PMID:20004271

Oral contraceptive use and psychiatric disorders in a nationally representative sample of women.

PubMed

Cheslack-Postava, Keely; Keyes, Katherine M; Lowe, Sarah R; Koenen, Karestan C

2015-02-01

The purpose of this study is to examine the association between oral contraceptive use (any current use, duration, and type) and major depressive disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) in a nationally representative sample of women in the USA. Data were drawn from 1,105 women aged 20-39 in the National Health and Nutrition Examination Surveys from 1999 to 2004. The associations between self-reported use of oral contraceptives in the past year and DSM-IV diagnosed and subthreshold MDD, GAD, and PD in the past year were assessed comparing oral contraceptive users to all non-users, former users, and former long-term users. Women using oral contraceptives had a lower past-year prevalence of all disorders assessed, other than subthreshold MDD. When adjusted for confounders, women using oral contraceptives in the past year had significantly lower odds of subthreshold PD, compared to former users (odds ratio (OR) = 0.34, 95 % CI 0.14-0.84). Effects estimates were strongest for monophasic (versus multiphasic) oral contraceptive users. Hormonal contraceptive use was associated with reduced risk of subthreshold PD. A potential mental health benefit of hormonal contraceptives has substantial public health implications; prospective longitudinal studies are needed to confirm whether hormonal contraceptive use improves mental health.

Skin patch and vaginal ring versus combined oral contraceptives for contraception.

PubMed

Lopez, Laureen M; Grimes, David A; Gallo, Maria F; Stockton, Laurie L; Schulz, Kenneth F

2013-04-30

The delivery of combination contraceptive steroids from a transdermal contraceptive patch or a contraceptive vaginal ring offers potential advantages over the traditional oral route. The transdermal patch and vaginal ring could require a lower dose due to increased bioavailability and improved user compliance. To compare the contraceptive effectiveness, cycle control, compliance (adherence), and safety of the contraceptive patch or the vaginal ring versus combination oral contraceptives (COCs). Through February 2013, we searched MEDLINE, POPLINE, CENTRAL, LILACS, ClinicalTrials.gov, and ICTRP for trials of the contraceptive patch or the vaginal ring. Earlier searches also included EMBASE. For the initial review, we contacted known researchers and manufacturers to identify other trials. We considered randomized controlled trials comparing a transdermal contraceptive patch or a contraceptive vaginal ring with a COC. Data were abstracted by two authors and entered into RevMan. For dichotomous variables, the Peto odds ratio (OR) with 95% confidence intervals (CI) was calculated. For continuous variables, the mean difference was computed. We also assessed the quality of evidence for this review. We found 18 trials that met our inclusion criteria. Of six patch studies, five examined the marketed patch containing norelgestromin plus ethinyl estradiol (EE); one studied a patch in development that contains levonorgestrel (LNG) plus EE. Of 12 vaginal ring trials, 11 examined the same marketing ring containing etonogestrel plus EE; one studied a ring being developed that contains nesterone plus EE.Contraceptive effectiveness was not significantly different for the patch or ring versus the comparison COC. Compliance data were limited. Patch users showed better compliance than COC users in three trials. For the norelgestromin plus EE patch, ORs were 2.05 (95% CI 1.83 to 2.29) and 2.76 (95% CI 2.35 to 3.24). In the levonorgestrel plus EE patch report, patch users were less

Safety, efficacy and patient satisfaction with continuous daily administration of levonorgestrel/ethinylestradiol oral contraceptives

PubMed Central

Benagiano, Giuseppe; Carrara, Sabina; Filippi, Valentina

2009-01-01

The progestational steroid norgestrel was synthesized and tested between 1960 and 1965 through an international cooperation between Wyeth, USA and Schering, Berlin. It is a mixture of two “enantiomers,” with only one form (designated as levonorgestrel) biologically active. When taken orally, it is rapidly absorbed, not subjected to a “first-pass” effect and is approximately 90% bioavailable, with a circulating half-life around 15 hours. Its contraceptive action is exerted at the central (hypothalamic) and peripheral (cervical mucus and endometrium) levels. Levonorgestrel (LNG), alone or in combination with ethinyl estradiol (EE), is the most widely employed contraceptive progestin: it is used in combined oral contraceptives, progestogen-only pills, long-acting contraceptive implants, intrauterine contraceptive systems and in emergency contraception. It is also the steroid of choice for new oral contraceptive regimens aimed at reducing the frequency of bleeding episodes. This novel approach, already tried more than 30 years ago, gained interest around the year 2000 when surveys of women’s attitudes toward monthly menstrual bleeding started to show a major change: more and more women declared that they would welcome a hormonal contraceptive method that reduced bleeding episodes to 4, 2 or even 1 per year. At this point, while the debate on the significance and “usefulness” of menstruation went on, attention focused on new regimens. The first new modality consisted of changing the 7-day medication-free interval, either shortening it to fewer than 7 days, or by the administration of low-dose estrogens during the interval between packages. Then, continuous administration regimens started to be investigated. This, however, did not happen suddenly, since, in specific situations, doctors had for years empirically utilized various continuous administration regimens. The first extended-cycle oral contraceptive regimen introduced in clinical practice is an 84

Self-reported and verified compliance in a phase 3 clinical trial of a novel low-dose contraceptive patch and pill.

PubMed

Kaunitz, Andrew M; Portman, David; Westhoff, Carolyn L; Archer, David F; Mishell, Daniel R; Foegh, Marie

2015-03-01

Pregnancy rates in US contraceptive clinical trials are increasing due to decreased treatment compliance. This study compared compliance with a new low-dose levonorgestrel (LNG) and ethinyl estradiol (EE) contraceptive patch (CP, Twirla™) with that of a low-dose combination oral contraceptive (COC) in a demographically diverse population. This analysis was part of an open-label, parallel-group, multicenter phase 3 study that randomized healthy sexually active women (17-40years) to 13cycles of LNG/EE CP or 6cycles of COC, then 7cycles of LNG/EE CP. We defined self-reported compliance as cycles that, according to diaries, show 21days of patch wear without missed days or any patch worn >7days or 21days of pill-taking without missed pill days. We verified compliance by detectable plasma presence of LNG and EE at cycles 2, 6, and 13. Of the intention-to-treat population with diary information (N=1328, mean age 26.4years, 46% minorities, 33% obese), 10.0% of the CP (n=998) versus 21.2% of the COC group (n=330) self-reported noncompliance after 6cycles (p<.001). Laboratory assessments verified 10-14% of participants in both groups as noncompliant. Self-reported perfect use did not vary between obese [body mass index (BMI) ≥30kg/m(2)] versus nonobese (BMI <30kg/m(2)) participants in both groups or when stratified by age, education, or race/ethnicity in the CP group. Self-reported compliance was significantly greater in the CP than COC group and did not vary by obesity status. Discrepancies between self-reported and verified compliance question reliability of patient diaries. This paper, based on an analysis of a phase 3 trial, shows that compliance was significantly greater with a new weekly transdermal CP than with a once-daily COC in obese as well as nonobese participants. Discrepancies between self-reported compliance and laboratory-verified compliance raise questions regarding the reliability of patient diaries. Copyright © 2015 Elsevier Inc. All rights reserved.

Consumers of oral contraceptives in a social marketing program in Honduras.

PubMed

Bailey, P E; Janowitz, B; Solis, M; Machuca, M; Suazo, M

1989-01-01

This paper presents data on the characteristics of oral contraceptive users in Honduras, obtained from a point-of-purchase survey conducted in pharmacies in 1986. The oral contraceptive Perla, provided by the Social Marketing Program, accounted for 42 percent of sales. Forty-five percent of those using Perla were considered "new" users; either they were purchasing contraceptives for the first time or had used only Perla. Almost half of those who switched to Perla previously had obtained their orals in the noncommercial sector. Brand substitution occurred among users of commercial brands at about the same rate as among Perla users (51 percent versus 55 percent). Most women switching contraceptives did so within two months of their last purchase.

Fertility and combined oral contraceptives - unintended pregnancies and planned pregnancies following oral contraceptive use - results from the INAS-SCORE study.

PubMed

Barnett, Clare; Hagemann, Christine; Dinger, Jürgen; Do Minh, Thai; Heinemann, Klaas

2017-02-01

To estimate the real-use contraceptive effectiveness of the combined oral contraceptive containing dienogest and estradiol valerate (DNG/EV) and whether DNG/EV compared to other combined oral contraceptives (oCOC) has a negative effect on return to fertility. Transatlantic, prospective, non-interventional cohort study conducted in the USA and seven European countries with two main exposure groups and one exposure subgroup: new users of DNG/EV and other COC (oCOC), particularly levonorgestrel-containing COCs (LNG). In a planned secondary analysis, pregnancy outcomes were investigated including contraceptive effectiveness and pregnancy following contraceptive cessation. The influence of age, parity and OC-type were assessed. 50,203 COC users were followed for 105,761 woman-years (WY). There were 677 unintended pregnancies reported: 451 in the USA and 226 in Europe. The contraceptive failure rate in Europe was 0.5 events/100 WY (95% CI: 0.4-0.5) and in the USA 1.9 events/100 WY (95% CI: 1.7-2.1). Differences in compliance (1.3 pregnancies/100 WY) accounted for 90% of the geographical difference seen between Europe and the USA. DNG/EV showed lower contraceptive failure rates compared to the comparators; 0.9% DNG/EV, 2.1% oCOC and 2.8% LNG after 4 years. Overall, 1167 (2.3%) of women stopped contraceptive use with the intention of becoming pregnant with 89% conceiving within 2 years. No significant differences were seen between groups after adjusting for age. DNG/EV is associated with similar contraceptive effectiveness in typical-use settings when compared to oCOC and LNG. There was no difference observed between cohorts in fertility following OC use.

Intraocular levels of methotrexate after oral low-dose treatment in chronic uveitis.

PubMed

Puchta, Joachim; Hattenbach, Lars-Olof; Baatz, Holger

2005-01-01

To determine the intraocular levels of methotrexate in low-dose treatment of noninfectious uveitis. One day after oral administration, the methotrexate level was measured in the aqueous humor and serum of a patient with noninfectious uveitis, who underwent cataract surgery. A fluorescence polarization immunoassay was used for determination. After oral administration, methotrexate was only measurable in aqueous humor but not in serum. In uveitis, orally administered low-dose methotrexate reaches detectable levels in aqueous humor, even in the absence of detectable levels in serum. Copyright (c) 2005 S. Karger AG, Basel.

Breast cancer among young U.S. women in relation to oral contraceptive use.

PubMed

White, E; Malone, K E; Weiss, N S; Daling, J R

1994-04-06

While most studies have found no association between oral contraceptive use and breast cancer, several studies of younger women have reported an association with long-term oral contraceptive use. PURPOSE. We studied the relationship of patterns of oral contraceptive use to breast cancer risk among younger women. These women have had oral contraceptives available their entire reproductive lives and are now entering the breast cancer-prone years. A population-based, case-control study of breast cancer was conducted in three counties in western Washington State among women born in 1945 or later, ages 21-45. Case patients were 747 women with breast cancer diagnosed in 1983-1990 and identified through the Seattle-Puget Sound Surveillance, Epidemiology, and End Results cancer registry. Control subjects were 961 women identified by random-digit telephone dialing. Subjects were interviewed in person, using pictures of brands of oral contraceptives and calendars of life events as recall aids. There was no increased incidence of breast cancer associated with ever having used oral contraceptives. Because only 8% of this cohort had never used oral contraceptives, short-term users (< 1 year) were combined with never users as the reference group for further analyses. A small increased risk of breast cancer was associated with long duration of oral contraceptive use (odds ratio for > or = 10 years = 1.3; 95% confidence interval [CI] = 0.9-1.9; P for trend = .03), particularly among women aged 35 years or younger (odds ratio for > or = 10 years = 1.7; 95% CI = 0.9-3.1). Breast cancer was also modestly related to oral contraceptive use early in reproductive life (odds ratio for use within 5 years of menarche = 1.3; 95% CI = 1.0-1.8; P for trend = .04) and to use of high-progestin-potency oral contraceptives for at least 1 year (odds ratio = 1.5; 95% CI = 1.1-2.1). These associations were adjusted for age, age at menarche, term pregnancy, induced abortion, and family history of

Experience with oral emergency contraception since the OTC switch in Germany.

PubMed

Kiechle, Marion; Neuenfeldt, Miriam

2017-03-01

In March 2015, the oral emergency contraceptives levonorgestrel (LNG) and ulipristal acetate (UPA) were released from prescription-only status in Germany. The main research question is to analyse whether the OTC status of oral emergency contraceptives has an influence on the patterns of use. All information is based on searches for public domain sources on emergency contraception. Searches were made for scientific publications, statistics, and surveys. Due to additional active ingredient properties, UPA is superior to LNG in terms of ovulation-inhibiting effect. Since the OTC switch, demand for oral emergency contraceptives has risen by almost 50%, especially at weekends when sexual encounters and thus contraceptive failures are most frequent. However, the age distribution of the users has not changed as a result of the OTC switch. Doctors still play an important role in advising on emergency contraception after the removal of the prescription-only requirement. Pregnancies despite emergency contraception are terminated in more than half of the cases. In federal states with higher rates of use of the morning-after pill, fewer terminations of pregnancy were performed. As a result of the OTC switch, more women and girls use the morning-after pill after unprotected intercourse and the time between unprotected intercourse and taking the oral emergency contraceptive decreases. This is of great advantage in terms of the mechanism of action. UPA is used more frequently than LNG. Only half of all people aged between 16 and 39 years in Germany are aware of the morning-after pill and 94% of women who had a pregnancy terminated in 2015 did not use any emergency contraception after the unprotected intercourse. In the population, there is still a great need for information and education on contraception and emergency contraception.

No interacting influence of lavender oil preparation silexan on oral contraception using an ethinyl estradiol/levonorgestrel combination.

PubMed

Heger-Mahn, Doris; Pabst, Günther; Dienel, Angelika; Schläfke, Sandra; Klipping, Christine

2014-12-01

Silexan is an oral Lavender oil preparation with proven anxiolytic efficacy. Given the high prevalence of anxiety and restlessness in younger women, oral contraceptives and Silexan will likely be co-administered. A double-blind, randomised, 2-period crossover study was performed to investigate the effects of Silexan on the pharmacokinetics and pharmacodynamics of Microgynon(®), a combination oral contraceptive containing ethinyl estradiol 0.03 mg (EE) and levonorgestrel 0.15 mg (LNG) in healthy, fertile, adult females. During 2 consecutive cycles of 28 days, oral contraception was given for 21 days combined with 1 × 160 mg/day Silexan or placebo. Plasma concentration-time profiles of EE and LNG were obtained on day 18 ± 1 up to 24 h after dosing. The primary outcome measure was the area under the concentration-time curve over a dosing interval of τ = 24 h (AUCτ) for EE and LNG plasma levels. An interaction with Silexan was formally excluded if the 90 % confidence interval for the AUCτ ratio during co-administration with Silexan or placebo was included within the range of 0.80-1.25. Secondary outcomes included EE and LNG peak concentration (C max) and time to C max (t max), follicle size, endometrial thickness, the Hoogland score, and serum levels of estradiol, progesterone, and sex hormone-binding globulin. A total of 24 women (mean age 27.3 years; mean body mass index 22.2 kg/m(2)) participated. The confidence intervals for the EE and LNG AUCτ and C max ratios fell within the pre-specified limits, indicating no interaction (point estimates [Silexan/placebo] AUCτ EE 0.97, LNG 0.94; C max EE 0.99, LNG 0.96). For LNG, t max was slightly delayed. No secondary outcome indicated any impairment of contraceptive efficacy. Co-administration of Silexan did not affect the efficacy of a combination oral contraceptive containing EE and LNG and was well tolerated.

Effects of oral contraceptive agents and sex steroids on carbohydrate metabolism.

PubMed

Kalkhoff, R K

1972-01-01

The article offers a general interpretation of the influence of oral contraceptive agents on glucose tolerance, emphasizing comparisons of synthetic sex hormones. Although there are conflicting reports on steroid-induced diabetes in normal women, their glucose curves are often higher when under oral contraceptive treatment, suggesting that oral contraceptives may induce a form of subclinical diabetes melitus that is reversible. Evidence from diabetic women suggests definite deliterious effects from contraceptive administration. Estradiol, estriol, and estrone may improve glucose tolerance in nondiabetic women and reduce insulin requirements in diabetics. Progesterone has little effect on carbohydrate tolerance, as did synthetic progestin. Conjugated equine estrogens (equilenine or Premarin) may provoke mild to moderate deterioration of carbohydrate tolerance. Parenterally administered natural estrogens and orally administered synthetic derivatives appear to differ sharply in their effects. Sex hormones' effects on carbohydrate metabolism likely involve interactions with insulin and endogenous glucocorticoids.

Rational use of oral contraceptives in the perimenopausal woman.

PubMed

Connell, E B

1993-12-01

Oral contraceptives have undergone extensive revision in their labeling over the past 10 years to remove warnings about cardiovascular and other risks and to highlight their noncontraceptive benefits. While these changes are becoming better known, the potential bone-sparing effects of oral contraceptives in the premenopausal and perimenopausal woman remain under-appreciated. Osteoporosis is a major health care problem worldwide in terms of both its associated morbidity and mortality and its economic impact. Although the benefits of postmenopausal hormone replacement therapy for the prevention and treatment of osteoporosis are generally recognized, little attention has been paid to strategies that might be used to maintain bone mass up to the time of menopause, at which time bone loss accelerates. An additional noncontraceptive benefit of oral contraceptives may be to maintain and build bone mass up to the time of menopause.

Physiologic and psychologic symptoms associated with use of injectable contraception and 20 microg oral contraceptive pills.

PubMed

Berenson, Abbey B; Odom, Susan D; Breitkopf, Carmen Radecki; Rahman, Mahbubur

2008-10-01

The objective of the study was to compare menstrual, physiologic, and psychologic symptoms over 2 years among women initiating use of depot medroxyprogesterone acetate or an oral contraceptive pill with a reduced pill-free interval and those not using hormonal contraception. A total of 608 women reported their experience regarding 17 symptoms prior to initiating contraception and every 6 months thereafter for 24 months. Longitudinal relationships between symptoms and contraceptives were assessed after adjusting for age, visits, and baseline status of symptoms. Oral contraceptive pills were protective against mastalgia (odds ratio [OR], 0.7), cramping (OR, 0.5), hair loss (OR, 0.6), acne (OR, 0.4), nervousness (OR, 0.5), and mood swings (OR, 0.7). Depot medroxyprogesterone acetate (DMPA) was protective against bloating (OR, 0.5) and mood swings (OR, 0.7) but caused weight gain (OR, 2.3), bleeding episodes more than 20 days (OR, 13.4), and missed periods (OR, 96.9). Both methods caused intermenstrual bleeding. Evidence-based data regarding beneficial and adverse symptoms associated with these methods may help clinicians counsel patients appropriately prior to contraceptive initiation.

Progestin-only pills for contraception.

PubMed

Grimes, David A; Lopez, Laureen M; O'Brien, Paul A; Raymond, Elizabeth G

2013-11-13

levonorgestrel progestin-only pill, desogestrel was not associated with a significantly lower risk of accidental pregnancy; the rate ratio was 0.27 (95% CI 0.06 to 1.19). However, the desogestrel progestin-only pill caused more bleeding problems, although this difference was not statistically significant. The trial comparing low-dose mifepristone versus a levonorgestrel progestin-only pill found similar pregnancy rates. In the trial comparing ethynodiol diacetate versus a combined oral contraceptive, irregular cycles occurred in all women assigned to the progestin-only pill (odds ratio 135.96; 95% CI 7.61 to 2421.02). In a trial comparing two progestin-only and two combined oral contraceptives, the progestin-only pill containing levonorgestrel 30 μg had higher efficacy than did the pill containing norethisterone 350 μg. An early trial found megestrol acetate inferior to other progestin-only pills in terms of efficacy. A study of the timing of pill initiation after birth found no important differences, but high losses to follow up undermined the trial. Evidence is insufficient to compare progestin-only pills to each other or to combined oral contraceptives.

Efficacy and safety of metformin or oral contraceptives, or both in polycystic ovary syndrome.

PubMed

Yang, Young-Mo; Choi, Eun Joo

2015-01-01

Polycystic ovary syndrome (PCOS) is an endocrinopathy that affects approximately 10% of reproductive-aged women throughout their lives. Women with PCOS present with heterogeneous symptoms including ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Therefore, lifelong individualized management should be considered. Pharmacological agents commonly used to manage the symptoms are metformin and oral contraceptive pills. Although these medications have been beneficial in treating PCOS symptoms, their efficacy and safety are still not entirely elucidated. This study aimed to report the efficacy and safety of metformin, oral contraceptives, or their combination in the treatment of PCOS and to define their specific individual roles. A literature search of original studies published in PubMed and Scopus was conducted to identify studies comparing metformin with oral contraceptives or evaluating the combination of both in PCOS. Eight clinical trials involving 313 patients were examined in the review. The intervention dosage of metformin ranged from 1,000 to 2,000 mg/d and that of oral contraceptives was ethinylestradiol 35 µg and cyproterone acetate 2 mg. Lower body mass index was observed with regimens including metformin, but increased body mass index was observed in monotherapy with oral contraceptives. Administration of metformin or oral contraceptives, especially as monotherapy, had a negative effect on lipid profiles. In addition, there are still uncertainties surrounding the effects of metformin or oral contraceptives in the management of insulin level, although they improved total testosterone and sex hormone-binding globulin levels. In the included studies, significant side effects due to metformin or oral contraceptives were not reported. The clinical trials suggest that metformin or oral contraceptives are at least patient convenient, efficacious, and safe for the treatment of PCOS. However, well-designed, prospective, long-term, large

Efficacy and safety of metformin or oral contraceptives, or both in polycystic ovary syndrome

PubMed Central

Yang, Young-Mo; Choi, Eun Joo

2015-01-01

Background Polycystic ovary syndrome (PCOS) is an endocrinopathy that affects approximately 10% of reproductive-aged women throughout their lives. Women with PCOS present with heterogeneous symptoms including ovulatory dysfunction, hyperandrogenism, and polycystic ovaries. Therefore, lifelong individualized management should be considered. Pharmacological agents commonly used to manage the symptoms are metformin and oral contraceptive pills. Although these medications have been beneficial in treating PCOS symptoms, their efficacy and safety are still not entirely elucidated. This study aimed to report the efficacy and safety of metformin, oral contraceptives, or their combination in the treatment of PCOS and to define their specific individual roles. Methods A literature search of original studies published in PubMed and Scopus was conducted to identify studies comparing metformin with oral contraceptives or evaluating the combination of both in PCOS. Results Eight clinical trials involving 313 patients were examined in the review. The intervention dosage of metformin ranged from 1,000 to 2,000 mg/d and that of oral contraceptives was ethinylestradiol 35 µg and cyproterone acetate 2 mg. Lower body mass index was observed with regimens including metformin, but increased body mass index was observed in monotherapy with oral contraceptives. Administration of metformin or oral contraceptives, especially as monotherapy, had a negative effect on lipid profiles. In addition, there are still uncertainties surrounding the effects of metformin or oral contraceptives in the management of insulin level, although they improved total testosterone and sex hormone-binding globulin levels. In the included studies, significant side effects due to metformin or oral contraceptives were not reported. Conclusion The clinical trials suggest that metformin or oral contraceptives are at least patient convenient, efficacious, and safe for the treatment of PCOS. However, well

Amygdala reactivity to negative stimuli is influenced by oral contraceptive use.

PubMed

Petersen, Nicole; Cahill, Larry

2015-09-01

The amygdala is a highly interconnected region of the brain that is critically important to emotional processing and affective networks. Previous studies have shown that the response of the amygdala to emotionally arousing stimuli can be modulated by sex hormones. Because oral contraceptive pills dramatically lower circulating sex hormone levels with potent analogs of those hormones, we performed a functional magnetic resonance imaging experiment to measure amygdala reactivity in response to emotional stimuli in women using oral contraceptives, and compared their amygdala reactivity with that of naturally cycling women. Here, we show that women who use oral contraceptive pills have significantly decreased bilateral amygdala reactivity in response to negatively valenced, emotionally arousing stimuli compared with naturally cycling women. We suggest that by modulating amygdala reactivity, oral contraceptive pills may influence behaviors that have previously been shown to be amygdala dependent-in particular, emotional memory. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Effects of Administration of Fostamatinib on Blood Concentrations of an Oral Contraceptive in Healthy Female Subjects

ClinicalTrials.gov

2012-02-17

Scientific Terminology Rheumatoid Arthritis, Healthy Female Volunteers, Pharmacokinetics, Oral Contraceptive, Drug-drug Interaction; Laymen Terminology Level of Oral Contraceptive in Blood, Oral Contraceptive, Rheumatoid Arthritis, Drug -Drug Interaction

Practice Bulletin No. 152: Emergency Contraception.

PubMed

2015-09-01

Emergency contraception, also known as postcoital contraception, is therapy used to prevent pregnancy after an unprotected or inadequately protected act of sexual intercourse. Common indications for emergency contraception include contraceptive failure (eg, condom breakage or missed doses of oral contraceptives) and failure to use any form of contraception (). Although oral emergency contraception was first described in the medical literature in the 1960s, the U.S. Food and Drug Administration (FDA) approved the first dedicated product for emergency contraception in 1998. Since then, several new products have been introduced. Methods of emergency contraception include oral administration of combined estrogen-progestin, progestin only, or selective progesterone receptor modulators and insertion of a copper intrauterine device (IUD). Many women are unaware of the existence of emergency contraception, misunderstand its use and safety, or do not use it when a need arises (). The purpose of this Practice Bulletin is to review the evidence for the efficacy and safety of available methods of emergency contraception and to increase awareness of these methods among obstetrician-gynecologists and other gynecologic providers.

Reproductive health preventive screening among clinic vs. over-the-counter oral contraceptive users

PubMed Central

Hopkins, Kristine; Grossman, Daniel; White, Kari; Amastae, Jon; Potter, Joseph E.

2015-01-01

Background Interest is growing in moving oral contraceptives over-the-counter (OTC), although concerns exist about whether women would continue to get preventive health screening. Study Design We recruited cohorts of US-resident women who obtained oral contraceptives from US family planning clinics (n=532) and OTC from pharmacies in Mexico (n=514) and interviewed them four times over 9 months. Based on self-reports of having a Pap smear within 3 years or ever having had a pelvic exam, clinical breast exam and testing for sexually transmitted infections (STIs), we assessed the prevalence of preventive screening using Poisson regression models. Results The prevalence of screening was high for both groups (>88% for Pap smear, pelvic exam and clinical breast exam and >71% for STI screening), while the prevalence ratios for screening were higher for clinic users, even after multivariable adjustment. Conclusions Results suggest that most women would obtain reproductive health preventive screening if oral contraceptives were available OTC, and also highlight the need to improve access to preventive screening for all low-income women. PMID:22520645

Comparative Study of the Effects of Combined Oral Contraceptives in Hemostatic Variables

PubMed Central

Stocco, Bianca; Fumagalli, Helen F.; Franceschini, Silvio A.; Martinez, Edson Z.; Marzocchi-Machado, Cleni M.; de Sá, Marcos Felipe S.; Toloi, Maria Regina T.

2015-01-01

Abstract Thrombotic risk is associated with the estrogen dose and type of progestin in combined oral contraceptives. Studies published since 1990 showed that third-generation progestins have larger risk to contribute to thrombosis development than the second-generation. However, there are conflicts in the literature regarding the thrombotic risk associated to the drospirenone progestin. So, this study aimed to evaluate the effects of 3 formulations of contraceptives containing ethinylestradiol (EE) (20 and 30 μg) combined with drospirenone versus levonorgestrel combined with EE (30 μg) in hemostatic parameters. This cross-sectional study included 70 healthy women between 18 and 30 years, BMI 19 to 30 kg/m2, not pregnant, non-smokers, and users or non-users (control) of contraceptives for a minimum period of 6 months. The following parameters were assessed: prothrombin time (PT), Factor VII, activated partial thromboplastin time (aPTT), Factor XII, fibrinogen, Factor 1 + 2, Protein C, Protein S, antithrombin, D-dimers, and plasminogen activator inhibitor-1. Significant alterations were found in PT, aPTT, fibrinogen, D-dimers, and protein S, all favoring a state of hypercoagulation for contraceptive containing DRSP/20EE. Both contraceptives containing DRSP/30EE and LNG/30EE promoted changes that favor the hypercoagulability in the coagulant variable PT and in the anticoagulant variables Protein S and Protein C, respectively. We suggest that the progestin drospirenone can contribute to an inadequate balance among procoagulant, anticoagulant, and fibrinolytic factors, since that the contraceptive containing the lowest dose of estrogen and drospirenone (DRSP/20EE) caused a higher number of hemostatic changes. PMID:25634167

Oral Contraceptives Attenuate Cardiac Autonomic Responses to Musical Auditory Stimulation: Pilot Study.

PubMed

Milan, Réveni Carmem; Plassa, Bruna Oliveira; Guida, Heraldo Lorena; de Abreu, Luiz Carlos; Gomes, Rayana L; Garner, David M; Valenti, Vitor E

2015-01-01

The literature presents contradictory results regarding the effects of contraceptives on cardiac autonomic regulation. The research team aimed to evaluate the effects of musical auditory stimulation on cardiac autonomic regulation in women who use oral contraceptives. The research team designed a transversal observational pilot study. The setting was the Centro de Estudos do Sistema Nervoso Autônomo (CESNA) in the Departamento de Fonoaudiologia at the Universidade Estadual Paulista (UNESP) in Marília, SP, Brazil. Participants were 22 healthy nonathletic and nonsedentary females, all nonsmokers and aged between 18 and 27 y. Participants were divided into 2 groups: (1) 12 women who were not taking oral contraceptives, the control group; and (2) 10 women who were taking oral contraceptives, the oral contraceptive group. In the first stage, a rest control, the women sat with their earphones turned off for 20 min. After that period, the participants were exposed to 20 min of classical baroque music (ie, "Canon in D Major," Johann Pachelbel), at 63-84 dB. Measurements of the equivalent sound levels were conducted in a soundproof room, and the intervals between consecutive heartbeats (R-R intervals) were recorded, with a sampling rate of 1000 Hz. For calculation of the linear indices, the research team used software to perform an analysis of heart rate variability (HRV). Linear indices of HRV were analyzed in the time domain: (1) the standard deviation of normal-to-normal R-R intervals (SDNN), (2) the root-mean square of differences between adjacent normal R-R intervals in a time interval (RMSSD), and (3) the percentage of adjacent R-R intervals with a difference of duration greater than 50 ms (pNN50). The study also analyzed the frequency domain-low frequency (LF), high frequency (HF), and LF/HF ratio. For the control group, the musical auditory stimulation reduced (1) the SDNN from 52.2 ± 10 ms to 48.4 ± 16 ms (P = .0034); (2) the RMSSD from 45.8 ± 22 ms to 41.2 �

Oral contraceptives for pain associated with endometriosis.

PubMed

Brown, Julie; Crawford, Tineke J; Datta, Shree; Prentice, Andrew

2018-05-22

Endometriosis is a common gynaecological condition which affects many women of reproductive age worldwide and is a major cause of pain and infertility. The combined oral contraceptive pill (COCP) is widely used to treat pain occurring as a result of endometriosis, although the evidence for its efficacy is limited. To determine the effectiveness, safety and cost-effectiveness of oral contraceptive preparations in the treatment of painful symptoms ascribed to the diagnosis of laparoscopically proven endometriosis. We searched the following from inception to 19 October 2017: the Cochrane Gynaecology and Fertility Group Specialised Register of Controlled Trials, the Cochrane CENTRAL Register of Studies Online (CRSO), MEDLINE, Embase, PsycINFO, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the trial registers ClinicalTrials.gov and the World Health Organization Clinical Trials Registry Platform (WHO ICTRP). We also handsearched reference lists of relevant trials and systematic reviews retrieved by the search. We included randomised controlled trials (RCT) of the use of COCPs in the treatment of women of reproductive age with symptoms ascribed to the diagnosis of endometriosis that had been made visually at a surgical procedure. Two review authors independently assessed study quality and extracted data. One review author was an expert in the content matter. We contacted study authors for additional information. The primary outcome was self-reported pain (dysmenorrhoea) at the end of treatment. Five trials (612 women) met the inclusion criteria. Only three trials (404 women) provided data that were suitable for analysis.Combined oral contraceptive pill versus placeboTwo trials compared COCP with a placebo. These studies were at high risk of bias. For GRADE outcomes (self-reported pain (dysmenorrhoea) at the end of treatment), the quality of the evidence very low. Evidence was downgraded for imprecision as it was based on a single, small trial and

Comparison of high-dose intermittent and low-dose continuous oral artemisinin in dogs with naturally occurring tumors.

PubMed

Hosoya, Kenji; Couto, C Guillermo; London, Cheryl A; Kisseberth, William C; Phelps, Mitchell A; Dalton, James T

2014-01-01

To evaluate the clinical toxicity and activity of orally administered artemisinin in dogs with spontaneous tumors, 24 client-owned dogs were randomly divided into two groups and received either low-continuous dose (3 mg/kg q 24 hr) or high-dose intermittent (three doses of 45 mg/kg q 6 hr repeated q 1 wk) of artemisinin per os. Treatment was continued for 21 days. Dogs were evaluated weekly for clinical effect and at the end of the treatment for hematologic and biochemical adverse events. Whole blood concentrations of artemisinin and dihydroartemisinin were measured by liquid chromatography/tandem mass spectrometry after the first dose of artemisinin in three dogs in each group. Blood concentrations of artemisinin and dihydroartemisinin were <0.1 μM at all time points, and there was no difference in blood concentration between the two dosing groups. The most frequent adverse event was anorexia, which was observed in 11% of the low-dose group and 29% of the high-dose group. Oral artemisinin, both in low-dose continuous and high-dose intermittent, is well tolerated in dogs but results in low bioavailability. Parenteral administration should be considered for future studies.

[Hyperplastic changes and oral contraceptives in Anglo-Saxon countries].

PubMed

Markuszewski, C

1978-09-18

One of the major problems being researched and studied by the World Health Organization is the incidence of harmful side effects in users of steroid contraceptives. A literature search indicates that Anglo-Saxon countries report alarming hyperplastic changes, particularly in the liver, blood clots, hyperlipidemia leading to high blood pressure, porphyria, atypical leiomyomas and cervical hyperplasia. Currently attention is being focused on the relationship between steroid contraceptives and breast cancer. Fazala and Paffenbarger in their study of 1770 women found such benign changes as fibroadenoma, mastopathia fibrosa cystica and papilloma intraductale. In women who had used oral contraceptives for 2-4 yrs, malignancies were 1.9% to 2.5% more frequent than in non-users; in 6 yrs of use, 11 times greater than in non-users. Estrogens, particularly mestranol has been recognized as being harmful to the liver. Length of usage is a definite factor. Beginning with 1960, relatively frequent occurrences of hepotoma in young women on the pill were noted. Caught at an early stage, peliosis hepatis can be reversed if the patient discontinues the use of contraceptives. In some cases, even after a long interval of 6 months to 10 yrs, the disease continued to develop. Liver cell adenoma in the U. S. occurs 1/500,00 to 1/1,000,000. After 5 to 7 yrs of using oral contraceptives, the chance of developing liver cell adenoma is 5 times greater; after 10 yrs of use, 35 times greater. Hepatomas rupture in 43.4% of cases when the patient had been on a contraceptive, while in only 22.2% in cases of non-users. The literature which the author investigated did not establish a clear proof that the hyperplastic changes discussed were due exclusively to usage of oral contraceptives.

Oral contraceptives and mood in women with and without premenstrual dysphoria: a theoretical model.

PubMed

Kurshan, N; Neill Epperson, C

2006-01-01

Despite numerous studies on the topic, there is no consensus to date on the effects of oral contraceptives on mood or the mechanism(s) by which they exert these effects. This review article presents a theoretical model to explain the way in which oral contraceptives may affect mood. Specifically, it is argued that progestins exert differential effects on endogenous levels of neurosteroids, thereby altering mood. After providing an overview of the effects of estrogen, progesterone, and progesterone's metabolites on cortical excitability and the role of neurosteroids in depression and premenstrual dysphoria, this article reviews the research that has been conducted on the relationship between oral contraceptives and neurosteroids. Finally, suggestions for future research are made with the dual aim of improving existing studies on the relationship between oral contraceptives and mood and further investigating the possibility that fluctuations in neurosteroid levels are responsible for the effects of oral contraceptives on mood.

Influence of transdermal rotigotine on ovulation suppression by a combined oral contraceptive

PubMed Central

Braun, Marina; Elshoff, Jan-Peer; Andreas, Jens-Otto; Müller, Louise Ischen; Horstmann, Rolf

2009-01-01

AIMS To assess the influence of the transdermally applied dopamine agonist rotigotine on ovulation suppression by a combined oral contraceptive (0.03 mg ethinyloestradiol and 0.15 mg levonorgestrel) in a randomized, double-blind crossover study in 40 healthy females. METHODS Treatment A consisted of the combined oral contraceptive for 28 days plus rotigotine for the first 13 days (2 mg (24 h)−1 on days 1–3, 3 mg (24 h)−1 maintenance dose thereafter). During treatment B, subjects received matching placebo patches instead of rotigotine. Pharmacodynamic parameters (progesterone, oestradiol, luteinizing hormone, and follicle stimulating hormone serum concentrations), pharmacokinetic parameters for ethinyloestradiol/levonorgestrel and rotigotine, and safety and tolerability of the treatment were assessed. RESULTS Progesterone serum concentrations remained below 2 ng ml−1 in all subjects during the luteal phase. Median serum concentrations of all other pharmacodynamic parameters were similar during both treatments. Pharmacokinetic parameters Cmax,ss and AUC(0,24 h)ss at steady state were similar with or without co-administration of rotigotine for both ethinyloestradiol and levonorgestrel with geometric mean ratios close to 1 and 90% confidence intervals within the acceptance range of bioequivalence (0.8, 1.25): Cmax,ss 1.05 (0.93, 1.19), AUC(0,24 h)ss 1.05 (0.9, 1.22) for ethinyloestradiol; Cmax,ss 1.01 (0.96, 1.06), AUC(0,24 h)ss 0.98 (0.95, 1.01) for levonorgestrel. Mean plasma concentrations of unconjugated rotigotine remained stable throughout the patch-on period (day 13). CONCLUSIONS Concomitant administration of 3 mg (24 h)−1 transdermal rotigotine had no impact on the pharmacodynamics and pharmacokinetics of a combined oral contraceptive containing 0.03 mg ethinyloestradiol and 0.15 mg levonorgestrel, suggesting that the dopamine agonist does not influence contraception efficacy. PMID:19740396

Practice Bulletin Summary No. 152: Emergency Contraception.

PubMed

2015-09-01

Emergency contraception, also known as postcoital contraception, is therapy used to prevent pregnancy after an unprotected or inadequately protected act of sexual intercourse. Common indications for emergency contraception include contraceptive failure (eg, condom breakage or missed doses of oral contraceptives) and failure to use any form of contraception (1-3). Although oral emergency contraception was first described in the medical literature in the 1960s, the U.S. Food and Drug Administration (FDA) approved the first dedicated product for emergency contraception in 1998. Since then, several new products have been introduced. Methods of emergency contraception include oral administration of combined estrogen-progestin, progestin only, or selective progesterone receptor modulators and insertion of a copper intrauterine device (IUD). Many women are unaware of the existence of emergency contraception, misunderstand its use and safety, or do not use it when a need arises (4-6). The purpose of this Practice Bulletin is to review the evidence for the efficacy and safety of available methods of emergency contraception and to increase awareness of these methods among obstetrician-gynecologists and other gynecologic providers.

Comparison of cycle control with a combined contraceptive vaginal ring and oral levonorgestrel/ethinyl estradiol.

PubMed

Bjarnadóttir, Ragnheidur I; Tuppurainen, Marjo; Killick, Stephen R

2002-03-01

The purpose of this study was to compare cycle control and tolerability of the NuvaRing (NV Organon, Oss, The Netherlands), a novel combined contraceptive vaginal ring, with a standard combined oral contraceptive pill. Healthy women aged 18 to 40 years who requested contraception received either NuvaRing or a combined oral contraceptive containing 30 microg ethinyl estradiol and 150 microg levonorgestrel for 6 cycles in 3 similarly designed studies. Each cycle comprised 3 weeks of ring or pill use, followed by 1 ring- or pill-free week. Two hundred forty-seven women began the studies, 121 women with NuvaRing and 126 women with the combined oral contraceptive. Withdrawal bleeding occurred in virtually all cycles in both groups. In the NuvaRing groups, the incidence of irregular bleeding was < or =5% in all cycles; this was lower than the combined oral contraceptive groups (5.4%-38.8%). Furthermore, the incidence of a normal intended bleeding pattern was significantly higher in the NuvaRing groups than in the combined oral contraceptive groups (P <.01). Both contraceptives were well tolerated. NuvaRing has excellent cycle control and is well tolerated.

Comparative effects of a contraceptive vaginal ring delivering a nonandrogenic progestin and continuous ethinyl estradiol and a combined oral contraceptive containing levonorgestrel on hemostasis variables.

PubMed

Rad, Mandana; Kluft, Cornelis; Ménard, Joël; Burggraaf, Jacobus; de Kam, Marieke L; Meijer, Piet; Sivin, Irving; Sitruk-Ware, Regine L

2006-07-01

This study aimed to compare the effects on hemostasis variables of a contraceptive vaginal ring with those of an oral contraceptive. Twenty-three and 22 healthy premenopausal women were randomized to the contraceptive vaginal ring (150 microg Nestorone and 15 microg ethinyl estradiol) or Stediril 30 during 3 cycles. Analysis of covariance was performed with baseline values as covariate. The contraceptive vaginal ring changed most hemostasis variables similarly but raised (95% confidence intervals of percent treatment differences) Factor VIIt (28% to 49%), extrinsic activated protein C resistance (14% to 65%), and sex hormone-binding globulin (117% to 210%) and lowered Protein S (-32% to -16%) and the global activated partial thromboplastin time-based activated protein C resistance (-12% to -2%) more than the oral contraceptive. The contraceptive vaginal ring affected some measured hemostasis variables and sex hormone-binding globulin differently from the oral contraceptive, most likely because of difference in androgenicity of the progestins. The results suggest that the contraindications for oral contraceptive use would also apply to the tested contraceptive vaginal ring.

Myths about oral contraceptives. Does OC availability result in increased sexual activity among teens?

PubMed

Chaney

1993-11-01

Parents, educators, public health officials, health-care providers, religious organizations, and advocacy groups are very concerned about the rise in teenage pregnancy and the increase in sexually transmitted diseases among the young. Some say the increased availability and acceptance of oral contraceptives is directly related to an increase in sexual activity among teens. Less than 50% of women use a contraceptive method at first intercourse. Use is much lower in Hispanic and African-American women than among White women; women with low socioeconomic status, living in one-parent households, or having sex at an early age are the least likely to use a contraceptive method at first intercourse. According to the National Survey of Family Growth, teens engaging in sexual intercourse for the first time, who use a contraceptive method, typically choose the condom. Oral contraceptive use is very low and use at first intercourse has not increased over time. It is only after the establishment of routine sexual intercourse that the pill becomes the preferred method. The use of a condom has more than doubled for the period from 1982 to 1988. Adolescents under age 16 are at greatest risk for unintended pregnancies because this group is the least likely to use any method of contraception. The increase in teen sexual activity over the years does not coincide with an increase in pill use. Education must begin in elementary schools, stressing abstinence, but also include facts about sex, contraception, and disease prevention, because 40% of teens are sexually active by 9th grade. Skills can focus on changing behavior, such as learning to delay intercourse, building self-esteem as well as proper use of contraceptives. Easy, nonthreatening access to medical care can prevent many unintended pregnancies and the spread of sexually transmitted diseases.

A comparison of second and third generations combined oral contraceptive pills' effect on mood.

PubMed

Shahnazi, Mahnaz; Farshbaf Khalili, Azizeh; Ranjbar Kochaksaraei, Fatemeh; Asghari Jafarabadi, Mohammad; Gaza Banoi, Kamal; Nahaee, Jila; Bayati Payan, Somayeh

2014-08-01

Most women taking combined oral contraceptives (COCs) are satisfied with their contraceptive method. However, one of the most common reasons reported for discontinuation of combined oral contraceptives (COCs) is mood deterioration. This study aimed to compare effects of the second and third generation oral contraceptive pills on the mood of reproductive women. This randomized, double-blind, controlled clinical trial was conducted in reproductive women at health centers in Tehran, Iran. Participants were randomized into the second and third generation oral contraceptive groups. Positive and negative moods were recorded using positive affect, negative affect scale (PANAS) tools at the end the second and fourth months of the study. Data analysis was carried out using ANOVA and P Values < 0.05 was considered significant. Statistically significant difference was seen in positive and negative mood changes in women receiving contraceptive pills. The second generation oral contraceptive pills resulted in a decrease in positive mood (95% CI: 43.39 to 38.32 in second month and 43.39 to 26.05 in four month) and increase in negative mood (95% CI: 14.23 to 22.04 in second month and 14.23 to 32.26 in four month - P < 0.001), but the third generation led to an increase in positive mood (95% CI: 22.42 to 25.60 in second month and 22.42 to 33.87 in four month) and decrease in negative mood (95% CI: 36.78 to 31.97 in second month and 36.78 to 22.65 in four month - P < 0.001). Third generation combined oral contraceptive pills have a better effect on mood in women in reproductive ages than the second generation pills. It can be recommended as a proper combined oral contraceptive in Iran.

A Comparison of Second and Third Generations Combined Oral Contraceptive Pills’ Effect on Mood

PubMed Central

Shahnazi, Mahnaz; Farshbaf Khalili, Azizeh; Ranjbar Kochaksaraei, Fatemeh; Asghari Jafarabadi, Mohammad; Gaza Banoi, Kamal; Nahaee, Jila; Bayati Payan, Somayeh

2014-01-01

Background: Most women taking combined oral contraceptives (COCs) are satisfied with their contraceptive method. However, one of the most common reasons reported for discontinuation of combined oral contraceptives (COCs) is mood deterioration. Objectives: This study aimed to compare effects of the second and third generation oral contraceptive pills on the mood of reproductive women. Materials and Methods: This randomized, double-blind, controlled clinical trial was conducted in reproductive women at health centers in Tehran, Iran. Participants were randomized into the second and third generation oral contraceptive groups. Positive and negative moods were recorded using positive affect, negative affect scale (PANAS) tools at the end the second and fourth months of the study. Data analysis was carried out using ANOVA and P Values < 0.05 was considered significant. Results: Statistically significant difference was seen in positive and negative mood changes in women receiving contraceptive pills. The second generation oral contraceptive pills resulted in a decrease in positive mood (95% CI: 43.39 to 38.32 in second month and 43.39 to 26.05 in four month) and increase in negative mood (95% CI: 14.23 to 22.04 in second month and 14.23 to 32.26 in four month - P < 0.001), but the third generation led to an increase in positive mood (95% CI: 22.42 to 25.60 in second month and 22.42 to 33.87 in four month) and decrease in negative mood (95% CI: 36.78 to 31.97 in second month and 36.78 to 22.65 in four month - P < 0.001). Conclusions: Third generation combined oral contraceptive pills have a better effect on mood in women in reproductive ages than the second generation pills. It can be recommended as a proper combined oral contraceptive in Iran. PMID:25389478

Emergency contraception.

PubMed

2012-12-01

Despite significant declines over the past 2 decades, the United States continues to have teen birth rates that are significantly higher than other industrialized nations. Use of emergency contraception can reduce the risk of pregnancy if used up to 120 hours after unprotected intercourse or contraceptive failure and is most effective if used in the first 24 hours. Indications for the use of emergency contraception include sexual assault, unprotected intercourse, condom breakage or slippage, and missed or late doses of hormonal contraceptives, including the oral contraceptive pill, contraceptive patch, contraceptive ring (ie, improper placement or loss/expulsion), and injectable contraception. Adolescents younger than 17 years must obtain a prescription from a physician to access emergency contraception in most states. In all states, both males and females 17 years or older can obtain emergency contraception without a prescription. Adolescents are more likely to use emergency contraception if it has been prescribed in advance of need. The aim of this updated policy statement is to (1) educate pediatricians and other physicians on available emergency contraceptive methods; (2) provide current data on safety, efficacy, and use of emergency contraception in teenagers; and (3) encourage routine counseling and advance emergency-contraception prescription as 1 part of a public health strategy to reduce teen pregnancy. This policy focuses on pharmacologic methods of emergency contraception used within 120 hours of unprotected or underprotected coitus for the prevention of unintended pregnancy. Emergency contraceptive medications include products labeled and dedicated for use as emergency contraception by the US Food and Drug Administration (levonorgestrel and ulipristal) and the "off-label" use of combination oral contraceptives.

Oral Contraceptive Use and Affective Changes Across the Menstral Cycle,

DTIC Science & Technology

1998-06-19

1986). The original study was done to describe the prevalence of perimenstrual symptoms in a population-based sample. The parent study used a cross ...4. TITLE AND SUBTITLE Oral Contraceptive Use and Affective Changes Across the Menstrual Cycle 5. FUNDING NUMBERS 6. AUTHOR(S) Jill J. O’Rear 7...University of Washington Abstract Oral Contraceptive Use and Affective Changes Across the Menstrual Cycle by Jill J. O’Rear Chairperson of the

The effects on ovarian activity of a monophasic oral contraceptive with 100 microg levonorgestrel and 20 microg ethinyl estradiol.

PubMed

Coney, P; DelConte, A

1999-11-01

An open-label, single-center, noncomparative study was conducted to determine the effects of a monophasic oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol on ovarian activity. The subjects were 26 healthy women 20 to 35 years of age who had normal ovulatory cycles and were not at risk for becoming pregnant. For 3 treatment cycles, they took 1 tablet of active drug daily for 21 days followed by placebo tablets for 7 days. Follicle diameters and serum progesterone and 17beta-estradiol levels were measured before, during, and after treatment. In 2 (2.7%) of 73 cycles, luteinized unruptured follicles were present and in another 2 (2.7%) cycles, ovulation was confirmed by the disappearance of the enlarged follicle. Ovarian activity, as reflected by mean serum progesterone levels, was restored after treatment. The results of this study are in agreement with those of other studies that showed suppression of ovarian activity in women treated with a monophasic oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. These results indicate that low-dose 100 microg levonorgestrel and 20 microg ethinyl estradiol given for 21 days is effective in suppressing ovarian activity and they confirm the contraceptive efficacy observed in clinical trials (Pearl index of 0.8).

The combined oral contraceptive pill containing drospirenone and ethinyl estradiol plus levomefolate calcium.

PubMed

Rapkin, Rachel B; Creinin, Mitchell D

2011-10-01

Neural tube defects are the second most common congenital anomaly in the United States, although their incidence may be decreased by periconception folic acid supplementation. A new oral contraceptive containing drospirenone and ethinyl estradiol plus levomefolate calcium was formulated to decrease the risk of neural tube defects in pregnancies conceived while taking or shortly after discontinuing this pill. Because of its novelty, very few studies have been performed to evaluate the efficacy, side effects and safety related to contraception, premenstrual dysphoric disorder and acne; therefore, literature evaluating similar contraceptives without levomefolate is reviewed. Additionally, we review studies evaluating the addition of levomefolate calcium to oral contraceptives containing 3 mg drospirenone and either 20 or 30 μg ethinyl estradiol. To date, no study has been performed to evaluate the effect this new oral contraceptive has on reducing the incidence of neural tube defects. This new pill has similar contraceptive efficacy, side effect, safety and benefits profile to other drospirenone-containing contraceptives. While also approved to prevent neural tube defects, no studies validate this claim and physician time is better spent counseling women, regardless of contraceptive choice, on the importance of folic acid supplementation during the child-bearing years.

Progestin and estrogen potency of combination oral contraceptives and endometrial cancer risk.

PubMed

Maxwell, G L; Schildkraut, J M; Calingaert, B; Risinger, J I; Dainty, L; Marchbanks, P A; Berchuck, A; Barrett, J C; Rodriguez, G C

2006-11-01

Using data from a case-control study of endometrial cancer, we investigated the relationship between the progestin and estrogen potency in combination oral contraceptives (OCs) and the risk of developing endometrial cancer. Subjects included 434 endometrial cancer cases and 2,557 controls identified from the Cancer and Steroid Hormone (CASH) study. OCs were classified into four categories according to the individual potencies of each hormonal constituent (high versus low estrogen or progestin potency). Logistic regression was used to evaluate associations between endometrial cancer risk and combination OC formulations. With non-users as the referent group, use of OCs with either high potency progestin [odds ratio for endometrial cancer (OR)=0.21, 95% confidence interval (CI)=0.10 to 0.43] or with low potency progestin (OR=0.39, 95% CI=0.25 to 0.60) were both associated with a decreased risk of endometrial cancer. Overall high progestin potency OCs did not confer significantly more protection than low progestin potency OCs (OR=0.52, 95% CI=0.24 to 1.14). However, among women with a body mass index of 22.1 kg/m2 or higher, those who used high progestin potency oral contraceptives had a lower risk of endometrial cancer than those who used low progestin potency oral contraceptives (OR=0.31, 95% CI=0.11 to 0.92) while those with a BMI below 22.1 kg/m2 did not (OR=1.36, 95% CI=0.39 to 4.70). The potency of the progestin in most OCs appears adequate to provide a protective effect against endometrial cancer. Higher progestin-potency OCs may be more protective than lower progestin potency OCs among women with a larger body habitus.

Semaglutide, a Once-Weekly Human GLP-1 Analog, Does Not Reduce the Bioavailability of the Combined Oral Contraceptive, Ethinylestradiol/Levonorgestrel

PubMed Central

Kapitza, Christoph; Nosek, Leszek; Jensen, Lene; Hartvig, Helle; Jensen, Christine B; Flint, Anne

2015-01-01

The effect of semaglutide, a once-weekly human glucagon-like peptide-1 (GLP-1) analog in development for type 2 diabetes (T2D), on the bioavailability of a combined oral contraceptive was investigated. Postmenopausal women with T2D (n = 43) on diet/exercise ± metformin received ethinylestradiol (0.03 mg)/levonorgestrel (0.15 mg) once daily for 8 days before (semaglutide-free) and during (steady-state 1.0 mg) semaglutide treatment (subcutaneous once weekly; dose escalation: 0.25 mg 4 weeks; 0.5 mg 4 weeks; 1.0 mg 5 weeks). Bioequivalence of oral contraceptives was established if 90%CI for the ratio of pharmacokinetic parameters during semaglutide steady-state and semaglutide-free periods was within prespecified limits (0.80–1.25). The bioequivalence criterion was met for ethinylestradiol area under the curve (AUC0–24 h) for semaglutide steady-state/semaglutide-free; 1.11 (1.06–1.15). AUC0–24 h was 20% higher for levonorgestrel at semaglutide steady-state vs. semaglutide-free (1.20 [1.15–1.26]). Cmax was within bioequivalence criterion for both contraceptives. Reductions (mean ± SD) in HbA1c (–1.1 ± 0.6%) and weight (–4.3 ± 3.1 kg) were observed. Semaglutide pharmacokinetics were compatible with once-weekly dosing; the semaglutide dose and dose-escalation regimen were well tolerated. Adverse events, mainly gastrointestinal, were mild to moderate in severity. Asymptomatic increases in mean amylase and lipase were observed. Three subjects had elevated alanine aminotransferase levels ≥3x the upper limit of normal during semaglutide/oral contraceptive coadministration, which were reported as adverse events, but resolved during follow-up. Semaglutide did not reduce the bioavailability of ethinylestradiol and levonorgestrel. PMID:25475122

Frequency of Candidiasis and Colonization of Candida albicans in Relation to Oral Contraceptive Pills.

PubMed

Aminzadeh, Atousa; Sabeti Sanat, Ali; Nik Akhtar, Saeed

2016-10-01

Candidiasis, the infection caused by Candida albicans , is one of the most common infections of the oral cavity in humans. Candidiasis causes irritation and is known for its carcinogenic effects. Thus, it is important to recognize the predisposing factors for this opportunistic infection. Several previous studies have demonstrated an increased frequency of vaginal candidiasis in relation to oral contraceptive consumption. Only a few studies on the relation between oral contraceptives and oral candidiasis have been previously conducted. This study aims to evaluate the possible relation between oral contraceptive pills and oral candidiasis. This analytic, case-control study included 40 non-pregnant women divided into two groups: 20 who used oral contraceptive pills and 20 who did not. The groups were matched according to age, oral health, and past and present medical history. Samples were collected from the tongue's dorsum using a cotton swab and inoculated on CHROMagar culture plates. The frequency of positive cultures and the number of Candida colonies were compared between the two groups using independent t-tests and Mann-Whitney statistical tests with SPSS18 software. The frequency of positive cultures of Candida albicans was higher (P value = 0.03) for the case group. Also, the number of C. albicans and C. krusei was significantly higher for the case group compared to the control group (P value = 0.04, P value = 0.03). The results of the present study demonstrate that oral contraceptives containing estradiol can lead to Candida colonization in the oral cavity. It is recommended that further studies comparing the influence of oral contraceptives on Candida's adherence to the epithelium is highly recommended.

Mineralocorticoid receptor haplotype, oral contraceptives and emotional information processing.

PubMed

Hamstra, D A; de Kloet, E R; van Hemert, A M; de Rijk, R H; Van der Does, A J W

2015-02-12

Oral contraceptives (OCs) affect mood in some women and may have more subtle effects on emotional information processing in many more users. Female carriers of mineralocorticoid receptor (MR) haplotype 2 have been shown to be more optimistic and less vulnerable to depression. To investigate the effects of oral contraceptives on emotional information processing and a possible moderating effect of MR haplotype. Cross-sectional study in 85 healthy premenopausal women of West-European descent. We found significant main effects of oral contraceptives on facial expression recognition, emotional memory and decision-making. Furthermore, carriers of MR haplotype 1 or 3 were sensitive to the impact of OCs on the recognition of sad and fearful faces and on emotional memory, whereas MR haplotype 2 carriers were not. Different compounds of OCs were included. No hormonal measures were taken. Most naturally cycling participants were assessed in the luteal phase of their menstrual cycle. Carriers of MR haplotype 2 may be less sensitive to depressogenic side-effects of OCs. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Influence of Menstrual Cycle and Oral Contraceptive Phase on Spinal Excitability.

PubMed

Casey, Ellen; Reese, Maria; Okafor, Ezi; Chun, Danielle; Gagnon, Christine; Nigl, Franz; Dhaher, Yasin Y

2016-09-01

Rates of musculoskeletal injury differ substantially between the genders, with females more likely to experience conditions such as anterior cruciate ligament (ACL) injuries than males in the same sports. Emerging evidence suggests a significant hormonal contribution. Most research has focused solely on how hormonal fluctuations affect connective tissue, but a direct link between hormonal shifts, ligamentous laxity, and ACL injury has not been borne out. There is also evidence to suggest that sex hormones can modulate the central nervous system, but how this affects neuromuscular control is not well understood. To determine whether changes in sex hormone concentrations would alter spinal excitability, measured across the menstrual and oral contraceptive pill cycle. We hypothesized that spinal excitability would fluctuate across the menstrual cycle (with increased excitability during the periovulatory phase due to peak estradiol concentration), but that there would be no fluctuation in oral contraceptive users. This was a prospective cohort study. The study took place at a biomechanics laboratory at a rehabilitation hospital. A total of 30 healthy women aged 18-35 who were similar in age, body composition, and exercise-training status were included. Fifteen of the women were eumenorrheic and nonusers of oral contraceptives (nonusers), and 15 of the women were taking oral contraceptives (users). H-reflex (Hmax/Mmax ratio), serum estradiol, and progesterone concentrations were measured at 3 time points during the menstrual and contraceptive pill cycle. The H-reflex (Hmax/Mmax ratio) remained stable across the menstrual and contraceptive pill cycle. Spinal excitability was lower in the users compared with the nonusers across all testing sessions, but this was not statistically significant. Our results suggest that acute fluctuations of endogenous estradiol and progesterone do not modulate spinal excitability. However, long-term exposure to exogenous estrogen and

Do oral contraceptives increase epileptic seizures?

PubMed

Reddy, Doodipala Samba

2017-02-01

Hormonal contraceptives are used by over 100 million people worldwide. Recently, there has been an emerging interest in studying the potential impact of oral contraceptives (OCs) on certain neurological conditions. It has been suspected for some time that hormonal birth control increases seizure activity in women with epilepsy, but there is little supportive data. Areas covered: Literature from PubMed and online sources was analyzed with respect to hormonal contraception and epilepsy or seizures. New evidence indicates that OCs can cause an increase in seizures in women with epilepsy. The epilepsy birth control registry, which surveyed women with epilepsy, found that those using hormonal contraceptives self-reported 4.5 times more seizures than those that did not use such contraceptives. A preclinical study confirmed these outcomes wherein epileptic animals given ethinyl estradiol, the primary component of OCs, had more frequent seizures that are more likely to be resistant. Expert commentary: OC pills may increase seizures in women with epilepsy and such refractory seizures are more likely to cause neuronal damage in the brain. Thus, women of child bearing age with epilepsy should consider using non-hormonal forms of birth control to avoid risks from OC pills. Additional research into the mechanisms and prospective clinical investigation are needed.

Extended-Cycle Levonorgestrel/Ethinylestradiol and Low-Dose Ethinylestradiol (Seasonique(®)): A Review of Its Use as an Oral Contraceptive.

PubMed

Burness, Celeste B

2015-06-01

A 91-day extended-cycle oral contraceptive (OC) consisting of levonorgestrel/ethinylestradiol 150/30 µg for 84 days and ethinylestradiol 10 µg for 7 days (Seasonique(®)) has recently been approved for the prevention of pregnancy in adult women in the EU. This regimen allows for a reduction in the number of withdrawal bleeding episodes to four per year, compared with 13 episodes per year with conventional 28-day regimens. Seasonique(®) was effective in preventing pregnancy in a large (n = 1006), noncomparative trial of healthy, sexually active women. In this trial, the overall Pearl index (pregnancies per 100 woman-years of use) in women aged 18-35 years (n = 621) was 0.76 and the Pearl index for method-failure (compliant use) was 0.26. Scheduled (withdrawal) bleeding and/or spotting remained fairly constant over time, with a mean of 2 days of bleeding and 1 day of spotting per each 91-day cycle. Unscheduled bleeding and unscheduled spotting was highest during the first few cycles of use and decreased thereafter. Seasonique(®) was generally well tolerated, with a tolerability profile in line with that expected for OCs. Seasonique(®) extends the contraceptive options currently available to women, particularly in those who desire fewer withdrawal bleeding episodes.

Oral contraceptives and the risk of gallbladder disease: a comparative safety study

PubMed Central

Etminan, Mahyar; Delaney, Joseph A.C.; Bressler, Brian; Brophy, James M.

2011-01-01

Background Recent concerns have been raised about the risk of gallbladder disease associated with the use of drospirenone, a fourth-generation progestin used in oral contraceptives. We conducted a study to determine the magnitude of this risk compared with other formulations of oral contraceptives. Methods We conducted a retrospective cohort study using the IMS LifeLink Health Plan Claims Database. We included women who were using an oral contraceptive containing ethinyl estradiol combined with a progestin during 1997–2009. To be eligible, women had to have been taking the oral contraceptive continuously for at least six months. We computed adjusted rate ratios (RRs) for gallbladder disease using a Cox proportional hazards model. In the primary analysis, gallbladder disease was defined as cholecystectomy; in a secondary analysis, it was defined as hospital admission secondary to gallbladder disease. Results We included 2 721 014 women in the cohort, 27 087 of whom underwent surgical or laparoscopic cholecystectomy during the follow-up period. Compared with levonorgestrel, an older second-generation progestin, a small, statistically significant increase in the risk of gallbladder disease was associated with desogestrel (adjusted RR 1.05, 95% confidence interval [CI] 1.01–1.09), drospirenone (adjusted RR 1.20, 95% CI 1.16–1.26) and norethindrone (adjusted RR 1.10, 95% CI 1.06–1.14). No statistically significant increase in risk was associated with the other formulations of oral contraceptive (ethynodiol diacetate, norgestrel and norgestimate). Interpretation In a large cohort of women using oral contraceptives, we found a small, statistically significant increase in the risk of gallbladder disease associated with desogestrel, drospirenone and norethindrone compared with levonorgestrel. However, the small effect sizes compounded with the possibility of residual biases in this observational study make it unlikely that these differences are clinically

Contraindications to progestin-only oral contraceptive pills among reproductive aged women

PubMed Central

White, Kari; Potter, Joseph E.; Hopkins, Kristine; Fernández, Leticia; Amastae, Jon; Grossman, Daniel

2012-01-01

Background Progestin-only oral contraceptive pills (POPs) have fewer contraindications to use compared to combined pills. However, the overall prevalence of contraindications to POPs among reproductive aged women has not been assessed. Study Design We collected information on contraindications to POPs in two studies: 1) the Self-Screening Study, a sample of 1,267 reproductive aged women in the general population in El Paso, Texas, and 2) the Prospective Study of Oral Contraceptive (OC) Users, a sample of current OC users who obtained their pills in El Paso clinics (n=532) or over the counter (OTC) in Mexican pharmacies (n=514). In the Self-Screening Study, we also compared women’s self-assessment of contraindications using a checklist to a clinician’s evaluation. Results Only 1.6% of women in the Self-Screening Study were identified as having at least one contraindication to POPs. The sensitivity of the checklist for identifying women with at least one contraindication was 75.0% (95% CI: 50.6–90.4%), and the specificity was 99.4% (95% CI: 98.8–99.7%). In total, 0.6% of women in the Prospective Study of OC Users reported having any contraindication to POPs. There were no significant differences between clinic and OTC users. Conclusion The prevalence of contraindications to POPs was very low in these samples. POPs may be the best choice for the first OTC oral contraceptive in the US. PMID:22364816

A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception.

PubMed

Shohel, Mohammad; Rahman, Mohammad Mahfuzur; Zaman, Asif; Uddin, Mir Muhammad Nasir; Al-Amin, Md Mamun; Reza, Hasan Mahmud

2014-04-04

Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12-24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either regimen, the earlier the treatment is given

A systematic review of effectiveness and safety of different regimens of levonorgestrel oral tablets for emergency contraception

PubMed Central

2014-01-01

Background Unintended pregnancy is a complex phenomenon which raise to take an emergency decision. Low contraceptive prevalence and high user failure rates are the leading causes of this unexpected situation. High user failure rates suggest the vital role of emergency contraception to prevent unplanned pregnancy. Levonorgestrel - a commonly used progestin for emergency contraception. However, little is known about its pharmacokinetics and optimal dose for use. Hence, there is a need to conduct a systematic review of the available evidences. Methods Randomized, double-blind trials were sought, evaluating healthy women with regular menstrual cycles, who requested emergency contraception within 72 h of unprotected coitus, to one of three regimens: 1.5 mg single dose levonorgestrel, two doses of 0.75 mg levonorgestrel given 12 h apart or two doses of 0.75 mg levonorgestrel given 24 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Results Every trial under consideration successfully established the contraceptive effectiveness of levonorgestrel for preventing unintended pregnancy. Moreover, a single dose of levonorgestrel 1.5 mg for emergency contraception supports its safety and efficacy profile. If two doses of levonorgestrel 0.75 mg are intended for administration, the second dose can positively be taken 12–24 h after the first dose without compromising its contraceptive efficacy. The main side effect was frequent menstrual irregularities. No serious adverse events were reported. Conclusions The review shows that, emergency contraceptive regimen of single-dose levonorgestrel is not inferior in efficacy to the two-dose regimen. All the regimens studied were very efficacious for emergency contraception and prevented a high proportion of pregnancies if taken within 72 h of unprotected coitus. Single levonorgestrel dose (1.5 mg) can substitute two 0.75 mg doses 12 or 24 h apart. With either

Quantification of the adverse effect of ethinylestradiol containing oral contraceptive pills when used in conjunction with growth hormone replacement in routine practice.

PubMed

Phelan, Niamh; Conway, Sophy H; Llahana, Sofia; Conway, Gerard S

2012-05-01

Oestrogen antagonizes the action of growth hormone (GH). For women with combined GH and oestrogen deficiency, transdermal oestradiol is more favourable in this regard compared to oral oestradiol. Oral contraceptive pills containing ethinylestradiol (EE) are commonly used in young women with GHD and there is little information on the impact of this form of oestrogen. A case note review of women with growth hormone deficiency (GHD) attending a tertiary endocrine clinic comparing the dose of GH and serum insulin-like growth factor 1 concentrations and the type of exogenous oestrogen. All women with GHD between the ages of 18 and 47 attending University College London Hospitals (UCLH) were included and grouped according to type of oestrogen replacement. Weight, GH dose and serum IGF-I concentrations were recorded at 121 visits in 88 women. The daily dose of GH was significantly higher and the GH responsivity was significantly lower in the EE group compared to those taking no oestrogen and transdermal oestrogen. The additional cost of GH for women using EE compared to transdermal oestradiol was £6016 per patient per year. Effectiveness of GH improved in all women changing from EE to another form of oestrogen. Use of oral contraceptive pills containing EE should be avoided in women receiving treatment with GH. Alternative options include oral or transdermal hormone replacement therapy (HRT) preparations for those that require oestrogen replacement or a progesterone-based regimen for contraceptive purposes. © 2012 Blackwell Publishing Ltd.

Dangerous triplet: Polycystic ovary syndrome, oral contraceptives and Kounis syndrome.

PubMed

Erol, Nurdan; Karaagac, Aysu Turkmen; Kounis, Nicholas G

2014-12-26

Polycystic ovary syndrome is characterized by ovulatory dysfunction, androgen excess and polycystic ovaries and is associated with hypertension, diabetes, metabolic syndrome and cardiovascular events. Oral contraceptives constitute first-line treatment, particularly when symptomatic hyperandrogenism is present. However, these drugs are associated with cardiovascular events and hypersensitivity reactions that pose problem in differential diagnosis and therapy. We present a 14 year-old female with polycystic ovary syndrome taking oral contraceptive and suffering from recurrent coronary ischemic attacks with increased eosinophils, and troponin levels suggesting Kounis syndrome.

[The efficiency of oral contraception containing drospirenone in treating symptoms of premenstrual syndrome or premenstrual dysphoric disorder in gyneacology practice].

PubMed

Svojanovská, K

2010-10-01

The efficiency of oral contraception containing drospirenone in treating symptoms of premenstrual dysphoric disorder (PMDD) was demonstrated in a number of studies. The objective of this observation was to use the "Premenstrual Symptoms Screening Tool" (PSST) to identify women who suffer from severe premenstrual syndrome (PMS) or PMDD and evaluate the benefits of their treatment through using the oral contraceptive containing drospirenone in regime 24/4 in gyneacology practice. The retrospective study was conducted from September 2008 to August 2009. Fifty-one women met by the PSST (Premenstrual Symptoms Screening Tool, Steiner et. al., 2003) the criteria of severe PMS/PMDD. Twenty-eight women took no contraception at the start of the evaluation and twenty-three already took oral contraceptives before changing to the oral contraceptive with drospirenone. The women completed the PSST and in the case of severe PMS/PMDD started treatment with the oral contraceptive containing 20 microg ethinylestradiol /EE/ + 3 mg drospirenone /drsp/ in regime 24/4. The next evaluation was conducted by the same PSST after 3 or 4 months of treatment with this oral contraceptive. The study involved 51 women between the ages of 15 and 44 years (average 25.7 years), who completed the PSST before and after 3 or 4 months of treatment with the oral contraceptive containing drospirenone. The summary score of all subjects significantly decreased from 24.6 before they started using the oral contraceptive with drospirenone to 7,2 after 3 or 4 months of treatment with this oral contraceptive. Significant declines in summary scores have been shown in both groups (in the group without oral contraception from 24.9 at the start of the observation to 8.2 after 3 or 4 months of using this oral contraceptive with drospirenone; and from 24.3 to 6.0 in the group with the change from using various oral contraceptives to using the contraceptive containing drospirenone). The application of PSST for detection

Laryngeal aerodynamics associated with oral contraceptive use: preliminary findings.

PubMed

Gorham-Rowan, Mary; Fowler, Linda

2009-01-01

The purpose of this study was to examine possible differences in laryngeal aerodynamic measures during connected speech associated with oral contraceptive (OC) use. Eight women taking an OC, and eight others not taking an OC, participated in the study. Three trials of syllable /p/repetitions were obtained using a circumferentially vented face mask and small translabial tube. All participants were recorded on or near days 7 and 14 of their menstrual cycle. Subglottal pressure (P(SG)) and average airflow rates were obtained to determine laryngeal airway resistance. Glottal airflow measures of peak flow, minimum flow, alternating flow, as well as relative sound level (RSL) were obtained. P(SG) was obtained from the pressure peak associated with/p/. All airflow parameters and RSL were obtained from the vowel portion. No significant differences were found related to day of recording or OC use, indicating that OC use does not significantly affect laryngeal airflow regulation. The reader will better understand the effects of hormones and oral contraceptives on the female voice, as well as the specific changes in vocal function that may occur in conjunction with the use of oral contraceptives.

Use of and access to oral and injectable contraceptives in Brazil.

PubMed

Farias, Mareni Rocha; Leite, Silvana Nair; Tavares, Noemia Urruth Leão; Oliveira, Maria Auxiliadora; Arrais, Paulo Sergio Dourado; Bertoldi, Andréa Dâmaso; Pizzol, Tatiane da Silva Dal; Luiza, Vera Lucia; Ramos, Luiz Roberto; Mengue, Sotero Serrate

2016-12-01

combined oral contraceptives were the most frequently reported (71.6%) and low-level levonorgestrel + ethinylestradiol combination accounted for 38.7% of them. The most frequently reported medicines are included in the Relação Nacional de Medicamentos Essenciais (RENAME - National List of Essential Medicines. Most women aged 15 to 49 who reported using contraceptives had access to the medicine and use monophasic combined oral contraceptives of appropriate efficiency and safety purchased by direct payment, mainly from retail pharmacies. Analisar a prevalência do uso atual de contraceptivos orais e injetáveis por mulheres brasileiras, segundo variáveis demográficas, socioeconômicas e aspectos relacionados ao acesso a esses medicamentos. Estudo transversal, analítico, baseado nos dados da Pesquisa Nacional sobre Acesso, Utilização e Promoção do Uso Racional de Medicamentos (PNAUM), de base populacional e amostra probabilística, realizada entre setembro/2013 e fevereiro/2014, em 20.404 domicílios urbanos brasileiros. A prevalência foi calculada a partir do relato das mulheres de 15 a 49 anos, não grávidas, sobre o uso de contraceptivos orais ou contraceptivos injetáveis. As variáveis independentes foram sexo, idade, escolaridade, nível socioeconômico, região geográfica e situação conjugal. Também foram analisados acesso, fontes de financiamento, fontes de obtenção e medicamentos citados. As análises estatísticas consideraram intervalos de confiança de 95% (IC95%) e teste Qui-quadrado de Pearson para avaliação da significância estatística das diferenças entre os grupos, considerando o nível de significância de 5%. A prevalência de uso de contraceptivos orais (CO) foi 28,2% e de contraceptivos injetáveis (CI), 4,5%. A prevalência de contraceptivos orais foi maior no Sul (37,5%) e menor no Norte (15,7%). Para contraceptivos injetáveis não houve diferença entre as regiões. O acesso foi maior para as usuárias de contraceptivos orais (90

Cardiovascular disease incidence among females in South Carolina by type of oral contraceptives, 2000-2013: a retrospective cohort study.

PubMed

Samson, Marsha E; Adams, Swann A; Merchant, Anwar T; Maxwell, Whitney D; Zhang, Jiajia; Bennett, Charles L; Hebert, James R

2016-11-01

Certain types of oral contraceptives can produce favorable effects on lipid metabolism and vascular tone, while others have potentially detrimental effects. Endogenous and exogenous hormones exert different effects on high-density lipoprotein (HDL) and low-density lipoprotein (LDL) depending on the type, combination, and dose of the hormone. The estrogenic and progestogenic effects of exogenous hormones on HDL and LDL are inconsistent. Studying surrogate end points (LDL, HDL levels) may provide a misleading picture of OCs. Medicaid data from 2000 to 2013 were used to assess the relationship between the type of OCs and CVD incidence. Multivariable logistic regression was used to model relationships between cardiovascular disease and OC use adjusting for potential confounders. Compared to combined oral contraceptives (COC), progestin-only oral contraceptives (POC) were associated with decreased heart disease and stroke incidence after adjusting for important covariates (OR 0.74; 95 % CI 0.57, 0.97 and OR 0.39; 95 % CI 0.16, 0.95, respectively). However, there was a positive association between POC + COC and both heart disease and stroke incidence (OR 2.28; 95 % CI 1.92, 2.70 and OR 2.12; 95 % CI 1.34, 3.35, respectively). In light of an association between POC use and decreased heart disease and stroke, women's CVD risk factors should be carefully considered when choosing which OC to use. Baseline CVD risk should be a part of the discussion between women and their primary care providers when making choices regarding OCs.

A comparison of the pharmacokinetic profile of an ascending-dose, extended-regimen combined oral contraceptive to those of other extended regimens.

PubMed

Darwish, Mona; Bond, Mary; Ricciotti, Nancy; Hsieh, Jennifer; Fiedler-Kelly, Jill; Grasela, Thaddeus

2014-11-01

Quartette (levonorgestrel [LNG]/ethinyl estradiol [EE] and EE) is an ascending-dose, extended-regimen combined oral contraceptive (COC) that consists of a constant dose of LNG 150 µg on days 1 to 84 with EE 20 µg on days 1 to 42, 25 µg on days 43 to 63, 30 µg on days 64 to 84, and 10 µg of EE monotherapy on days 85 to 91. A population pharmacokinetic (PK) model for EE was developed using nonlinear mixed-effects modeling to characterize the PK profile of EE administered in Quartette and other extended-regimen LNG/EE COCs. Model-predicted plasma concentration-time profiles demonstrated a stepwise increase in systemic exposure to EE during the first 84 days of the cycle following each EE dose change. Lower concentrations of EE were noted during the final 7-day period of EE 10 µg. Gradual increases in EE seen with Quartette may decrease the incidence of unscheduled bleeding frequently observed during early cycles of extended-regimen COCs. © The Author(s) 2014.

The link between oral contraceptive use and prevalence in autism spectrum disorder.

PubMed

Strifert, Kim

2014-12-01

Autism spectrum disorder (ASD) is a group of developmental disabilities that include full syndrome autism, Asperger's syndrome, and other pervasive developmental disorders. The identified prevalence of ASD has increased in a short time period across multiple studies causing some to conclude that it has reached epidemic proportions in the U.S. Many possible explanations for the rise in numbers of individuals diagnosed with ASD have been offered and yet, causes and contributing factors for ASD are inadequately understood. Current evidence suggests that both genetics and environment play a part in causing ASD. One possible risk factor for the increase in prevalence has been profoundly overlooked in the existing biomedical and epidemiologic literature. As the prevalence of ASD has risen in the last sixty years, so has the prevalence of the usage of the oral contraceptives and other modern hormonal delivery methods. In 1960 about one million American women were using oral contraceptives, today close to 11 million women in the U.S. use oral contraceptives. Eighty-two percent of sexually active women in the U.S. have used oral contraceptives at some point during their reproductive years. Thus, the growth in use of progesterone/estrogen-based contraceptives in the United State has reached near-ubiquitous levels among women in the child-bearing age range. The suppression of ovulation produced by estrogen-progesterone is an indisputable abnormality. It is logical to consider the outcome of the ovum that would have been normally released from the ovary during ovulation. To date there is no comprehensive research into the potential neurodevelopmental effects of oral contraceptive use on progeny. The issue has been only sparsely considered in the biomedical literature. This article hypothesizes that the compounds, estrogen and progesterone, used in oral contraceptives modify the condition of the oocyte and give rise to a potent risk factor that helps explain the recent increase

Higher risk of venous thrombosis associated with drospirenone-containing oral contraceptives: a population-based cohort study

PubMed Central

Gronich, Naomi; Lavi, Idit; Rennert, Gad

2011-01-01

Background: Combined oral contraceptives are a common method of contraception, but they carry a risk of venous and arterial thrombosis. We assessed whether use of drospirenone was associated with an increase in thrombotic risk relative to third-generation combined oral contraceptives. Methods: Using computerized records of the largest health care provider in Israel, we identified all women aged 12 to 50 years for whom combined oral contraceptives had been dispensed between Jan. 1, 2002, and Dec. 31, 2008. We followed the cohort until 2009. We used Poisson regression models to estimate the crude and adjusted rate ratios for risk factors for venous thrombotic events (specifically deep vein thrombosis and pulmonary embolism) and arterial thromboic events (specifically transient ischemic attack and cerebrovascular accident). We performed multivariable analyses to compare types of contraceptives, with adjustment for the various risk factors. Results: We identified a total of 1017 (0.24%) venous and arterial thrombotic events among 431 223 use episodes during 819 749 woman-years of follow-up (6.33 venous events and 6.10 arterial events per 10 000 woman-years). In a multivariable model, use of drospirenone carried an increased risk of venous thrombotic events, relative to both third-generation combined oral contraceptives (rate ratio [RR] 1.43, 95% confidence interval [CI] 1.15–1.78) and second-generation combined oral contraceptives (RR 1.65, 95% CI 1.02–2.65). There was no increase in the risk of arterial thrombosis with drospirenone. Interpretation: Use of drospirenone-containing oral contraceptives was associated with an increased risk of deep vein thrombosis and pulmonary embolism, but not transient ischemic attack or cerebrovascular attack, relative to second- and third-generation combined oral contraceptives. PMID:22065352

Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel.

PubMed

Kapitza, Christoph; Nosek, Leszek; Jensen, Lene; Hartvig, Helle; Jensen, Christine B; Flint, Anne

2015-05-01

The effect of semaglutide, a once-weekly human glucagon-like peptide-1 (GLP-1) analog in development for type 2 diabetes (T2D), on the bioavailability of a combined oral contraceptive was investigated. Postmenopausal women with T2D (n = 43) on diet/exercise ± metformin received ethinylestradiol (0.03 mg)/levonorgestrel (0.15 mg) once daily for 8 days before (semaglutide-free) and during (steady-state 1.0 mg) semaglutide treatment (subcutaneous once weekly; dose escalation: 0.25 mg 4 weeks; 0.5 mg 4 weeks; 1.0 mg 5 weeks). Bioequivalence of oral contraceptives was established if 90%CI for the ratio of pharmacokinetic parameters during semaglutide steady-state and semaglutide-free periods was within prespecified limits (0.80-1.25). The bioequivalence criterion was met for ethinylestradiol area under the curve (AUC0-24 h ) for semaglutide steady-state/semaglutide-free; 1.11 (1.06-1.15). AUC0-24 h was 20% higher for levonorgestrel at semaglutide steady-state vs. semaglutide-free (1.20 [1.15-1.26]). Cmax was within bioequivalence criterion for both contraceptives. Reductions (mean ± SD) in HbA1c (-1.1 ± 0.6%) and weight (-4.3 ± 3.1 kg) were observed. Semaglutide pharmacokinetics were compatible with once-weekly dosing; the semaglutide dose and dose-escalation regimen were well tolerated. Adverse events, mainly gastrointestinal, were mild to moderate in severity. Asymptomatic increases in mean amylase and lipase were observed. Three subjects had elevated alanine aminotransferase levels ≥3x the upper limit of normal during semaglutide/oral contraceptive coadministration, which were reported as adverse events, but resolved during follow-up. Semaglutide did not reduce the bioavailability of ethinylestradiol and levonorgestrel. © 2015 The Authors. The Journal of Clinical Pharmacology Published by Wiley Periodicals, Inc. on behalf of American College of Clinical Pharmacology.

Ethinyl estradiol and levonorgestrel pharmacokinetics with a low-dose transdermal contraceptive delivery system, AG200-15: a randomized controlled trial.

PubMed

Archer, David F; Stanczyk, Frank Z; Rubin, Arkady; Foegh, Marie

2012-06-01

This study evaluated the ethinyl estradiol (EE) and levonorgestrel (LNG) pharmacokinetic profiles of AG200-15, a transdermal contraceptive delivery system, compared with a combination oral contraceptive (COC) containing EE 35 mcg and norgestimate 250 mcg. A Phase 1, open-label, single-center study in 36 healthy women was conducted over three cycles with a randomized crossover design. After a run-in cycle of 21 days on and 7 days off with AG200-15, participants were randomized to receive one of two treatments: a 21/7-day cycle of AG200-15 either followed or preceded by one cycle of the COC. This trial is registered on ClinicalTrials.gov under the identifier NCT01243580. During the third week of AG200-15 use, mean (±standard deviation) maximum serum concentration (C(max)), area under the curve(0-168 h) and steady-state concentration (C(ss48-168 h)) for EE were 51.3 ± 17.3 pg/mL, 6.26 ± 2.46 ng h/mL and 35.7 ± 14.5 pg/mL, respectively; for LNG, the corresponding values were 2400 ± 1140 pg/mL, 317 ± 159 ng h/mL and 1847 ± 930 pg/mL, respectively. The AG200-15 EE C(max) was approximately 60% lower and the EE C(ss) was 15%-20% lower than those obtained with the COC. The calculated daily dose of AG200-15 was equivalent to a 30-mcg EE COC. The most common adverse events (AEs; >10%) in the AG200-15 group were headache, nausea and application-site irritation. All drug-related AEs were mild, and no serious AEs were reported. EE and LNG daily exposure during AG200-15 treatment was within the range reported for a low-dose COC. The daily EE dose with AG 200-15 was equivalent to a 30-mcg COC and was safe and well tolerated. Copyright © 2012 Elsevier Inc. All rights reserved.

New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control.

PubMed

Nelson, Anita

2010-08-09

To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills. This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation. The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation. The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled bleeding episodes (to meet women's desires for fewer and shorter menses) and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding). Hopefully, this unique formation will motivate women to be more successful contraceptors.

A continuous regimen of levonorgestrel/ethinyl estradiol for contraception and elimination of menstruation.

PubMed

Jensen, Jeffrey T

2008-03-01

Clinicians and patients desiring amenorrhea for therapeutic or social reasons will find continuous-use 90 microg levonorgestrel/20 microg ethinyl estradiol to be an attractive oral contraceptive dosing option. Although other formulations of oral contraceptives can be dosed in a continuous manner off-label, the convenience of a 28-day dose pack represents a major advance that will likely increase acceptability of the strategy. The availability of FDA-approved continuous-use 90 microg levonorgestrel/20 microg ethinyl estradiol will help mainstream continuous oral contraception in the same way that Preven and Plan B helped legitimize and mainstream emergency contraception. Patients wishing to use continuous 90 microg levonorgestrel/20 microg ethinyl estradiol must recognize and accept that unscheduled breakthrough bleeding is typical during the first four to six cycles of use. Control of cycle-related symptoms may emerge as an off-label indication for use.

Low Level of Knowledge of Contraceptive Methods among Pregnant Teens in Brazil.

PubMed

Brito, Milena Bastos; Alves, Fernanda Scoppetta Sampaio; Souza, Marlene Quadro; Requião, Samara Rezende

2018-06-01

To describe knowledge and use of contraceptive methods among pregnant teens in Brazil. A cross-sectional survey. A tertiary care center in Bahia, Brazil. Pregnant teens 10-19 years old. Participants were asked about contraceptive knowledge and previous contraceptive use. Contraceptive knowledge, previous contraceptive use, and contraceptive intentions for after pregnancy. Other survey topics included demographic characteristics, school attendance, and sexual history. A total of 90 participants wereincluded in the study, with an average age of 15.4 ± 1.7 years, and a mean age at first sexual intercourse of 13.8 ± 1.2 years. Most participants were unmarried (58/90), of mixed race (57/90), had a household income below minimum wage (59/83), lived with their parents (54/90), and unemployment (81/90). More than 80% were not using contraception or were using it irregularly whenthey became pregnant. Most participants reported knowledge of condoms (82/90), of the combined oral contraceptive pill (75/90) and of injectable contraceptives (68/90). However, less than half reported knowledge oflong-acting reversible contraceptive methods. In terms of contraceptive intentions after pregnancy, the most commonly cited methods were the contraceptive injection (36/90), the intrauterine device (17/90) and the combined pill (9/90). In this study we found a low level of knowledge of contraceptive methods, and especially of long-acting reversible contraceptive methods, among pregnant teens in Northeast Brazil. Low socioeconomic status and high rates of unplanned pregnancy might be reasons for insufficient sexual and reproductive health counseling in this population. Copyright © 2017 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

How does intimate partner violence affect condom and oral contraceptive Use in the United States?: A systematic review of the literature.

PubMed

Bergmann, Julie N; Stockman, Jamila K

2015-06-01

Intimate partner violence (IPV) is estimated to affect 25% of adult women in the United States alone. IPV directly impacts women's ability to use contraception, resulting in many of unintended pregnancies and STIs. This review examines the relationship between IPV and condom and oral contraceptive use within the United States at two levels: the female victim's perspective on barriers to condom and oral contraceptive use, in conjunction with experiencing IPV (Aim 1) and the male perpetrator's perspective regarding condom and oral contraceptive use (Aim 2). We systematically reviewed and synthesized all publications meeting the study criteria published since 1997. We aimed to categorize the results by emerging themes related to each study aim. We identified 42 studies that met our inclusion criteria. We found 37 studies that addressed Aim 1. Within this we identified three themes: violence resulting in reduced condom or oral contraceptive use (n=15); condom or oral contraceptive use negotiation (n=15); which we further categorized as IPV due to condom or oral contraceptive request, perceived violence (or fear) of IPV resulting in decreased condom or oral contraceptive use, and sexual relationship power imbalances decreasing the ability to use condoms or oral contraceptives; and reproductive coercion (n=7). We found 5 studies that addressed Aim 2. Most studies were cross-sectional, limiting the ability to determine causality between IPV and condom or oral contraceptive use; however, most studies did find a positive relationship between IPV and decreased condom or oral contraceptive use. Quantitative, qualitative, and mixed methods research has demonstrated the linkages between female IPV victimization/male IPV perpetration and condom or oral contraceptive use. However, additional qualitative and longitudinal research is needed to improve the understanding of dynamics in relationships with IPV and determine causality between IPV, intermediate variables (e

[Oral contraception, glucid metabolism and monitoring criteria].

PubMed

Gaspard, U

1988-02-01

Combined oral contraceptives (OCs) entail insulin resistence and decreased glucose tolerance proportional to their dose and type of progestin. Derivatives of 19-nortestosterone have more deleterious effects than do derivatives of 17-acetoxy progesterone. The effects are usually reversible and limited, and the diabetogenic role of currently available low-dose OCs is small. Metabolic and vascular risks must still be taken into account in prescribing OCs because hyperglycemia and hyperinsulinemia are significant vascular risk factors. Women with histories of OC use have increased risks of fatal and nonfatal myocardial infarct, cerebrovascular accidents, and peripheral vascular disease, but the increases are not always significant. Age and smoking are known to be primary risk factors whose effects are increased by OCs. Reduction of the estrogen dose of OCs may have resulted in a significant reduction of the venous thromboembolic risk, while reduction of the progestin dose may have resulted in a decreased incidence of venous accidents. The mechanisms of action by which OCs amplify existing vascular risks are largely unknown. Research with methods capable of quantifying insulin resistence suggests that a post-receptor intracellular effect is responsible for insulin resistence and diminished intracellular metabolism of glucose in users of OCs. Because OCs are ordinarily used by healthy young women over long periods of time with minimal medical supervision, it is desirable to identify cases in which cardiovascular and other undesirable secondary effects are likely. OCs are contraindicated for any woman with a history of cardiac accidents, venous or arterial vascular problems, or hypertension. Obesity is a relative contraindication because it may coexist with a problem of glucose metabolism and constitute a diabetic risk factor. Other diabetic risk factors that must be evaluated are age, family or personal history of gestational diabetics, and transitory problems of glucose

A new oral contraceptive regimen for endometriosis management: preliminary experience with 24/4-day drospirenone/ethinylestradiol 3 mg/20 mcg.

PubMed

Mabrouk, Mohamed; Solfrini, Serena; Frascà, Clarissa; Del Forno, Simona; Montanari, Giulia; Ferrini, Giulia; Paradisi, Roberto; Seracchioli, Renato

2012-06-01

We report our preliminary experience with the use of a low-dose oral contraceptive containing Drospirenone/Ethinylestradiol 3 mg/20 mcg, both in cyclic and continuous regimen for endometriosis management. A total of 93 women were retrospectively included: 52 were treated by medical therapy (exclusive combined oral contraceptives (COC)-users), while 41 were submitted to surgery followed by postoperative therapy (postoperative COC-users). A clinical examination was performed at baseline and at 6-months follow-up. Presence and intensity of endometriosis-related symptoms were assessed by a visual analogue scale. Presence and dimension of endometriotic lesions were evaluated by transvaginal ultrasonography. Adverse effects and tolerability were analysed. In exclusive COC-users, significant reductions in dysmenorrhoea and dyspareunia scores and in endometrioma mean diameter were observed at follow-up. In postoperative COC-users, anatomical and symptom recurrence rates at follow-up were 4.9% and 17%, respectively. The most frequent adverse effects were spotting and headache. No difference between cyclic and continuous regimen in terms of symptom relief, lesion progression and tolerability was observed. From our preliminary experience, Drospirenone/Ethinylestradiol 3 mg/20 mcg seems to be promising in endometriosis management.

Cycle control with an extended-regimen oral contraceptive combining levonorgestrel and ethinyl estradiol that includes continuous low-dose ethinyl estradiol instead of the traditional hormone-free interval.

PubMed

Nappi, Rossella E; Lobo Abascal, Paloma; Hsieh, Jennifer; Micheletti, Marie-Christine

2017-01-01

To evaluate scheduled and unscheduled bleeding and spotting over 1 year of treatment with 91-day extended-regimen combined oral contraception (COC) providing continuous low-dose ethinyl estradiol (EE) in place of the traditional 7-day hormone-free interval (HFI). This post hoc analysis of a multicenter, open-label, 1-year, Phase 3 study of extended-regimen COC with 30 µg EE/150 µg levonorgestrel (LNG) for 84 days and EE 10 µg for 7 days included 799 sexually active, adult women who completed at least one 91-day cycle of therapy. Subjects recorded bleeding and spotting episodes daily using electronic diaries. Logistic regression analyses are reported as ORs with 95% CIs. There was a 10% increase (OR =1.102; 95% CI: 1.006-1.206) in the likelihood of reporting no scheduled bleeding for each additional 91-day cycle completed. From the third 91-day cycle, more than one fifth of women reported no scheduled bleeding (third cycle =23% [121/533]; fourth cycle =22% [97/446]). Among women who reported no scheduled bleeding at Cycle 1 (136/758 [18%]), ≥45% showed sustained lack of scheduled bleeding in later cycles. There were increases of 53% (OR =1.531; 95% CI: 1.393-1.683) and 31% (OR =1.307; 95% CI: 1.205-1.418) in the likelihood of reporting 0 to ≤6 days vs >6 days of unscheduled bleeding and spotting, respectively, for each additional 91-day cycle. By Cycle 2, more than 80% of women reported no unscheduled bleeding or ≤6 days of unscheduled bleeding during each 91-day cycle. Improved cycle control with decreased bleeding over time was shown during extended-regimen COC with 30 µg EE/150 µg LNG for 84 days and continuous low-dose EE instead of the traditional 7-day HFI. Women considering this regimen should be informed that those who complete at least one 91-day COC cycle will likely experience less bleeding/spotting in future cycles.

Cycle control with an extended-regimen oral contraceptive combining levonorgestrel and ethinyl estradiol that includes continuous low-dose ethinyl estradiol instead of the traditional hormone-free interval

PubMed Central

Nappi, Rossella E; Lobo Abascal, Paloma; Hsieh, Jennifer; Micheletti, Marie-Christine

2017-01-01

Purpose To evaluate scheduled and unscheduled bleeding and spotting over 1 year of treatment with 91-day extended-regimen combined oral contraception (COC) providing continuous low-dose ethinyl estradiol (EE) in place of the traditional 7-day hormone-free interval (HFI). Patients and methods This post hoc analysis of a multicenter, open-label, 1-year, Phase 3 study of extended-regimen COC with 30 µg EE/150 µg levonorgestrel (LNG) for 84 days and EE 10 µg for 7 days included 799 sexually active, adult women who completed at least one 91-day cycle of therapy. Subjects recorded bleeding and spotting episodes daily using electronic diaries. Logistic regression analyses are reported as ORs with 95% CIs. Results There was a 10% increase (OR =1.102; 95% CI: 1.006–1.206) in the likelihood of reporting no scheduled bleeding for each additional 91-day cycle completed. From the third 91-day cycle, more than one fifth of women reported no scheduled bleeding (third cycle =23% [121/533]; fourth cycle =22% [97/446]). Among women who reported no scheduled bleeding at Cycle 1 (136/758 [18%]), ≥45% showed sustained lack of scheduled bleeding in later cycles. There were increases of 53% (OR =1.531; 95% CI: 1.393–1.683) and 31% (OR =1.307; 95% CI: 1.205–1.418) in the likelihood of reporting 0 to ≤6 days vs >6 days of unscheduled bleeding and spotting, respectively, for each additional 91-day cycle. By Cycle 2, more than 80% of women reported no unscheduled bleeding or ≤6 days of unscheduled bleeding during each 91-day cycle. Conclusion Improved cycle control with decreased bleeding over time was shown during extended-regimen COC with 30 µg EE/150 µg LNG for 84 days and continuous low-dose EE instead of the traditional 7-day HFI. Women considering this regimen should be informed that those who complete at least one 91-day COC cycle will likely experience less bleeding/spotting in future cycles. PMID:29042818

Study of low-density lipoprotein receptor regulation by oral (steroid) contraceptives: desogestrel, levonorgestrel and ethinyl estradiol in JEG-3 cell line and placental tissue.

PubMed

Ramakrishnan, Gopalakrishnan; Rana, Anita; Das, Chandana; Chandra, Nimai Chand

2007-10-01

The aim of this study was to compare in vitro the role of two oral contraceptives, desogestrel (a less androgenic derivative of levonorgestrel) and levonorgestrel--alone and in combination with ethinyl estradiol--on low-density lipoprotein (LDL) receptor regulation by assessing receptor protein expression and functional effectiveness. Placental tissue and cultured placental cells (JEG-3) were used to study the expression and endocytotic activity of LDL receptor protein. The expression of the receptor was assessed by immunocytochemistry and immunoblot assays with and without contraceptive challenge. Functioning activity of LDL receptor was studied by measuring the rate of uptake of LDL by placental cells. Quantification of LDL was based on the total cholesterol content of the lipoprotein. A combination of desogestrel (20 ng/mL of incubation medium) and ethinyl estradiol (10 ng/mL of incubation medium) maintained the LDL receptor at high level of expression and functioning mode. In contrast, the double-blind preparation of levonorgestrel (20 ng/mL) and ethinyl estradiol (10 ng/mL) had shown much lower expression as well as receptor-mediated LDL uptake. The concentration of contraceptives used in this study was similar to the prevailing concentration of oral contraceptives in clinical use. Higher expression of LDL receptor and enhanced rate of LDL uptake by the receptor protein projects the possibility that there might be less atherosclerosis-related disorders from the combination of desogestrol and ethinyl estradiol.

Evaluation of the Effect of Tofacitinib on the Pharmacokinetics of Oral Contraceptive Steroids in Healthy Female Volunteers

PubMed Central

Menon, Sujatha; Riese, Richard; Wang, Ronnie; Alvey, Christine W.; Shi, Haihong; Petit, Wendy

2016-01-01

Abstract Tofacitinib is an oral Janus kinase inhibitor. Tofacitinib metabolism is primarily mediated by cytochrome P450 3A4. This phase 1 randomized, open‐label, 2‐way crossover study (NCT01137708) evaluated the effect of tofacitinib 30 mg twice daily on the single‐dose pharmacokinetics of combination oral contraceptives ethinylestradiol (EE) and levonorgestrel (LN). EE and LN were administered as a single Microgynon 30® tablet (30 μg EE and 150 μg LN) to 19 healthy women. In the presence of tofacitinib, the area under the curve from time zero to infinity (AUC∞) increased by 6.6% and 0.9% for EE and LN, respectively. Maximal plasma concentrations decreased by 10.4% for EE and increased by 12.2% for LN when coadministered with tofacitinib. The 90% confidence intervals for the adjusted geometric mean ratios for AUC∞ fell within the 80%–125% region for both EE and LN. Mean half‐life was similar in the presence and absence of tofacitinib: 13.8 and 13.3 hours, respectively, for EE; 25.9 and 25.4 hours, respectively, for LN. Tofacitinib had no clinically relevant net inhibitory or inductive effect on the pharmacokinetics of EE and LN. Therefore, there is no evidence to suggest dose adjustments of oral contraceptive drugs containing EE or LN when coadministered with tofacitinib. PMID:27138968

Evaluation of the Effect of Tofacitinib on the Pharmacokinetics of Oral Contraceptive Steroids in Healthy Female Volunteers.

PubMed

Menon, Sujatha; Riese, Richard; Wang, Ronnie; Alvey, Christine W; Shi, Haihong; Petit, Wendy; Krishnaswami, Sriram

2016-09-01

Tofacitinib is an oral Janus kinase inhibitor. Tofacitinib metabolism is primarily mediated by cytochrome P450 3A4. This phase 1 randomized, open-label, 2-way crossover study (NCT01137708) evaluated the effect of tofacitinib 30 mg twice daily on the single-dose pharmacokinetics of combination oral contraceptives ethinylestradiol (EE) and levonorgestrel (LN). EE and LN were administered as a single Microgynon 30® tablet (30 μg EE and 150 μg LN) to 19 healthy women. In the presence of tofacitinib, the area under the curve from time zero to infinity (AUC∞ ) increased by 6.6% and 0.9% for EE and LN, respectively. Maximal plasma concentrations decreased by 10.4% for EE and increased by 12.2% for LN when coadministered with tofacitinib. The 90% confidence intervals for the adjusted geometric mean ratios for AUC∞ fell within the 80%-125% region for both EE and LN. Mean half-life was similar in the presence and absence of tofacitinib: 13.8 and 13.3 hours, respectively, for EE; 25.9 and 25.4 hours, respectively, for LN. Tofacitinib had no clinically relevant net inhibitory or inductive effect on the pharmacokinetics of EE and LN. Therefore, there is no evidence to suggest dose adjustments of oral contraceptive drugs containing EE or LN when coadministered with tofacitinib. © 2016, The American College of Clinical Pharmacology.

Are hormonal components of oral contraceptives associated with impaired female sexual function? A questionnaire-based online survey of medical students in Germany, Austria, and Switzerland.

PubMed

Wallwiener, Christian W; Wallwiener, Lisa-Maria; Seeger, Harald; Schönfisch, Birgitt; Mueck, Alfred O; Bitzer, Johannes; Zipfel, Stephan; Brucker, Sara Y; Taran, Florin-Andrei; Wallwiener, Markus

2015-10-01

To investigate in a large cohort of young university women whether different progestins and different ethinyl estradiol (EE) dosages in oral hormonal contraceptives (OHCs) adversely affect sexual function. Female medical students from German, Austrian, and Swiss universities (14/1/1) completed an anonymous online questionnaire comprising the 19 Female Sexual Function Index (FSFI) questions and 17 additional questions concerning demographics, lifestyle, sexual activity, and contraceptive use. OHCs were categorized by EE dose (≤20, <20 to ≤30, and >30 µg) and partially androgenic or antiandrogenic progestins. FSFI scores were analyzed by contraceptive method using descriptive statistics and standard nonparametric tests. We analyzed 2612 questionnaires submitted by respondents aged ≤30 years [mean age (SD) 23.5 (2.5) years]. Of 2126 contraceptive users, 1535 (72.2 %) used OHCs. Median FSFI total scores (ranges) were 28.2 (2.0-36.0) for all respondents. Median FSFI was significantly lower in non-users (24.4) versus users (28.7) of contraception (p < 0.001). Stratified analysis showed that 279/486 (57.4 %) respondents using no contraceptives, 563/1535 (36.7 %) using OHCs, 71/227 (31.3 %) using non-oral hormonal contraceptives, and 96/351 (27.4 %) using non-hormonal contraceptives were at risk for female sexual dysfunction (FSFI total score <26.55). FSFI scores for the three EE dosage categories and progestin components did not differ significantly. For OHCs, the FSFI score was lower than for other contraceptives but there was no significant association with EE dose or progestins, possibly due to small sample sizes. Further research needs to clarify the role of OHCs in female sexual function.

Pharmacokinetics and tolerability of voriconazole and a combination oral contraceptive co-administered in healthy female subjects

PubMed Central

Andrews, Emma; Damle, Bharat D; Fang, Annie; Foster, Grover; Crownover, Penelope; LaBadie, Robert; Glue, Paul

2008-01-01

AIM To assess the two-way pharmacokinetic interaction between voriconazole and Ortho-Novum® 1/35, an oral contraceptive containing norethindrone 1 mg and ethinyl oestradiol 35 μg. METHODS In this open-label, three-period, fixed-sequence study, 16 healthy females received voriconazole (400 mg q12 h, day 1; 200 mg q12 h, days 2–4) (period 1), oral contraceptive (q24 h, days 12–32) (period 2), and combination voriconazole (400 mg q12 h, day 57; 200 mg q12 h, days 58–60) and oral contraceptive (q24 h, days 40–60) (period 3). RESULTS Voriconazole geometric mean AUCτ and Cmax increased 46% (12 682–18 495 ng h ml−1; 90% confidence interval [CI] 32, 61) and 14% (2485–2840 ng ml−1; 90% CI 3, 27), respectively, when co-administered with oral contraceptive vs. voriconazole alone. Ethinyl oestradiol geometric mean AUCτ and Cmax increased 61% (1031–1657 ng h ml−1; 90% CI 50, 72) and 36% (119–161 ng ml−1; 90% CI 28, 45), respectively, and norethindrone geometric mean AUCτ and Cmax increased 53% (116–177 ng h ml−1; 90% CI 44, 64) and 15% (18–20 ng ml−1; 90% CI 3, 28), respectively, during voriconazole co-administration vs. oral contraceptive alone. Neither ethinyl oestradiol nor norethindrone levels were reduced in subjects following voriconazole co-administration. Adverse events (AEs) were generally mild, occurring less in subjects receiving voriconazole alone (36 events) vs. oral contraceptive alone (88 events) or combination treatment (68 events); four subjects experienced a severe AE. CONCLUSIONS Co-administration of voriconazole and oral contraceptive increased systemic exposures of all analytes relative to respective monotherapy. Although generally safe and well tolerated, it is recommended that patients receiving co-administered voriconazole and oral contraceptive be monitored for development of AEs commonly associated with these medications. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT Voriconazole, a broad-spectrum antifungal drug, is a

Evaluation of lipid profile in adolescents during long-term use of combined oral hormonal contraceptives.

PubMed

Guazzelli, Christina Aparecida Falbo; Lindsey, Prescilla Chow; de Araújo, Fabio Fernando; Barbieri, Márcia; Petta, Carlos Alberto; Aldrighi, Jose Mendes

2005-02-01

The study evaluated the effects of the long-term use of a combined oral hormonal contraceptive containing 30 microg ethinyl estradiol and 75 microg gestodene in adolescents. Thirty-three volunteers, aged from 14 to 19 years, who used the oral contraceptive for three consecutive years, were studied. Evaluation of total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides was made before use and after 1, 2 and 3 years. During the 3-year study period, total cholesterol, HDL-C, LDL-C and triglyceride levels were significantly higher than previous measurements, but average values did not exceed the normal range. Compared to the first year, the second- and third-year cholesterol, HDL-C, LDL-C and triglyceride levels were not significantly different.

Therapeutically equivalent pharmacokinetic profile across three application sites for AG200-15, a novel low-estrogen dose contraceptive patch.

PubMed

Stanczyk, Frank Z; Archer, David F; Rubin, Arkady; Foegh, Marie

2013-06-01

AG200-15 Agile Patch (AP) is a novel 7-day contraceptive patch providing ethinyl estradiol (EE) exposure comparable to low-dose combination oral contraceptives. This study determined whether application of the AP to three different anatomical sites (lower abdomen, buttock and upper torso) influences the pharmacokinetic profile of EE and levonorgestrel (LNG). In this open-label, three-period, crossover study, 24 subjects were randomized to one of six treatment sequences; each included application of patch to abdomen, buttock and upper torso, with the AP worn on one site for 7 days. After a 7-day washout, a new patch was applied to the next anatomical site. Multiple blood samples were collected up to 240 h after patch application. For plasma EE levels, median time to maximum drug concentration (Tmax, 24-48 h) and mean maximum concentration (Cmax, 47.9-61.5 pg/mL) were similar among application sites. Compared with lower abdomen, EE exposure was higher (16%-30%) at buttock and upper torso (15%-22%). For plasma LNG levels, median Tmax (72-120 h) and mean Cmax (1436-1589 pg/mL) were similar across application sites. Compared with lower abdomen, LNG exposure was higher at buttock (1%-7%) and upper torso (16%-17%). No serious adverse events (AEs) or AE-related discontinuations occurred. The most common treatment-emergent AEs were nausea, application site pruritus and headache, with frequencies comparable across anatomical sites. Absorption from the abdomen was slightly lower versus other sites; however, exposure to EE and LNG for all sites was therapeutically equivalent. The AP was well tolerated at all three anatomical sites. Copyright © 2013 Elsevier Inc. All rights reserved.

Maintaining physiological testosterone levels by adding dehydroepiandrosterone to combined oral contraceptives: I. Endocrine effects.

PubMed

Coelingh Bennink, Herjan J T; Zimmerman, Yvette; Laan, Ellen; Termeer, Hanneke M M; Appels, Nicole; Albert, Adelin; Fauser, Bart C J M; Thijssen, Jos H H; van Lunsen, Rik H W

2017-11-01

To determine whether adding dehydroepiandrosterone to combined oral contraceptives (COCs) maintains physiological levels of free testosterone. A randomized, double-blind, placebo-controlled, two-way crossover study conducted in 81 healthy women (age range: 20-35 years; Body mass index (BMI) range: 18-35 kg/m 2 ) using oral contraceptives. Androgens, sex hormone-binding globulin (SHBG), estradiol (E2) and estrone (E1) were measured, and free testosterone and the free testosterone index were calculated. Subjects discontinued oral contraceptive use for at least one menstrual cycle before being randomized to receive five cycles of ethinyl estradiol (EE) combined with either levonorgestrel (EE/LNG group) or drospirenone (EE/DRSP group) together with either dehydroepiandrosterone (DHEA) (50 mg/day orally) or placebo. Subsequently, all subjects crossed over to the other treatment arm for an additional five cycles. Both COCs decreased the levels of all androgens measured. Significant decreases (p<.05) were found with EE/LNG and EE/DRSP for total testosterone (54.5% and 11.3%, respectively) and for free testosterone (66.8% and 75.6%, respectively). Adding DHEA to the COCs significantly increased all androgens compared to placebo. Moreover, including DHEA restored free testosterone levels to baseline values in both COC groups and total testosterone levels to baseline in the EE/LNG group and above baseline in the EE/DRSP group. SHBG concentrations were significantly higher with EE/DRSP compared to EE/LNG (p<.0001). The addition of DHEA did not affect the levels of SHBG. Taking COCs reduces total and free testosterone levels and increases SHBG concentrations. By coadministration with DHEA, physiological levels of total and free testosterone are restored while using EE/LNG. With EE/DRSP, only the free testosterone level is normalized by DHEA coadministration. A daily oral dose of 50-mg DHEA maintains physiological free and total testosterone levels in women who are using an EE

New low-dose, extended-cycle pills with levonorgestrel and ethinyl estradiol: an evolutionary step in birth control

PubMed Central

Nelson, Anita

2010-01-01

Aim: To review milestones in development of oral contraceptive pills since their introduction in the US 50 years ago in order to better understand how a new formulation with low-dose estrogen in an extended-cycle pattern fits into the evolution of birth control pills. Methods: This is a review of trends in the development of various birth controls pills and includes data from phase III clinical trials for this new formulation. Results: The first birth control pill was a very high-dose monophasic formulation with the prodrug estrogen mestranol and a first-generation progestin. Over the decades, the doses of hormones have been markedly reduced, and a new estrogen and several different progestins were developed and used in different dosing patterns. The final element to undergo change was the 7-day pill-free interval. Many of these same changes have been made in the development of extended-cycle pill formulation. Conclusion: The newest extended-cycle oral contraceptive formulation with 84 active pills, each containing 20 μg ethinyl estradiol and 100 μg levonorgestrel, represents an important evolution in birth control that incorporates lower doses of estrogen (to reduce side effects and possibly reduce risk of thrombosis), fewer scheduled bleeding episodes (to meet women’s desires for fewer and shorter menses) and the use of low-dose estrogen in place of placebo pills (to reduce the number of days of unscheduled spotting and bleeding). Hopefully, this unique formation will motivate women to be more successful contraceptors. PMID:21072303

The lowest-dose, extended-cycle combined oral contraceptive pill with continuous ethinyl estradiol in the United States: a review of the literature on ethinyl estradiol 20 μg/levonorgestrel 100 μg + ethinyl estradiol 10 μg.

PubMed

Krishnan, Sheila; Kiley, Jessica

2010-08-10

Extended-cycle oral contraceptives (OCs) are increasing in popularity in the United States. A new extended-cycle OC that contains the lowest doses of ethinyl estradiol (EE) and levonorgestrel (LNG) + continuous EE throughout the cycle is now available. It provides 84 days of a low-dose, combined active pill containing levonorgestrel 100 μg and ethinyl estradiol 20 μg. Instead of 7 days of placebo following the active pills, the regimen delivers 7 days of ethinyl estradiol 10 μg. Existing studies reveal a similar efficacy and adverse effect profile compared with other extended-regimen OCs. Specifically, the unscheduled bleeding profile is similar to other extended-cycle OCs and improves with the increase in the duration of use. Although lower daily doses of hormonal exposure have potential benefit, to our knowledge, there are no published studies indicating that this specific regimen offers a lower incidence of hormone-related side effects or adverse events. In summary, this new extended-cycle OC provides patients a low-dose, extended-regimen OC option without sacrificing efficacy or tolerability.

Utility of low-dose oral aspirin challenges for diagnosis of aspirin-exacerbated respiratory disease.

PubMed

Jerschow, Elina; Ren, Zhen; Hudes, Golda; Sanak, Marek; Morales, Esperanza; Schuster, Victor; Spivack, Simon D; Rosenstreich, David

2016-04-01

Aspirin-exacerbated respiratory disease (AERD) is diagnosed through graded aspirin challenges that induce hypersensitivity reactions and eicosanoid level changes. It is not known whether diagnostically useful changes also occur after low-dose aspirin challenges that do not induce hypersensitivity reactions. To investigate the utility of low-dose oral aspirin challenges for diagnosing AERD by measuring different clinical parameters and eicosanoid changes. Sixteen patients with AERD and 13 patients with aspirin-tolerant asthma underwent oral challenges with low-dose (20 or 40 mg) aspirin and diagnostic oral graded aspirin challenges (up to 325 mg of aspirin). Forced expiratory volume in 1 second, nasal peak flow, the fraction of exhaled nitric oxide (FeNO), and eicosanoid levels in plasma and urine were analyzed. In patients with AERD but not in those with aspirin-tolerant asthma, 40-mg aspirin challenges induced a significant mean (SEM) decrease from baseline in FeNO (19% [5.1%]; P = .001) without causing any hypersensitivity reaction. The FeNO decrease also occurred after higher-dose aspirin challenges (27.8% [4.9%]; P < .001). The sensitivity and specificity of 40-mg aspirin-induced FeNO changes for identifying AERD were 90% and 100% with an area under the curve of 0.98 (95% CI, 0.92-1.00). The low-dose challenge also induced a significant leukotriene E4 urine increase in patients with AERD (from 6.32 [0.08] to 6.91 [0.15] log-pg/mg creatinine; P < .001), but the sensitivity and specificity of these changes were less than for the FeNO changes. The low-dose aspirin-induced decrease in FeNO in patients with AERD may be useful for the diagnosis of aspirin allergy without inducing a hypersensitivity reaction. clinicaltrials.gov Identifier: NCT01320072. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Minor oral surgery without stopping daily low-dose aspirin therapy: a study of 51 patients.

PubMed

Madan, Gautam A; Madan, Sonal G; Madan, Gauri; Madan, A D

2005-09-01

The risk of excessive bleeding prompts physicians to stop low-dose long-term aspirin regimens before surgery, which puts the patient at risk from adverse thrombotic events. We hypothesize that most minor oral surgical procedures can be carried out safely without stopping low-dose aspirin. All minor oral surgery patients at our hospital (Madan Dental Hospital, Ahmedabad, India) from May 2002 to May 2003, who were also on long-term low-dose aspirin therapy regimens (acetylsalicylic acid 75 mg to 100 mg/day), were included. Investigation of bleeding time and platelet count was performed. If within normal limits, aspirin was not stopped before surgery. Patients were operated under local anesthesia on an outpatient basis. All wounds were sutured and followed up at 24, 48, and 72 hours, 1 week, and 2 weeks after the procedure. The study included 51 patients (32 males, 19 females), ranging in age from 45 to 70 years. Preoperative values were within normal limits for all patients. Aspirin was not stopped for a single patient. There was no excessive intraoperative bleeding in all cases except 1; there was no postoperative bleeding in all cases. We conclude that most minor oral surgery procedures can be carried out safely without stopping long-term low-dose aspirin regimen.

Safety evaluation of long term oral treatment of methanol sub-fraction of the seeds of Carica papaya as a male contraceptive in albino rats.

PubMed

Goyal, S; Manivannan, B; Ansari, A S; Jain, S C; Lohiya, N K

2010-02-03

The manuscript is one of the series of attempts in authenticating scientific documentation of the seeds of Carica papaya being traditionally used for contraception. To establish safety of the methanol sub-fraction (MSF) of the seeds of Carica papaya as a male contraceptive following long term oral treatment. MSF was administered orally to albino rats at multiples of contraceptive dose (CD) at 50 (1x), 100 (2x), 250 (5x) and 500 (10x)mg/kg body weight daily for 52 weeks. Body weight, organs weight, morbidity, mortality, clinical chemistry, sperm analysis, histopathology and serum testosterone were evaluated to assess the safety and contraceptive efficacy. MSF treatment at various dose regimens, daily for 52 weeks did not show significant changes in body weight, organs weight, food and water intake and pre-terminal deaths compared to those of control animals. Sperm count and viability in 50mg/kg body weight treated animals and the weight of epididymis, seminal vesicle and prostate of all the treated animals showed significant reduction compared to control. Cauda epididymal spermatozoa of 50mg/kg body weight treated animals were immotile. Azoospermia was observed in 100, 250 and 500 mg/kg body weight treated animals. Serum clinical parameters, serum testosterone and histopathology of vital organs were comparable to those of control animals. Histology of testis revealed adverse effects on the process of spermatogenesis, while the histology of epididymis, seminal vesicles and ventral prostate showed no changes compared to control. The long term daily oral administration of MSF affects sperm parameters without adverse side effects and is clinically safe as a male contraceptive. Copyright 2009 Elsevier Ireland Ltd. All rights reserved.

New contraceptive eligibility checklists for provision of combined oral contraceptives and depot-medroxyprogesterone acetate in community-based programmes.

PubMed Central

Stang, A.; Schwingl, P.; Rivera, R.

2000-01-01

Community-based services (CBS) have long used checklists to determine eligibility for contraceptive method use, in particular for combined oral contraceptives (COCs) and the 3-month injectable contraceptive depot-medroxyprogesterone acetate (DMPA). As safety information changes, however, checklists can quickly become outdated. Inconsistent checklists and eligibility criteria often cause uneven access to contraceptives. In 1996, WHO produced updated eligibility criteria for the use of all contraceptive methods. Based on these criteria, new checklists for COCs and DMPA were developed. This article describes the new checklists and their development. Several rounds of expert review produced checklists that were correct, comprehensible and consistent with the eligibility requirements. Nevertheless, field-testing of the checklists revealed that approximately half (48%) of the respondents felt that one or more questions still needed greater comprehensibility. These findings indicated the need for a checklist guide. In March 2000, WHO convened a meeting of experts to review the medical eligibility criteria for contraceptive use. The article reflects also the resulting updated checklist. PMID:10994285

Metformin plus oral contraceptive may decrease plasma sCD40 ligand in women with PCOS patients.

PubMed

Kebapcilar, Levent; Kebapcilar, Ayse Gul; Bilgir, Oktay; Taner, Cuneyt Eftal; Bozkaya, Giray; Yildiz, Yasar; Sari, Ismail

2011-02-01

To evaluate sCD40L levels in women with polycystic ovary syndrome (PCOS) who use combination therapy with metformin and oral contraceptives. Total of 60 patients with PCOS was studied to evaluate and compare with a non-PCOS group consisting of 30 subjects. A low-dose oral contraceptive containing ethinyl oestradiol-cyproterone acetate (EE/CA) and metformin (M; 850 mg metformin twice a day) were given for three cycles. Plasma sCD40L was measured before and after the treatment of 3 months. At baseline, the sCD40L levels of the patients with PCOS was significantly higher than those of control subjects (3.1 ± 2.0 vs. 2.05 ± 1.0, respectively; p=0.002). An average of 3 months of EE/CA-M therapy induced a significant decrease of sCD40L levels in the PCOS group (3.1 ± 2.0 vs. 2.5 ± 1.0; p=0.026). After having treated patients with PCOS, the sCD40L level was not completely normalised when compared to the healthy controls (2.5 ± 1.0 vs. 2.05 ± 1.0; p=0.039). PCOS is associated with elevated levels of sCD40L. Adding metformin therapy to EE/CA may decrease sCD40L levels in women PCOS. However, after the treatment for PCOS subjects, the sCD40L was not completely normalised when compared patients to healthy controls.

An update on emergency contraception.

PubMed

Bosworth, Michele C; Olusola, Patti L; Low, Sarah B

2014-04-01

Emergency contraception decreases the risk of unintended pregnancy after unprotected sexual intercourse or after suspected failure of routine contraception (e.g., a condom breaking). Oral methods include combined contraceptive pills (i.e., Yuzpe method), single- or split-dose levonorgestrel, and ulipristal. The Yuzpe method and levonorgestrel are U.S. Food and Drug Administration-approved for use 72 hours postcoitus, whereas the newest method, ulipristal, is approved for up to 120 hours postcoitus. The copper intrauterine device may be used as emergency contraception up to seven days after unprotected intercourse. It is nonhormonal and has the added benefit of long-term contraception. Advanced provision of emergency contraception may be useful for all patients, and for persons using ulipristal because it is available only by prescription. Physicians should counsel patients on the use and effectiveness of emergency contraception, the methods available, and the benefits of routine and consistent contraception use.

Evaluating the practice of Iranian community pharmacists regarding oral contraceptive pills using simulated patients.

PubMed

Foroutan, Nazanin; Dabaghzadeh, Fatemeh

2016-01-01

As oral contraceptive pills are available over the counter in pharmacies, pharmacists are professionally responsible for checking and informing patients about every aspect of taking these drugs. Simulated patient method is a new and robust way to evaluate professional performance of pharmacists. The aim of the present study was to evaluate the pharmacy practice of Iranian pharmacists regarding over-the-counter use of oral contraceptive pills using simulated patient method. Simulated patients visited pharmacy with a prescription containing ciprofloxacin and asked for oral contraceptive pills. The pharmacist was expected to ask important questions for using these drugs and to inform the patient about them properly. Moreover, the Pharmacists should advise patients in regard to the possible interaction. Ninety four pharmacists participated in this study. In 24 (25.3%) visits, the liable pharmacist was not present at the time of purchase. Furthermore, In 13 (18.57 %) visits by the simulated patients, the liable pharmacists did not pay any attention to the simulated patients even when they asked for consultation. Twenty nine (41.43%) pharmacists did not ask any question during dispensing. Nausea was the most frequent described side effect by pharmacists (27 (38.57%)). Yet important adverse effects of oral contraceptive pills were not mentioned by the pharmacists except for few ones. Only twelve (17.14%) pharmacists mentioned the possible interaction. There was a significant relation between the pharmacists' gender and detection of possible interaction (p value= 0.048). The quality of the pharmacists' consultations regarding the over the counter use of oral contraceptive pills was not satisfactory and required improvement.

Early Impact Of The Affordable Care Act On Oral Contraceptive Cost Sharing, Discontinuation, And Nonadherence.

PubMed

Pace, Lydia E; Dusetzina, Stacie B; Keating, Nancy L

2016-09-01

The oral contraceptive pill is the contraceptive method most commonly used by US women, but inconsistent use of the pill is a contributor to high rates of unintended pregnancy. The relationship between consumer cost sharing and consistent use of the pill is not well understood, and the impact of the elimination of cost sharing for oral contraceptive pills in a mandate in the Affordable Care Act (ACA) is not yet known. We analyzed insurance claims for 635,075 women with employer-sponsored insurance who were initiating use of the pill, to examine rates of discontinuation and nonadherence, their relationship with cost sharing, and trends before and during the first year after implementation of the ACA mandate. We found that cost sharing for oral contraceptives decreased markedly following implementation, more significantly for generic than for brand-name versions. Higher copays were associated with greater discontinuation of and nonadherence to generic pills than was the case with zero copayments. Discontinuation of the use of generic or brand-name pills decreased slightly but significantly following ACA implementation, as did nonadherence to brand-name pills. Our findings suggest a modest early impact of the ACA on improving consistent use of oral contraceptives among women initiating their use. Project HOPE—The People-to-People Health Foundation, Inc.

Adverse mood symptoms with oral contraceptives.

PubMed

Poromaa, Inger Sundström; Segebladh, Birgitta

2012-04-01

In spite of combined oral contraceptives (COCs) having been available for more than 50 years, surprisingly little is known about the prevalence of truly COC-related adverse mood symptoms and about the underlying biological mechanisms of proposed changes in mood and affect. Precise estimates of COC-related adverse mood symptoms are not available due to the lack of placebo-controlled trials. In prospective trials the frequency of women who report deteriorated mood or deteriorated emotional well-being varies between 4 and 10%, but it can be assumed that the causal relation in these prevalence rates is overestimated. Adverse mood symptoms and somatic symptoms are most pronounced during the pill-free interval of the treatment cycles, but whether extended COC regimens would be more favorable in this respect is not known. COCs with anti-androgenic progestagens, such as drospirenone and desogestrel, appear more favorable in terms of mood symptoms than progestagens with a more androgenic profile. Available data suggest that lower doses of ethinylestradiol could be beneficial. © 2012 The Authors Acta Obstetricia et Gynecologica Scandinavica© 2012 Nordic Federation of Societies of Obstetrics and Gynecology.

[Place of persistence trouble during oral contraception and subsequent use of emergency contraception].

PubMed

Jamin, C; Lachowsky, M

2015-10-01

In order to improve the understanding of hormonal contraceptive failures, this study evaluates the persistence of oral contraception and the use of emergency contraception (EC) during persistence incidents. We made the hypothesis of the existence of a strong link between the risk of unplanned pregnancies and these two parameters. In this study, we also evaluated women's perception of EC in order to elucidate the reasons of EC insufficient use. One survey was carried out on Internet on a representative sample of women, aged 16-45. In this survey, 3775 French women were interviewed (source-population). We defined a target population of 2415 fertile women who had heterosexual intercourse during the last 12 months, and a population of 760 women at risk of unintended pregnancy who had unprotected sexual intercourse during the last 12 months(risk-population). A little more than 30% of the target population, meaning 20% of the source-population (n=745) stopped their contraceptive method temporarily for an average time of two months. Almost 60% of women had a risk of unwanted pregnancy during this period without contraception, which is 59% of the risk-population. Only 20% of women among the population at risk used EC. The main reasons given for EC insufficient use were the misperception of the risk of pregnancy, the lack of knowledge about EC and its way of use. For the first time, this survey shows that 13% of women (of the source population) decide to stop temporarily their contraceptive method for an average time of two months per year. Fifty-nine percent of unplanned pregnancy situations are due to this poor contraception persistence. Although there is a need to reduce the risk of women being at risk, it seems also highly desirable to overcome the consequences of this poor persistence. Giving information about EC and a systematic prescription during contraception consultations would lead to an increased use of EC. Copyright © 2014 Elsevier Masson SAS. All rights

The effect of oral contraception on cardiometabolic risk factors in women with elevated androgen levels.

PubMed

Krysiak, Robert; Gilowska, Małgorzata; Okopień, Bogusław

2017-02-01

In unselected reproductive-aged women, use of combined estrogen-progestin oral contraceptive pills has been linked with an increased risk of vascular disease. The aim of this study was to investigate the effect of oral contraception on cardiometabolic risk factors in a population of women with hyperandrogenism. The study included 16 untreated women with elevated testosterone levels and 15 matched healthy women who were then treated with oral contraceptive pills containing ethinyl estradiol (30μg) and drospirenone (3mg). Plasma lipids, glucose homeostasis markers, circulating levels of androgens, uric acid, high-sensitivity C-reactive protein (hsCRP), fibrinogen and homocysteine, as well as urinary albumin-to-creatinine ratio (UACR) were assessed at baseline and after 12 weeks of treatment. Compared to healthy women, women with elevated androgen levels showed increased plasma levels of hsCRP, fibrinogen and homocysteine, as well as a higher value of UACR. Oral contraception reduced androgen levels only in hyperandrogenic women. In healthy women, ethinyl estradiol plus drospirenone increased plasma levels of insulin, hsCRP, fibrinogen and homocysteine, while in women with elevated androgen levels their effect was limited only to a small increase in hsCRP. Our results suggest that a deteriorating effect of oral contraceptive pills containing ethinyl estradiol and drospirenone in hyperandrogenic women is weaker than in healthy young women and that ethinyl estradiol/drospirenone combination therapy may be safely used in the former group of patients. Copyright © 2016. Published by Elsevier Urban & Partner Sp. z o.o.

Combined Oral Contraceptives and Sexual Function in Women-a Double-Blind, Randomized, Placebo-Controlled Trial.

PubMed

Zethraeus, Niklas; Dreber, Anna; Ranehill, Eva; Blomberg, Liselott; Labrie, Fernand; von Schoultz, Bo; Johannesson, Magnus; Hirschberg, Angelica Lindén

2016-11-01

There is a lack of knowledge about how oral contraceptives may affect sexual function. To determine whether there is a causal effect of oral contraceptives on sexuality. We hypothesized that a widely used pill impairs sexuality. A double-blind, randomized, placebo-controlled trial. Enrollment began in February 2012 and was completed in August 2015. Karolinska University Hospital, Stockholm, Sweden. A total of 340 healthy women, aged 18-35 years, were randomized to treatment, and 332 completed the study. A combined oral contraceptive (150 μg levonorgestrel and 30 μg ethinylestradiol) or placebo for 3 months of treatment. The primary outcome was the aggregate score on the Profile of Female Sexual Function (PFSF). Secondary outcomes were the seven domains of the PFSF, the Sexual Activity Log, and the Personal Distress Scale. Overall sexual function was similar in women in the oral contraceptive and placebo groups. The PFSF domains desire (-4.4; 95% confidence interval [CI], -8.49 to -0.38; P = .032), arousal (-5.1; 95% CI, -9.63 to -0.48; P = .030), and pleasure (-5.1; 95% CI, -9.97 to -0.32; P = .036) were significantly reduced in comparison to placebo, whereas orgasm, concern, responsiveness, and self-image were similar between groups. The mean frequency of satisfying sexual episodes and personal distress were also similar between groups. This study shows no negative impact of a levonorgestrel-containing oral contraceptive on overall sexual function, although three of seven sexual function domains were adversely affected.

The Effects of Hormonal Contraception on the Voice: History of Its Evolution in the Literature.

PubMed

Rodney, Jennifer P; Sataloff, Robert Thayer

2016-11-01

Women of reproductive age commonly use hormonal contraceptives, the vocal effects of which have been studied. Otolaryngologists should be aware of this relationship to make recommendations on hormonal contraception as it relates to each patient's voice requirements. A comprehensive literature review of PubMed was completed. The terms "contraception," "vocal folds," "vocal cords," and "voice" were searched in various combinations. Articles from 1971 to 2015 that addressed the effects of contraception on the vocal folds were included. In total, 24 articles were available for review. Historically, contraception was believed to affect the voice negatively. However, more recent studies using low-dose oral contraceptive pills (OCPs) show that they stabilize the voice. However, stabilization generally occurs only during sustained vowel production; connected speech appears unaffected. Therefore, singers may be the only population that experiences clinically increased vocal stability as a result of taking hormonal contraceptives. Only combined OCPs have been studied; other forms of hormonal contraception have not been evaluated for effects on the voice. Significant variability exists between studies in the physical attributes of patients and parameters tested. Hormonal contraception likely has no clinically perceptible effects on the speaking voice. Singers may experience increased vocal stability with low-dose, combined OCP use. Other available forms of contraception have not been studied. Greater consistency in methodology is needed in future research, and other forms of hormonal contraception require study. Copyright © 2016 The Voice Foundation. Published by Elsevier Inc. All rights reserved.

Effects of menstrual cycle phase and oral contraceptives on alertness, cognitive performance, and circadian rhythms during sleep deprivation

NASA Technical Reports Server (NTRS)

Wright, K. P. Jr; Badia, P.; Czeisler, C. A. (Principal Investigator)

1999-01-01

The influence of menstrual cycle phase and oral contraceptive use on neurobehavioral function and circadian rhythms were studied in healthy young women (n = 25) using a modified constant routine procedure during 24 h of sleep deprivation. Alertness and performance worsened across sleep deprivation and also varied with circadian phase. Entrained circadian rhythms of melatonin and body temperature were evident in women regardless of menstrual phase or oral contraceptive use. No significant difference in melatonin levels, duration, or phase was observed between women in the luteal and follicular phases, whereas oral contraceptives appeared to increase melatonin levels. Temperature levels were higher in the luteal phase and in oral contraceptive users compared to women in the follicular phase. Alertness on the maintenance of wakefulness test and some tests of cognitive performance were poorest for women in the follicular phase especially near the circadian trough of body temperature. These observations suggest that hormonal changes associated with the menstrual cycle and the use of oral contraceptives contribute to changes in nighttime waking neurobehavioral function and temperature level whereas these factors do not appear to affect circadian phase.

Are oral emergency contraceptives a safe and effective form of long-term birth control?

PubMed

Kraus, Connie; Hooper-Lane, Christopher

2017-10-01

Yes, but not as effective as some other methods. Annual pregnancy rates in women using pericoital levonorgestrel 150 mcg to 1 mg range from 4.9% to 8.9%; menstrual irregularity is the most common adverse effect (strength of recommendation [SOR]: B, Cochrane review of lower-quality trials). In women younger than 35 years who have sexual intercourse 6 or fewer times per month, correct and consistent use of pericoital levonorgestrel 1.5 mg results in an annual pregnancy rate of 11% (SOR: B, one large prospective, open-label trial). Pericoital contraception is less effective than long-acting reversible contraceptives (annual pregnancy rates of 0.05%-0.8%) or perfect use of combined oral contraceptives (0.3% annual pregnancy rate), but similar to, or better than, typical use of combined oral contraception (9%) and condoms (18%).

Ovarian activity and safety of a novel levonorgestrel/ethinyl estradiol continuous oral contraceptive regimen.

PubMed

Archer, David F; Kovalevsky, George; Ballagh, Susan A; Grubb, Gary S

2009-09-01

A continuous regimen of oral levonorgestrel (LNG) 90 mcg/ethinyl estradiol (EE) 20 mcg was evaluated for inhibition of ovulation, time to return to ovulation after stopping treatment and safety. This open-label study was conducted in healthy women aged 18-35 years. Ovulation was documented before treatment, and then participants received oral tablets containing LNG 90 mcg/EE 20 mcg to be taken continuously for three 28-day intervals. Ovarian activity was assessed three times per week during the treatment period with transvaginal ultrasound scans and measurements of serum 17beta-estradiol, progesterone, follicle-stimulating hormone and luteinizing hormone concentrations. Safety assessments included physical examinations, laboratory evaluations and adverse event records. Thirty-seven of the 58 subjects who received treatment met predefined criteria for efficacy analysis. No on-treatment ovulations occurred in the efficacy or intent-to-treat population. There was evidence of ovulation within 37 days of stopping treatment for 46 (98%) of 47 subjects evaluated posttreatment. The final subject with a history of polycystic ovarian syndrome ovulated by Day 66. The safety profile observed during this 84-day continuous regimen was similar to that seen with other low-dose oral contraceptives administered in a cyclic regimen. The continuous LNG/EE regimen completely inhibited ovulation, with little evidence of follicular development and with rapid return of ovulatory capacity after stopping treatment.

Noncontraceptive use of oral combined hormonal contraceptives in polycystic ovary syndrome-risks versus benefits.

PubMed

Dokras, Anuja

2016-12-01

The use of steroid sex hormones for noncontraceptive benefits has been endorsed by several medical societies. In women with polycystic ovary syndrome (PCOS), hormonal contraceptives are first-line therapy for concurrent treatment of menstrual irregularity, acne, and hirsutism. The association of PCOS with obesity, diabetes, and dyslipidemia frequently brings up the debate regarding risks versus benefits of hormonal contraceptives in this population. In women with PCOS, the lack of large-scale studies evaluating the risks with varying doses of ethinyl estradiol, types of progestins, and presence of confounding factors such as obesity, smoking, and other cardiometabolic comorbidities is a significant limitation in these deliberations. Although it is important to assess the absolute risk for major morbidities including cardiovascular events, currently, there are a paucity of long-term data for these outcomes in PCOS. Most of the current studies do not suggest an increase in risk of prediabetes/diabetes, clinically significant dyslipidemia, inflammatory changes, or depressive/anxiety symptoms with oral contraceptive pill use. Screening of women with PCOS for cardiometabolic and psychiatric comorbidities is routinely recommended. This information should be used by health care providers to individualize the choice of hormonal contraceptive treatment, adequately counsel patients regarding risks and benefits, and formulate an appropriate follow-up plan. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Contraception today.

PubMed

Benagiano, Giuseppe; Bastianelli, Carlo; Farris, Manuela

2006-12-01

Modern contraceptive methods represent more than a technical advance: they are the instrument of a true social revolution-the "first reproductive revolution" in the history of humanity, an achievement of the second part of the 20th century, when modern, effective methods became available. Today a great diversity of techniques have been made available and-thanks to them, fertility rates have decreased from 5.1 in 1950 to 3.7 in 1990. As a consequence, the growth of human population that had more than tripled, from 1.8 to more than 6 billion in just one century, is today being brought under control. At the turn of the millennium, all over the world, more than 600 million married women are using contraception, with nearly 500 million in developing countries. Among married women, contraceptive use rose in all but two developing countries surveyed more than once since 1990. Among unmarried, sexually active women, it grew in 21 of 25 countries recently surveyed. Hormonal contraception, the best known method, first made available as a daily pill, can today be administered through seven different routes: intramuscularly, intranasally, intrauterus, intravaginally, orally, subcutaneously, and transdermally. In the field of oral contraception, new strategies include further dose reduction, the synthesis of new active molecules, and new administration schedules. A new minipill (progestin-only preparation) containing desogestrel has been recently marketed in a number of countries and is capable of consistently inhibiting ovulation in most women. New contraceptive rings to be inserted in the vagina offer a novel approach by providing a sustained release of steroids and low failure rates. The transdermal route for delivering contraceptive steroids is now established via a contraceptive patch, a spray, or a gel. The intramuscular route has also seen new products with the marketing of improved monthly injectable preparations containing an estrogen and a progestin. After the first

Perspectives on variability in pharmacokinetics of an oral contraceptive product☆

PubMed Central

Jusko, William J.

2017-01-01

The early literature and reviews have described the pharmacokinetics (PK) of oral contraceptive (OC) compounds such as ethinyl estradiol (EE) and levonorgestrel (LNG) in women as subject to large intersubject variability. This was partly due to the use of diverse radioimmunoassays, limited sampling periods and an incomplete understanding of single- vs. multiple-dose kinetics and the role of EE in causing both inhibition of hepatic metabolism along with induction of sex hormone binding globulin. Over the past two decades, LNG and EE have been used as target drugs for the assessment of possible drug interactions upon introduction of many new therapeutic agents. This has resulted in at least 17 publications that describe the PK of LNG and EE in women using various 150 mcg/30 mcg products under fairly standard multiple-dose conditions. A review of these studies indicates only moderate variability in the Cmax and area under the curve both within and across these studies. There is impressive similarity in these drug exposure indices found in studies carried out with several products by investigators at numerous sites and countries. PMID:27475034

[Oral contraceptives: a new suspicion].

PubMed

Cohen, J

1979-05-05

It is possible that oral contraception (OC) may cause hepatic side effects, such as liver tumors, jaundice, and biliar lithiasis. Carcinogenic side effects of OC depend widely on age, education, marital status, and, apparently, even religion of users. Cervical cancer, endometrial cancer, and breast cancer are problems continuously investigated with different results. Contradictory studies have been conducted on the possibility of infections of the urinary tract in OC users, and on the possibility of congenital abnormalities in children of OC users. Statistics concerning OC must be carefully studied, and the balance between advantages and risks carefully weighted. Patients on OC must be regularly surveilled throughout the period of treatment.

Treatment of unscheduled bleeding in continuous oral contraceptive users with doxycycline: a randomized controlled trial.

PubMed

Kaneshiro, Bliss; Edelman, Alison; Carlson, Nichole; Morgan, Kristin; Nichols, Mark; Jensen, Jeffrey

2010-06-01

To estimate whether doxycycline, a matrix metalloproteinase inhibitor, would decrease unscheduled bleeding associated with initiation of a continuous oral contraceptive pill. Participants initiating a continuous oral contraceptive pill (20 micrograms of ethinyl estradiol/90 micrograms of levonorgestrel) were randomly assigned to receive either doxycycline (100 mg orally twice daily) or placebo taken for 5 days at the onset of each bleeding or spotting episode during the first 84 days of the study period. For the final 28 days of the study, participants were observed on the oral contraceptive pill alone. The primary outcome was the number of bleeding and spotting days. A sample size of 66 (33 in each arm) was calculated to detect a 50% reduction in bleeding (beta=0.80, alpha=0.05) and accounted for a 30% dropout rate. Sixty-six women were randomly assinged (33 in each study group). There were no significant differences during the 84-day treatment in bleeding or spotting days (doxycycline [mean {standard error}, placebo, P=.32) or the length of the longest bleeding or spotting episode (doxycycline, placebo, P=.70) between study groups. Similarly, no significant differences in bleeding patterns existed between groups during the final 28 days. Doxycycline, administered once bleeding has started, does not decrease unscheduled bleeding or shorten episodes of unscheduled bleeding in continuous oral contraceptive pill users. I.

A combined oral contraceptive affects mucosal SHIV susceptibility factors in a pigtail macaque model

PubMed Central

Ostergaard, Sharon Dietz; Butler, Katherine; Ritter, Jana M.; Johnson, Ryan; Sanders, Jeanine; Powell, Nathaniel; Lathrop, George; Zaki, Sherif R.; McNicholl, Janet M.; Kersh, Ellen N.

2015-01-01

Background Injectable hormonal contraception may increase women’s risk of HIV acquisition, and can affect biological risk factors in animal models of HIV. We established, for the first time, a model to investigate whether combined oral contraceptives (COC) alter SHIV susceptibility in macaques. Methods Seven pigtail macaques were administered a monophasic levonorgestrel (LNG)/ethinyl estradiol (EE) COC at 33% or 66% of the human dose for 60 days. Menstrual cycling, vaginal epithelial thickness and other SHIV susceptibility factors were monitored for a mean of 18 weeks. Results Mean vaginal epithelial thicknesses was 290.8 μm at baseline and 186.2 μm during COC (p=0.0141, Mann Whitney test). Vaginal pH decreased from 8.5 during to 6.5 post- treatment (0.0176 two-tailed t-test). Measured microflora was unchanged. Conclusions COC caused thinning of the vaginal epithelium and vaginal pH changes, which may increase SHIV susceptibility. 0.033 mg LNG + 0.0066 mg EE appeared effective in suppressing ovulation. PMID:25536296

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs.

PubMed

Larson, Jeanne C; Allstadt, Sara D; Fan, Timothy M; Khanna, Chand; Lunghofer, Paul J; Hansen, Ryan J; Gustafson, Daniel L; Legendre, Alfred M; Galyon, Gina D; LeBlanc, Amy K; Martin-Jimenez, Tomas

2016-01-01

To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. 5 healthy purpose-bred hounds. The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received rapamycin (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and noncompartmental analyses. Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in nanograms per milliliter. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, need to be determined.

Laryngeal Aerodynamics Associated with Oral Contraceptive Use: Preliminary Findings

ERIC Educational Resources Information Center

Gorham-Rowan, Mary; Fowler, Linda

2009-01-01

The purpose of this study was to examine possible differences in laryngeal aerodynamic measures during connected speech associated with oral contraceptive (OC) use. Eight women taking an OC, and eight others not taking an OC, participated in the study. Three trials of syllable /p[subscript alpha] /repetitions were obtained using a…

Antimullerian hormone and obesity: insights in oral contraceptive users

PubMed Central

Steiner, Anne Z.; Stanczyk, Frank Z.; Patel, Stan; Edelman, Alison

2009-01-01

Background The study was conducted to examine the impact of oral contraceptives (OCs) on serum antimullerian hormone (AMH) levels by obesity status in reproductive-age women. Study design Ovulatory women, ages 18–35 years, of normal (< 25 kg/m2; n = 10) and obese (> 30 kg/m2; n = 10) body mass index (BMI) received a low-dose OC (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for two cycles. Serum samples obtained at several time points during active pill use and hormone-free intervals were analyzed for AMH, FSH, LH, estradiol and inhibin B. Results AMH levels did not differ by OC cycle day in either BMI group. On average, AMH levels were 34% lower in the obese group (2.9±2.1 versus 4.4±1.8ng/ml, p<0.05). Modeling to determine differences in AMH throughout the cycle based on obesity status demonstrated significiantly lower levels (p<0.05), whereras serum AMH, FSH, LH, estradiol and inhibin B levels revealed no correlations when all time points were included. Conclusions In reproductive-aged women, serum AMH levels do not appear to fluctuate during OC use but AMH levels are significantly lower in obese women. Lower levels do not appear to be due to differences in gonadotropin levels or ovarian activity. PMID:20159182

High- and low-dose oral delayed-release mesalamine in children with mild-to-moderately active ulcerative colitis.

PubMed

Winter, Harland S; Krzeski, Piotr; Heyman, Melvin B; Ibarguen-Secchia, Eduardo; Iwanczak, Barbara; Kaczmarski, Maciej; Kierkus, Jaroslaw; Kolaček, Sanja; Osuntokun, Bankole; Quiros, J Antonio; Shah, Manoj; Yacyshyn, Bruce; Dunnmon, Preston M

2014-12-01

The aim of the study was to assess the safety and efficacy of high- and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of children with mild-to-moderately active ulcerative colitis. Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of ≥ 10 to ≤ 55 and a truncated Mayo Score of ≥ 1 for both rectal bleeding and stool frequency, were enrolled. They received body weight-dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27-71 mg · g(-1) · day(-1)) or high-dose group (53-118 mg · g(-1) · day(-1)). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score ≥ 10 with a decrease from baseline by ≥ 20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity. The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low- and high-dose groups, respectively (P = 0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups. Both low- and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose.

High- and Low-Dose Oral Delayed-Release Mesalamine in Children With Mild-to-Moderately Active Ulcerative Colitis

PubMed Central

Winter, Harland S.; Krzeski, Piotr; Heyman, Melvin B.; Ibarguen-Secchia, Eduardo; Iwanczak, Barbara; Kaczmarski, Maciej; Kierkus, Jaroslaw; Kolaček, Sanja; Osuntokun, Bankole; Quiros, J. Antonio; Shah, Manoj; Yacyshyn, Bruce; Dunnmon, Preston M.

2014-01-01

ABSTRACT Objective: The aim of the study was to assess the safety and efficacy of high- and low-dose oral, delayed-release mesalamine in a randomized, double-blind, active control study of children with mild-to-moderately active ulcerative colitis. Methods: Patients ages 5 to 17 years, with a Pediatric Ulcerative Colitis Activity Index (PUCAI) score of ≥10 to ≤55 and a truncated Mayo Score of ≥1 for both rectal bleeding and stool frequency, were enrolled. They received body weight–dependent doses of oral, delayed-release mesalamine for 6 weeks in a low- (27–71 mg · g−1 · day−1) or high-dose group (53–118 mg · g−1 · day−1). The primary endpoint was treatment success, defined as the proportion of patients who achieved remission (PUCAI score <10) or partial response (PUCAI score ≥10 with a decrease from baseline by ≥20 points). Secondary endpoints included truncated Mayo Score and global assessment of change of disease activity. Results: The modified intent-to-treat population included 81 of 83 patients enrolled. Treatment success by PUCAI was achieved by 23 of 41 (56%) and 22 of 40 (55%) patients in the mesalamine low- and high-dose groups, respectively (P = 0.924). Truncated Mayo Score (low-dose 30 [73%] and high-dose 28 [70%] patients) and other efficacy results did not differ between the groups. The type and severity of adverse events were consistent with those reported in previous studies of adults with ulcerative colitis and did not differ between groups. Conclusions: Both low- and high-dose oral, delayed-release mesalamine doses were equally effective as short-term treatment of mild-to-moderately active ulcerative colitis in children, without a specific benefit or risk to using either dose. PMID:25419597

Evaluation of a continuous regimen of levonorgestrel/ethinyl estradiol for contraception and control of menstrual symptoms.

PubMed

Jensen, Jeffrey T; Archer, David F

2008-02-01

Considerable recent interest has focused on new methods of delivery of oral contraceptives that reduce or eliminate the hormone-free interval in order to improve convenience and acceptability, but maintain contraceptive efficacy, minimize side effects and reduce or eliminate the frequency of withdrawal bleeding episodes. Studies in several countries, including the US, have documented that many women would prefer to have no episodes of withdrawal bleeding when using oral contraceptives. This review focuses on a unique oral contraceptive formulation containing levonogestrel 90 microg and ethinyl estradiol 20 microg, approved for use in a continuous dosing regimen designed to eliminate withdrawal bleeding throughout the entire year.

Added health benefits of the levonorgestrel contraceptive intrauterine system and other hormonal contraceptive delivery systems.

PubMed

Fraser, Ian S

2013-03-01

It has been recognized for well over half a century that hormonal preparations designed as contraceptives are also capable of offering health benefits through the treatment and prevention of benign gynecological disease and even some systemic conditions. Increasing attention is now being paid to the extent and detail of such added health benefits, and it is becoming clear that the long-acting, low-dose, hormonal contraceptive delivery systems may offer particular advantages in this regard. Conventional databases were thoroughly searched, especially for publications from 2006 to 2012, which addressed non-contraceptive-related indications for therapy and prevention. A considerable literature now exists to demonstrate the multiple and substantial noncontraceptive health benefits of long-acting progestogen-releasing systems, especially the levonorgestrel-releasing intrauterine system. These benefits mainly relate to disturbances of menstruation and related symptoms, such as heavy menstrual bleeding (due to many causes); iron deficiency; pelvic pain, especially around endometriosis; and endometrial hyperplasia. The long-acting estrogen-progestogen systems may carry similar added health benefits to those of the combined oral contraceptives, but data are still lacking. Added health benefits are now becoming an important part of the contraceptive choice equation, and the long-acting delivery systems are recognized as suitable primary therapies for a range of gynecological disorders. Copyright © 2013 Elsevier Inc. All rights reserved.

[Oral contraception and the vascular risk].

PubMed

Garnier, L F; Gruel, Y

1989-01-01

Vascular risk, mainly thromboembolitic risk, attributed to oral contraceptives (OCs) since 1962, has been primarily linked to ethinyl estradiol (EE). OCs which combine estrogen and have been associated with cerebral vascular accidents. A 1977 study showed a 40% increase of mortality due to cardiovascular complications in women taking OCs. There were of both an arterial and a venous character. The risk of myocardial infarction was 3 times more frequent among OC users. Deep venous thrombosis and pulmonary embolism were more numerous. Some other risk factors include smoking, hypertension, diabetes, and age 35. The risk of heart attack vanishes a few years after stopping OC use. The reduction of EE (and similarly progesterone) dosage from 100-50 mcg also lower the risk of hypertension, cerebral vascular accidents, and venous thrombosis. Prolonged use of OCs causes disorders of hemostasis affecting the walls of blood vessels, modifying the viscosity of blood flow (increase of hematocrits, reduction of venous tonus), modifying plasmatic coagulation (increase of platelets, increase of factors VII and X and plasma fibrinogen, and decrease of antithrombin III activity), and increased fibrinolysis. These anomalies are exclusively associated with high doses of estrogens. 5% of women using OCs develop moderate hypertension of 5-10 mm Hg of systolic pressure 5 years later, but after cessation it is reversed. OCs stimulate the renin-angiotensin-aldosterone system causing accelerated production of angiotensin II with the resultant forceful vasotension. 3 months after quitting OC use, high blood pressure returns to normal. EE can provoke diabetes; it increases very low density lipoprotein (VLDL) and high density lipoprotein (HDL) production, but total cholesterol is hardly affected. The androgenic property of progestogens reduces HDL. Combined OCs are contraindicated for women with hypertension, hyperlipidemia, diabetes, and a family history of vascular accidents.

[Emergency contraception with levonorgestrel].

PubMed

Saraví, Fernando D

2007-01-01

Emergency contraception may avoid pregnancy after unprotected intercourse or when regular contraceptive measures fail. Levonorgestrel, a synthetic gestagen, is recommended for emergency contraception as a single 1.5-mg dose or, alternatively, two 0.75-mg doses taken 12 h apart. Its efficacy is moderate, preventing about 80% of pregnancies. Efficacy is higher the earlier after unprotected intercourse the drug is taken, but it may be administered up to 5 days post-coitum. Tolerance is similar to, or better than, those of other oral emergency contraceptives. Adverse effects include nausea, vomiting, headache, breast tenderness and transient alteration of menstrual bleeding pattern. It is not known whether levonogestrel increases the risk of ectopic pregnancy when the treatment fails. Its use as an ongoing contraceptive method is discouraged. When given before the preovulatory LH peak, levonorgestrel blocks or delays ovulation. It may also affect sperm migration in the female reproductive tract and have an effect on fertilization. Although it has been often postulated, there is no evidence for an anti-implantatory effect. Acquaintance with the method is quite variable among different societies, but it remains underutilized even where it is well known. Advance provision of the drug has been proposed as a way to promote its use. In clinical trials, advance provision did not adversely modify sexual or regular contraceptive behavior, but it did not reduce pregnancy or abortion rate either. Therefore, emergency contraception with levonorgestrel should be regarded as a backup method which is not a substitute for the continued use of more effective contraceptive methods.

Evaluation of smartphone oral contraceptive reminder applications.

PubMed

Gal, Noga; Zite, Nikki B; Wallace, Lorraine S

2015-01-01

Oral contraceptives (OCs) are the most widely used contraceptive method among women of reproductive age in the United States (US). Routine download and use of health-related smartphone applications (apps) continues to increase. The purpose of this study was to evaluate the utility of English-language, smartphone-platform OC reminder apps currently available for download in the US. During June-July 2013, official Internet-based, mobile app platforms for the two major smartphone operating systems in the US-Android (Google Play Store) and iPhone (iTunes)-were searched. "Birth control," "the pill," and "contraception" were entered into the search-bar of each Smartphone store. Apps were assessed for the following: cost, health care professionals' involvement in app development, reminder mechanisms, and functionality. Of the 39 unique OC reminder apps meeting inclusion criteria, 7 (18%) did not operate as intended when downloaded. Most apps functioned without an Internet connection (97%) and included pop-up notifications (84%). Certain app features overcome common causes of missing an alarm, and hypothetically, may minimize likelihood of an OC user missing a daily pill. Health care providers should inform users of potential pitfalls and advise them that an OC reminder app should be not be used as a sole reminder method. Copyright © 2015 Elsevier Inc. All rights reserved.

International Active Surveillance Study of Women Taking Oral Contraceptives (INAS-OC Study).

PubMed

Dinger, Juergen C; Bardenheuer, Kristina; Assmann, Anita

2009-11-18

A 24-day regimen of contraceptive doses of drospirenone and ethinylestradiol (DRSP/EE 24d) was recently launched. This regimen has properties which may be beneficial for certain user populations (e.g., women suffering from premenstrual dysphoric disorder or acne). However, it is unknown whether this extended regimen has an impact on the cardiovascular risk associated with the use of oral contraceptives (OCs). The INternational Active Surveillance study of women taking Oral Contraceptives (INAS-OC) is designed to investigate the short- and long-term safety of the new regimen in a population which is representative for the typical user of oral contraceptives. A large, prospective, controlled, non-interventional, long-term cohort study with active surveillance of the study participants has been chosen to ensure reliable and valid results. More than 2,000 gynecologists in the US and 5 European countries (Austria, Germany, Italy, Poland, and Sweden) will recruit more than 80,000 OC users. The two to five year follow-up of these women will result in at least 220,000 documented women-years. The main clinical outcomes of interest for the follow-up are deep venous thrombosis, pulmonary embolism, acute myocardial infarction and cerebrovascular accidents. Secondary objectives are general safety, effectiveness and drug utilization pattern of DRSP/EE 24d, return to fertility after stop of OC use, as well as the baseline risk for users of individual OC formulations. Because of the non-interference character of this study, potential participants (first-time users or switchers) are informed about the study only after the decision regarding prescription of a new OC. There are no specific medical inclusion or exclusion criteria. Study participation is voluntary and a written informed consent is required. After the baseline questionnaire, follow-up questionnaires will be mailed to the participants every 6 months for up to 5 years after baseline. Self-reported serious adverse events

Injectable and oral contraceptive use and cancers of the breast, cervix, ovary, and endometrium in black South African women: case-control study.

PubMed

Urban, Margaret; Banks, Emily; Egger, Sam; Canfell, Karen; O'Connell, Dianne; Beral, Valerie; Sitas, Freddy

2012-01-01

Oral contraceptives are known to influence the risk of cancers of the female reproductive system. Evidence regarding the relationship between injectable contraceptives and these cancers is limited, especially in black South Africans, among whom injectable contraceptives are used more commonly than oral contraceptives. We analysed data from a South African hospital-based case-control study of black females aged 18-79 y, comparing self-reported contraceptive use in patients with breast (n = 1,664), cervical (n = 2,182), ovarian (n = 182), and endometrial (n = 182) cancer, with self-reported contraceptive use in 1,492 control patients diagnosed with cancers with no known relationship to hormonal contraceptive use. We adjusted for potential confounding factors, including age, calendar year of diagnosis, education, smoking, alcohol, parity/age at first birth, and number of sexual partners. Among controls, 26% had used injectable and 20% had used oral contraceptives. For current and more recent users versus never users of oral or injectable contraceptives, the odds ratios (ORs) for breast cancer were significantly increased in users of oral and/or injectable contraceptives (OR 1.66, 95% CI 1.28-2.16, p<0.001) and separately among those exclusively using oral (1.57, 1.03-2.40, p = 0.04) and exclusively using injectable (OR 1.83, 1.31-2.55, p<0.001) contraceptives; corresponding ORs for cervical cancer were 1.38 (1.08-1.77, p = 0.01), 1.01 (0.66-1.56, p = 0.96), and 1.58 (1.16-2.15, p = 0.004). There was no significant increase in breast or cervical cancer risk among women ceasing hormonal contraceptive use ≥10 y previously (p = 0.3 and p = 0.9, respectively). For durations of use ≥5 y versus never use, the ORs of ovarian cancer were 0.60 (0.36-0.99, p = 0.04) for oral and/or injectable contraceptive use and 0.07 (0.01-0.49, p = 0.008) for injectable use exclusively; corresponding ORs for endometrial cancer were 0.44 (0

Importance and knowledge of oral contraceptives in antepartum, low-income, African American adolescents.

PubMed

Gilliam, Melissa L; Knight, Sara; McCarthy, Martin

2003-12-01

To assess motivation, sense of self-efficacy and knowledge of oral contraceptives (OC) in antepartum, African-American Adolescents and young adults following OC counseling. Gravid African-American females, less than 25 years of age, receiving prenatal care at the Prentice Ambulatory Clinic at Northwestern Memorial Hospital were eligible for this study. Participants were enrolled after 34 weeks gestation, received one session of standardized OC counseling and then completed a series of questions regarding importance, confidence and knowledge of OCs. Forty-three adolescents and young adults participated in this study. Almost all participants agreed that it was important to plan their next pregnancy and to avoid unplanned pregnancies. On average, participants were extremely confident they could take a pill each day. Yet, while most were confident that they knew what to do if they missed one pill, only 37% actually knew what to do if they missed one pill. Despite high motivation and confidence in their ability to take OCs following pregnancy, many in this cohort did not fully understand the counseling that they had received. It is important for clinicians to bear in mind that patients may express motivation and confidence about using OCs, but still lack knowledge of the more complex and critical aspects of OC use. Additional education and support are needed in high-risk populations to ensure effective contraceptive knowledge.

Parental Gender Equality and Use of Oral Contraceptives Among Young Women: A Longitudinal, Population-based Study in Sweden.

PubMed

Rashid, Mamunur; Kader, Manzur

2014-07-01

Little is known about how parental gender equality early in their children lives can influence daughters' decision to use contraceptive pills. The study aimed at exploring whether maternal working time and paternity leave in Sweden during the first two years of their daughters' lives is associated with the use of oral contraceptives when they are adolescents or young adults. The study population was selected from a cohort of all Swedish fathers and mothers who had their first child together between 1988 and 1989 (n = 57,520 family units). Multivariate logistic regression was used to estimate the association. Mothers' longer working time was mildly associated with daughters' oral contraceptive pill use, though no clear trend was observed. Longer paternity leave periods (>30 days) were not associated with use of oral contraceptives among their daughters, but 1-30 day periods showed a mild positive association. For maternal working time, there seems to be an association, but trends by working hours are not clear. There is no clear association between paternity leave during the first two years of their daughters' life and the use of oral contraceptives when they are adolescents and young adults.

Oral Low-Dose Chemotherapy: Successful Treatment of an Alveolar Rhabdomyosarcoma during Pregnancy

PubMed Central

Siepermann, Meinolf; Koscielniak, Ewa; Dantonello, Tobias; Klee, Dirk; Boos, Joachim; Krefeld, Barbara; Borkhardt, Arndt; Hoehn, Thomas; Asea, Alexzander; Wessalowski, Rüdiger

2011-01-01

We report for the first time the impact of neoadjuvant oral low-dose chemotherapy consisting of oral trofosfamide, idarubicin, and etoposide (O-TIE) in the case of alveolar Rhabdomyosarcoma (RMS) in the lower jaw of an 18-year-old woman at 27-weeks of gestation, without fetal complications and a highly efficient anti-tumor response. Our study suggests the possible application of O-TIE treatment in a neoadjuvant setting during pregnancy and recommends a schedule that can be considered for the treatment of patients with high-risk sarcomas who cannot be treated with intensive chemotherapy for various reasons. PMID:22076833

Understanding the cognitive impact of the contraceptive estrogen Ethinyl Estradiol: tonic and cyclic administration impairs memory, and performance correlates with basal forebrain cholinergic system integrity.

PubMed

Mennenga, Sarah E; Gerson, Julia E; Koebele, Stephanie V; Kingston, Melissa L; Tsang, Candy W S; Engler-Chiurazzi, Elizabeth B; Baxter, Leslie C; Bimonte-Nelson, Heather A

2015-04-01

Ethinyl Estradiol (EE), a synthetic, orally bio-available estrogen, is the most commonly prescribed form of estrogen in oral contraceptives, and is found in at least 30 different contraceptive formulations currently prescribed to women as well as hormone therapies prescribed to menopausal women. Thus, EE is prescribed clinically to women at ages ranging from puberty to reproductive senescence. Here, in two separate studies, the cognitive effects of cyclic or tonic EE administration following ovariectomy (Ovx) were evaluated in young female rats. Study I assessed the cognitive effects of low and high doses of EE, delivered tonically via a subcutaneous osmotic pump. Study II evaluated the cognitive effects of low, medium, and high doses of EE administered via a daily subcutaneous injection, modeling the daily rise and fall of serum EE levels with oral regimens. Study II also investigated the impact of low, medium and high doses of EE on the basal forebrain cholinergic system. The low and medium doses utilized here correspond to the range of doses currently used in clinical formulations, and the high dose corresponds to doses prescribed to a generation of women between 1960 and 1970, when oral contraceptives first became available. We evaluate cognition using a battery of maze tasks tapping several domains of spatial learning and memory as well as basal forebrain cholinergic integrity using immunohistochemistry and unbiased stereology to estimate the number of choline acetyltransferase (ChAT)-producing cells in the medial septum and vertical/diagonal bands. At the highest dose, EE treatment impaired multiple domains of spatial memory relative to vehicle treatment, regardless of administration method. When given cyclically at the low and medium doses, EE did not impact working memory, but transiently impaired reference memory during the learning phase of testing. Of the doses and regimens tested here, only EE at the highest dose impaired several domains of memory

The Emotional Responses of Married Women Receiving Oral Contraceptives

PubMed Central

Ringrose, C. A. Douglas

1965-01-01

One hundred women taking oral contraceptives were questioned concerning their opinions about personal and sociological effects of this method of conception control. Fifty-three per cent reported improved coital satisfaction while 4% noted the opposite effect. Libido was increased in 22% and decreased in 13%. One woman in five believed that an increase in premarital and extramarital sexual activity would take place in the general population as a result of tablet-induced infertility. The problem of population control is discussed. It is paradoxical that the incidence of unplanned pregnancies continues to increase despite the availability of completely reliable conception control. This reflects present inability to communicate contraceptive knowledge to the appropriate people. PMID:14292887

Contraceptive use among low-income urban married women in India.

PubMed

Kumar, Manisha; Meena, Jyoti; Sharma, Sumedha; Poddar, Anju; Dhalliwal, Vikas; Modi-Satish Chander Modi, S C; Singh, Kamlesh

2011-02-01

The reports of a rise in contraceptive practices have not been matched by a similar decrease in population, so there is a need to look into the causes of this discrepancy. To obtain information from low-income urban married women regarding their contraceptive knowledge, practices, and utilization of the services. Percentage of low-income urban married women using contraception, different types of contraception used, influence of education on choice of contraception. All nonpregnant married women between the ages of 18 and 45 years, belonging to low-income groups were selected for study. Statistical analysis was done using EPI Info ver-5.0. Chi square test was used to test the significance of data. Contraceptive use among these women was 52%; the most common method was tubal ligation. Educated women used spacing methods more often than uneducated women. Women had adequate awareness regarding type of contraceptives available but had no idea about the timing of starting contraception after delivery and about emergency contraception. The low-income urban population is aware of the importance of limiting the family size and has family planning facilities yet has less contraceptive usage because of low level of education, increased rate of discontinuation, and lack of proper knowledge of the use of contraception. © 2010 International Society for Sexual Medicine.

Evaluation of a new, low-dose levonorgestrel intrauterine contraceptive system over 5 years of use.

PubMed

Gemzell-Danielsson, Kristina; Apter, Dan; Dermout, Sylvia; Faustmann, Thomas; Rosen, Kimberly; Schmelter, Thomas; Merz, Martin; Nelson, Anita

2017-03-01

To evaluate the efficacy and safety of a new, low-dose levonorgestrel intrauterine contraceptive system (LNG-IUS 12) for up to 5 years of use. In this Phase III study, 2885 nulliparous and parous women aged 18-35 years were randomized to LNG-IUS 8 or LNG-IUS 12 for 3 years. After 3 years, women using LNG-IUS 12 could continue for up to 2 additional years (5 years total). The primary outcome was occurrence of pregnancy (Pearl Index). Secondary outcomes included safety, bleeding, dysmenorrhea, discontinuations, and user satisfaction. From August 2007 through May 2008, out of 2885 women who were enrolled, 1453 were randomized to LNG-IUS 12. Placement was attempted in 1452/1453 (full analysis set). Mean age at baseline was 27.1 years; 39.5% were nulliparous. The cumulative 5-year Pearl Index (PI) was 0.29; the 5-year cumulative failure rate was 1.4%. The 5-year PI for ectopic pregnancy was 0.18. Over 5 years, 55.3% of women reported study drug-related treatment-emergent adverse events (TEAEs). Crude incidences of pelvic inflammatory disease, uterine perforation, and complete/partial LNG-IUS 12 expulsion were 0.6%, 0.2%, and 3.7%, respectively. Women using LNG-IUS 12 generally experienced less frequent bleeding over time. The incidence of amenorrhea during the last 90-day reference interval (end of Year 5) was 22.6%. Overall, 870 (59.9%) and 550 (37.9%) women completed 3 and 5 years of treatment, respectively; 77.8% of women who entered the extension phase completed 5 years of use. Over 5 years, 22.6% discontinued due to TEAEs, including 13 women who discontinued due to pregnancy; 76 discontinued due to bleeding problems including amenorrhea; and 163 discontinued due to desire for pregnancy, 71.2% of whom conceived within 12 months. In this study including parous and nulliparous women, LNG-IUS 12 was highly effective over 5 years of use and associated with a favorable safety profile. LNG-IUS 12 offers women a low-dose contraceptive option for up to 5 years. Copyright �

Injectable contraception. New and existing options.

PubMed

Kaunitz, A M

2000-12-01

DMPA and MPA/E2C contraception offer women safe, effective, convenient, and reversible birth control choices. The use of DMPA, a 3-month injectable, is characteristically associated with amenorrhea. Lactating women and women in whom contraceptive doses of estrogen are contraindicated can use this progestin-only birth control method. Return of fertility can be delayed in women discontinuing DMPA to become pregnant. In some cases, the use of DMPA also confers important noncontraceptive and therapeutic benefits. A monthly estrogen/progestin injectable contraceptive, MPA/E2C should appeal to women who are concerned about daily pill taking, who prefer regular cycles to amenorrhea, and who find monthly injections acceptable and accessible. As is true for oral contraceptives, MPA/E2C represents an appropriate choice for women who prefer a rapidly reversible contraceptive. Currently, the proposed contraindications for MPA/E2C parallel those for combined oral contraceptives. As MPA/E2C contraception becomes available for American women, clinicians will learn how to best include this new method among the array of contraceptive choices. By individualizing contraceptive selection, counseling, and management approaches based on the relevant behavioral and medical considerations reviewed herein, clinicians can maximize their patients' success with injectable contraceptives. The more innovative that clinicians, family planning agencies, and insurers are in facilitating access to care (including reinjections), the more women will be able to avail themselves of safe, effective, and reversible methods of contraception. In addition to the physician's office or health clinic, other sites at which women might receive contraceptive injections include employee health clinics, college health clinics, or perhaps the pharmacy where the prescription is filled. Self-administration may become an appropriate option for some users of injectable contraception.

An effective hormonal male contraceptive using testosterone undecanoate with oral or injectable norethisterone preparations.

PubMed

Kamischke, Axel; Heuermann, Tanja; Krüger, Kathrin; von Eckardstein, Sigrid; Schellschmidt, Ilka; Rübig, Alexander; Nieschlag, Eberhard

2002-02-01

Suppression of spermatogenesis to azoospermia is the goal of hormonal male contraception based on T combined with gestagens. The combination of the long-acting T, ester testosterone undecanoate (TU), with norethisterone (NET) enanthate (E) showed high efficacy. In the present study, we tested the validity of this approach by varying the NET dose and mode of application. The aim of the study was to achieve high rates of suppression of spermatogenesis as reflected by sperm counts, monitor gonadotropins as well as other hormones, and evaluate any possible side effects. In a phase II clinical trial, groups of normal volunteers received: 1000 mg TU im at wk 2, 6, 12, and 18 combined with 200 mg NETE im at wk 0, 6, 12, and 18 (group I); 1000 mg TU im and 400 mg NETE im at wk 0, 6, 12, and 18 (group II); and 1000 mg TU im at wk 0, 6, 12, and 18 with daily oral NET acetate (NETA) from wk 0 to 24 (group III). In all groups marked suppression of gonadotropins resulted in a significant decrease of spermatogenesis and azoospermia in 13/14, 11/12, and 12/14 men in groups I to III, respectively. The remaining men all had less than 1 million sperm/ml. Reversible side effects included increase in body weight, erythrocytes, hemoglobin, and hematocrit and decrease in high-density lipoprotein cholesterol and alkaline phosphatase in all groups and increase in liver enzymes in the oral NETA group. This study documents the high efficacy of TU in combination with NET and confirms that this dose and mode of application (1000 mg TU im every 6 wk plus 400 mg NETE im every 6 wk or plus 10 mg daily oral NETA) is as effective as the previously reported regimen containing 1000 mg TU + 200 mg NETE im every 6 wk. The contraceptive efficacy of this combination of TU and NETE should be evaluated in further clinical trials.

Perspectives on variability in pharmacokinetics of an oral contraceptive product.

PubMed

Jusko, William J

2017-01-01

The early literature and reviews have described the pharmacokinetics (PK) of oral contraceptive (OC) compounds such as ethinyl estradiol (EE) and levonorgestrel (LNG) in women as subject to large intersubject variability. This was partly due to the use of diverse radioimmunoassays, limited sampling periods and an incomplete understanding of single- vs. multiple-dose kinetics and the role of EE in causing both inhibition of hepatic metabolism along with induction of sex hormone binding globulin. Over the past two decades, LNG and EE have been used as target drugs for the assessment of possible drug interactions upon introduction of many new therapeutic agents. This has resulted in at least 17 publications that describe the PK of LNG and EE in women using various 150 mcg/30 mcg products under fairly standard multiple-dose conditions. A review of these studies indicates only moderate variability in the C max and area under the curve both within and across these studies. There is impressive similarity in these drug exposure indices found in studies carried out with several products by investigators at numerous sites and countries. Copyright © 2016 Elsevier Inc. All rights reserved.

Injectable and Oral Contraceptive Use and Cancers of the Breast, Cervix, Ovary, and Endometrium in Black South African Women: Case–Control Study

PubMed Central

Urban, Margaret; Banks, Emily; Egger, Sam; Canfell, Karen; O'Connell, Dianne; Beral, Valerie; Sitas, Freddy

2012-01-01

Background Oral contraceptives are known to influence the risk of cancers of the female reproductive system. Evidence regarding the relationship between injectable contraceptives and these cancers is limited, especially in black South Africans, among whom injectable contraceptives are used more commonly than oral contraceptives. Methods and Findings We analysed data from a South African hospital-based case–control study of black females aged 18–79 y, comparing self-reported contraceptive use in patients with breast (n = 1,664), cervical (n = 2,182), ovarian (n = 182), and endometrial (n = 182) cancer, with self-reported contraceptive use in 1,492 control patients diagnosed with cancers with no known relationship to hormonal contraceptive use. We adjusted for potential confounding factors, including age, calendar year of diagnosis, education, smoking, alcohol, parity/age at first birth, and number of sexual partners. Among controls, 26% had used injectable and 20% had used oral contraceptives. For current and more recent users versus never users of oral or injectable contraceptives, the odds ratios (ORs) for breast cancer were significantly increased in users of oral and/or injectable contraceptives (OR 1.66, 95% CI 1.28–2.16, p<0.001) and separately among those exclusively using oral (1.57, 1.03–2.40, p = 0.04) and exclusively using injectable (OR 1.83, 1.31–2.55, p<0.001) contraceptives; corresponding ORs for cervical cancer were 1.38 (1.08–1.77, p = 0.01), 1.01 (0.66–1.56, p = 0.96), and 1.58 (1.16–2.15, p = 0.004). There was no significant increase in breast or cervical cancer risk among women ceasing hormonal contraceptive use ≥10 y previously (p = 0.3 and p = 0.9, respectively). For durations of use ≥5 y versus never use, the ORs of ovarian cancer were 0.60 (0.36–0.99, p = 0.04) for oral and/or injectable contraceptive use and 0.07 (0.01–0.49, p = 0.008) for injectable use exclusively

Effect of eslicarbazepine acetate on the pharmacokinetics of a combined ethinylestradiol/levonorgestrel oral contraceptive in healthy women.

PubMed

Falcão, Amilcar; Vaz-da-Silva, Manuel; Gama, Helena; Nunes, Teresa; Almeida, Luís; Soares-da-Silva, Patrício

2013-08-01

To investigate the effect of once-daily (QD) eslicarbazepine acetate (ESL) 800 mg and 1,200 mg administration on pharmacokinetics of a combined ethinylestradiol/levonorgestrel oral contraceptive (OC) in women of childbearing potential. Two two-way, crossover, two-period, randomized, open-label studies were performed in 20 healthy female subjects, each. In one period (ESL+OC period), subjects received ESL 800 mg QD in one study and ESL 1200 mg QD in the other study, for 15 days; concomitantly with the Day 14 ESL dose, an oral single dose of 30 μg ethinylestradiol and 150 μg levonorgestrel was administered. In the other period (OC alone), a single dose of 30 μg ethinylestradiol and 150 μg levonorgestrel was administered. Three weeks or more separated the periods. An analysis of variance (ANOVA) was used to test for differences between pharmacokinetic parameters of 30 μg ethinylestradiol and 150 μg levonorgestrel following ESL+OC and OC alone, and 90% confidence intervals (90%CI) for the ESL+OC/OC alone geometric mean ratio (GMR) were calculated. ESL significantly decreased the systemic exposure to both ethinylestradiol and levonorgestrel. GMR (90%CI) for AUC0-24 of ethinylestradiol were 68% (64%; 71%) following 1,200 mg ESL and 75% (71%; 79%) following 800 mg ESL. GMR (90%CI) for AUC0-24 of levonorgestrel were 76% (68%; 86%) following 1,200 mg ESL and 89% (82%; 97%) following 800 mg ESL. A clinically relevant dose-dependent effect of ESL administration on the pharmacokinetics of ethinylestradiol and levonorgestrel was observed. Therefore, to avoid inadvertent pregnancy, women of childbearing potential should use other adequate methods of contraception during treatment with ESL, and, in case ESL treatment is discontinued, until CYP3A4 activity returns to normal. Copyright © 2013 Elsevier B.V. All rights reserved.

[Post-abortion contraception: effects of contraception services and reproductive intention].

PubMed

Borges, Ana Luiza Vilela

2016-02-01

Contraceptive counseling and the supply of contraceptive methods are part of post-abortion care and positively influence the subsequent use of contraceptive methods. Studies showing such evidence have been conducted predominantly in countries with no legal restrictions on abortion and with adequate care for women that terminate a pregnancy. However, little is known about contraceptive practices in contexts where abortion is illegal, as in Brazil, in which post-abortion contraceptive care is inadequate. The objective of this study was to analyze the effect of contraceptive care on male condom use and oral and injectable contraceptives in the six months post-abortion, considering reproductive intention. The results showed that contraceptive care only has a positive effect on the use of oral contraceptives in the first six months post-abortion, as long as the woman had a medical consultation in the same month in which she received information on contraception. One or the other intervention alone had no significant impact.

Parental Gender Equality and Use of Oral Contraceptives Among Young Women: A Longitudinal, Population-based Study in Sweden

PubMed Central

Rashid, Mamunur; Kader, Manzur

2014-01-01

Background: Little is known about how parental gender equality early in their children lives can influence daughters’ decision to use contraceptive pills. Aim: The study aimed at exploring whether maternal working time and paternity leave in Sweden during the first two years of their daughters’ lives is associated with the use of oral contraceptives when they are adolescents or young adults. Materials and Methods: The study population was selected from a cohort of all Swedish fathers and mothers who had their first child together between 1988 and 1989 (n = 57,520 family units). Multivariate logistic regression was used to estimate the association. Results: Mothers’ longer working time was mildly associated with daughters’ oral contraceptive pill use, though no clear trend was observed. Longer paternity leave periods (>30 days) were not associated with use of oral contraceptives among their daughters, but 1-30 day periods showed a mild positive association. Conclusion: For maternal working time, there seems to be an association, but trends by working hours are not clear. There is no clear association between paternity leave during the first two years of their daughters’ life and the use of oral contraceptives when they are adolescents and young adults. PMID:25077078

Oral low-dose chemotherapy: successful treatment of an alveolar rhabdomyosarcoma during pregnancy.

PubMed

Siepermann, Meinolf; Koscielniak, Ewa; Dantonello, Tobias; Klee, Dirk; Boos, Joachim; Krefeld, Barbara; Borkhardt, Arndt; Hoehn, Thomas; Asea, Alexzander; Wessalowski, Rüdiger

2012-01-01

We report for the first time the impact of neoadjuvant oral low-dose chemotherapy consisting of oral trofosfamide, idarubicin, and etoposide (O-TIE) in the case of alveolar rhabdomyosarcoma (RMS) in the lower jaw of an 18-year-old woman at 27 weeks of gestation, without fetal complications and a highly efficient anti-tumor response. Our study suggests the possible application of O-TIE treatment in a neoadjuvant setting during pregnancy and recommends a schedule that can be considered for the treatment of patients with high-risk sarcomas who cannot be treated with intensive chemotherapy for various reasons. Copyright © 2011 Wiley Periodicals, Inc.

Oral contraceptives in the immediate postpartum period.

PubMed

Hume, A L; Hijab, J C

1991-04-01

Although there is a critical need for effective contraception in the immediate postpartum period for women who are not breastfeeding, this need must be balanced against the inherent risks. The most effective form of contraceptive protection--oral contraceptives (OCs)--can present an increased risk of thromboembolism in the period after delivery. The thrombotic changes associated with pregnancy, and the statistics and vascular damage following a delivery, can combine to create greater potential for thromboembolism after delivery than during pregnancy. Reported here is the case of a 21-year-old woman who, 4 weeks postpartum, developed pain and swelling in the right lower calf and mottled discoloration extending from the proximal thigh to the toes. A diagnosis of deep venous thrombosis was made and heparin was administered. In the hospital, the patient experienced pleuritic chest pain and diaphoresis. A ventilation-perfusion scan indicated a pulmonary embolism. 1 week after delivery, the patient had initiated use of Triphasil. Although this woman had other risk factors (obesity, light cigarette smoking, and a sedentary life-style), OC use in the immediate postpartum period may have been the final factor precipitating the thromboembolic event. It is recommended that OC use should be delayed until at least 2 weeks postpartum in women without other risk factors for thromboembolism and until 4-6 weeks postpartum in those with such factors.

[Effect of short-acting combined oral contraceptives on bleeding after induced abortion].

PubMed

Wang, X F; Zhong, M; Liu, J

2017-11-07

Objective: To explore the effect of short-acting combined oral contraceptives on vaginal bleeding after induced abortion. Methods: A total of 726 patients, who had took induced abortion from July 2016 to September 2016 in obstetrics and gynecology outpatient department of Nanfang Hospital, Southern Medical University, were included and divided into the observation group and the control group according to whether they took short-acting combined oral contraceptives after induced abortion, with 312 cases, 414 cases respectively.The vaginal bleeding days, amounts of bleeding, the endometrial thickness 3 weeks later, and whether the patient had menstrual recovery on time were observed and analyzed. Results: The observation group had less bleeding days and amount of bleeding, compared with the control group.69.87% (218/312) patients of the observation group had more than 8mm of endometrial thickness on postoperative day 21, while 61.11% (253/414) of the observation group did, the difference was statistically significant ( P =0.034).90.06% (281/312) patients of the observation group had menstrual recovery on time, while 82.61% (342/414) of the observation group did, the difference was statistically significant ( P =0.004). Conclusion: Short-acting combined oral contraceptives after induced abortion can significantly shorten the vaginal bleeding days, reduce the amount of bleeding, promote endometrial repair and menstrual recovery.There fore, it has important clinical significance and application value.

21 CFR 310.501 - Patient package inserts for oral contraceptives.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Patient package inserts for oral contraceptives. 310.501 Section 310.501 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... the requirements of this section is misbranded under section 502 of the Federal Food, Drug, and...

21 CFR 310.501 - Patient package inserts for oral contraceptives.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Patient package inserts for oral contraceptives. 310.501 Section 310.501 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN... the requirements of this section is misbranded under section 502 of the Federal Food, Drug, and...

SODIUM BICARBONATE FACILITATES LOW-DOSE ORAL TOLERANCE TO PEANUT IN MICE

EPA Science Inventory

Rationale: Oral tolerance specifically inhibits production of allergic IgE antibody and is therefore a potential method for suppressing food allergy. We have previously demonstrated that a single oral dose of one mg is sufficient to induce oral tolerance to egg white but not pean...

Flutamide-metformin plus an oral contraceptive (OC) for young women with polycystic ovary syndrome: switch from third- to fourth-generation OC reduces body adiposity.

PubMed

Ibáñez, Lourdes; De Zegher, Francis

2004-08-01

Low-dose flutamide-metformin has been developed as a background therapy for non-obese adolescents and young women with hyperinsulinaemic hyperandrogenism, a variant of polycystic ovary syndrome (PCOS). We verified whether the lipolytic efficacy of flutamide-metformin in women with PCOS is enhanced by giving an oral contraceptive (OC) co-therapy that contains drospirenone, instead of gestodene, as progestin. An open-labelled study was carried out in which non-obese women with PCOS (n = 29; age approximately 20 years), who had been on a combination of flutamide (62.5 mg/day), metformin (850 mg/day) and ethinylestradiol-gestodene for 8-15 months, were randomized for replacement of the gestodene OC by a drospirenone OC. Assessments of endocrine-metabolic state and body composition (by dual-energy X-ray absorptiometry) were performed at randomization and after 6 months. The switch to drospirenone OC was accompanied by a reduction of total and abdominal fat (mean -0.8 and -0.5 kg) and by an increment of lean body mass (+0.6 kg; all P < 0.01), so that body adiposity was strikingly reduced without changing body weight. In non-obese women with PCOS, low-dose flutamide-metformin reduces total and abdominal fat excess more effectively if contraceptive co-therapy contains drospirenone, instead of gestodene, as progestin. Copyright 2004 European Society of Human Reproduction and Embryology

Access to data and the information explosion: oral contraceptives and risk of cancer.

PubMed

Weiner, J M; Shirley, S; Gilman, N J; Stowe, S M; Wolf, R M

1981-09-01

This report describes a technically feasible method to deal with the enormous volume of literature published regarding oral contraceptives. This subject was discussed in 3735 publications during the period from November 1977 through October 1980. Our findings showed that those papers reporting original, numeric relationships involving risk of cancer and use of oral contraceptives were one percent of the total 3735 publications. However, only seven of the 27 articles involved were authored by individuals from departments of obstetrics and gynecology. Further, only four of the 27 were published in journals devoted to obstetrics and gynecology. The analyses suggest a form of censorship taking place, in that the obstetrics/gynecology specialists do not have ready access to the primary data.

New approaches to male non-hormonal contraception.

PubMed

Nya-Ngatchou, Jean-Jacques; Amory, John K

2013-03-01

A non-hormonal male contraceptive is a contraceptive that does not involve the administration of hormones or hormone blockers. This review will focus on the use of lonidamine derivatives and inhibitors of retinoic acid biosynthesis and function as approaches to male non-hormonal contraception. Two current lonidamine derivatives, adjudin and H2-gamendazole, are in development as male contraceptives. These potent anti-spermatogenic compounds impair the integrity of the apical ectoplasmic specialization, resulting in premature spermiation and infertility. Another approach to male contraceptive development is the inhibition of retinoic acid in the testes, as retinoic acid signaling is necessary for spermatogenesis. The administration of the retinoic acid receptor antagonist BMS-189453 reversibly inhibits spermatogenesis in mice. Similarly, oral dosing of WIN 18,446, which inhibits testicular retinoic acid biosynthesis, effectively contracepts rabbits. Hopefully, one of these approaches to non-hormonal male contraception will prove to be safe and effective in future clinical trials. Copyright © 2013 Elsevier Inc. All rights reserved.

New approaches to male non-hormonal contraception

PubMed Central

Nya-Ngatchou, Jean-Jacques; Amory, John K.

2012-01-01

A non-hormonal male contraceptive is a contraceptive that does not involve the administration of hormones or hormone blockers. This review will focus on the use of lonidamine derivatives and inhibitors of retinoic acid biosynthesis and function as approaches to male non-hormonal contraception. Two current lonidamine derivatives, Adjudin and H2-gamendazole, are in development as male contraceptives. These potent anti-spermatogenic compounds impair the integrity of the apical ectoplasmic specialization, resulting in premature spermiation and infertility. Another approach to male contraceptive development is the inhibition of retinoic acid in the testes, as retinoic acid signaling is necessary for spermatogenesis. The administration of the retinoic acid receptor antagonist BMS-189453 reversibly inhibits spermatogenesis in mice. Similarly, oral dosing of WIN 18,446, which inhibits testicular retinoic acid biosynthesis, effectively contracepts rabbits. Hopefully, one of these approaches to non-hormonal male contraception will prove to be safe and effective in future clinical trials. PMID:22995542

Utilization of and Adherence to Oral Contraceptive Pills and Associated Disparities in the United States: A Baseline Assessment for the Impact of the Affordable Care Act of 2010.

PubMed

Lin, Hsien-Chang; Lee, Hsiao-Yun

2015-01-01

This study investigated sociological factors that may influence women's utilization of and adherence to oral contraceptive pills. This was a retrospective cross-sectional study using the 2010-2012 Medical Expenditure Panel Survey. Female adults aged 18-50 years were included. Logistic regression was performed to discern women's decisions to use oral contraceptive pills or not. Ordinary least squares and Poisson regressions were conducted to examine the number of oral contraceptive pills received, refill frequency, and annual out-of-pocket expenditure on oral contraceptive pills. Covariates were based on the Andersen model of health care utilization. Among the study sample (weighted n = 207,007,531), 14.8% were oral contraceptive pill users. Factors positively related to oral contraceptive pill use included non-Hispanic white ethnicity, younger age, not currently married, having private insurance, residing in the Midwest, higher education level, and higher annual family income. Being non-Hispanic white and having a higher education level were positively related to oral contraceptive pill adherence. Our findings therefore demonstrate disparities in oral contraceptive pill utilization and adherence, especially according to women's race/ethnicity and educational level. This study serves as a baseline assessment for the impact of the Affordable Care Act on oral contraceptive pill utilization and adherence for future studies. © The Author(s) 2015.

Compliance and use behaviour, an issue in injectable as well as oral contraceptive use? A study of injectable and oral contraceptive use in Johannesburg.

PubMed

Beksinska, M E; Rees, V H; Nkonyane, T; McIntyre, J A

1998-04-01

This study examines the compliance, use behaviour and knowledge of method of women using injectable and oral contraceptives in two clinic sites in the Johannesburg area, South Africa. An interviewer administered questionnaire was used to collect information in the clients' home language. A total of 400 women were interviewed in the clinics. The mean age of clients was 26.2 years (range 13 to 43 years). Of the clients not wanting to get pregnant, 30.4 per cent of injectable users and 18.4 per cent of oral contraceptive (OC) users had stopped using their method temporarily before returning to the same method (called the nonuse segment) and had not used any other form of contraception during this time. Almost one third of injectable users (31.2 per cent) had been late for their next injection at least once. Although nearly all women using injectables had experienced some menstrual disturbances, over one third (38.5 per cent) had not been informed by the providers about the possibility of these changes. Many women gave the disruption of their menstrual cycle as the reason for the nonuse segment. The majority of OC users lacked information on how to use their method correctly. Nearly all women expressed an interest in obtaining more information on their current method and other available methods. This study shows that compliance is an issue in injectable as well as OC users.

Oral contraceptive use is associated with prostate cancer: an ecological study

PubMed Central

Fleshner, Neil E

2011-01-01

Background Several recent studies have suggested that oestrogen exposure may increase the risk of prostate cancer (PCa). Objectives To examine associations between PCa incidence and mortality and population-based use of oral contraceptives (OCs). It was hypothesised that OC by-products may cause environmental contamination, leading to an increased low level oestrogen exposure and therefore higher PCa incidence and mortality. Methods The hypothesis was tested in an ecological study. Data from the International Agency for Research on Cancer were used to retrieve age-standardised rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report were used to retrieve data on contraceptive use. A Pearson correlation and multivariable linear regression were used to associate the percentage of women using OCs, intrauterine devices, condoms or vaginal barriers to the age standardised prostate cancer incidence and mortality. These analyses were performed by individual nations and by continents worldwide. Results OC use was significantly associated with prostate cancer incidence and mortality in the individual nations worldwide (r=0.61 and r=0.53, respectively; p<0.05 for all). PCa incidence was also associated with OC use in Europe (r=0.545, p<0.05) and by continent (r=0.522, p<0.05). All other forms of contraceptives (ie, intra-uterine devices, condoms or vaginal barriers) were not correlated with prostate cancer incidence or mortality. On multivariable analysis the correlation with OC was independent of a nation's wealth. Conclusion A significant association between OCs and PCa has been shown. It is hypothesised that the OC effect may be mediated through environmental oestrogen levels; this novel concept is worth further investigation. PMID:22102643

Oral contraceptive use is associated with prostate cancer: an ecological study.

PubMed

Margel, David; Fleshner, Neil E

2011-01-01

Background Several recent studies have suggested that oestrogen exposure may increase the risk of prostate cancer (PCa). Objectives To examine associations between PCa incidence and mortality and population-based use of oral contraceptives (OCs). It was hypothesised that OC by-products may cause environmental contamination, leading to an increased low level oestrogen exposure and therefore higher PCa incidence and mortality. Methods The hypothesis was tested in an ecological study. Data from the International Agency for Research on Cancer were used to retrieve age-standardised rates of prostate cancer in 2007, and data from the United Nations World Contraceptive Use 2007 report were used to retrieve data on contraceptive use. A Pearson correlation and multivariable linear regression were used to associate the percentage of women using OCs, intrauterine devices, condoms or vaginal barriers to the age standardised prostate cancer incidence and mortality. These analyses were performed by individual nations and by continents worldwide. Results OC use was significantly associated with prostate cancer incidence and mortality in the individual nations worldwide (r=0.61 and r=0.53, respectively; p<0.05 for all). PCa incidence was also associated with OC use in Europe (r=0.545, p<0.05) and by continent (r=0.522, p<0.05). All other forms of contraceptives (ie, intra-uterine devices, condoms or vaginal barriers) were not correlated with prostate cancer incidence or mortality. On multivariable analysis the correlation with OC was independent of a nation's wealth. Conclusion A significant association between OCs and PCa has been shown. It is hypothesised that the OC effect may be mediated through environmental oestrogen levels; this novel concept is worth further investigation.

Low-dose oral microemulsion ciclosporin for severe, refractory ulcerative colitis.

PubMed

de Saussure, P; Soravia, C; Morel, P; Hadengue, A

2005-08-01

The optimal modalities of treatment with oral microemulsion ciclosporin in patients with severe, steroid-refractory ulcerative colitis are uncertain. To assess the applicability, in terms of efficacy and tolerability, of a standard oral microemulsion ciclosporin treatment protocol targeting relatively low blood ciclosporin concentrations, in patients with severe, steroid-resistant ulcerative colitis. Patients with a severe attack of ulcerative colitis and no satisfactory response to intravenous corticosteroids were started on oral microemulsion ciclosporin. Dosages were adapted according to a standard protocol, targeting a blood predose ciclosporin concentration (C0) of 100-200 ng/mL. Patients without a clinical response on day 8 were scheduled for colectomy. Sixteen patients were enrolled. A clinical response was observed in 14/16 (88%). The mean clinical activity index scores and concentrations of C-reactive protein on days 0, 4 and 8 were 11.8, 6.7 and 4.1, and 50.3, 19.3 and 9.7 mg/L respectively. The mean C0 (days 0-8) was 149 pg/mL. The mean creatinine clearance rates on days 0 and 8 were 88 and 96 mL/min. One patient had an acute elevation of transaminases that resulted in discontinuing ciclosporin. Even when dosed for a target C0 of 100-200 ng/mL, oral microemulsion ciclosporin for severe, steroid-refractory ulcerative colitis achieves an efficacy similar to that attained with higher, potentially more toxic levels. The oral route should replace intravenous treatment in this clinical setting.

Update on emergency contraception.

PubMed

Fok, Wing Kay; Blumenthal, Paul D

2016-12-01

Emergency contraception provides a critical and time-sensitive opportunity for women to prevent undesired pregnancy after intercourse. Both access and available options for emergency contraception have changed over the last several years. Emergency contraceptive pills can be less effective in obese women. The maximum achieved serum concentration of levonorgestrel (LNG) is lower in obese women than women of normal BMI, and doubling the dose of LNG (3 mg) increases its concentration maximum, approximating the level in normal BMI women receiving one dose of LNG. Repeated use of both LNG and ulipristal acetate (UPA) is well tolerated. Hormonal contraception can be immediately started following LNG use, but should be delayed for 5 days after UPA use to avoid dampening the efficacy of UPA. The copper intrauterine device (IUD) is the only IUD approved for emergency contraception (and the most effective method of emergency contraception), but use of LNG IUD as emergency contraception is currently being investigated. Accurate knowledge about emergency contraception remains low both for patients and healthcare providers. Emergency contraception is an important yet underutilized tool available to women to prevent pregnancy. Current options including copper IUD and emergency contraceptive pills are safe and well tolerated. Significant gaps in knowledge of emergency contraception on both the provider and user level exist, as do barriers to expedient access of emergency contraception.

Contraceptive efficacy, compliance and beyond: factors related to satisfaction with once-weekly transdermal compared with oral contraception.

PubMed

Urdl, Wolfgang; Apter, Dan; Alperstein, Alan; Koll, Peter; Schönian, Siegfried; Bringer, Jacques; Fisher, Alan C; Preik, Michael

2005-08-01

To investigate contraceptive efficacy, compliance and user's satisfaction with transdermal versus oral contraception (OC). Randomized, open-label, parallel-group trial conducted at 65 centers in Europe and South Africa. One thousand four hundred and eighty-nine women received a contraceptive patch (n = 846) or an OC (n = 643) for 6 or 13 cycles. Overall/method-failure Pearl Indices were 0.88/0.66 with the patch and 0.56/0.28 with the OC (p = n.s.). Compliance was higher at all age groups with the patch compared to the OC. Significantly more users were very satisfied with the contraceptive patch than with the OC. The percentage of patch users being very satisfied increased with age whereas it did not in the OC group. Likewise, improvements of premenstrual symptoms as well as emotional and physical well-being increased with age in the patch-group in contrast to the OC group. Ratings of satisfaction with the study medication correlated weakly with emotional (r = 0.33) and physical well-being (r = 0.39) as well as premenstrual symptoms (r = 0.30; p < 0.001). Contraceptive efficacy of the patch is comparable to OC, but compliance is consistently better at all age groups. Higher satisfaction with the patch at increasing age may be attributed to improvements in emotional and physical well-being as well as reduction of premenstrual symptoms.

International Active Surveillance Study of Women Taking Oral Contraceptives (INAS-OC Study)

PubMed Central

2009-01-01

Background A 24-day regimen of contraceptive doses of drospirenone and ethinylestradiol (DRSP/EE 24d) was recently launched. This regimen has properties which may be beneficial for certain user populations (e.g., women suffering from premenstrual dysphoric disorder or acne). However, it is unknown whether this extended regimen has an impact on the cardiovascular risk associated with the use of oral contraceptives (OCs). The INternational Active Surveillance study of women taking Oral Contraceptives (INAS-OC) is designed to investigate the short- and long-term safety of the new regimen in a population which is representative for the typical user of oral contraceptives. Methods/Design A large, prospective, controlled, non-interventional, long-term cohort study with active surveillance of the study participants has been chosen to ensure reliable and valid results. More than 2,000 gynecologists in the US and 5 European countries (Austria, Germany, Italy, Poland, and Sweden) will recruit more than 80,000 OC users. The two to five year follow-up of these women will result in at least 220,000 documented women-years. The main clinical outcomes of interest for the follow-up are deep venous thrombosis, pulmonary embolism, acute myocardial infarction and cerebrovascular accidents. Secondary objectives are general safety, effectiveness and drug utilization pattern of DRSP/EE 24d, return to fertility after stop of OC use, as well as the baseline risk for users of individual OC formulations. Because of the non-interference character of this study, potential participants (first-time users or switchers) are informed about the study only after the decision regarding prescription of a new OC. There are no specific medical inclusion or exclusion criteria. Study participation is voluntary and a written informed consent is required. After the baseline questionnaire, follow-up questionnaires will be mailed to the participants every 6 months for up to 5 years after baseline. Self

Combined oral contraceptives and body weight: do oral contraceptives cause weight gain? A primate model.

PubMed

Edelman, A; Jensen, J T; Bulechowsky, M; Cameron, J

2011-02-01

The aim of this study was to determine if oral contraceptive (OC) use affects body weight, body composition and metabolism in primates. Reproductive-age female rhesus monkeys of normal and obese BMI were studied to document baseline weight stability, then treated continuously with an OC (dosed to achieve equivalent human serum levels for a 30 µg ethinyl estradiol/150 µg levonorgestrel preparation) for 237 days. Monkeys were monitored for changes in body weight, levels of physical activity (measured by a triaxial Actical accelerometer), food/caloric intake, percent body fat (dual energy X-ray absorptiometry, DEXA) and metabolism (24 h metabolic rate and serum metabolic substrate and hormone concentrations). All 10 monkeys completed the study protocol with no adverse events. While body weight (-0.73% change) and percent body fat (-1.78% change) of the normal BMI group did not significantly decrease from baseline, obese monkeys showed a significant decrease in body weight (-8.58% change, P < 0.01) and percent body fat (-12.13% change P = 0.02) with OC treatment. In both the obese (P = 0.03) and the normal BMI (P = 0.01) groups, there was a significant increase in basal metabolic rate with OC use. No changes were seen in food intake, activity level or % lean muscle mass with OC use for either BMI-based group. Overall, OC use appears to cause a slight increase in basal metabolic rate in female monkeys, leading to a decrease in body weight and percent body fat in obese individuals.

Regional lipiodolized chemotherapy for cholangiocarcinoma associated with oral contraceptives.

PubMed Central

McAleer, J. J.; Dickey, W.; Clarke, R.; Johnston, G. W.; Callender, M. E.

1987-01-01

We describe a case of cholangiocarcinoma in a young woman, who presented with cholestatic jaundice following oral contraceptive ingestion. Following diagnostic laparotomy she received intra-arterial 'lipiodolized' chemotherapy. Intravenous mitozantrone was given for 2 years and she is asymptomatic, with computed tomographic evidence of tumour response, 27 months after diagnosis. We suggest that this form of treatment is of value for cholangiocarcinoma. PMID:2821526

Oral contraceptive use may not preclude condom use: a study of non‐pregnant African‐American adolescent females

PubMed Central

Crosby, Richard A; DiClemente, Ralph J; Wingood, Gina M; Salazar, Laura F; Rose, Eve; Sales, Jessica M; Caliendo, Angela M

2007-01-01

Objective To determine the association between oral contraceptive and condom use, and laboratory‐confirmed sexually transmitted infection (STI) among African‐American adolescent females at a high risk of STI acquisition. Methods A cross‐sectional study of 715 African‐American adolescent females (15–21 years old) was conducted. Data collection included (a) an audio‐computer‐assisted self‐interview and a self‐collected vaginal swab for nucleic acid amplification testing of Trichomonas vaginalis, Chlamydia trachomatis and Neisseria gonorrhoeae. Results The age‐adjusted odds ratio (AOR) indicated a modest protective effect of oral contraceptive use against unprotected vaginal sex (UVS) using a 60‐day recall period (AOR = 0.66; 95% CI 0.43 to 0.99). The age‐adjusted difference in mean frequency of UVS in the past 60 days was non‐significant (p = 0.23) as was condom use at last sex (p = 0.34). The age‐AOR relative to STI prevalence also showed a protective effect (AOR = 0.60; 95% CI 0.36 to 0.98) for those using oral contraceptives. Conclusion The findings suggest that the use of oral contraceptives may not preclude safer sex practices for the prevention of STIs among high‐risk African‐American adolescent females. PMID:17569720

Current oral contraceptive use instructions: an analysis of patient package inserts.

PubMed

Williams-Deane, M; Potter, L S

1992-01-01

Oral contraceptive use instructions contained in manufacturers' patient package inserts (PPIs) are often inconsistent or conflicting, both among manufacturers and among different brands and regimens from the same manufacturer. Instructions on what to do about missed pills are often incomplete or inadequate, as are instructions on backup contraceptive use when pills are missed. The format of many PPIs is confusing and makes instructions difficult to find and read. Comprehending the PPIs requires the user to read at a 10th-12th-grade level, far higher than the generally accepted 5th-6th grade level considered standard for health education materials.

Cluster headache in women: relation with menstruation, use of oral contraceptives, pregnancy, and menopause

PubMed Central

van Vliet, J A; Favier, I; Helmerhorst, F M; Haan, J; Ferrari, M D

2006-01-01

In contrast with migraine, little is known about the relation between cluster headache and menstrual cycle, oral contraceptives, pregnancy, and menopause. A population based questionnaire study was performed among 224 female cluster headache patients, and the possible effect of hormonal influences on cluster headache attacks studied. For control data, a similar but adjusted questionnaire was sent to healthy volunteers and migraine patients. It was found that menstruation, use of oral contraceptives, pregnancy, and menopause had a much smaller influence on cluster headache attacks than in migraine. Cluster headache can, however, have a large impact on individual women, for example to refrain from having children. PMID:16407458

Reproductive Health Outcomes of Insured Women Who Access Oral Levonorgestrel Emergency Contraception

PubMed Central

Raine-Bennett, Tina; Merchant, Maqdooda; Sinclair, Fiona; Lee, Justine W.; Goler, Nancy

2015-01-01

Objectives To assess the level of risk for women who seek emergency contraception through various clinical routes and the opportunities for improved care provision. Methods This study looked at a retrospective cohort to assess contraception and other reproductive health outcomes among women aged 15-44 who accessed oral levonorgestrel emergency contraception through an office visit or the call center at Kaiser Permanente Northern California from 2010 to 2011. Results Of 21,421 prescriptions, 14,531(67.8%) were accessed through the call center. In the subsequent 12 months, 12,127(56.6%) women had short-acting contraception (pills, patches, rings, depot medroxyprogesterone) dispensed and 2,264(10.6%) initiated very effective contraception (intrauterine contraception, implants, sterilization). Initiation of very effective contraception was similar for women who accessed it through the call center -1,569(10.8%) and office visits – 695(10.1%) (adjusted OR 1.02 95% confidence interval (CI) 0.93-1.13). In the subsequent 6 months, 2,056(9.6%) women became pregnant. Women who accessed emergency contraception through the call center were less likely to become pregnant within 3 months of accessing emergency contraception than woman who accessed it through office visits (adjusted OR 0.82 95% CI 0.72-0.94); however they were more likely to become pregnant within 4-6 months (adjusted OR 1.37 95%CI 1.16-1.60). Among women who were tested for chlamydia and gonorrhea, 689(7.8%) and 928(7.9%) were positive in the 12 months before and after accessing emergency contraception, respectively. Conclusions Protocols to routinely address unmet need for contraception at every call for emergency contraception and all office visits including visits with primary care providers should be investigated. PMID:25751211

Effects of low-dose monophasic levonorgestrel with ethinyl estradiol preparation on serum lipid levels: A twenty-four month clinical trial.

PubMed

Young, R L; DelConte, A

1999-11-01

The aim of this 24-cycle study was to evaluate the effects on serum lipid concentrations of an oral contraceptive preparation containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. Forty-two healthy women were enrolled in a study designed to evaluate the effects on serum lipid concentrations of an oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol. Lipid data were evaluated for 28 women who completed 24 cycles of treatment with a preparation of 100 microg levonorgestrel with 20 microg ethinyl estradiol for 21 days followed by placebo for 7 days. Concentrations of triglycerides, total cholesterol, high-density lipoprotein cholesterol, high-density lipoprotein cholesterol subfractions 2 and 3, low-density lipoprotein cholesterol, and apolipoproteins A-I and B were analyzed. Mean percentage changes from baseline were tested for significance by means of paired Student t tests. Total cholesterol, high-density lipoprotein cholesterol, high-density lipoprotein subfraction 2, and apolipoprotein A-I concentrations were not significantly changed from baseline. Neither was the ratio of high-density lipoprotein subfraction 2 to high-density lipoprotein subfraction 3. Mean percentage increases in concentrations of triglyceride, high-density lipoprotein subfraction 3, apolipoprotein B, and low-density lipoprotein cholesterol and increases in the ratios of total cholesterol to high-density lipoprotein cholesterol, low-density lipoprotein cholesterol to high-density lipoprotein cholesterol, and apolipoprotein B to apolipoprotein A-I were significant (P <.05) at >/=1 cycle. By cycle 24, however, only the concentration of high-density lipoprotein subfraction 3 remained significantly elevated. Changes in the plasma lipid profiles among women receiving monophasic 100 microg levonorgestrel with 20 microg ethinyl estradiol were similar to those seen with other low-dose oral contraceptives, but by cycle 24 only 1 of 7 mean values

Crying, oral contraceptive use and the menstrual cycle.

PubMed

Romans, Sarah E; Clarkson, Rose F; Einstein, Gillian; Kreindler, David; Laredo, Sheila; Petrovic, Michele J; Stanley, James

2017-01-15

Crying, a complex neurobiological behavior with psychosocial and communication features, has been little studied in relationship to the menstrual cycle. In the Mood and Daily Life study (MiDL), a community sample of Canadian women aged 18-43 years, n=76, recorded crying proneness and crying frequency daily for six months along with menstrual cycle phase information. Crying proneness was most likely during the premenstruum, a little less likely during menses and least likely during the mid-cycle phase, with statistically significant differences although the magnitude of these differences were small. By contrast, actual crying did not differ between the three menstrual cycle phases. Oral contraceptive use did not alter the relationship between menstrual cycle phase and either crying variable. A wide range of menstrual cycle phase - crying proneness patterns were seen with visual inspection of the individual women's line graphs. timing of ovulation was not ascertained. Using a three phase menstrual cycle division precluded separate late follicular and early luteal data analysis. The sample size was inadequate for a robust statistical test of actual crying. reproductive aged women as a group report feeling more like crying premenstrually but may not actually cry more during this menstrual cycle phase. Individual patterns vary substantially. Oral contraceptive use did not affect these relationships. Suggestions for future research are included. Copyright © 2016 Elsevier B.V. All rights reserved.

An epigenetic basis for autism spectrum disorder risk and oral contraceptive use.

PubMed

Strifert, Kim

2015-12-01

In the United States 1 in 68 children are diagnosed with autism spectrum disorder (ASD). Although the etiology is unknown, many scientists believe ASD is caused by a combination of genetic and environmental factors and/or epigenetic factors. The widespread use of oral contraceptives is one environmental risk factor that has been greatly overlooked in the biomedical literature. Oral contraceptives, synthetic hormones created to imitate natural human hormones and disrupt endogenous endocrine function to inhibit pregnancy, may be causing the harmful neurodevelopmental effects that result in the increased prevalence of ASD. It is conceivable that the synthetic hormones repeatedly assault the oocyte causing persistent changes in expression of the estrogen receptor beta gene. Ethinylestradiol, a known endocrine disruptor, may trigger DNA methylation of the estrogen receptor beta gene causing decreased mRNA resulting in impaired brain estrogen signaling in progeny. In addition, it is possible the deleterious effects are transgenerational as the estrogen receptor gene and many of its targets may be imprinted and the methylation marks protected from global demethylation and preserved through fertilization and beyond to progeny generations. This article will delineate the hypothesis that ethinylestradiol activates DNA methylation of the estrogen receptor beta gene causing decreased mRNA resulting in diminished brain estrogen signaling in offspring of mothers exposed to oral contraceptives. Considering the detrimental epigenetic and transgenerational effects proposed, it calls for further study. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Treatment with liraglutide--a once-daily GLP-1 analog--does not reduce the bioavailability of ethinyl estradiol/levonorgestrel taken as an oral combination contraceptive drug.

PubMed

Jacobsen, Lisbeth V; Vouis, Jan; Hindsberger, Charlotte; Zdravkovic, Milan

2011-12-01

Liraglutide is a once-daily human GLP-1 analog for treatment of type 2 diabetes. Like other GLP-1 analogs, liraglutide delays gastric emptying, which could potentially affect absorption of concomitantly administered oral drugs. This study investigated the effect of liraglutide on the pharmacokinetics of the components of an oral contraceptive (ethinyl estradiol/levonorgestrel). Postmeno-pausal healthy women (n = 21) were included. A single dose of this contraceptive was administered. Blood samples for ethinyl estradiol/levonorgestrel measurements were drawn until 74 hours post dosing of the contraceptive during liraglutide and placebo treatments. The 90% confidence interval (CI) of the ratio of the area under the curve (AUC) (1.06; 90% CI, 0.99-1.13) for ethinyl estradiol (during liraglutide and placebo) was within defined limits, demonstrating equivalence. The 90% CI for the ratio of AUC for levonorgestrel was not fully contained within the limits (1.18; 90% CI, 1.04-1.34) (levonorgestrel AUC was 18% greater with liraglutide vs placebo). However, equivalence was demonstrated for levonorgestrel AUC(0-t) (1.15; 90% CI, 1.06-1.24). Equivalence was not demonstrated for maximum concentration (C(max)); values for ethinyl estradiol and levonorgestrel C(max) were 12% and 13% lower with liraglutide versus placebo, respectively. Both reached C(max) ~1.5 hours later with liraglutide. No clinically relevant reduction in bioavailability of ethinyl estradiol/levonorgestrel occurred.

Clarification of contraceptive drug pharmacokinetics in obesity☆

PubMed Central

Jusko, William J.

2017-01-01

Related to concerns about the role of obesity in the efficacy of contraceptive drugs, a review of the literature was carried out in regard to the pharmacokinetics of ethinyl estradiol and various progestins given by various routes of administration. Most studies show that obese women exhibit modestly lower plasma concentrations of these drugs (circa 30%) when given the same doses as normal-weight women. While the mechanism is uncertain, precedence in the literature suggests that this is due to body weight-related differences in metabolism rates. Confusing in some of the literature is that a few studies have reported erroneously calculated pharmacokinetic parameters after multiple dosing of oral contraceptives. A demonstration of appropriate pharmacokinetic methodology is provided. PMID:27542520

Effect of two oral contraceptives with different ethinyl estradiol and levonorgestrel concentrations on the urinary excretion of biochemical vasoactive markers.

PubMed

Mueck, A O; Seeger, H; Petersen, G; Schulte-Wintrop, E; Wallwiener, D

2001-12-01

In the present study the effect on the urinary excretion of vasoactive markers of two oral contraceptives (OCs), i.e., Leios, containing 0.02 mg ethinyl estradiol and 0.1 mg levonorgestrel, and Stediril 30, containing 0.03 mg ethinyl estradiol and 0.15 mg levonorgestrel, was investigated. cGMP, prostacyclin and its antagonist thromboxane, serotonin, and urodilatin, a natriuretic and diuretic peptide formed in the kidney, were measured as markers. In a comparative, double-blind, randomized, parallel group study, 34 women received Leios and 33 women Stediril 30. Nocturnal urine was collected before treatment and during cyclic treatment after 3 and 12 cycles. Both contraceptives significantly enhanced cGMP excretion after 12 cycles. The prostacyclin metabolite remained unchanged for both formulations, but the excretion of the thromboxane metabolite was significantly decreased after 12 cycles. Thus, the ratio of prostacyclin to thromboxane, crucial for the resulting effect on vascular tone, increased significantly. For the serotonin metabolite, no changes were observed for both contraceptives. The excretion of urodilatin significantly increased for both preparations after 12 cycles compared to the pretreatment values. These results indicate that the low-dose OCs Leios and Stediril 30 may stimulate the production of some vasoactive markers, at least after 12 cycles of treatment. The positive influence of these contraceptives on the various markers investigated may improve vascular tone, impede development of atherosclerosis and arterial thrombosis, and improve water and electrolyte homeostasis. These effects most likely can be attributed to the estrogenic component. Levonorgestrel may elicit no impact on these estrogen-induced changes that, however, seem only to be manifested after a longer treatment period.

Oral contraceptives and the prothrombin time.

PubMed

Pangrazzi, J; Roncaglioni, M C; Donati, M B

1980-02-02

Dr. De Teresa and others reported that mean prothrombin time ratio of 12 patients on long-term anticoagulation with warfarin was significantly higher when they were also taking oral contraceptives (OCs). A study of prothrombin complex activity was recently conducted in female rats treated with an estrogen-progestogen combination (lynestrenol 5 mg; mestranol 0.3 mg/kg body weight) which resulted in a 100% infertility in this species. After 1 treatment for only 1 estral cycle, OC-treated rats had a significantly longer Normotest clotting time (37.7+ or-0.5 sec) than control rats (31.0+or-0.4); the difference was even more notable after 10 cycles. Although this finding has not been reported in women on OCs, it may be that the estrogen-induced "lability" of the prothrombin complex occurs in humans only in special conditions, such as anticoagulation. Alternatively, liver dysfunction occurring among women on OCs may be responsible for reduced metabolism of warfarin, contributing to the effectiveness of the anticoagulation. Further pharmacology studies should be done to clarify the interaction between OCs and oral anticoagulants.

A comparison of the efficacy of topical tretinoin and low-dose oral isotretinoin in rosacea.

PubMed

Ertl, G A; Levine, N; Kligman, A M

1994-03-01

Twenty-two patients with severe or recalcitrant rosacea were divided into three treatment groups in a randomized, double-blind trial that compared low-dose oral isotretinoin (10 mg/d), topically applied tretinoin (0.025% cream), and the combined use of both isotretinoin and tretinoin. For the first 16 weeks of the trial, subjects received one of these three trial regimens. For the final 16 weeks, isotretinoin was withheld while tretinoin cream or a placebo cream was continued. Twenty subjects completed the trial. Each treatment produced therapeutic benefits with regard to the number of papules and pustules and erythema. Treatment with oral isotretinoin appeared to give a more rapid onset of improvement, but there were no differences between the groups after 16 weeks. This level of improvement continued during the succeeding 16 weeks of observation whether the subjects used the tretinoin or the placebo cream. Adverse events were minimal and well tolerated in all groups. Low-dose oral isotretinoin and topical tretinoin cream therapy appear to be beneficial in the treatment of severe or recalcitrant rosacea. No additive benefit is noted with the combined use of these two modalities.

A Comparative Efficacy of Low-Dose Combined Oral Contraceptives Containing Desogestrel and Drospirenone in Premenstrual Symptoms

PubMed Central

Wichianpitaya, Jirath; Taneepanichskul, Surasak

2013-01-01

Objective. To compare the efficacy of low-dose COC containing desogestrel (DSG) with drospirenone (DRSP) in the changes of premenstrual symptoms. Methods. In an open-label randomized controlled trial, 90 women with premenstrual syndrome who required COC were randomly recruited and allocated equally to receive either 6 cycles of 20 micrograms ethinyl estradiol (EE)/150 micrograms DSG (DSG group) or 20 micrograms EE/3 mg DRSP (DRSP group) in 24/4 extended regimen. Analysis of covariance and repeated analysis of variance were used to determine the difference of mean Women's Health Assessment Questionnaire (WHAQ) scores changes between groups, within group, and in premenstrual, menstrual, and postmenstrual phases. Results. Baseline characteristics and WHAQ scores were comparable. At the ends of the 3rd and the 6th cycles, mean WHAQ scores of all the 3 phases in DRSP group showed significant reduction and were significantly lower than those in DSG group. DSG group showed significant reduction in both premenstrual and menstrual phases after the 6th cycle. Adverse effects were comparable in both groups. In conclusion, low-dose COC containing either DSG or DRSP reduced premenstrual symptoms, but the latter showed greater efficacy and earlier reduction. PMID:23577032

Effect of betel chewing on the frequency of sister chromatid exchanges in pregnant women and women using oral contraceptives.

PubMed

Ghosh, P K; Ghosh, R

1988-06-01

The incidence of sister chromatid exchange (SCE) was investigated in the lymphocyte chromosomes of betel chewing and non-chewing normal women, pregnant women, and women using oral contraceptives. The frequency of SCE was found to be 7.82 +/- 0.24 and 8.27 +/- 0.27 in non-chewing pregnant women and women using oral contraceptives respectively, which were significantly higher than the mean value of 5.21 +/- 0.18 observed in non-chewing normal women. Betel chewing induced higher SCE in pregnant women and women using oral contraceptives, the frequencies being 11.79 +/- 0.38 and 12.51 +/- 0.44, respectively, which were significantly higher than the SCE frequency of 6.28 +/- 0.21 found in normal betel chewing females.

Bleeding pattern with drospirenone 3 mg+ethinyl estradiol 20 mcg 24/4 combined oral contraceptive compared with desogestrel 150 mcg+ethinyl estradiol 20 mcg 21/7 combined oral contraceptive.

PubMed

Anttila, Leena; Kunz, Michael; Marr, Joachim

2009-11-01

The study was conducted to compare cycle control, bleeding pattern and efficacy of two low-dose combined oral contraceptives. Four hundred fifty-three women were randomized to receive a 24/4 regimen of drospirenone 3 mg/ethinyl estradiol 20 mcg (drsp 3 mg/EE 20 mcg; n=230) or a 21/7 regimen of desogestrel 150 mcg/EE 20 mcg (DSG 150 mcg/EE 20 mcg; n=223), and recorded bleeding daily over 7 treatment cycles. The duration [mean 4.7 (SD 1.5)-5.2 (SD 2.2) days in the drsp 3 mg/EE 20 mcg 24/4 group and 5.1 (SD 1.5)-5.4 (SD 2.1) days in the DSG 150 mcg/ EE 20 mcg group] and maximum intensity ("normal bleeding" for >50% of all subjects) of scheduled bleeding in Cycles 1-6 was comparable between treatment groups. The incidence of unscheduled bleeding during Cycles 2-6 was also similar between the two groups (drsp 3 mg/EE 20 mcg, 8.8-17.3%; DSG 150 mcg/ EE 20 mcg, 9.4-16.3%). Drsp 3 mg/EE 20 mcg 24/4 achieved an acceptable bleeding profile with reliable cycle control, comparable with an established formulation.

An assessment of the quality of advice provided by patent medicine vendors to users of oral contraceptive pills in urban Nigeria.

PubMed

Ujuju, Chinazo; Adebayo, Samson B; Anyanti, Jennifer; Oluigbo, Obi; Muhammad, Fatima; Ankomah, Augustine

2014-01-01

In Nigeria about 50% of oral contraceptive pill users obtain their products from proprietary patent medicine vendors (PPMVs). This group of service providers are poorly trained and have very limited knowledge about contraception. This paper investigated the nature of the advice offered to simulated current and potential users of oral contraceptive pills. The main objective was to assess the nature and quality of advice provided by PPMVs to pill users. This study is based on findings from a 'mystery client' approach in which three scenarios related to contraceptive pill use were simulated. Each of the 12 mystery clients simulated one of the following three scenarios: new pill users (new to family planning or switching from condom to pills); user seeking a resupply of pills; and dissatisfied pill users intending to discontinue use. Simple random sampling was used to select 410 PPMVs from a total of 1,826 in four states in Nigeria. Qualitative study using in-depth interviews was also conducted. A majority of the PPMVs had pills in stock on the day of the survey and resupplied pills to the clients. PPMVs also understood the reason and importance of referring clients who were new adopters of oral contraceptive methods to a health facility; 30% of the PPMVs referred new adopters to a health facility. However, demand from clients who do not want to go to health care facilities (for various reasons) necessitated the provision of oral contraceptive pills to 41% of the first time users. Some PPMVs prescribed treatment to mystery clients who presented with perceived complications arising from the use of pills, while 49% were referred to a health facility. The advice given by PPMVs often falls short of safety guidelines related to the use of oral contraceptive pills. There is a need to continuously update knowledge among the PPMVs to ensure that they provide quality oral contraceptive services as PPMVs bridge the gap between medical experts and users in rural communities.

An assessment of the quality of advice provided by patent medicine vendors to users of oral contraceptive pills in urban Nigeria

PubMed Central

Ujuju, Chinazo; Adebayo, Samson B; Anyanti, Jennifer; Oluigbo, Obi; Muhammad, Fatima; Ankomah, Augustine

2014-01-01

Introduction In Nigeria about 50% of oral contraceptive pill users obtain their products from proprietary patent medicine vendors (PPMVs). This group of service providers are poorly trained and have very limited knowledge about contraception. This paper investigated the nature of the advice offered to simulated current and potential users of oral contraceptive pills. The main objective was to assess the nature and quality of advice provided by PPMVs to pill users. Method This study is based on findings from a ‘mystery client’ approach in which three scenarios related to contraceptive pill use were simulated. Each of the 12 mystery clients simulated one of the following three scenarios: new pill users (new to family planning or switching from condom to pills); user seeking a resupply of pills; and dissatisfied pill users intending to discontinue use. Simple random sampling was used to select 410 PPMVs from a total of 1,826 in four states in Nigeria. Qualitative study using in-depth interviews was also conducted. Results A majority of the PPMVs had pills in stock on the day of the survey and resupplied pills to the clients. PPMVs also understood the reason and importance of referring clients who were new adopters of oral contraceptive methods to a health facility; 30% of the PPMVs referred new adopters to a health facility. However, demand from clients who do not want to go to health care facilities (for various reasons) necessitated the provision of oral contraceptive pills to 41% of the first time users. Some PPMVs prescribed treatment to mystery clients who presented with perceived complications arising from the use of pills, while 49% were referred to a health facility. Conclusion The advice given by PPMVs often falls short of safety guidelines related to the use of oral contraceptive pills. There is a need to continuously update knowledge among the PPMVs to ensure that they provide quality oral contraceptive services as PPMVs bridge the gap between medical

Comparison of scales for evaluating premenstrual symptoms in women using oral contraceptives.

PubMed

Coffee, Andrea L; Kuehl, Thomas J; Sulak, Patricia J

2008-05-01

To compare two scales used in research to evaluate daily premenstrual mood symptoms during use of a monophasic oral contraceptive. Subanalysis of data from a prospective study. University-affiliated medical center. SUBJECTS; One hundred two reproductive-aged (18-48 yrs) women taking a monophasic oral contraceptive containing ethinyl estradiol and drospirenone in the standard 21-7 fashion (21 days of hormones followed by 7 days of placebo), and who had self-identified premenstrual symptoms of headache, mood changes, or pelvic pain. Subjects completed a single-item questionnaire, the Scott & White Daily Diary of Symptoms, and a multiple-item questionnaire, the Penn State Daily Symptom Report (DSR), to assess their premenstrual symptoms. The Scott & White diary used a visual analog scale of 0-10 to assess pelvic pain, headache, and mood (a composite of anxiety, depression, and irritability). The Penn State DSR contained 17 items: 10 behavioral and seven physical components, each rated on a scale of 0-4, with one item that specifically rated mood swings. Scores from the two scales were compared by using Spearman correlation coefficients, the Kendall W for concordance, and linear regression of ranked sums for study cycles. The Scott & White mood score significantly correlated with the total of the 17 items on the Penn State DSR, as well as the 10 behavioral items, the seven physical items, and the single mood-swing item (p<0.0001); specific coefficients of concordance were 0.44, 0.23, 0.10, and 0.28, respectively, and R2 values were 0.39, 0.39, 0.30, and 0.34, respectively. The daily Scott & White mood score was positively correlated with all 17 elements of the Penn State DSR (0.25-0.57). The greatest correlation was seen with the mood-swing element. Both instruments demonstrated the same patterns during the 21-7 oral contraceptive cycle, with symptoms increasing immediately before and peaking during the 7-day hormone-free interval. A single-item daily mood score using

The current status of oral contraceptive clinical development in Japan.

PubMed

Kuwabara, Y

1989-01-01

Since the oral contraceptive guideline was issued in April 1987, Japanese pharmaceutical firms have been asking physicians to perform clinical studies of the low-dose OCs. At present, eight products from six companies are under clinical development. Ethinyl estradiol (30-35 micrograms per tablet) as an estrogen component is common to all the test drugs. The progestin component in each OC is norethindrone, levonorgestrel, or desogestrel. Phase I clinical studies on small numbers of healthy volunteers showed that they could tolerate the test drugs without any serious complaints. The effects on endocrine systems, including the inhibition of ovulation, were also examined. Pharmacokinetic parameters of active ingredients were comparable to those of Western women, and no substantial difference seemed to exist between Japanese and Western women. As an example, the results of phase I studies of OJK-777 (Ortho-Novum 7/7/7) are mentioned. Phase III clinical studies, which are "open studies," are now under progress with more than 3,000 women. The major objectives are to examine (1) how well the drugs are tolerated, and the dropout rates; (2) the effects on cycle control, especially bleeding patterns; (3) effects on the cardiovascular system, including coagulation and lipid metabolism; (4) effects on hormone secretions. Although some women have been taking the test drugs for more than 12 cycles, overall statistics are not yet available, because the guideline requires long-term administration (for more than 24 cycles). However, some characteristic features observed thus far are discussed.

Contraceptive Development.

ERIC Educational Resources Information Center

Troen, Philip; And Others

This report provides an overview of research activities and needs in the area of contraceptive development. In a review of the present state, discussions are offered on the effectiveness and drawbacks of oral contraceptives, intrauterine devices, barrier methods, natural family planning, and sterilization. Methods of contraception that are in the…

Contraceptive choices for women with endocrine complications.

PubMed

Loriaux, D L; Wild, R A

1993-06-01

Previous confusion regarding the interference by oral contraceptives in measurements of endocrine function have been largely eliminated by the advent of improved, more sensitive assays. There are few if any contraindications to oral contraceptive use in patients with thyroid disease. Patients with prolactinoma can be treated with bromocriptine to restore fertility and prevent mineral loss. However, as a less expensive alternative, oral contraceptives can be prescribed to correct mineral loss, because there is no convincing evidence of an adverse effect on prolactinomas by the steroidal content of the pill. Oral contraceptives comprise a near ideal treatment modality for women with polycystic ovary disease because, among other effects, oral contraceptives reduce synthesis of androgen by inhibiting pituitary gonadotropin secretion.

Low-dose flutamide-metformin therapy for hyperinsulinemic hyperandrogenism in non-obese adolescents and women.

PubMed

Ibáñez, Lourdes; de Zegher, Francis

2006-01-01

Polycystic ovary syndrome (PCOS) is a variable disorder that is characterized in adolescents and young women by a broad spectrum of anomalies, including hyperandrogenemia, insulin resistance, dyslipidemia, body adiposity and low-grade inflammation. At present, there is no approved therapy for PCOS. Recent studies indicate that a low-dose combination of flutamide (Flu; a generic androgen-receptor blocker) and metformin (Met; a generic insulin-sensitizer) normalizes the adolescent PCOS spectrum more than an oral contraceptive (OC); in young women, the PCOS spectrum was found to be more normalized by OC plus Flu-Met than by OC alone. Within the pathophysiological cascade of PCOS, Flu-Met seems to counter upstream anomalies like hyperinsulinemia or hyperandrogenism, thereby preventing or reversing downstream effects. In contrast, an OC essentially masks downstream symptoms like hirsutism, acne or irregular menses, whereas the upstream aberrations remain unaltered or may even be worsened. The available experience with Flu-Met is limited but promising. We emphasize that Flu-Met may (as part of its efficacy) induce ovulation but is contra-indicated post-conception because of potential embryotoxicity; therefore, it seems wise to combine Flu-Met with an oral or a transdermal oestro-progestagen or with a non-endocrine method of contraception. May this update prompt further research into Flu-Met's therapeutic potential in patients with PCOS. Until the abovementioned effects have been broadly confirmed, Flu-Met should not be regarded as a standard therapy for widespread clinical practice.

A survey of bonobo (Pan paniscus) oral contraceptive pill use in North American zoos.

PubMed

Agnew, Mary K; Asa, Cheryl S; Clyde, Victoria L; Keller, Dominique L; Meinelt, Audra

2016-09-01

Contraception is an essential tool in reproductive management of captive species. The Association of Zoos and Aquariums (AZA) Reproductive Management Center (RMC) gathers data on contraception use and provides recommendations. Although apes have been given oral contraceptive pills (OCPs) for at least 30 years, there have been no published reports with basic information on why the pill is administered, formulations and brands used, and effects on physiology and behavior. Here, we report survey results characterizing OCP use in bonobos (Pan paniscus) housed in North American zoos, as well as information accumulated in the RMC's Contraception Database. Of 26 females treated, there have been no failures and nine reversals. The most commonly administered OCP formulation in bonobos contained ethinyl estradiol (EE) 35 μg/norethindrone 1 mg. Few females on combined oral contraceptives (COCs) were given a continuous active pill regimen; a hormone-free interval of at least 5 days was allowed in most. Crushing the pill and mixing with juice or food was common. Females on COCs seldom experienced breakthrough estrus or bleeding, while these conditions were sometimes observed for females on continuous COCs. All females on COCs exhibited some degree of perineal swelling, with a mean score of 3 or 3+ most commonly reported. Behavioral changes included less sexual behavior, dominant females becoming subordinate, and a negative effect on mood. No appreciable change in weight was noted. Taken together, these results indicate that OCPs are an effective and reversible contraceptive option for bonobos that can be used by zoos and sanctuaries to limit reproduction. Zoo Biol. 35:444-453, 2016. © Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

[Contraception and sexology].

PubMed

Black, J S

1991-01-01

This work argues that contraceptive education urgently requires a new approach that will take into account the client's sexuality at the time the choice of method is made. Emotional factors such as a conscious or unconscious desire for pregnancy or motherhood, family pressures to produce a grandchild, or shame and distrust of contraception may contribute to contraceptive failure. Methods applied at the time of coitus such as condoms or spermicides may not be appropriate for clients for who contraception is a source of anxiety or guilt. The more effective, noncoital-dependent methods including oral contraceptives (OCs), IUDs, and sterilization may generate anxiety over infertility. Their efficacy may lack appeal for clients who enjoy an element of risk. The practitioner's attitude and knowledge may be further influences on the counseling over method choice. Among reversible methods, OCs are ideal for most women as long as they individually prescribed. OCs may be particularly important to the sexual expression of specific groups such as those over 35 with no risk factors other than age. Low-dose progestin-only OCs may be prescribed for this group, although about 10% of users change methods because of menstrual problems. IUDs are usually successfully used by women who have been carefully selected to exclude contraindications. In some cases the partner may be annoyed by the string, which can be rolled up and pushed out of the way or shortened by the practitioner. IUDs are often the best alternative for women with contraindications to OCs or who tolerate their side effects poorly. Spermicides may cause dermatoses or allergies that cause the woman to avoid intercourse. Some women dislike using spermicides because they must be applied prior to each use. Their bad taste is a disadvantage for some couples. Involving the male partner in application of the spermicide may remove some objections. The Billings or cervical mucus method should be avoided by women with irregular

Contraceptive knowledge and attitudes among 14-24-year-olds in New South Wales, Australia.

PubMed

Ritter, Todd; Dore, Anne; McGeechan, Kevin

2015-06-01

To investigate correlates of contraceptive knowledge and attitudes and describe differences in contraceptive knowledge by contraceptive category among young people in New South Wales. A total of 119 young people aged 14 to 24, recruited from youth centres, completed a contraceptive knowledge and attitude survey. Overall contraceptive knowledge was low. Females had significantly better knowledge than males. There was high knowledge about condoms and withdrawal and low knowledge about shorter-term hormonal methods (oral contraceptive pill and vaginal ring) and long-acting reversible contraceptive (LARC) methods. Nearly half of respondents agreed that 'contraceptives make sex seem less romantic', while 58% agreed that 'contraceptives are difficult to use'. Despite this, both genders had positive attitudes to contraception, with females' attitudes significantly more positive than males. While young people, particularly young women, expressed attitudes conducive to contraceptive use, many are unaware of basic facts about methods, including highly effective LARC. Our findings reflect the modest reproductive and sexual health education received by Australian young people and cultural norms of condoms and oral contraceptives as default methods and highlight the need to improve knowledge, among young men, in particular, about the most effective contraceptive methods. © 2015 Public Health Association of Australia.

[Periodontal status in a sample of Senegalese women using hormonal contraception].

PubMed

Seck-Diallo, A; Cissé, M L; Benoist, H M; Diouf, A; Ahnoux-Kouadio, A; Diallo, T; Sembene, M; Moreau, J C; Diallo, P D

2008-03-01

Hormonal contraception is based on the use of synthetic hormones containing variable doses of oestrogen and progesterone making it possible to avoid pregnancy in a temporary and reversible way. The objective of this study is to evaluate the periodontal status of a sample of Senegalese women under hormonal contraceptive. One hundred women using contraception since at least 6 month were paired on the age, the socio-economic profile and oral hygiene with a control group. Oral hygiene (plaque index (PI) of Silness and Löe), the inflammation (gingival index (GI) of Löe and Silness), probing depth and clinical attachment loss were recorded. With equal hygiene, the scores of the gingival index were significantly higher among women under contraceptive (p < 0.001). Inflammation was significantly more marked for the women who used contraception in injectable form compared to the control group (p < 0.001). Probing depth (3.01 +/- 0.04) and clinical attachment loss (3.19 +/- 0.08) were significantly more important among women under contraceptive (p < 0.001). The women under contraceptive seem to set up a group at risk for developing a periodontal disease, it is thus necessary to systematise periodontal appraisal before and during contraceptive use period.

Impact of a passive social marketing intervention in community pharmacies on oral contraceptive and condom sales: a quasi-experimental study.

PubMed

Farris, Karen B; Aquilino, Mary L; Batra, Peter; Marshall, Vince; Losch, Mary E

2015-02-13

Almost 50% of pregnancies in the United States are unwanted or mistimed. Notably, just over one-half of unintended pregnancies occurred when birth control was being used, suggesting inappropriate or poor use or contraceptive failure. About two-thirds of all women who are of reproductive age use contraceptives, and oral hormonal contraceptives remain the most common contraceptive method. Often, contraceptive products are obtained in community pharmacies. The purpose of this study was to determine whether a pharmacy-based intervention would impact sales of contraceptive products in pharmacies. This study was conducted in Iowa and used a quasi-experimental design including 55 community pharmacies (independent and grocery) in 12 counties as the intervention and 32 grocery pharmacies in 10 counties as a comparison group. The passive intervention was focused towards 18-30 year old women who visited community pharmacies and prompted those of childbearing age to "plan your pregnancy" and "consider using birth control". The intervention was delivered via educational tri-fold brochures, posters and 'shelf talkers.' Data sources for evaluation were contraceptive sales from intervention and comparison pharmacies, and a mixed negative binomial regression was used with study group*time interactions to examine the impact of the intervention on oral contraceptive and condom sales. Data from 2009 were considered baseline sales. From 2009 to 2011, condom sales decreased over time and oral contraceptives sales showed no change. Overall, the units sold were significantly higher in grocery pharmacies than in independent pharmacies for both contraceptive types. In the negative binomial regression for condoms, there was an overall significant interaction between the study group and time variables (p = 0.003), indicating an effect of the intervention, and there was a significant slowing in the drop of sales at time 3 in comparison with time 1 (p < 0.001). There was a statistically

Comparison of combined hormonal vaginal ring with ultralow-dose combined oral contraceptive pills in the management of heavy menstrual bleeding: A pilot study.

PubMed

Agarwal, N; Gupta, M; Kriplani, A; Bhatla, N; Singh, N

2016-01-01

The aim of this study was to compare combined hormonal vaginal ring with ultralow-dose combined oral contraceptive (COC) pills in management of heavy menstrual bleeding (HMB). Fifty patients were randomised into Group I: vaginal ring (n = 25) and group II: COC pills (n = 25). Menstrual blood loss (MBL) was assessed at baseline, 1, 3 and 6 months (while on treatment) and at 9 months (3 months after stopping therapy). There was significant reduction in baseline pictorial blood loss assessment chart (PBAC) score from 440 ± 188 (Mean ± SD) to 178 ± 95, 139 ± 117, 112 ± 84 and 120 ± 108 in group I and from 452 ± 206 to 204 ± 152, 179 ± 125, 176 ± 164 and 202 ± 167 in group II at 1, 3, 6 and 9 months, respectively (p = 0.001). Reduction in MBL was 72% and 62% at 6 months and up to 71% and 55% at 9 months in group I and group II, respectively (p = 0.001). Reduction in MBL with ring was greater at higher baseline PBAC score but lesser in patients with fibroid > 2 cm. Combined vaginal hormonal treatment for HMB is as effective as oral hormonal therapy, with minor and transient side effects and persistence of response after cessation of therapy.

Low-dose retinoic acid enhances in vitro invasiveness of human oral squamous-cell-carcinoma cell lines

PubMed Central

Uchida, D; Kawamata, H; Nakashiro, K; Omotehara, F; Hino, S; Hoque, M O; Begum, N-M; Yoshida, H; Sato, M; Fujimori, T

2001-01-01

Retinoids inhibit the proliferation of several types of tumour cells, and are used for patients with several malignant tumours. In this study, we examined the effect of retinoic acids (RAs) on the invasive potentials of the oral squamous cell carcinoma (SCC) cells, BHY and HNt. BHY cells expressed all of retinoid nuclear receptors (RARα, β, γ, and RXRα) and cytoplasmic retinoic acid binding proteins (CRABP1 and CRABP2). HNt cells lacked the expression of RARβ, but expressed other nuclear receptors and CRABPs. All-trans retinoic acid (ATRA) and 13-cis retinoic acid (13-cisRA) (10−6and 10−7M) inhibited the growth of the cells, but low-dose ATRA and 13-cisRA (10−8M) marginally affected the growth of the cells. Surprisingly, low-dose RAs enhanced the activity of tissue-type plasminogen activator (tPA), and activated pro-matrix metalloproteinases (proMMP2 and proMMP9). Activation of proMMP2 and proMMP9 was inhibited by aprotinin, a serine-proteinase, tPA inhibitor. Furthermore, low-dose RAs enhanced the in vitro invasiveness of BHY cells. These results indicate that low-dose RAs enhances the in vitro invasiveness of oral SCC cells via an activation of proMMP2 and proMMP9 probably mediated by the induction of tPA. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11437413

[Contraception in the future].

PubMed

Hamzaoui, R; Boukhris, M

1994-02-01

In the last decade, global use of contraceptive methods has increased. About 50% of couples of childbearing age use a modern contraceptive method. This evolution and a positive change in attitude towards male contraception has encouraged research in fertility regulation to enlarge and to improve acceptance of the contraceptive mix. Current injectable contraceptives interfere with the menstrual cycle. Research is exploring ways to minimize such secondary effects by reducing the total hormone dose and by changing the way the active product is delivered (e.g., microspheres). An injectable prototype is an analogue of levonorgestrel (HRP 002). A new IUD is made of leather suspended by a nylon suture which has been inserted into the uterine muscle. RU-486, often used to interrupt early pregnancy, is being tested as an oral contraceptive (OC). It inhibits secretion of gonadotropins and ovulation. It holds promise as an OC with no estrogen component. Since it also inhibits endometrial development and thus prevents implantation, it may someday be used for emergency contraception (i.e., postcoital contraception). New contraceptive implants under study include Norplant RII (2 rods of levonorgestrel lasting for 3 years), Implanon (desogestrel), and Capranor (biodegradable implant lasting 2 years). The female condom consists of a flexible polyurethane sheath with a flexible ring at each end. It has the potential to protect against sexually transmitted diseases since it covers the labial lips and is impermeable to HIV. France and Switzerland have both approved its use. It will enter the UK market at the end of the year. Approval for marketing has been sought in the US.

Oral progestogen combined with testosterone as a potential male contraceptive: additive effects between desogestrel and testosterone enanthate in suppression of spermatogenesis, pituitary-testicular axis, and lipid metabolism.

PubMed

Wu, F C; Balasubramanian, R; Mulders, T M; Coelingh-Bennink, H J

1999-01-01

The effects of a synthetic oral progestogen, desogestrel (DSG), administered with low dose testosterone (T) were investigated to determine the optimal combination for suppression of gonadotropins and spermatogenesis to targets compatible with effective male contraception. Twenty-four healthy male volunteers (33.2 +/- 0.9 yr) were randomly assigned to 3 groups (n = 8) to receive: 1) 300 microg DSG orally daily and 100 mg T enanthate, i.m., weekly; 2) 300 microg DSG and 50 mg T enanthate; or 3) 150 microg DSG and 100 mg T enanthate for 24 weeks. To investigate the individual contribution to the combined action, DSG was administered alone for the first 3 weeks, and T enanthate was added on day 22. After 24-week treatment, sperm density in 78% (18 of 23) of the subjects became azoospermic, whereas 91.7% (22 of 24) and 95.8% (23 of 24) suppressed to less than 1 million/mL and less than 3 million/mL, respectively. The 300 microg DSG with 50 mg T enanthate combination induced azoospermia in 8 of 8 subjects, and the suppression of sperm density was significantly greater than that in the 300 microg DSG/100 mg T enanthate group, but was not different from that in the 150 microg DSG/100 mg T enanthate group. DSG (300 or 150 microg daily) alone in the first 3 weeks suppressed LH, FSH, and T to 60.6%, 48.0%, and 35.4%, respectively, of the baseline. Addition of T enanthate (50 and 100 mg weekly) raised plasma T to the physiological range and induced a further fall in LH and FSH to the limits of assay detection. There was no consistent difference in mean LH and FSH levels among the three groups during treatment or recovery, except that FSH remained detectable in a higher proportion of samples from the group receiving 300 microg DSG with 50 mg T enanthate. Total cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol decreased by 9.3 +/- 1.7%, 10.3 +/- 2.6%, and 7.7 +/- 2.8%, respectively, during treatment with DSG alone with no difference

Across many behaviors, long-term oral contraceptive use lowers risk for ovarian, endometrial cancer

Cancer.gov

DCEG researchers investigated whether the relationship between oral contraceptive use and risks for ovarian, endometrial, breast, and colorectal cancers change when looking at groups of women who have different health behaviors.

Use of Oral Contraceptives for Management of Acne Vulgaris: Practical Considerations in Real World Practice.

PubMed

Harper, Julie C

2016-04-01

Acne vulgaris may be effectively treated with combination oral contraceptive pills (COCs) in women. COCs may be useful in any woman with acne in the absence of known contraindications. When prescribing a COC to a woman who also desires contraception, the risks of the COC are compared with the risks associated with pregnancy. When prescribing a COC to a woman who does not desire contraception, the risks of the COC must be weighed against the risks associated with acne. COCs may take 3 cycles of use to show an effect in acne lesion count reductions. Copyright © 2016 Elsevier Inc. All rights reserved.

Estimating Systemic Exposure to Levonorgestrel from an Oral Contraceptive

PubMed Central

Basaraba, Cale N; Westhoff, Carolyn L; Pike, Malcolm C; Nandakumar, Renu; Cremers, Serge

2017-01-01

Objective The gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-hour steady-state area-under-the-curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-hour steady-state AUC of a particular OC. Study Design We conducted a 13-sample, 24-hour pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30 μg ethinyl estradiol and 150 μg levonorgestrel (LNG) in 17 normal-weight healthy white women, and a single-dose 9-sample study of the same OC after a one-month washout. We compared the 13-sample steady-state results with several steady-state and single-dose results calculated using parsimonious sampling schemes. Results The 13-sample steady-state 24-hour LNG AUC was highly correlated with the steady-state 24-hour trough value (r = 0.95; 95% CI [0.85, 0.98]) and with the steady-state 6, 8, 12 and 16-hour values (0.92 ≤ r ≤ 0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-hour AUC value (r = 0.70; 95% CI [0.27, 0.90] and 0.77; 95% CI [0.40, 0.92], respectively). Conclusions Single time-point concentrations at steady-state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects. PMID:28041990

Effects of a combined oral contraceptive containing 20 mcg of ethinylestradiol and 3 mg of drospirenone on the blood pressure, renin-angiotensin-aldosterone system, insulin resistance, and androgenic profile of healthy young women.

PubMed

Giribela, Cassiana Rosa Galvão; Consolim-Colombo, Fernanda Marciano; Nisenbaum, Marcelo Gil; Moraes, Tercio Lemos de; Giribela, Aricia Helena Galvão; Baracat, Edmund Chada; Melo, Nilson Roberto de

2015-01-01

Combined oral contraceptives (COCs) may increase the risk for cardiovascular disease depending on the ethynyl estradiol (EE) dose and the androgenicity of the progestogens. Our objective was to evaluate the impact of a COC containing 20 mcg EE + 3 mg drospirenone on blood pressure (BP), renin-angiotensin-aldosterone system, insulin resistance, and androgenic profile of healthy young women. Eighty-one healthy young women aged 30 ± 1 years (case group, n = 49, received COC; control group, n = 32, used no COC) were assessed twice, before and after the 6-month study. Statistical analysis employed the paired t-tests and expressed the data in mean and standard deviation. Results were as follows: no changes in BP or in BMI; a significant increase in aldosterone, plasma renin activity, triglycerides, and total cholesterol levels, but a non-significant increase in HDL and no significant changes in LDL levels (these parameters remained within normal ranges); a significant increase in the HOMA-IR index and a significant decrease in dehydroepiandrosterone sulfate (SDHEA), androstenedione, total testosterone, and free testosterone levels; no significant variations in the control group parameters. An oral contraceptive combination of a low EE dose and an anti-androgenic progestogen does not negatively influence the risk factors for a cardiovascular disease.

Ovulatory effects of three oral contraceptive regimens: a randomized, open-label, descriptive trial.

PubMed

Seidman, Larry; Kroll, Robin; Howard, Brandon; Ricciotti, Nancy; Hsieh, Jennifer; Weiss, Herman

2015-06-01

This study describes ovarian activity suppression of a 21/7-active low-dose combined oral contraceptive (COC) regimen that included only ethinyl estradiol (EE) during the traditional hormone-free interval (HFI) and two commercially available 28-day regimens, a 24/4 and a 21/7 regimen. The randomized, open-label, parallel-group descriptive study was conducted at two US sites. Healthy, reproductive-aged women (n=146) were randomized to one of three groups for three consecutive 28-day cycles, as follows: treatment 1 (n=39 completed): 21/7-active COC [21 days of 150 mcg desogestrel (DSG)/20 mcg EE, followed by 7 days of 10 mcg EE (DSG/EE+7 days EE)], treatment 2 (n=39 completed): 24 days of 3mg drospirenone (DRSP)/20 mcg EE, followed by 4 placebo (PBO)-pill days (DRSP/EE+4 days PBO) and treatment 3 (n=42 completed): 21 days of 100 mcg levonorgestrel (LNG)/20 mcg EE, followed by 7 PBO-pill days (LNG/EE+7 days PBO). The primary outcome was ovarian activity suppression assessed by transvaginal ultrasound and serum hormone concentrations and classified using the Hoogland and Skouby (H/S) method. Ovarian activity rate (H/S grade 4 or 5) was low for all three treatments: 0% [95% confidence interval (CI) 0-2.8] for DSG/EE+7 days EE, 1% (95% CI 0.2-5.2) for DRSP/EE+4days PBO and 1% (95% CI 0-3.9) for LNG/EE+7 days PBO. All three treatments showed similar suppression of serum progesterone, 17β-estradiol, follicle-stimulating hormone and luteinizing hormone levels. The 21/7-active low-dose COC regimen (DSG/EE+7 days EE) showed ovarian activity suppression that was similar to the 24/4 (DRSP/EE+4 days PBO) and 21/7 (LNG/EE+7days PBO) regimens. The 21/7-active low-dose COC regimen (DSG/EE+7 days EE) that included only EE during the traditional HFI showed suppression of ovarian follicular activity that was similar to the 24/4 (DRSP/EE+4days PBO) and the 21/7 (LNG/EE+7 days PBO) comparator regimens. Copyright © 2015 Elsevier Inc. All rights reserved.

Oral Contraceptive Use and Reproductive Characteristics Affect Survival in Patients With Epithelial Ovarian Cancer

PubMed Central

Kolomeyevskaya, Nonna V.; Szender, J. Brian; Zirpoli, Gary; Minlikeeva, Albina; Friel, Grace; Cannioto, Rikki A.; Brightwell, Rachel M.; Grzankowski, Kassondra S.; Moysich, Kirsten B.

2015-01-01

Objectives Prognostic risk factors influencing survival in patients with epithelial ovarian cancer (EOC) include tumor stage, grade, histologic subtype, debulking, and platinum status. Little is known about the impact of hormonal milieu and reproductive factors before cancer diagnosis on clinical outcome. We sought to evaluate whether oral contraceptive (OC) use carries any prognostic significance on overall survival (OS) in patients with EOC. Methods Newly diagnosed patients with EOC, fallopian tube, and primary peritoneal cancers between 1982 and 1998 were prospectively evaluated with a comprehensive epidemiologic questionnaire. A retrospective chart review was performed to abstract clinicopathologic data, including OS. A Kaplan-Meier analysis was performed to compare survival across various exposures. A Cox regression model was used to compute adjusted hazards ratios (aHRs) and 95% confidence intervals (CIs). Results We identified 387 newly diagnosed cancers with evaluable information in this cohort. Decreased risk of death was observed in women who reported prior use of OC (aHR, 0.79; 95% CI, 0.58–1.09), previous pregnancy (aHR, 0.77; 95% CI, 0.57–1.04), or a live birth (aHR, 0.81; 95% CI, 0.60–1.08) after adjusting for age at diagnosis, stage, and histologic subtype. Oral contraceptive use was associated with a crude reduced risk of death (HR, 0.55; 95% CI, 0.42–0.72), with reported median OS of 81 months in OC users versus 46 months in nonusers. Patients who reported a single live birth experienced the largest potential survival advantage (aHR, 0.61; 95% CI, 0.39–0.94). Oral contraceptive use and prior pregnancy were associated with improved survival across all strata. Conclusions Oral contraceptive use may have lasting effects on epithelial ovarian tumor characteristics conferring favorable prognosis. Putative mechanisms that affect tumor biology include complex interactions between ovarian cells, host immune cells, and hormonal microenvironment

Oral contraception and adolescent women with insulin-dependent diabetes mellitus: risks, benefits, and implications for practice.

PubMed

Betschart, J

1996-01-01

Healthcare providers who work with adolescents with diabetes are in an ideal position to provide education and support regarding contraceptive issues. Diabetes educators and other health professionals who counsel teens focus on other aspects of diabetes care and management but frequently do not address sexual issues or assess contraceptive practices. The purpose of this paper is to review oral contraceptive issues for teens with diabetes and to provide practice implications for health professionals who are in a favorable position to influence the quality of diabetes and general health care for these adolescents.

Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception

PubMed Central

Oduwole, Olayiwola O.; Vydra, Natalia; Wood, Nicholas E. M.; Samanta, Luna; Owen, Laura; Keevil, Brian; Donaldson, Mandy; Naresh, Kikkeri; Huhtaniemi, Ilpo T.

2014-01-01

Testosterone (T), alone or in combination with progestin, provides a promising approach to hormonal male contraception. Its principle relies on enhanced negative feedback of exogenous T to suppress gonadotropins, thereby blocking the testicular T production needed for spermatogenesis, while simultaneously maintaining the extragonadal androgen actions, such as potency and libido, to avoid hypogonadism. A serious drawback of the treatment is that a significant proportion of men do not reach azoospermia or severe oligozoospermia, commensurate with contraceptive efficacy. We tested here, using hypogonadal luteinizing hormone/choriongonadotropin receptor (LHCGR) knockout (LHR−/−) mice, the basic principle of the T-based male contraceptive method, that a specific T dose could maintain extragonadal androgen actions without simultaneously activating spermatogenesis. LHR−/− mice were treated with increasing T doses, and the responses of their spermatogenesis and extragonadal androgen actions (including gonadotropin suppression and sexual behavior) were assessed. Conspicuously, all dose responses to T were practically superimposable, and no dose of T could be defined that would maintain sexual function and suppress gonadotropins without simultaneously activating spermatogenesis. This finding, never addressed in clinical contraceptive trials, is not unexpected in light of the same androgen receptor mediating androgen actions in all organs. When extrapolated to humans, our findings may jeopardize the current approach to hormonal male contraception and call for more effective means of inhibiting intratesticular T production or action, to achieve consistent spermatogenic suppression.—Oduwole, O. O., Vydra, N., Wood, N. E. M., Samanta, L., Owen, L., Keevil, B., Donaldson, M., Naresh, K., Huhtaniemi, I. T. Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception. PMID:24599970

[ORAL CONTRACEPTIVES AND MOOD/SEXUAL DISORDERS IN WOMEN].

PubMed

Sirakov, M; Tomova, E

2015-01-01

Oral contraceptives are used since more than 50 years and are very popular due to offering more than 99% confidence in preventing pregnancy. Over 100 million women worldwide use oral contraceptives. In the UK 27% of women between 16 and 49 y. use pills. In the United States they are about 30%, in Germany - 40%, and in The Netherlands - 60%. According to a study by B. Pehlivanov, 2008, in Bulgaria only 4% of women use OC. (1) Despite the convenience and security, in the U.S.A. 29% of women taking OC interrupt prematurely their use (2), while the percentage of adolescents appears to be higher (3) Earlier studies of the reasons for refusal of OC focus on their influence on the menstrual cycle, as well as on some physical side effects such as the appearance of hair growth, weight gain, bloating etc. They paid very little attention to their impact on mood and sexual behavior of women (4). Newer studies suggest that the side effects associated with mood and sexual behavior proved more powerful factor leading to early termination of the use of OC (5). This paper is a review of the literature and evaluation of the facts presented in studies from different countries. They found a high incidence of symptoms such as anxiety, susceptibility to stress, mood changes, incl. depression, anxiety, increased irritability and affection of sexual desire of women. (6) There are many indications that OC-users are at increased risk of suicide and mental illnesses. (9).

Resting state alpha frequency is associated with menstrual cycle phase, estradiol and use of oral contraceptives.

PubMed

Brötzner, Christina P; Klimesch, Wolfgang; Doppelmayr, Michael; Zauner, Andrea; Kerschbaum, Hubert H

2014-08-19

Ongoing intrinsic brain activity in resting, but awake humans is dominated by alpha oscillations. In human, individual alpha frequency (IAF) is associated with cognitive performance. Noticeable, performance in cognitive and emotional tasks in women is associated with menstrual cycle phase and sex hormone levels, respectively. In the present study, we correlated frequency of alpha oscillation in resting women with menstrual cycle phase, sex hormone level, or use of oral contraceptives. Electroencephalogram (EEG) was recorded from 57 women (aged 24.07 ± 3.67 years) having a natural menstrual cycle as well as from 57 women (aged 22.37 ± 2.20 years) using oral contraceptives while they sat in an armchair with eyes closed. Alpha frequency was related to the menstrual cycle phase. Luteal women showed highest and late follicular women showed lowest IAF or center frequency. Furthermore, IAF as well as center frequency correlated negatively with endogenous estradiol level, but did not reveal an association with endogenous progesterone. Women using oral contraceptives showed an alpha frequency similar to women in the early follicular phase. We suggest that endogenous estradiol modulate resting alpha frequency. Copyright © 2014 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of the Menstrual Cycle and Oral Contraception on Singers' Pitch Control

ERIC Educational Resources Information Center

La, Filipa M. B.; Sundberg, Johan; Howard, David M.; Sa-Couto, Pedro; Freitas, Adelaide

2012-01-01

Purpose: Difficulties with intonation and vibrato control during the menstrual cycle have been reported by singers; however, this phenomenon has not yet been systematically investigated. Method: A double-blind randomized placebo-controlled trial assessing effects of the menstrual cycle and use of a combined oral contraceptive pill (OCP) on pitch…

Quantitative bias analysis of a reported association between perfluoroalkyl substances (PFAS) and endometriosis: The influence of oral contraceptive use.

PubMed

Ngueta, Gerard; Longnecker, Matthew P; Yoon, Miyoung; Ruark, Christopher D; Clewell, Harvey J; Andersen, Melvin E; Verner, Marc-André

2017-07-01

An association between serum levels of perfluoroalkyl substances (PFAS) and endometriosis has recently been reported in an epidemiologic study. Oral contraceptive use to treat dysmenorrhea (pelvic pain associated with endometriosis) could potentially influence this association by reducing menstrual fluid loss, a route of excretion for PFAS. In this study, we aimed to evaluate the influence of differential oral contraceptive use on the association between PFAS and endometriosis. We used a published life-stage physiologically based pharmacokinetic (PBPK) model to simulate plasma levels of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) from birth to age at study participation (range 18-44years). In the simulated population, PFAS level distributions matched those for controls in the epidemiologic study. Prevalence and geometric mean duration (standard deviation [SD]) of oral contraceptive use in the simulated women were based on data from the National Health and Nutrition Examination Survey; among the women with endometriosis the values were, respectively, 29% and 6.8 (3.1) years; among those without endometriosis these values were 18% and 5.3 (2.8) years. In simulations, menstrual fluid loss (ml/cycle) in women taking oral contraceptives was assumed to be 56% of loss in non-users. We evaluated the association between simulated plasma PFAS concentration and endometriosis in the simulated population using logistic regression. Based on the simulations, the association between PFAS levels and endometriosis attributable to differential contraceptive use had an odds ratio (95% CI) of 1.05 (1.02, 1.07) for a log e unit increase in PFOA and 1.03 (1.02, 1.05) for PFOS. In comparison, the epidemiologic study reported odds ratios of 1.62 (0.99, 2.66) for PFOA and 1.25 (0.87, 1.80) for PFOS. Our results suggest that the influence of oral contraceptive use on the association between PFAS levels and endometriosis is relatively small. Copyright © 2017 Elsevier

The contraception needs of the perimenopausal woman.

PubMed

Hardman, Sarah M R; Gebbie, Ailsa E

2014-08-01

Perimenopausal women have low fertility but must still be advised to use contraception until natural sterility is reached if they are sexually active. Patterns of contraceptive use vary in different countries worldwide. Long-acting reversible contraceptive methods offer reliable contraception that may be an alternative to sterilisation. Hormonal methods confer significant non-contraceptive benefits, and each individual woman should weigh up the benefits and risks of a particular method. No method of contraception is contraindicated by age alone, although combined hormonal contraception and injectable progestogens are not recommended for women over the age of 50 years. The intrauterine system has particular advantages as a low-dose method of effective hormonal contraception, which also offers control of menstrual dysfunction and endometrial protection in women requiring oestrogen replacement. Condoms are recommended for personal protection against sexually transmitted infections in new relationships. Standard hormone replacement therapy is not a method of contraception. Copyright © 2014 Elsevier Ltd. All rights reserved.

Over-the-Counter Access to Oral Contraceptives.

PubMed

Grossman, Daniel

2015-12-01

Making oral contraceptives (OCs) available over the counter (OTC) could help to reduce the high rate of unintended pregnancy in the United States. Surveys show widespread support for OTC access to OCs among US women. Studies indicate that women can accurately use checklists to identify contraindications to OCs. Continuation is as good or better among OTC users compared with women using OCs obtained by prescription. Women and clinicians have expressed concerns related to making OCs available OTC. These concerns can be addressed by existing data or through research required by the Food and Drug Administration as part of the application to make OCs available OTC. Copyright © 2015 Elsevier Inc. All rights reserved.

The CORALIE study: improving patient education to help new users better understand their oral contraceptive.

PubMed

de Reilhac, Pia; Plu-Bureau, Geneviève; Serfaty, David; Letombe, Brigitte; Gondry, Jean; Christin-Maitre, Sophie

2016-10-01

Combined oral contraceptives (COCs) are the most widely used contraceptive method in Europe. Paradoxically, rates of unintended pregnancy and abortion are still remarkably high. A lack of knowledge about COCs is often reported to lead to poor adherence, suggesting an unmet need for adequate contraceptive counselling. Our objective was to investigate the impact on the knowledge level of users of a structured approach to deliver contraceptive information for a first COC prescription. The Oral Contraception Project to Optimise Patient Information (CORALIE) is a multicentre, prospective, randomised study conducted in France between March 2009 and January 2013. The intervention involved providing either an 'essential information' checklist or unstructured counselling to new COC users. The outcome measure was a questionnaire that assessed whether the information provided to the new user by the gynaecologist had been correctly understood. One hundred gynaecologists and an expert committee used the Delphi method to develop an 'essential information' checklist, after which 161 gynaecologists were randomised to two groups. Group I (n = 81) used the checklist with 324 new COC users and group II (n = 80) delivered unstructured information to 307 new COC users. The average score for understanding the information delivered during the visit was significantly higher in women in group I than in the women in group II, even after adjustment for age and previous history of pregnancy: 16.48/20 vs 14.27/20 (p < 0.0001). Delivering structured information for a first COC prescription is beneficial for understanding contraception. Our tool could ultimately contribute to increased adherence and should be investigated in a prospective study of long-term outcomes.

Influence of oral contraceptives on endogenous pain control in healthy women.

PubMed

Rezaii, Taraneh; Ernberg, Malin

2010-06-01

This study investigated the influence of oral contraceptives (OC) on diffuse noxious inhibitory control (DNIC) in healthy women. Fifteen women taking OC and 17 normally menstruating women (No-OC) were tested during high and low endogenous estrogens sessions. Saliva was sampled for analysis of endogenous estradiol level. Mechanical pressure (test stimuli) was applied to the masseter muscle and finger. The pain induced by this pressure was assessed on a 0-10 numerical rating scale (NRS) before, during, and after immersion of the contralateral hand in ice-cold water (cold pressor test, CPT) to induce DNIC. For all subjects, pain induced by the test stimuli decreased significantly during the CPT (P < 0.001). The decrease in general was larger in the No-OC group, with a significant difference between groups in the masseter muscle in the low session (P < 0.027). There were no significant differences between groups or sessions in estradiol levels. These results indicate that endogenous pain modulation may be less effective in OC users.

Evaluation of Potential Drug–Drug Interaction Between Delayed‐Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women

PubMed Central

Nestorov, Ivan; Zhao, Guolin; Meka, Venkata; Leahy, Mark; Kam, Jeanelle; Sheikh, Sarah I.

2017-01-01

Abstract Delayed‐release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti‐inflammatory and neuroprotective properties. This 2‐period crossover study was conducted to evaluate the potential for drug–drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty‐six healthy women were enrolled; 32 completed the study. After the lead‐in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration–time curve over the dosing interval and peak plasma concentration contained within the 0.8–1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol–based OCs may be used with DMF without dose modification. PMID:28783872

Pharmacokinetics of orally administered low-dose rapamycin in healthy dogs: A pilot study

PubMed Central

Larson, Jeanne C.; Allstadt, Sara D.; Fan, Timothy M.; Khanna, Chand; Lunghofer, Paul J.; Hansen, Ryan J.; Gustafson, Daniel L.; Legendre, Alfred M.; Galyon, Gina D.; LeBlanc, Amy K.; Martin-Jimenez, Tomas

2017-01-01

Objective To determine the pharmacokinetics of orally administered rapamycin in healthy dogs. Animals 5 healthy purpose-bred hounds. Procedures The study consisted of 2 experiments. In experiment 1, each dog received rapamycin (0.1 mg/kg, PO) once; blood samples were obtained immediately before and at 0.5, 1, 2, 4, 6, 12, 24, 48, and 72 hours after administration. In experiment 2, each dog received (0.1 mg/kg, PO) once daily for 5 days; blood samples were obtained immediately before and at 3, 6, 24, 27, 30, 48, 51, 54, 72, 75, 78, 96, 96.5, 97, 98, 100, 102, 108, 120, 144, and 168 hours after the first dose. Blood rapamycin concentration was determined by a validated liquid chromatography-tandem mass spectrometry assay. Pharmacokinetic parameters were determined by compartmental and non-compartmental analyses. Results Mean ± SD blood rapamycin terminal half-life, area under the concentration-time curve from 0 to 48 hours after dosing, and maximum concentration were 38.7 ± 12.7 h, 140 ± 23.9 ng•h/mL, and 8.39 ± 1.73 ng/mL, respectively, for experiment 1, and 99.5 ± 89.5 h, 126 ± 27.1 ng•h/mL, and 5.49 ± 1.99 ng/mL, respectively, for experiment 2. Pharmacokinetic parameters for rapamycin after administration of 5 daily doses differed significantly from those after administration of 1 dose. Conclusions and Clinical Relevance Results indicated that oral administration of low-dose (0.1 mg/kg) rapamycin to healthy dogs achieved blood concentrations measured in ng/mL. The optimal dose and administration frequency of rapamcyin required to achieve therapeutic effects in tumor-bearing dogs, as well as toxicity after chronic dosing, needs to be determined. PMID:26709938

Expert opinion on a flexible extended regimen of drospirenone/ethinyl estradiol contraceptive.

PubMed

Han, Leo; Jensen, Jeffrey T

2014-10-01

Oral contraceptives are often prescribed in extended or continuous forms in order to manage menstrual bleeding and menstrual-related side effects. However, with extended regimens, unscheduled intracycle bleeding can become problematic. Flexible extended dosing of a contraceptive containing drospirenone (DRSP) and ethinyl estradiol (EE) was designed to improve bleeding profiles during extended cycles through active management of bleeding symptoms. We examine the rationale for flexible extended dosing as well as review the dosing regimen. We will focus on the findings of the two most important clinical trials regarding flexible extended DRSP/EE (3 mg/20 μg), including the bleeding profiles of women in those trials. Pharmacology, mechanisms of action, efficacy as well as safety of DRSP containing pills will also be reviewed. Flexible extended dosing of DRSP/EE (3 mg/20 μg) has similar pharmacokinetics and contraceptive efficacy of both conventional and fixed extended regimens. However, it has the added benefit of fewer days of bleeding/spotting compared to conventional and fixed extended regimens.

Women's perceptions of contraceptive efficacy and safety.

PubMed

Kakaiya, Roshni; Lopez, Lia L; Nelson, Anita L

2017-01-01

Adoption of contraceptive implants and intrauterine devices has been less than might be expected given their superior efficacy and convenience. The purpose of this study was to assess knowledge and beliefs held by women, which may influence their contraceptive choices and theirongoing utilization of contraceptive methods. English speaking, nonpregnant, reproductive-age women, who were not surgically sterilized, were individually interviewed to obtain limited demographic characteristics and to assess their knowledge about the efficacy of various contraceptive methods in typical use and about the relative safety of oral contraceptives. A convenience sample of 500 women aged 18-45 years, with education levels that ranged from middle school to postdoctoral level was interviewed. The efficacy in typical use of both combined oral contraceptives and male condoms was correctly estimated by 2.2%; over two-thirds of women significantly over estimated the efficacy of each of those methods in typical use. Oral contraceptives were thought to be at least as hazardous to a woman's health as pregnancy by 56% of women. The majority of reproductive aged women surveyed substantially overestimated the efficacy of the two most popular contraceptive methods, often saying that they were 99% effective. Women with higher education levels were most likely to overestimate efficacy of oral contraceptives. Women of all ages and education levels significantly overestimated the health hazards of oral contraceptives compared to pregnancy. Overestimation of effectiveness of these methods of contraception, may contribute to lower adoption of implants and intrauterine devices. When individualizing patient counselling, misperceptions must be identified and addressed with women of all educational backgrounds. Not applicable.

Simultaneous total occlusion of two coronary arteries associated with use of drospirenone-ethinyl estradiol (oral contraceptive).

PubMed

Atmaca, Hüsnü; Köprülü, Diyar; Kiriş, Tuncay; Zeren, Gönül; Şahin, İrfan

2018-01-01

Although the use of oral contraceptives is associated with an increased risk of venous thromboembolic disease, the risk of myocardial infarction (MI) is unclear. A new, third-generation contraceptive agent, drospirenone-ethinyl estradiol, which contains less estrogen and a new progestogen, drospirenone, in a different combination, has been considered more reliable in terms of risk of MI. However, there have been some cases of MI associated with the use of drospirenone-ethinyl estradiol, despite the protective effects of this oral contraceptive. In this report, a 33-year-old woman who had used drospirenone-ethinyl estradiol for 6 months was admitted with MI and symptoms of cardiogenic shock. Coronary angiography revealed the total occlusion of 2 coronary arteries and so percutaneous coronary intervention was performed. To the best of our knowledge, this is the first case report of simultaneous total occlusion of 2 coronary arteries associated with the use of drospirenone-ethinyl estradiol in the English-language medical literature.

Standard dose versus low dose non-vitamin K antagonist oral anticoagulants in Asian patients with atrial fibrillation: A meta-analysis of contemporary randomized controlled trials.

PubMed

Wang, Kang-Ling; Giugliano, Robert P; Goto, Shinya; Chiu, Chun-Chih; Lin, Chun-Yi; Lai, En-Yu; Chiang, Chern-En

2016-12-01

Although randomized controlled trials (RCTs) indicated that standard dose non-vitamin K antagonist oral anticoagulants (NOACs) were more compelling, low dose NOACs are commonly used in clinical practice in Asia. The purpose of this study was to assess the relative therapeutic benefit and risk of standard dose vs low dose NOACs in Asian patients enrolled in contemporary RCTs. We performed a prespecified meta-analysis of 3155 Asian patients with NOACs in the RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy) and ENGAGE AF-TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48) trials. Efficacy and safety with standard dose vs low dose NOACs were compared by risk ratios (RRs) and 95% confidence intervals (CIs) in a random-effects model. An evidence network incorporating additional Asian patients from ROCKET AF, J- ROCKET AF, and ARISTOTLE was constructed with the Bayesian method. Risks of stroke or systemic embolism and ischemic stroke were significantly reduced with standard dose vs low dose NOACs (RR 0.62, 95% CI 0.45-0.85; and RR 0.55, 95% CI 0.38-0.79, respectively). Rates of major, intracranial, and life-threatening bleeding with 2 dosing regimens were broadly similar (RR 1.31, 95% CI 0.74-2.33; RR 1.54, 95% CI 0.72-3.30; and RR 1.49, 95% CI 0.87-2.55, respectively). Absolute rates of all-cause mortality and the net clinical outcome with standard dose NOACs were lower but not statistically significant (absolute reduction 0.4% per year and 1.1% per year, respectively). Network meta-analyses demonstrated that standard dose NOACs had the most favorable risk-benefit profile among oral anticoagulants. In Asian patients, standard dose NOACs represent a more appealing therapeutic option than low dose NOACs, with a significant reduction in ischemic stroke without an excess of major bleeding. Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.

Forgettable contraception.

PubMed

Grimes, David A

2009-12-01

The term "forgettable contraception" has received less attention in family planning than has "long-acting reversible contraception." Defined here as a method requiring attention no more often than every 3 years, forgettable contraception includes sterilization (female or male), intrauterine devices, and implants. Five principal factors determine contraceptive effectiveness: efficacy, compliance, continuation, fecundity, and the timing of coitus. Of these, compliance and continuation dominate; the key determinants of contraceptive effectiveness are human, not pharmacological. Human nature undermines methods with high theoretical efficacy, such as oral contraceptives and injectable contraceptives. By obviating the need to think about contraception for long intervals, forgettable contraception can help overcome our human fallibility. As a result, all forgettable contraception methods provide first-tier effectiveness (contraceptives today with exclusively first-tier effectiveness is the one that can be started -- and then forgotten for years.

Oral contraceptives cause evolutionarily novel increases in hormone exposure

PubMed Central

Lovett, Jennie L; Chima, Margo A; Wexler, Juliana K; Arslanian, Kendall J; Friedman, Andrea B; Yousif, Chantal B; Strassmann, Beverly I

2017-01-01

Abstract Background and objectives In the evolutionary past, women spent most of their reproductive lives either pregnant or in lactational amenorrhea, and rarely menstruated. The current pattern of frequent menses, and the associated increase in endogenous hormonal exposure, has been implicated in the current breast cancer epidemic. It is not known, however, whether oral contraceptives further increase, or actually decrease, hormonal exposure over one menstrual cycle. Here, we examined variation in hormonal exposure across seven oral contraceptive (OC) formulations, and produced the first quantitative comparison of exogenous versus endogenous hormone exposure. Methodology Data from 12 studies of serum estradiol (E2) and progesterone (P4) were aggregated to create a composite graph of endogenous hormone levels over one menstrual cycle in European or American women (age 19–40 years). Pharmacokinetic package insert data, also from Western women, were used to calculate exposures for hormones in seven different OC formulations. Endogenous and exogenous hormone levels were compared after adjusting for the relative binding affinity (RBA) of progestin to the progesterone receptor and ethinyl estradiol (EE) to the estrogen receptor. Results After adjusting for RBA, median ethinyl estradiol exposure across 28 days in the OCs was 11.4 nmol/l, similar to median E2 exposure. One formulation, however, was 40% higher in ethinyl estradiol exposure relative to median endogenous estradiol. Median exposure from progestins in OCs (1496 nmol/l) was 4-fold higher than the median endogenous exposure from P4 (364 nmol/l). Exposure from OC progestins ranged from one sixtieth to 8-fold median endogenous P4 over 28 days. Conclusions and implications Given that breast cancer risk increases with hormonal exposure, our finding that four widely prescribed formulations more than quadruple progestin exposure relative to endogenous progesterone exposure is cause for concern. As not all

Low-dose levonorgestrel and ethinyl estradiol patch and pill: a randomized controlled trial.

PubMed

Kaunitz, Andrew M; Portman, David; Westhoff, Carolyn L; Archer, David F; Mishell, Daniel R; Rubin, Arkady; Foegh, Marie

2014-02-01

To compare a new low-dose levonorgestrel and ethinyl estradiol contraceptive patch (Patch) with a combination oral contraceptive (Pill; 100 micrograms levonorgestrel, 20 micrograms ethinyl estradiol) regarding efficacy, safety, compliance, and unscheduled uterine bleeding. Women (17-40 years; body mass index 16-60) were randomized in a 3:1 ratio to one of two groups: Patch only (13 cycles) or Pill (six cycles) followed by Patch (seven cycles). Investigators evaluated adverse events during cycles 2, 4, 6, 9, and 13. Participants recorded drug administration and uterine bleeding on daily diary cards. Compliance was assessed by measuring levonorgestrel and ethinyl estradiol plasma levels. Pearl Index (pregnancies per 100 woman-years) was calculated to evaluate efficacy. Participants (N=1,504) were randomized to Patch (n=1,129) or Pill (n=375). Approximately 30% were obese, more than 40% were racial or ethnic minorities, and more than 55% were new users of hormonal contraceptives. Laboratory-verified noncompliance (undetectable plasma drug levels) was 11% of Patch and 12.6% of Pill users at cycle 6. Pearl Indices (95% confidence intervals) for the intention-to-treat population (cycles 1-6) were 4.45 (2.34-6.57) for Patch and 4.02 (0.50-7.53) for Pill; excluding laboratory-verified noncompliant participants, Pearl Indices were 2.82 (0.98-4.67) for Patch and 3.80 (0.08-7.52) for Pill (differences not statistically significant). Incidence of unscheduled bleeding and incidence and severity of adverse events were similar for both contraceptives (no statistically significant difference). Efficacy and safety of the new contraceptive Patch are comparable to those of a Pill. Laboratory-verified noncompliance and bleeding profile are similar between the two treatments. The Patch was well tolerated. ClinicalTrials.gov, www.clinicaltrials.gov, NCT01181479. I.

Therapeutic, prophylactic, untoward, and contraceptive effects of combined oral contraceptives: catholic teaching, natural law, and the principle of double effect when deciding to prescribe and use.

PubMed

Casey, Murray Joseph; Salzman, Todd A

2014-01-01

Combined oral contraceptives (COC) have been demonstrated to have significant benefits for the treatment and prevention of disease. These medications also are associated with untoward health effects, and they may be directly contraceptive. Prescribers and users must compare and weigh the intended beneficial health effects against foreseeable but unintended possible adverse effects in their decisions to prescribe and use. Additionally, those who intend to abide by Catholic teachings must consider prohibitions against contraception. Ethical judgments concerning both health benefits and contraception are approached in this essay through an overview of the therapeutic, prophylactic, untoward, and contraceptive effects of COC and discussion of magisterial and traditional Catholic teachings from natural law. Discerning through the principle of double effect, proportionate reason, and evidence gathered from the sciences, medical and moral conclusions are drawn that we believe to be fully compliant with good medicine and Catholic teaching.

Low use of contraceptives among rural women in Maitha, Uttar Pradesh, India.

PubMed

Saroha, Ekta; Altarac, Maja; Sibley, Lynn M

2013-05-01

Low contraceptive utilisation and high fertility in rural Uttar Pradesh (UP), India, is a major concern for the world's second most populous country. The association between reasons for low contraceptive utilisation and maternal factors has been inadequately researched. Data from the 'morbidity and performance assessment' study were analysed to explore reasons for low contraceptive utilisation and their association with maternal factors among 308 women in Maitha, rural UP, India. Chi-square, t-test, ANOVA, and logistic regression analyses were conducted. Majority (84.2%) of the rural women in Maitha, UP, India were not using any contraceptives. Upper caste, literate wives, and wives whose husbands were literate were more likely to use contraceptives. About one-third of the women did not want to use a contraceptive because they wanted another child. Large numbers (65.3%) of women wanted to use contraceptives but were unable to do so due to lack of knowledge (38.9%), fear of side-effects (15.5%), husband/family disapproval (15.5%), inconvenience (10.7%), and other reasons (19.1%). Maternal parity, wives' and husband's literacy were significantly associated with the reasons for low contraceptive utilisation (p < 0.05). Contraceptive utilisation can be Improved by taking into consideration such maternal characteristics. All state subsidised contraceptives should be more widely known, understood and made available.

The 1998 Canadian Contraception Study.

ERIC Educational Resources Information Center

Fisher, William A.; Boroditsky, Richard; Bridges, Martha L.

1999-01-01

Describes the 1998 Canadian Contraception Study, a mailed survey which asked women about contraceptive practices past, present, and future (including use of oral contraceptives, condoms, and sterilization); familiarity with and opinion about different contraception methods; and general sexual and reproductive health. The paper also examines…

Sumatriptan (50 mg tablets vs. 25 mg suppositories) in the acute treatment of menstrually related migraine and oral contraceptive-induced menstrual migraine: a pilot study.

PubMed

Facchinetti, Fabio; Allais, Gianni; Nappi, Rossella E; Gabellari, Ilaria Castagnoli; Di Renzo, Gian Carlo; Genazzani, Andrea R; Bellafronte, Manuela; Roncolato, Maurizio; Benedetto, Chiara

2010-10-01

Migraine attacks are common in the perimenstrual period (menstrually-related migraine, MRM) and can be particularly exacerbated by the cyclic suspension of oral contraceptives (oral contraceptive-induced menstrual migraine, OCMM). This cross-over, randomised study evaluated the efficacy and tolerability of rectal (25 mg) and oral (50 mg) sumatriptan in the treatment of 232 menstrual migraine attacks (135 MRM and 97 OCMM). Two hours after suppository administration, 72% of patients in the MRM group achieved pain relief and 24% were pain free; after tablet administration, the percentages were 66% and 27%, respectively. In the OCMM group 55% of patients improved at 2 h with suppositories and 46% with tablets, 27% of patients were pain-free after suppositories and 18% after tablets. Fifty percent of patients given suppositories were pain-free at 4 h post-treatment and 47% of those given tablets. Sumatriptan also effectively alleviated symptoms associated with migraine, such as nausea, vomiting and photo/phonophobia. A single dose of medication sufficed for pain relief without relapse in 47.4% of the attacks (MRM: 66%; OCMM: 33%). Both formulations were well tolerated.

Combined oral contraceptive treatment for bleeding complaints with the etonogestrel contraceptive implant: a randomised controlled trial.

PubMed

Hou, Melody Y; McNicholas, Colleen; Creinin, Mitchell D

2016-10-01

Estimate symptom improvement rate of women with bleeding complaints using the etonogestrel contraceptive implant when started on continuous combined oral contraceptives (COC). We conducted a double-blinded randomised controlled trial of women reporting troublesome bleeding related to their etonogestrel contraceptive implant and desiring intervention. Participants received continuous COCs or placebo for four weeks to evaluate self-reported bleeding improvement at four weeks. Participants could continue study treatment or prescribed COCs for another eight weeks if desired. We planned to enroll 130 participants between two sites (80% power to detect a 20% effect size at a 0.05 significance level, with 10% loss to follow up). We closed the study after enrolling 26 participants due to recruitment futility. All women on COCs and 75% of placebo users reported bleeding improvement at four weeks (p = 0.09), with 92% and 42%, respectively, reporting significant improvement (p = 0.03). The median number of days until bleeding stopped for at least four days in COC and placebo users was 1 day (range 1-9) and 4.5 days (range 1-28), respectively (p = 0.63). Eight (75%) COC and five (42%) placebo users opted to continue study treatment (p = 0.41). Despite bleeding improvement, women who desired implant removal at enrollment were more likely to re-request removal than those who initially considered other interventions (3 of 5 [60%] vs 1 of 17 [6%], p = 0.03). Although women who have troublesome bleeding while using the contraceptive implant may experience improvement with no treatment over 4 weeks, women using COCs are more likely to report significant improvement. Clinicaltrials.gov registration number: NCT01963403.

Strategies for communicating contraceptive effectiveness.

PubMed

Lopez, Laureen M; Steiner, Markus; Grimes, David A; Hilgenberg, Deborah; Schulz, Kenneth F

2013-04-30

data, one trial showed that effectiveness categories were better than pregnancy numbers. In another trial, audiovisual aids worked better than the usual oral presentation. Strategies should be tested in clinical settings and measured for their effect on contraceptive choice. More detailed reporting of intervention content would help in interpreting results. Reports could also include whether the instruments used to assess knowledge or attitudes were tested for validity or reliability. Follow-up should be incorporated to assess retention of knowledge over time. The overall quality of evidence was considered to be low for this review, given that five of the seven studies provided low or very low quality evidence.

Oral contraceptive pills induced hemichorea in an adolescent female with polycystic ovarian disease.

PubMed

Sharmila, Vijayan; Babu, Thirunavukkarasu Arun

2015-01-01

Chorea is a neurological adverse effect of oral contraceptive pills (OCPs). The onset of chorea following OCPs usage varies widely from few weeks to several years. We report a rare case of chorea which developed within a week of starting OCPs in an adolescent girl with polycystic ovarian disease.

Ongoing contraception after use of emergency contraception from a specialist contraceptive service.

PubMed

Cameron, Sharon T; Glasier, Anna; Johnstone, Anne; Rae, Leanne

2011-10-01

A consultation for emergency contraception (EC) gives way to an opportunity to provide women with an ongoing effective method of contraception. A review of the case notes of women seeking EC from a large family planning clinic in Edinburgh, Scotland, was conducted to determine what percentage of women were provided with an effective method of ongoing contraception. Case notes of 460 women presenting for EC over a 2-year period were reviewed. Women were of mean age 26 years (range 15-49 years) and presented because they had used no contraception (47%), experienced condom failure (42%) or missed oral contraceptive pills (9%). Only 2% (n=11) were given an intrauterine device for EC. All women who had missed contraceptive pills prior to taking EC opted to continue this method. Only 23% (n=89) of women using no method or condoms at EC received supplies of an effective contraceptive method (pills, patch, injectable). Two thirds (n=263) of the women chose condoms for ongoing contraception. Research is required to develop strategies to improve the uptake of effective contraception after EC. Copyright © 2011 Elsevier Inc. All rights reserved.

An open label, comparative study of the effects of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol and 100 microg levonorgestrel on hemostatic, lipids, and carbohydrate metabolism variables.

PubMed

Endrikat, Jan; Klipping, C; Cronin, M; Gerlinger, C; Ruebig, A; Schmidt, W; Düsterberg, B

2002-03-01

In this open label, randomized study we compared the influence of a dose-reduced oral contraceptive containing 20 microg ethinyl estradiol (EE) and 100 microg levonorgestrel (20 EE) with a reference preparation containing 30 microg EE and 150 microg levonorgestrel (30 EE) on hemostatic, lipids, and carbohydrate metabolism variables. Data from 48 volunteers were obtained. The direction of the change (increase or decrease) in most of the hemostatic variables were similar in both treatment groups. In particular, prothrombin fragment 1 + 2 increased during treatment, reaching a median percent change of 40% in the 20 EE group and of 17% in the 30 EE group after one year. D-Dimer fibrin split products remained virtually unchanged, with no change at Cycle 13. The median HDL2 cholesterol levels decreased by 26% in the 20 EE group and by 39.8% in 30 EE group (p = 0.0045 for group difference) after one year. The median one year change for LDL cholesterol was 3.23% in the 20 EE group, compared to 25% in the 30 EE group, for VLDL 11.1% compared to 38.8%, respectively, and for total triglycerides 10.0% compared to 37.5%, respectively. The median absolute change for the area under the curve (AUC)(0-3h) for glucose at treatment Cycle 13 was 41.25 mmol/L x min in the 20 EE group and 73.50 mmol/L x min in the 30 EE group. The AUC(0-3h) insulin at treatment Cycle 13 decreased in the 20 EE group by 1635.0 pmolL x min and increased in the 30 EE group by 11797.5 pmolL x min (p = 0.0491 for group difference). Both study treatments were safe and well tolerated by the volunteers. In conclusion, the balanced one-third dose reduction in this new oral contraceptive evoked similar effects on the hemostatic variables, but favorable results for the lipid and carbohydrate profiles.

Estimating systemic exposure to levonorgestrel from an oral contraceptive.

PubMed

Basaraba, Cale N; Westhoff, Carolyn L; Pike, Malcolm C; Nandakumar, Renu; Cremers, Serge

2017-04-01

The gold standard for measuring oral contraceptive (OC) pharmacokinetics is the 24-h steady-state area under the curve (AUC). We conducted this study to assess whether limited sampling at steady state or measurements following use of one or two OCs could provide an adequate proxy in epidemiological studies for the progestin 24-h steady-state AUC of a particular OC. We conducted a 13-sample, 24-h pharmacokinetic study on both day 1 and day 21 of the first cycle of a monophasic OC containing 30-mcg ethinyl estradiol and 150-mcg levonorgestrel (LNG) in 17 normal-weight healthy White women and a single-dose 9-sample study of the same OC after a 1-month washout. We compared the 13-sample steady-state results with several steady-state and single-dose results calculated using parsimonious sampling schemes. The 13-sample steady-state 24-h LNG AUC was highly correlated with the steady-state 24-h trough value [r=0.95; 95% confidence interval (0.85, 0.98)] and with the steady-state 6-, 8-, 12- and 16-h values (0.92≤r≤0.95). The trough values after one or two doses were moderately correlated with the steady-state 24-h AUC value [r=0.70; 95% CI (0.27, 0.90) and 0.77; 95% CI (0.40, 0.92), respectively]. Single time-point concentrations at steady state and after administration of one or two OCs gave highly to moderately correlated estimates of steady-state LNG AUC. Using such measures could facilitate prospective pharmaco-epidemiologic studies of the OC and its side effects. A single time-point LNG concentration at steady state is an excellent proxy for complete and resource-intensive steady-state AUC measurement. The trough level after two single doses is a fair proxy for steady-state AUC. These results provide practical tools to facilitate large studies to investigate the relationship between systemic LNG exposure and side effects in a real-life setting. Copyright © 2017 Elsevier Inc. All rights reserved.

Evaluation of effects of an oral contraceptive containing ethinylestradiol combined with drospirenone on adrenal steroidogenesis in hyperandrogenic women with polycystic ovary syndrome.

PubMed

De Leo, Vincenzo; Morgante, Giuseppe; Piomboni, Paola; Musacchio, Maria Concetta; Petraglia, Felice; Cianci, Antonio

2007-07-01

To investigate whether the administration of an oral contraceptive containing the new antiandrogenic drospirenone is associated with reduced adrenal androgen synthesis in hyperandrogenic women with diagnosis of polycystic ovary syndrome. Drospirenone, an analogue of spironolactone and aldosterone antagonist, is a novel progestin under clinical development that is similar to the natural hormone progesterone, combining potent progestogenic with antimineralocorticoid and antiandrogenic activities. Prospective study. Healthy volunteers in University Department of Obstetrics and Gynecology. Fifteen women ages 18 to 28 years with the diagnosis of polycystic ovary syndrome. Three months of contraceptive use (30 mcg ethinylestradiol, 3 mg drospirenone). An adrenocorticotropic hormone test was performed before and after the study. Adrenal production of cortisol was unchanged after therapy with oral contraceptives. An interesting observation was reduced basal concentrations of androgens such as androstenedione, dehydroepiandrosterone sulfate, testosterone, and free testosterone during therapy. The ratios of the areas of substrates to products before and after oral contraceptive administration were compared for differences in 17alpha-hydroxylase (17-hydroxyprogesterone/progesterone) and 17,20-lyase (androstenedione/17-hydroxyprogesterone); activities were significantly reduced, indicating a reduction in the activities of these enzymes. The present results show for the first time that oral contraceptives containing drospirenone affect adrenal steroidogenesis by reducing synthesis and release of androgens in response to adrenocorticotropic hormone, leaving adrenal production of cortisol unchanged.

Pituitary, ovarian and additional contraceptive effects of an estradiol-based combined oral contraceptive: results of a randomized, open-label study.

PubMed

Endrikat, Jan; Parke, Susanne; Trummer, Dietmar; Serrani, Marco; Duijkers, Ingrid; Klipping, Christine

2013-02-01

The estrogen step-down/progestogen step-up 28-day estradiol valerate/dienogest (E(2)V/DNG) oral contraceptive effectively inhibits ovulation; however, limited data are available regarding its effects on estradiol (E2), progesterone, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) or its additional extraovarian contraceptive effects. In this secondary analysis, 100 women received E(2)V 3 mg on days 1-2, E(2)V 2 mg/DNG 2 mg on days 3-7, E(2)V 2 mg/DNG 3 mg on days 8-24, E(2)V 1 mg on days 25-26 and placebo on days 27-28 for one treatment cycle. Measures included the presence/absence of cervical mucus; endometrial thickness; and serum E2, progesterone, and gonadotropin levels. E2, progesterone, LH and FSH levels did not exhibit the typical ovulatory increase and remained relatively stable during the cycle. E(2)V/DNG reduced mean maximal endometrial thickness and proportion of women with visible cervical mucus. All parameters returned to pretreatment levels during the posttreatment cycle. E(2)V/DNG provides extraovarian contraceptive effects (reducing endometrial thickness and cervical mucus production) in addition to inhibiting ovulation, assuring contraceptive efficacy. Copyright © 2013 Elsevier Inc. All rights reserved.

A comparative analysis of the modification of sexual desire of users of oral hormonal contraceptives and intrauterine contraceptive devices.

PubMed

Martin-Loeches, M; Ortí, R M; Monfort, M; Ortega, E; Rius, J

2003-09-01

To compare the influence of oral hormonal contraceptives (OCs) and the use of intrauterine contraceptive devices (IUDs) on the modification of sexual desire. A prospective observational study of 1073 women using OCs or an IUD at the Family Planning Center 'Marina Alta' in Alicante, Spain. In order to evaluate the relative risk regarding the decrease in libido attributed to each contraceptive method, a logistic regression analysis was undertaken which considered the factors of age adjustment, level of studies, family planning information, relationship with partner, age when sexual relationships were initiated, parity, contraceptive method previously used and the duration of use of the contraceptive method. No differences in the decrease of sexual desire were observed between the use of the OC and IUD (odds ratio (OR) 1.32; 95% confidence interval (CI) 0.70-2.49), yet differences were noted, however, in relation to age (OR 1.05; 95% CI 1.01-1.10). Although these differences were not statistically significant, a high level of awareness regarding family planning was shown to increase sexual desire when compared to a lower level of information on this subject (OR 0.64; 95% CI 0.41-1.01). Sexual desire was seen to decrease if the quality of the relationship with the partner was average (OR 2.24; 95% CI 1.36-3.69) or poor (OR 4.69; 95% CI 1.93-11.4). Nulliparous women showed a greater decrease in sexual desire in relation to women who had already given birth (OR 1.57; 95% CI 1.00-2.47). Sexual desire was greater if the contraceptive method had already been in use for 6-12 months (OR 0.41; 95% CI 0.17-0.98). Sexual desire does not vary in relation to the use of OCs or IUDs, yet it does decrease with age, in nulliparous women and in those with an average or poor relationship with their partner. Furthermore, sexual desire shows an increase between the first 6 and 12 months of contraceptive treatment.

Pretreatment with oral contraceptives in infertile anovulatory patients with polycystic ovary syndrome who receive gonadotropins for controlled ovarian stimulation.

PubMed

Palomba, Stefano; Falbo, Angela; Orio, Francesco; Russo, Tiziana; Tolino, Achille; Zullo, Fulvio

2008-06-01

This study was intended to assess the effects of oral contraceptives given before treatment in infertile anovulatory patients with polycystic ovary syndrome who receive gonadotropins for controlled ovarian stimulation. Pretreatment with oral contraceptives increased the mono-ovulatory cycles, the duration of stimulation for noncanceled cycles, and the number of vials of gonadotropins used. It also reduced the number of dominant follicles and the peak E(2) levels for dominant follicles. No effect was observed in rates of cycle cancellation, pregnancy, abortion, live birth, multiple pregnancies, and ovarian hyperstimulation syndrome.

Reproductive health outcomes of insured adolescent and adult women who access oral levonorgestrel emergency contraception.

PubMed

Raine-Bennett, Tina; Merchant, Maqdooda; Sinclair, Fiona; Lee, Justine W; Goler, Nancy

2015-04-01

To assess the level of risk for adolescents and women who seek emergency contraception through various clinical routes and the opportunities for improved care provision. This study looked at a retrospective cohort to assess contraception and other reproductive health outcomes among adolescents and women aged 15-44 years who accessed oral levonorgestrel emergency contraception through an office visit or the call center at Kaiser Permanente Northern California from 2010 to 2011. Of 21,421 prescriptions, 14,531 (67.8%) were accessed through the call center. In the subsequent 12 months, 12,127 (56.6%) adolescents and women had short-acting contraception (pills, patches, rings, depot medroxyprogesterone) dispensed and 2,264 (10.6%) initiated very effective contraception (intrauterine contraception, implants, sterilization). Initiation of very effective contraception was similar for adolescents and women who accessed it through the call center-1,569 (10.8%) and office visits-695 (10.1%) (adjusted odds ratio [OR] 1.02, 95% confidence interval [CI] 0.93-1.13). In the subsequent 6 months, 2,056 (9.6%) adolescents and women became pregnant. Adolescents and women who accessed emergency contraception through the call center were less likely to become pregnant within 3 months of accessing emergency contraception than woman who accessed it through office visits (adjusted OR 0.82, 95% CI 0.72-0.94); however, they were more likely to become pregnant within 4-6 months (adjusted OR 1.37, 95% CI 1.16-1.60). Among adolescents and women who were tested for chlamydia and gonorrhea, 689 (7.8%) and 928 (7.9%) were positive in the 12 months before and after accessing emergency contraception, respectively. Protocols to routinely address unmet needs for contraception at every call for emergency contraception and all office visits, including visits with primary care providers, should be investigated.

The emotional impact of genetic testing and aspects of counseling prior to prescription of oral contraceptives.

PubMed

Gartner, Verena; Weber, Michael; Eichinger, Sabine

2008-11-01

Oral contraceptives increase the thrombotic risk in women with factor V Leiden. Emotional aspects of genetic testing prior to the prescription of oral contraceptives (OC), aspects of counseling and referral patterns are widely unknown. Two hundred forty-seven women with and 132 women without factor V Leiden were interviewed by questionnaire. One hundred sixty-one women (65%) with factor V Leiden and 63 (48%) with wild-type factor V responded. One hundred seventy-one women (76%) reported being emotionally disturbed by genetic testing. Eighty percent of women with factor V Leiden and 16% of women with wild-type factor V were discouraged from OC use. Three percent of women with factor V Leiden were encouraged to take OC. Forty-one percent of women with factor V Leiden used at least one hormone contraceptive method after diagnosis. Only 46 women (29%) with factor V Leiden were counseled about the relevance of the mutation in case of pregnancy. Testing for factor V Leiden has considerable emotional impact. Recommendations after testing are not consistently driven by the test result.

Low-dose metronomic, multidrug therapy with the PEP-C oral combination chemotherapy regimen for mantle cell lymphoma.

PubMed

Coleman, Morton; Martin, Peter; Ruan, Jia; Furman, Richard; Niesvizky, Ruben; Elstrom, Rebecca; George, Patricia; Leonard, John; Kaufmann, Thomas

2008-03-01

The prednisone, etoposide, procarbazine and cyclophosphamide (PEP-C) oral combination chemotherapy regimen (prednisone 20 mg, cyclophosphamide 50 mg, etoposide 50 mg, and procarbazine 50 mg with an oral anti-emetic) was employed at our center to treat 22 patients with heavily pretreated, recurrent mantle cell lymphoma (MCL). All medications were administered daily until leukocytes fell to <3.0 x 10(9)/L whereupon treatment was withheld until recovery from the nadir. Therapy was then reinstituted on a daily, alternate day, or fractionated basis (e.g. 5 of 7 days) depending on patient tolerance. Doses given per day were held constant. Eighty-two percent achieved an objective response with 46% complete responses and 36% partial responses. Median time on therapy was 17 months. The regimen was well tolerated. Our findings demonstrate that low-dose oral agents administered in combination for continuous, prolonged periods with minimal drug-free intervals (metronomic therapy) may represent a novel, effective, easily tolerated approach to MCL and that this treatment approach warrants further exploration.

Effect of progestin vs. combined oral contraceptive pills on lactation: A double-blind randomized controlled trial

PubMed Central

Espey, Eve; Ogburn, Tony; Leeman, Larry; Singh, Rameet; Schrader, Ronald

2013-01-01

Objective To estimate the effect of progestin-only vs. combined hormonal contraceptive pills on rates of breastfeeding continuation in postpartum women. Secondary outcomes include infant growth parameters, contraceptive method continuation and patient satisfaction with breastfeeding and contraceptive method. Methods In this randomized controlled trial, postpartum breastfeeding women who desired oral contraceptives were assigned to progestin-only vs. combined hormonal contraceptive pills. At two and eight weeks postpartum, participants completed in-person questionnaires that assessed breastfeeding continuation and contraceptive use. Infant growth parameters including weight, length and head circumference were assessed at eight weeks postpartum. Telephone questionnaires assessing breastfeeding, contraceptive continuation and satisfaction were completed at 3-7 weeks and 4 and 6 months. Breastfeeding continuation was compared between groups using Cox proportional hazards regression. Differences in baseline demographic characteristics and in variables between the two intervention groups were compared using chi-square tests, Fisher’s Exact test, or two-sample t-tests as appropriate. Results Breastfeeding continuation rates, contraceptive continuation, and infant growth parameters did not differ between users of progestin-only and combined hormonal contraceptive pills. Infant formula supplementation and maternal perception of inadequate milk supply were associated with decreased rates of breastfeeding in both groups. Conclusions Choice of combined or progestin-only birth control pills administered two weeks postpartum did not adversely affect breastfeeding continuation. PMID:22143258

Effect of the hepatitis C virus protease inhibitor faldaprevir on the pharmacokinetics of an oral contraceptive containing ethinylestradiol and levonorgestrel in healthy female volunteers.

PubMed

Sabo, John P; Lang, Benjamin; Elgadi, Mabrouk; Huang, Fenglei

2015-01-01

Faldaprevir is a potent hepatitis C virus (HCV) NS3/4A protease inhibitor. Faldaprevir is known to inhibit P-glycoprotein, CYP3A4, and UDP-glucuronosyltransferase 1A1. This study evaluated the effect of steady-state 240 mg faldaprevir on the pharmacokinetics (PK) of an oral contraceptive containing ethinylestradiol (EE) and levonorgestrel (LNG) in healthy premenopausal women. In period 1, subjects received EE/LNG once daily (QD) for 14 days. Blood samples were taken on days 1, 11, and 12, with intensive PK blood sampling for EE and LNG on day 13. In period 2, subjects received EE-LNG QD and 240 mg faldaprevir QD on days 14 to 21 (240 mg faldaprevir twice daily on day 14). Blood samples were taken on days 14, 19, and 20, with PK profiling samples obtained for EE and LNG on day 21. A total of 15/16 subjects completed the study. Overall, EE and LNG exposure (assessed by the area under the curve) was approximately 1.4-fold higher when EE and LNG were coadministered with faldaprevir than when administered alone. Median t1/2 (terminal half-life in plasma at steady state) values were prolonged for both EE (2.4 h longer) and LNG (4.7 h longer) when EE and LNG were coadministered with faldaprevir. The mean oral clearance and apparent volume of distribution of both EE and LNG were lower (∼ 30%) when EE and LNG were coadministered with faldaprevir. Coadministration of faldaprevir and an oral contraceptive resulted in a moderate increase in exposure to both EE and LNG. However, this increase was not considered clinically meaningful, and no dose adjustment of oral contraceptives was deemed necessary. (This study has been registered at ClinicalTrials.gov under registration number NCT01570244.). Copyright © 2015, American Society for Microbiology. All Rights Reserved.

[Potential advantages of triphasic combined oral contraceptives in the light of recent epidemiological and endocrinometabolic data].

PubMed

Gaspard, U; Dubois, M

1982-09-01

New epidemiologic data on the vascular risks of oral contraceptives (OCs) were assessed to determine whether the recently introduced low dose triphasic pills offer greater potential safety for OC users than previous formulations. Epidemiologic studies have demonstrated that vascular accidents are less frequent with OCs containing lower doses of both estrogens and progestins. The new triphasic pills have the lowest steroid content of any pills yet developed and less of a progestin climate than low dose monophasic pills. The gradual increases in the progestin dose, from 50 mcg on days 1-6 to 75 mcg on days 7-11 and 125 mcg on days 12-21 and of ethinyl estradiol from 30 mcg on days 1-6 to 40 on days 7-11 and back to 30 on days 12-21 reflect the natural cycle of steroid secretion. The endometrial mucus is better developed than under low dose monophasic pills, permitting better cycle control. Triphasic pills have been shown in all studies to block secretion by the hypothalamus and pituitary of the gonadotropins follicle stimulating hormone and luteinizing hormone, resulting in absence of follicular maturation and of ovulation. Even with the small dose of levonorgestrel, the cervical mucus is rendered inhospitable to capacitation and passage of sperm. The impact on glucose tolerance of low doses of ethinyl estradiol, even after long use, is minimal, but the 19 norsteroids used in most combined pills have a more significant impact. To the directly stimulating effect of progestins on pancreatic insulin secretion is added the development of increased peripheral resistence apparently due to a decrease in the number of insulin receptors in the target tissue. The decrease appears to be dose dependent and proportional to the androgenicity of the progestin. A recent study indicated that triphasic pills caused less of a deterioration in glucose tolerance than standard or low-dose combined OCs or a biphasic formulation. This finding was significant because of the possibility that

Supplementation with vitamin B6 reduces side effects in Cambodian women using oral contraception.

PubMed

Var, Chivorn; Keller, Sheryl; Tung, Rathavy; Freeland, Dylan; Bazzano, Alessandra N

2014-08-26

Hormonal contraceptives may produce side effects that deter women from their use as a method of family planning. In nutritionally vulnerable populations these effects may be more pronounced due to micronutrient deficiencies and health status. Previous studies have been unable to resolve whether micronutrient supplementation may reduce such side effects. In a longitudinal study, 1011 women obtaining oral contraception through the public health system in rural Cambodia were allocated to either intervention or control groups, receiving either daily Vitamin B6 supplement or care as usual (without placebo). The intervention participants (n = 577) reported fewer side effects in three categories: nausea/no appetite, headache, and depression compared with control group participants (n = 434). Women taking Vitamin B6 supplement were less likely to report side effects in a nutritionally vulnerable population. Underlying nutrition status should be considered by clinicians and reproductive health policy makers in the context of providing contraceptive services. Further investigation into micronutrient supplementation, particularly with B6, in reproductive-aged women using hormonal contraception should be conducted in other settings to determine the potential for widespread adoption.

Pituitary and ovarian hormone activity during the 7-day hormone-free interval of various combined oral contraceptive regimens.

PubMed

Cho, Michael; Atrio, Jessica; Lim, Aaron H; Azen, Colleen; Stanczyk, Frank Z

2014-07-01

The objective was to investigate changes in luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2) and progesterone (P) during the hormone-free interval (HFI) of 6 combined oral contraceptives (COCs). Blood samples were obtained from 62 women. When COCs were grouped by ethinyl estradiol (EE) dose, there was a significant positive mean slope for LH and FSH during the HFI for the 30- and 35 mcg-EE doses, whereas 20 showed a gradual nonsignificant slope. All E2 slopes were significant. P remained suppressed with all doses. A more rapid rebound of gonadotropin levels is found with higher doses of EE during the HFI. This study showed a more rapid rebound of pituitary hormone levels among women using higher-EE-dosage formulations, which was demonstrated by the statistically significant slope for mean LH and FSH from day 1 to day 7 of the HFI. The degree of suppression did not vary across progestin generations. It remains to be established whether women who experience side effects during their HFI may benefit from using a COC with a lower EE dose to minimize changes in endogenous pituitary hormone levels. Copyright © 2014 Elsevier Inc. All rights reserved.

Oral contraceptive use changes brain activity and mood in women with previous negative affect on the pill--a double-blinded, placebo-controlled randomized trial of a levonorgestrel-containing combined oral contraceptive.

PubMed

Gingnell, Malin; Engman, Jonas; Frick, Andreas; Moby, Lena; Wikström, Johan; Fredrikson, Mats; Sundström-Poromaa, Inger

2013-07-01

Most women on combined oral contraceptives (COC) report high levels of satisfaction, but 4-10% complain of adverse mood effects. The aim of this randomized, double-blinded, placebo-controlled trial was to investigate if COC use would induce more pronounced mood symptoms than placebo in women with previous history of COC-induced adverse mood. A second aim was to determine if COC use is associated with changes in brain reactivity in regions previously associated with emotion processing. Thirty-four women with previous experience of mood deterioration during COC use were randomized to one treatment cycle with a levonorgestrel-containing COC or placebo. An emotional face matching task (vs. geometrical shapes) was administered during functional magnetic resonance imaging (fMRI) prior to and during the COC treatment cycle. Throughout the trial, women recorded daily symptom ratings on the Cyclicity Diagnoser (CD) scale. During the last week of the treatment cycle COC users had higher scores of depressed mood, mood swings, and fatigue than placebo users. COC users also had lower emotion-induced reactivity in the left insula, left middle frontal gyrus, and bilateral inferior frontal gyri as compared to placebo users. In comparison with their pretreatment cycle, the COC group had decreased emotion-induced reactivity in the bilateral inferior frontal gyri, whereas placebo users had decreased reactivity in the right amygdala. COC use in women who previously had experienced emotional side effects resulted in mood deterioration, and COC use was also accompanied by changes in emotional brain reactivity. These findings are of relevance for the understanding of how combined oral contraceptives may influence mood. Placebo-controlled fMRI studies in COC sensitive women could be of relevance for future testing of adverse mood effects in new oral contraceptives. Copyright © 2012 Elsevier Ltd. All rights reserved.

Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol-containing oral contraceptive in healthy adult women.

PubMed

Trezza, Christine; Ford, Susan L; Gould, Elizabeth; Lou, Yu; Huang, Chuyun; Ritter, James M; Buchanan, Ann M; Spreen, William; Patel, Parul

2017-07-01

This study aimed to investigate whether cabotegravir (CAB), an integrase inhibitor in development for treatment and prevention of human immunodeficiency virus-1, influences the pharmacokinetics (PK) of a levonorgestrel (LNG) and ethinyl oestradiol (EO)-containing oral contraceptive (OC) in healthy women. In this open-label, fixed-sequence crossover study, healthy female subjects received LNG 0.15 mg/EO 0.03 mg tablet once daily Days 1-10 alone and with oral CAB 30 mg once daily Days 11-21. At the end of each treatment period, subjects underwent predose sampling for concentrations of follicle-stimulating hormone, luteinizing hormone, and progesterone and serial PK sampling for plasma LNG, EO, and CAB concentrations. Twenty women were enrolled, and 19 completed the study. One subject was withdrawn due to an adverse event unrelated to study medications. Geometric least squares mean ratios (90% confidence interval) of LNG + CAB vs. LNG alone for LNG area under the plasma concentration-time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.12 (1.07-1.18) and 1.05 (0.96-1.15), respectively. Geometric least squares mean ratio (90% confidence interval) of EO + CAB vs. EO alone for EO area under the plasma concentration-time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.02 (0.97-1.08) and 0.92 (0.83-1.03), respectively. Steady-state CAB PK parameters were comparable to historical values. There was no apparent difference in mean luteinizing hormone, follicle-stimulating hormone, and progesterone concentrations between periods. No clinically significant trends in laboratory values, vital signs, or electrocardiography values were observed. Repeat doses of oral CAB had no significant effect on LNG/EO PK or pharmacodynamics, which supports CAB coadministration with LNG/EO OCs in clinical practice. © 2017 ViiV Healthcare. British Journal of Clinical Pharmacology published by John

Lack of effect of oral cabotegravir on the pharmacokinetics of a levonorgestrel/ethinyl oestradiol‐containing oral contraceptive in healthy adult women

PubMed Central

Trezza, Christine; Ford, Susan L.; Gould, Elizabeth; Lou, Yu; Huang, Chuyun; Ritter, James M.; Buchanan, Ann M.; Spreen, William

2017-01-01

Aims This study aimed to investigate whether cabotegravir (CAB), an integrase inhibitor in development for treatment and prevention of human immunodeficiency virus‐1, influences the pharmacokinetics (PK) of a levonorgestrel (LNG) and ethinyl oestradiol (EO)–containing oral contraceptive (OC) in healthy women. Methods In this open‐label, fixed‐sequence crossover study, healthy female subjects received LNG 0.15 mg/EO 0.03 mg tablet once daily Days 1–10 alone and with oral CAB 30 mg once daily Days 11–21. At the end of each treatment period, subjects underwent predose sampling for concentrations of follicle‐stimulating hormone, luteinizing hormone, and progesterone and serial PK sampling for plasma LNG, EO, and CAB concentrations. Results Twenty women were enrolled, and 19 completed the study. One subject was withdrawn due to an adverse event unrelated to study medications. Geometric least squares mean ratios (90% confidence interval) of LNG + CAB vs. LNG alone for LNG area under the plasma concentration–time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.12 (1.07–1.18) and 1.05 (0.96–1.15), respectively. Geometric least squares mean ratio (90% confidence interval) of EO + CAB vs. EO alone for EO area under the plasma concentration–time curve over the dosing interval of duration τ and maximum observed plasma concentration were 1.02 (0.97–1.08) and 0.92 (0.83–1.03), respectively. Steady‐state CAB PK parameters were comparable to historical values. There was no apparent difference in mean luteinizing hormone, follicle‐stimulating hormone, and progesterone concentrations between periods. No clinically significant trends in laboratory values, vital signs, or electrocardiography values were observed. Conclusions Repeat doses of oral CAB had no significant effect on LNG/EO PK or pharmacodynamics, which supports CAB coadministration with LNG/EO OCs in clinical practice. PMID:28087972

Use of combined oral contraceptives and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases

PubMed Central

Coupland, Carol; Hippisley-Cox, Julia

2015-01-01

Objective To investigate the association between use of combined oral contraceptives and risk of venous thromboembolism, taking the type of progestogen into account. Design Two nested case-control studies. Setting General practices in the United Kingdom contributing to the Clinical Practice Research Datalink (CPRD; 618 practices) and QResearch primary care database (722 practices). Participants Women aged 15-49 years with a first diagnosis of venous thromboembolism in 2001-13, each matched with up to five controls by age, practice, and calendar year. Main outcome measures Odds ratios for incident venous thromboembolism and use of combined oral contraceptives in the previous year, adjusted for smoking status, alcohol consumption, ethnic group, body mass index, comorbidities, and other contraceptive drugs. Results were combined across the two datasets. Results 5062 cases of venous thromboembolism from CPRD and 5500 from QResearch were analysed. Current exposure to any combined oral contraceptive was associated with an increased risk of venous thromboembolism (adjusted odds ratio 2.97, 95% confidence interval 2.78 to 3.17) compared with no exposure in the previous year. Corresponding risks associated with current exposure to desogestrel (4.28, 3.66 to 5.01), gestodene (3.64, 3.00 to 4.43), drospirenone (4.12, 3.43 to 4.96), and cyproterone (4.27, 3.57 to 5.11) were significantly higher than those for second generation contraceptives levonorgestrel (2.38, 2.18 to 2.59) and norethisterone (2.56, 2.15 to 3.06), and for norgestimate (2.53, 2.17 to 2.96). The number of extra cases of venous thromboembolism per year per 10 000 treated women was lowest for levonorgestrel (6, 95% confidence interval 5 to 7) and norgestimate (6, 5 to 8), and highest for desogestrel (14, 11 to 17) and cyproterone (14, 11 to 17). Conclusions In these population based, case-control studies using two large primary care databases, risks of venous thromboembolism associated with combined oral

Oral contraceptives and colorectal cancer risk: a meta-analysis

PubMed Central

Fernandez, E; Vecchia, C La; Balducci, A; Chatenoud, L; Franceschi, S; Negri, E

2001-01-01

Several studies have suggested an inverse association between use of combined oral contraceptives (OC) and the risk of colorectal cancer and here we present a meta-analysis of published studies. Articles considered were epidemiological studies published as full papers in English up to June 2000 that included quantitative information on OC use. The pooled relative risks (RR) of colorectal cancer for ever OC use from the 8 case-control studies was 0.81 (95% confidence interval (CI): 0.69–0.94), and the pooled estimate from the 4 cohort studies was 0.84 (95% CI: 0.72–0.97). The pooled estimate from all studies combined was 0.82 (95% CI: 0.74–0.92), without apparent heterogeneity. Duration of use was not associated with a decrease in risk, but there was some indication that the apparent protection was stronger for women who had used OCs more recently (RR = 0.46; 95% CI: 0.30–0.71). A better understanding of this potential relation may help informed choice of contraception. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11237397

Contraception in Japan: Current trends.

PubMed

Yoshida, Honami; Sakamoto, Haruka; Leslie, Asuka; Takahashi, Osamu; Tsuboi, Satoshi; Kitamura, Kunio

2016-06-01

High proportion of Japanese uses condoms; lower proportion uses oral contraceptive pills (OCPs). We examined the longitudinal patterns for contraceptive usage in Japan and evaluated differences before and after OCP government approval. We accessed nationally representative survey data for women aged 16-49years from 1950 to 2014. Usage of condoms and OCP was 83.4% and 3.0%, respectively in 2014. OCP use before (1.21%) and after (1.97%) government approval did not differ significantly (p=.58). The prevalence of OCP usage remains low in Japan. A wide gap in use between Japan and other developed countries exists. Through a wide gap in OCP use between Japan and other countries, we revealed how choices of contraceptive methods and their benefits could be openly available for women of reproductive age, and how health care professionals disseminate appropriate knowledge about contraception for women in need. Copyright © 2016 Elsevier Inc. All rights reserved.

New contraceptive patch wearability assessed by investigators and participants in a randomized phase 3 study.

PubMed

Kaunitz, Andrew M; Portman, David; Westhoff, Carolyn L; Mishell, Daniel R; Archer, David F; Foegh, Marie

2015-03-01

To evaluate skin irritation and patch adhesiveness of a new weekly low-dose levonorgestrel (LNG) and ethinyl estradiol (EE) contraceptive patch (LNG/EE patch). This analysis was part of an open-label, parallel-group, multicenter, phase 3 study that randomized healthy women to the LNG/EE patch (one patch weekly for three consecutive weeks, followed by a patch-free week for 13 cycles) or to an oral contraceptive for six cycles followed by seven LNG/EE patch cycles. Participants selected patch application sites of abdomen, buttock or upper torso. Investigators rated patch adhesiveness and skin irritation using standardized scales. Participants rated skin irritation and itching daily using standardized scales and recorded patch fall-off on daily diary cards. A total of 32,508 patches were applied (n=1273). At the five clinic visits in which investigators rated the patches, they rated adhesiveness=0 (no lift) for ≥84% of participants and skin irritation=absent/mild for 97% of patches. Participants reported that 2-3.7% of patches fell off and rated skin irritation as absent or mild for 92- 95% of patches, according to site. Investigator- and participant-rated assessments of LNG/EE patch adhesiveness and irritation demonstrated a low incidence of patch detachment, skin irritation and pruritus. This secondary analysis of a phase 3 clinical trial of a new weekly low-dose LNG and EE contraceptive patch, which used assessment by both investigators and participants, observed a low incidence of skin irritation, pruritus and patch detachment. Copyright © 2015 Elsevier Inc. All rights reserved.

The effect of oral contraceptives on current wheezing in young women.

PubMed

Erkoçoğlu, M; Kaya, A; Azkur, D; Özyer, Ş; Özcan, C; Beşli, M; Civelek, E; Kocabaş, C N

2013-01-01

Emerging evidence suggests that sex steroid hormones may influence respiratory symptoms. The existing literature about the role of oral contraceptive pill (OCP) on respiratory disease is scarce and conflicting especially during the adolescent period. In this study, we aimed to investigate the effect of OCPs on current wheezing among adolescents and young adults. A questionnaire was administered face-to-face to adolescents and young women by a physician. The questionnaire included ISAAC survey-comprised questions on ever wheezing, current wheezing, allergic diseases, smoking history (active or passive), and family history of allergic diseases and questions on OCP usage status. The effect of OCPs on wheezing was evaluated by logistic regression analysis. A total of 487 subjects aged between 11.3 and 25.6years participated in the study and 196 (40.2%) reported that they had used OCPs. 7.4% of the participants had physician-diagnosed asthma and 10.3% of them were active smokers. It was detected that OCPs were associated with increased risk for current wheezing (odds ratio, 2.36; 95% CI, 1.25-4.47 adjusted for asthma and current smoker) and this risk was related with the usage during the past year. Young women taking oral contraceptives had a higher rate of current wheezing, suggesting that sex steroids may be of importance for respiratory health. Copyright © 2011 SEICAP. Published by Elsevier Espana. All rights reserved.

Oral delivery of plant-derived HIV-1 p24 antigen in low doses shows a superior priming effect in mice compared to high doses.

PubMed

Lindh, Ingrid; Bråve, Andreas; Hallengärd, David; Hadad, Ronza; Kalbina, Irina; Strid, Åke; Andersson, Sören

2014-04-25

During early infection with human immunodeficiency virus type 1 (HIV-1), there is a rapid depletion of CD4(+) T-cells in the gut-associated lymphoid tissue (GALT) in the gastrointestinal tract. Therefore, immediate protection at these surfaces is of high priority for the development of an HIV-1 vaccine. Thus, transgenic plants expressing HIV-1 antigens, which are exposed to immune competent cells in the GALT during oral administration, can be interesting as potential vaccine candidates. In the present study, we used two HIV-1 p24 antigen-expressing transgenic plant systems, Arabidopsis thaliana and Daucus carota, in oral immunization experiments. Both transgenic plant systems showed a priming effect in mice and induced humoral immune responses, which could be detected as anti-p24-specific IgG in sera after an intramuscular p24 protein boost. Dose-dependent antigen analyses using transgenic A. thaliana indicated that low p24 antigen doses were superior to high p24 antigen doses. Copyright © 2014. Published by Elsevier Ltd.

Effect of mavoglurant (AFQ056), a selective mGluR5 antagonist, on the pharmacokinetics of a combined oral contraceptive containing ethinyl estradiol and levonorgestrel in healthy women.

PubMed

Sivasubramanian, Rama; Chakraborty, Abhijit; Rouzade-Dominguez, Marie-Laure; Neelakantham, Srikanth; Jakab, Annamaria; Mensinga, Tjeert; Legangneux, Eric; Woessner, Ralph; Ufer, Mike

2015-07-01

To compare the pharmacokinetics (PKs) of a combination oral contraceptive (OC) when given alone or concomitantly with the selective metabotropic glutamate receptor 5 antagonist mavoglurant (AFQ056). This open-label, fixed-sequence, two-period study included 30 healthy female subjects aged 18-40 years. In period 1, a single oral dose of an OC containing 30 μg ethinyl estradiol (EE)/150 μg levonorgestrel (LNG) was administered alone. In period 2, the OC was administered with a clinically relevant multiple dose of mavoglurant 100 mg b.i.d. under steady-state conditions. Plasma concentrations of EE and LNG were measured up to 72 hours post administration, and the PK parameters Cmax and AUClast were estimated using noncompartmental methods. The geometric mean ratios of EE Cmax and AUClast obtained with and without mavoglurant were 0.97 (90% confidence interval (CI): 0.90-1.06) and 0.94 (90% CI: 0.86-1.03), respectively. The corresponding Cmax and AUClast for LNG were 0.81 (90% CI: 0.75-0.87) and 0.68 (90% CI: 0.63-0.73), respectively. In conclusion, EE PK was unchanged, whereas Cmax and AUClast of LNG were 19% and 32% lower, respectively, when given with mavoglurant Further investigation regarding the impact on contraceptive efficacy is warranted.

A quality of care issue: appropriate use and efficacy knowledge of five contraceptive methods: views of men and women living in low socioeconomic settlements of Karachi, Pakistan.

PubMed

Fikree, Fariyal F; Saleem, Sarah; Sami, Neelofar

2005-09-01

To assess knowledge regarding availability, affordability, appropriate use and efficacy for five non-permanent contraceptive methods. Married Muslim women and men (500 each) were randomly selected from two low socioeconomic settlements in Karachi, Pakistan. Interviews to assess their knowledge on a range of contraceptive and abortion themes were conducted. Four hundred men and 357 women were selected from this larger sample based on their knowledge of condoms, withdrawal, oral pills, injectables and IUDs. Nearly half of the sampled men (56%) and women (48%) were contraceptive users. Knowledge regarding contraception, a specific method, its availability and affordability was high. Appropriate use knowledge for condoms was 73% among men (users 78%, non-users 60%; p-value < or = 0.001 ) and 5% among women. Efficacy knowledge was generally poor. Low knowledge levels regarding appropriate use and efficacy even among contraceptive users suggests, that quality of family planning services should not be limited to service delivery issues but extend to appropriate use and efficacy knowledge levels among clients.

Matched-pairs analysis of ovarian suppression during oral versus vaginal hormonal contraceptive use

PubMed Central

Petrie, Kelsey A.; Torgal, Anu H.; Westhoff, Carolyn L.

2011-01-01

Background This study was conducted to compare ovarian suppression during oral versus vaginal hormonal contraceptive use. Secondary aims included comparison of endometrial thickness and bleeding patterns. Methods In two open-label trials assessing ovarian suppression, 33 compliant women completed both studies. They first used OCs [randomized to either 20 mcg ethinyl estradiol (EE)/100 mcg levonorgestrel (LNG) or 30 mcg EE/150 mcg LNG] and subsequently used contraceptive vaginal rings (CVR) (daily release of 15 mcg EE/120 mcg etonogestrel), all 21/7 day regimens. Participants had at least one run-in cycle using each contraceptive method prior to evaluation. During one cycle of each method, women underwent bi-weekly transvaginal sonography to measure ovarian follicular diameters and endometrial thickness. We also noted presence of a corpus luteum or a ruptured follicle as a marker of ovulation. Participants recorded bleeding days on paper calendars. We used matched pairs analyses as appropriate. Results During follow-up, we identified at least one ovarian follicle ≥8 mm in 20/33 (61%) OC users and 12/33 (36%) CVR users (matched pairs analysis, p=0.02). Similar trends were seen for larger follicles; however we had limited statistical power to evaluate these differences. Median follicular diameter among OC users was larger than median follicular diameter among CVR users (p=0.01). We did not observe a corpus luteum or ruptured follicle in any participant during either study. Endometrial thickness was similar during OC and CVR use (mean 4.1 ± 1.4 mm versus 4.1 ± 1.6 mm, p=0.9) as was the number of bleeding or spotting days (mean 2.1 ± 2.4 versus 1.9 ± 2.1, p=0.8). OC dose was unrelated to follicle diameter, endometrial thickness, or bleeding. Conclusions Ovarian follicles ≥8 mm were more common in 33 compliant women during OC use than during CVR use indicating CVR use results in greater ovarian suppression than OC use. PMID:22018131

Contraception in The Netherlands: the low abortion rate explained.

PubMed

Ketting, E; Visser, A P

1994-07-01

This article gives a review of the main factors that are related to the low abortion rate in the Netherlands. Attention is payed to figures on abortion and the use of contraceptive methods since the beginning of the 1960s up to the end of the 1980s. The strong acceptance of family planning was influenced by changing values regarding sexuality and the family, the transition from an agricultural to a modern industrial society, rapid economic growth, declining influence of the churches on daily life, introduction of modern mass media and the increased general educational level. The introduction of modern contraceptives (mainly the pill and contraceptive sterilization) was stimulated by a strong voluntary family planning movement, fear for overpopulation, a positive role of GPs, and the public health insurance system. A reduction of unwanted pregnancies has been accomplished through successful strategies for the prevention of teenage pregnancy (including sex education, open discussions on sexuality in mass media, educational campaigns and low barrier services) as well as through wide acceptance of sterilization. The Dutch experience with family planning shows the following characteristics: a strong wish to reduce reliance on abortion, ongoing sexual and contraceptive education related to the actual experiences of the target groups, and low barrier family planning services.

Safety and Efficacy of Low-Dose Oral Immunotherapy for Hen's Egg Allergy in Children.

PubMed

Yanagida, Noriyuki; Sato, Sakura; Asaumi, Tomoyuki; Nagakura, Kenichi; Ogura, Kiyotake; Ebisawa, Motohiro

2016-01-01

The minimal dose for oral immunotherapy (OIT) tolerance is unknown. We investigated the efficacy and safety of low-dose OIT with 1/32 of the volume of a whole egg. Thirty-three children (aged ≥5 years) with egg allergies confirmed by oral food challenge against 1/32 of a heated whole egg (194 mg of egg protein) were enrolled. The OIT group ingested a scrambled egg once a day. The volume was gradually increased up to a maximum of 1/32 of a heated whole egg. Egg consumption was completely absent in the control group. There were no significant differences in background between the OIT and control groups. Respectively, 71% (15/21) and 0% (0/12) of the patients in the OIT and control groups exhibited sustained unresponsiveness to 1/32 of a whole egg 2 weeks after stopping OIT after 12 months (p < 0.001); 33% (7/21) and 0% (0/12; p = 0.032), respectively, showed sustained unresponsiveness to 1/2 of a whole egg. Egg white- or ovomucoid-specific IgE levels in the OIT group were significantly lower than at baseline after 12 months. Egg white- or ovomucoid-specific IgG as well as IgG4 levels in the OIT group were significantly higher than baseline levels after 1, 3, 6, and 12 months. Adverse allergic reactions were rare, and most symptoms were mild. Low-dose OIT induced sustained unresponsiveness to 1/32 and 1/2 of a whole egg, with no severe symptoms. To improve food allergies, continuous intake of small amounts of these foods may be as effective as the consumption of larger quantities. © 2017 The Author(s) Published by S. Karger AG, Basel.

[The difficulties of contraception: conflicts and paradoxes].

PubMed

Cribier, F

1988-06-01

might be better met by contraception that leaves some risk of failure, such as low-dose progestins or local methods. Their relative efficacy may allow the ambivalent desire for a child not to be completely stifled. Cases also arise in which patients use contraceptives to mask problems and to give the illusion of a normally functioning body. The possibility of having a child is very seldom raised during contraceptive consultations, perhaps because for the physician contraception subconsciously evokes the forces of death. The doctor can take refuge in the technical aspects of contraception, ignoring the emotional needs of the client.

Multiple oral dosing of ketoconazole influences pharmacokinetics of quinidine after intravenous and oral administration in beagle dogs.

PubMed

Kuroha, M; Shirai, Y; Shimoda, M

2004-10-01

In this study, we investigated the effect of multiple oral dosing of ketoconazole (KTZ) on pharmacokinetics of quinidine (QN), a CYP3A substrate with low hepatic clearance, after i.v. and oral administration in beagle dogs. Four dogs were given p.o. KTZ for 20 days (200 mg, b.i.d.). QN was administered either i.v. (1 mg/kg) or p.o. (100 mg) 10 and 20 days before the KTZ treatment and 10 and 20 days after start of KTZ treatment. Multiple oral dosing of KTZ decreased significantly alpha and beta, whereas increased t(1/2beta), V(1), and k(a). The KTZ treatment also decreased significantly both total body clearance (Cl(tot)) and oral clearance (Cl(oral)). No significant change in bioavailability was observed in the presence of KTZ. Co-administration of KTZ increased C(max) of QN to about 1.5-fold. Mean resident time after i.v. administration (MRT(i.v.)), and after oral administration (MRT(p.o.)) of QN were prolonged to about twofold, whereas mean absorption time (MAT) was decreased to 50%. Volume of distribution at steady state (V(d(ss))) of QN was unchanged in the presence of KTZ. These alterations may be because of a decrease in metabolism of QN by inhibition of KTZ on hepatic CYP3A activity. In conclusion, multiple oral dosing of KTZ affected largely pharmacokinetics of QN after i.v. and oral administration in beagle dogs. Therefore, KTZ at a clinical dosing regimen may markedly change the pharmacokinetics of drugs primarily metabolized by CYP3A with low hepatic clearance in dogs. In clinical use, much attention should be paid to concomitant administration of KTZ with the drug when given either p.o. or i.v.

Effect of oral contraceptive agents on ascorbic acid metabolism in the rhesus monkey.

PubMed

Weininger, J; King, J C

1982-06-01

Ascorbic acid (AA) metabolism was studied in six sexually mature female rhesus monkeys with normal menstrual cycles before and during oral contraceptive administration. The animals were fed a commercial monkey stock diet (15% protein) containing no AA and given a 100 mg AA tablet daily throughout the study. After an initial adaptation period and a control period (total 8 months), combined-type oral contraceptive agents (OCAs) (50 micrograms mestranol and 1 mg norethindrone for 21 days each month) were administered to each monkey for 4 months. Serum copper and ceruloplasmin were significantly elevated during OCA treatment. There were no significant changes in plasma or leukocyte AA values during OCA use; however, urinary AA excretion decreased significantly. During the last month of the control period and the 3rd month of OCA treatment, 50 muCi of 1-14C-L-ascorbic acid were injected intravenously into each monkey. Urinary excretion of radioactivity, measured for 1 month, indicated a significantly faster AA turnover rate during the period of OCA use. These results suggest that women using OCAs may have an increased dietary requirement for AA.

Influence of an oral contraceptive containing drospirenone on insulin sensitivity of healthy women.

PubMed

Cagnacci, Angelo; Piacenti, Ilaria; Zanin, Renata; Xholli, Anjeza; Tirelli, Alessandra

2014-07-01

Oral contraceptives (OCs) containing androgenic second and third generation progestins decrease insulin sensitivity (SI). In this study we investigated whether an oral contraceptive containing the anti-androgenic progestin drospirenone (DRSP) still alters SI. Lipid modifications were investigated as well. Eleven young healthy women were allocated to receive for 6 months ethinyl-estradiol (EE) 30μg plus DRSP (3mg). SI and glucose utilization independent of insulin (Sg) was investigated by the minimal model method. Lipid modifications were also analyzed. SI did not vary during EE/DRSP (from 3.72±2.62 to 3.29±2.93; p=0.73). Similarly, values of Sg did not vary (from 0.03±0.02 to 0.032±0.014; p=0.87). An increase was observed in HDL cholesterol (9.4±9.8mg/dl; p=0.05) and triglycerides (46.9±75.1mg/dl; p=0.046), with no modification in LDL cholesterol (-4.64±1.704mg/dl; p=0.6). EE/DRSP does not deteriorate SI. These results are reassuring for the long-term use of this association. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

[Contraception and adolescence].

PubMed

Amate, P; Luton, D; Davitian, C

2013-06-01

The mean age of first sexual intercourse is still around 17 in France, but a lot of teenagers are concerned by contraception before, with approximately 25% of sexually active 15-year-old girls. The contraceptive method must take into consideration some typical features of this population, as sporadic and non-planned sexual activity, with several sexual partners in a short period of time. In 2004, the "Haute Autorité de santé" has recommended, as first-line method, combined oral contraceptive (COC) pills, in association with male condoms. Copper-containing intrauterine contraceptive devices (IUCD) and etonogestrel-containing subcutaneous implant have been suggested but not recommended. However, oral contraceptive pill, as a user-based method, carries an important typical-use failure rate, because remembering taking a daily pill, and dealing with stop periods, may be challenging. Some easier-to-use method should be kept in mind, as 28-day COC packs, transdermal contraceptive patches, and vaginal contraceptive rings. Moreover, American studies have shown that long-acting reversible contraceptives (LARC), i.e. IUCD and implant, have many advantages for teenagers: very effective, safe, invisible. They seem well-fitted for this population, with high satisfaction and continuation rates, as long as side effects are well explained. Thus, LARC methods should be proposed more widely to teenagers. Anyway, before prescribing a contraceptive method, it is important to determine the specific situation of every teenager, to let them choose the method that they consider as appropriate in their own case, and to think about the availability of the chosen method. It is necessary to explain how to handle mistakes or misses with user-based contraceptive methods, and emergency contraception can be anticipated and prescribed in advanced provision. The use of male condoms should be encouraged for adolescents, with another effective contraceptive method, in order to reduce the high risk

Effect of a high-fructose diet on glucose tolerance, plasma lipid and hemorheological parameters during oral contraceptive administration in female rats.

PubMed

Olatunji, Lawrence Aderemi; Oyeyipo, Ibukun Peter; Usman, Taofeek Oluwamayowa

2013-01-01

Oral contraceptive (OC) use and increased fructose feeding have been associated with altered cardiometabolic effects. The effect of increased dietary fructose during OC use on cardiometabolic parameters is unknown. We investigated the effects of a high-fructose diet on body weight gain, fasting blood glucose, glucose tolerance, plasma lipid and hemorheological parameters in female rats treated with a combination of OC steroids (norgestrel/ethinyl estradiol; NEE). Rats were given (p.o.) vehicle, high-dose NEE (10.0 μg norgestrel/1.0 μg ethinyl estradiol) or low-dose NEE (1.0 μg norgestrel/0.1 μg ethinyl estradiol) with or without high dietary fructose daily for 6 weeks. Results demonstrated that high-dose NEE but not low-dose NEE treatment led to significant increases in hematocrit, blood viscosity, and decreases in body weight gain, glucose tolerance, and plasma HDL-cholesterol level. Both NEE treatments resulted in significant increases in plasma viscosity and triglyceride. Increased dietary fructose without NEE treatment produced significant increases in fasting blood glucose, hematocrit, blood and plasma viscosities, while increased dietary fructose significantly potentiated the effects on blood and plasma viscosities observed during NEE treatment. Conversely, the effects of NEE treatment on body weight gain, glucose tolerance, plasma triglyceride and HDL-cholesterol were significantly attenuated. In conclusion, the results indicate that increase in dietary fructose may worsen abnormal blood rheology. The results also demonstrate that increased dietary fructose may not impact negatively on glucose and lipid metabolisms during OC use. The findings imply that fructose-enriched diet might be an important consideration during OC use regarding blood rheological properties.

Evaluation of Potential Drug-Drug Interaction Between Delayed-Release Dimethyl Fumarate and a Commonly Used Oral Contraceptive (Norgestimate/Ethinyl Estradiol) in Healthy Women.

PubMed

Zhu, Bing; Nestorov, Ivan; Zhao, Guolin; Meka, Venkata; Leahy, Mark; Kam, Jeanelle; Sheikh, Sarah I

2017-11-01

Delayed-release dimethyl fumarate (DMF) is an oral therapy for relapsing multiple sclerosis with anti-inflammatory and neuroprotective properties. This 2-period crossover study was conducted to evaluate the potential for drug-drug interaction between DMF (240 mg twice daily) and a combined oral contraceptive (OC; norgestimate 250 μg, ethinyl estradiol 35 μg). Forty-six healthy women were enrolled; 32 completed the study. After the lead-in period (OC alone), 41 eligible participants were randomized 1:1 to sequence 1 (OC and DMF coadministration in period 1; OC alone in period 2) or sequence 2 (regimens reversed). Mean concentration profiles of plasma norelgestromin (primary metabolite of norgestimate) and ethinyl estradiol were superimposable following OC alone and OC coadministered with DMF, with 90% confidence intervals of geometric mean ratios for area under the plasma concentration-time curve over the dosing interval and peak plasma concentration contained within the 0.8-1.25 range. Low serum progesterone levels during combined treatment confirmed suppression of ovulation. The pharmacokinetics of DMF (measured via its primary active metabolite, monomethyl fumarate) were consistent with historical data when DMF was administered alone. No new safety concerns were identified. These results suggest that norgestimate/ethinyl estradiol-based OCs may be used with DMF without dose modification. © 2017, The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Contrasting effects of low versus high ascorbate doses on blood pressure responses to oral nitrite in L-NAME-induced hypertension.

PubMed

Pinheiro, Lucas C; Ferreira, Graziele C; Vilalva, Kelvin H; Toledo, José C; Tanus-Santos, Jose E

2018-04-01

Nitrite reduces blood pressure (BP) in both clinical and experimental hypertension. This effect is attributable to the formation of nitric oxide (NO) and other NO-related species, which may be improved by ascorbate or other antioxidants. However, the BP responses to oral nitrite result, at least in part, of increased gastric S-nitrosothiol formation. This study tested the hypothesis that ascorbate may destroy S-nitrosothiols and therefore not all doses of ascorbate enhance the BP responses to oral nitrite. We assessed the BP responses to oral sodim nitrite (0.2 mmol/kg) in L-NAME hypertensive rats pretreated with ascorbate (0, 0.02, 0.2, or 2 mmol/kg). Plasma and gastric wall concentrations of nitrite and nitroso compounds concentrations were determined using an ozone-based reductive chemiluminescence assay. Nitrate concentrations were determined using the Griess reaction. Free thiol concentrations were determined by a colorimetric assay. The BP responses to nitrite exhibited a bell-shape profile as they were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated BP responses. In parallel with BP responses, nitrite-induced increases in plasma nitrite and RSNO species were not modified by ascorbate 0.02 mmol/l, whereas the 0.2 mmol/kg dose enhanced and the 2 mmol/kg dose attenuated them. Similar experiments were carried out with an equimolar dose of S-nitrosogluthathione. Ascorbate dose-dependently impaired the BP responses to S-nitrosogluthathione, and the corresponding increases in plasma RSNO, but not in plasma nitrite concentrations. This is the first study to show that while ascorbate dose-dependently impairs the BP responses to oral S-nitrosogluthathione, there are contrasting effects when low versus high ascorbate doses are compared with respect to its effects on the blood pressure responses to oral nitrite administration. Our findings may have special implications to patients taking

Venous Thromboembolism Due to Oral Contraceptive Intake and Spending Nights in a Vehicle -A Case from the 2016 Kumamoto Earthquakes.

PubMed

Sueta, Daisuke; Akahoshi, Rika; Okamura, Yoshinori; Kojima, Sunao; Ikemoto, Tomokazu; Yamamoto, Eiichiro; Izumiya, Yasuhiro; Tsujita, Kenichi; Kaikita, Koichi; Katabuchi, Hidetaka; Hokimoto, Seiji

2017-01-01

A 40-year-old woman experiencing sudden dyspnea went to her personal doctor for advice. She was previously diagnosed with endometriosis and prescribed oral contraceptives for treatment. During earthquakes, she spent 7 nights sleeping in a vehicle. The patient had swelling and pain in her left leg and high D-dimer concentration levels. A contrast-enhanced computed tomography scan revealed a contrast deficit in the bilateral pulmonary artery and in the left lower extremity. She was diagnosed with pulmonary thromboembolism (PTE), and anticoagulation therapy was initiated. This present case is the first report of PTE attributed to the use of oral contraceptives after earthquakes.

Ischemic stroke occurring during intercourse in young women on oral contraceptives.

PubMed

Miller, P Elliott; Brown, Lorrel; Khandheria, Paras; Resar, Jon R

2014-08-01

Ischemic stroke occurring during intercourse in young patients is exceedingly rare. We present 2 cases of young women taking oral contraceptives, each presenting with an ischemic stroke. Transthoracic echocardiography revealed a patent foramen ovale in one patient and an atrial septal defect in the other. The most likely cause of stroke in both patients is embolic. Despite conflicting evidence, young patients presenting with ischemic stroke and found to have a patent foramen ovale or atrial septal defect should be considered for possible device-based closure. Copyright © 2014 Elsevier Inc. All rights reserved.

A randomized comparative trial of two low-dose oral isotretinoin regimens in moderate to severe acne vulgaris

PubMed Central

Dhaked, Daulat Ram; Meena, Ram Singh; Maheshwari, Anshul; Agarwal, Uma Shankar; Purohit, Saroj

2016-01-01

Background: Oral isotretinoin is highly effective in all forms and grades of acne, even in lower dosages (<0.5 mg/kg/day). There is a paucity of comparative data on the various low-dose regimens of oral isotretinoin in the Indian literature. Objectives: To assess and compare the efficacy and tolerability of two low-dose oral isotretinoin treatment regimens (20 mg daily and 20 mg alternate days) in moderate to severe acne vulgaris. Materials and Methods: A total of 240 patients with moderate to severe acne vulgaris were selected and randomized into two groups and treated with a fixed dose of 20 mg of isotretinoin (Group A - daily and Group B - alternate days) for 24 weeks and followed up for 12 weeks post therapy. Results: A total of 234 patients completed the study. At the end of therapy, decrease in the total acne loads up to 98.99% (Group A) and 97.69% (Group B) was achieved from the baseline (P < 0.01), excellent response was observed in 98.3% (Group A) and 93.96% (Group B) patients (P = 0.166). In the severe acne, Group A performed significantly better than Group B until the end of 36 weeks. While in the moderate acne, significant difference in the response between both groups was observed only up to 12 weeks. No serious side effect was observed. Conclusion: Both isotretinoin regimens were well tolerated and found to be an effective treatment for moderate to severe acne vulgaris. However, in moderate acne 20 mg alternate day regimen may be preferred. A 20 mg daily regimen is a better choice for severe acne in terms of response. Limitation: Small sample size and short follow-up period. PMID:27730033

Three-step method for menstrual and oral contraceptive cycle verification.

PubMed

Schaumberg, Mia A; Jenkins, David G; Janse de Jonge, Xanne A K; Emmerton, Lynne M; Skinner, Tina L

2017-11-01

Fluctuating endogenous and exogenous ovarian hormones may influence exercise parameters; yet control and verification of ovarian hormone status is rarely reported and limits current exercise science and sports medicine research. The purpose of this study was to determine the effectiveness of an individualised three-step method in identifying the mid-luteal or high hormone phase in endogenous and exogenous hormone cycles in recreationally-active women and determine hormone and demographic characteristics associated with unsuccessful classification. Cross-sectional study design. Fifty-four recreationally-active women who were either long-term oral contraceptive users (n=28) or experiencing regular natural menstrual cycles (n=26) completed step-wise menstrual mapping, urinary ovulation prediction testing and venous blood sampling for serum/plasma hormone analysis on two days, 6-12days after positive ovulation prediction to verify ovarian hormone concentrations. Mid-luteal phase was successfully verified in 100% of oral contraceptive users, and 70% of naturally-menstruating women. Thirty percent of participants were classified as luteal phase deficient; when excluded, the success of the method was 89%. Lower age, body fat and longer menstrual cycles were significantly associated with luteal phase deficiency. A step-wise method including menstrual cycle mapping, urinary ovulation prediction and serum/plasma hormone measurement was effective at verifying ovarian hormone status. Additional consideration of age, body fat and cycle length enhanced identification of luteal phase deficiency in physically-active women. These findings enable the development of stricter exclusion criteria for female participants in research studies and minimise the influence of ovarian hormone variations within sports and exercise science and medicine research. Copyright © 2016 Sports Medicine Australia. Published by Elsevier Ltd. All rights reserved.

[Arterial diseases in women using combined hormonal contraceptives].

PubMed

Novotná, M; Unzeitig, V; Novotný, T

2002-05-01

To determine the association between myocardial infarction and cerebral stroke and use of combined oral contraceptives. Review of literature. Department of Obstetrics and Gynaecology, Hospital of Merciful Brothers, Brno, Czech Republic. Identification of methodologically sound studies able to address the topic. Studies were identified by Medline database search. Five the most recent and important studies were the main source of information (Oxford Family Planning Association Contraception Study 1984, Royal College of General Practitioners' Study 1994, WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception 1996, 1997, Transnational Study on Oral Contraceptives and the Health of Young Women 1997, Myocardial Infarction and Oral Contraceptives Study, 1997). Generally there was no evidence of a significantly increased risk of arterial wall disease in healthy non smoked users younger than 35 years. No difference between second and third generation oral contraceptives on risk of arterial wall disease were found. In the most of cases of myocardial infarction or stroke one or more risk factor were identified. Two of the most relevant risk factors are smoking and the absence of blood pressure control. The risk of arterial cardiovascular system diseases seems not to be increased at no-risk users (healthy non-smoker younger than 35 years).

Drospirenone/ethinylestradiol 3mg/20microg (24/4 day regimen): a review of its use in contraception, premenstrual dysphoric disorder and moderate acne vulgaris.

PubMed

Fenton, Caroline; Wellington, Keri; Moen, Marit D; Robinson, Dean M

2007-01-01

Drospirenone 3mg with ethinylestradiol 20microg (Yaz) is a low-dose combined oral contraceptive (COC) administered in a regimen of 24 days of active tablets followed by a short hormone-free interval (4 days; 24/4 regimen). Drospirenone, unlike other synthetic progestogens used in COCs, is a 17alpha-spirolactone derivative and a 17alpha-spironolactone analogue with antimineralocorticoid and antiandrogenic properties. Drospirenone/ethinylestradiol 3mg/20microg (24/4) is approved in the US for the prevention of pregnancy in women, for the treatment of the symptoms of premenstrual dysphoric disorder (PMDD) and for the treatment of moderate acne vulgaris in women who wish to use an oral contraceptive for contraception.Drospirenone/ethinylestradiol 3mg/20microg (24/4) provided 99% contraceptive protection over 1 year of treatment in two large studies. The same treatment regimen over three treatment cycles also significantly improved the emotional and physical symptoms associated with PMDD, and improved moderate acne vulgaris over six treatment cycles in double-blind trials. It was generally well tolerated, with adverse events generally typical of those experienced with other COCs and which were most likely to occur in the first few cycles. Clinical trials indicate that drospirenone/ethinylestradiol 3mg/20microg (24/4) is a good long-term contraceptive option, and additionally offers relief of symptoms that characterise PMDD and has a favourable effect on moderate acne vulgaris.

Pre-gravid oral contraceptive use in relation to birth weight: a prospective cohort study

PubMed Central

Hatch, EE; Hahn, KA; Mikkelsen, EM; Riis, AH; Sorensen, HT; Rothman, KJ; Wise, LA

2015-01-01

Few studies have evaluated the association between pregravid oral contraceptive (OC) use and birth weight, and findings have been conflicting. We conducted a prospective cohort study of 5921 pregnancy planners in Denmark to evaluate recency, duration, and type of OC used before conception in relation to infant birth weight. Participants completed online questionnaires and reported detailed information on contraceptive history and covariates at baseline. Participants completed bimonthly follow-up questionnaires to update their pregnancy status for up to12 months or until conception occurred. Birth weight data were ascertained from the Danish Medical Birth Registry for 4046 live births delivered by study participants between 2008 and 2010. We used multivariable linear and log-binomial regression analyses to control for confounding. Mean birth weight was higher among women who had used OCs within 0–1 months (mean difference = 97 g, CI: 26, 168) or 2–6 months (mean difference=40 g, CI: −5, 85) before conception, compared with more than 12 months before conception. Mean birth weight was lower among women who had used OCs for long durations (mean difference comparing ≥12 with <4 years of OC use = −85 g, CI: −158, −11). Our findings indicate that pregravid OC use within 6 months of conception may be associated with a small increase in birth weight, but that long duration of use may have the opposite effect. Results were stronger among male infants, among 2nd and 4th generation OC users, and among users of OCs with a higher estrogen dose. PMID:26076921

The acute effects of a low and high dose of oral L-arginine supplementation in young active males at rest.

PubMed

Forbes, Scott C; Bell, Gordon J

2011-06-01

L-arginine (2-amino-5-guanidinovaleric acid) is a conditionally essential amino acid. Intravenous (IV) administration of l-arginine invokes a large metabolic (nitrate/nitrite (NO(x))) and hormonal (growth hormone (GH), insulin-like growth factor 1 (IGF-1), and insulin) response; however, research examining oral l-arginine supplementation is conflicting, potentially owing to dose. The purpose of this study was examine a low and high dose of oral l-arginine on blood l-arginine, NO(x), GH, IGF-1, and insulin response. Fourteen physically active males (age: 25 ± 5 years; weight: 78.0 ± 8.5 kg; height: 179.4 ± 4.7 cm) volunteered to be in a randomized, double-blind, repeated-measures study. Following an overnight fast, an IV catheter was placed in a forearm vein and a resting blood sample was drawn at ∼0800 hours. Each subject was then provided 1 of 3 treatment conditions (placebo, low (0.075 g·kg(-1) of body mass), or high (0.15 g·kg(-1) of body mass of l-arginine)). Blood samples were drawn at 30, 60, 90, 120, and 180 min after consumption. l-arginine plasma concentrations significantly increased (p < 0.001) to a similar level at any time point in both the low- and high-dose conditions; there was no change over time in the placebo condition. There was no significant difference between conditions for NO(x), GH, IGF-1, or insulin. Based on these findings, a low dose of l-arginine was just as effective at increasing plasma l-arginine concentrations as a high dose; however, neither dose was able to promote a significant increase in NO(x), GH, IGF-1, or insulin at rest.

Oral contraceptive use and female genital arousal: methodological considerations.

PubMed

Seal, Brooke N; Brotto, Lori A; Gorzalka, Boris B

2005-08-01

This study explored effects of oral contraceptive pill (OCP) use on physiological sexual arousal as measured by a vaginal photoplethysmograph. Sixteen women aged 18-29 viewed audiovisual neutral and erotic stimuli before and an average of 6 weeks following the onset of OCP use. Although subjective measures of sexual arousal, including perceptions of genital arousal, significantly increased in response to erotic stimuli both before and after OCP onset, physiological sexual arousal only increased before OCP use. A comparison of individual responses before and after OCP onset reveals a much higher degree of intrasubject variability after OCP onset. We discuss these findings as they relate to OCP use as a confounding methodological variable to consider in future investigations employing vaginal photoplethysmography.

Cost-effectiveness of emergency contraception options over 1 year.

PubMed

Bellows, Brandon K; Tak, Casey R; Sanders, Jessica N; Turok, David K; Schwarz, Eleanor B

2018-05-01

The copper intrauterine device is the most effective form of emergency contraception and can also provide long-term contraception. The levonorgestrel intrauterine device has also been studied in combination with oral levonorgestrel for women seeking emergency contraception. However, intrauterine devices have higher up-front costs than oral methods, such as ulipristal acetate and levonorgestrel. Health care payers and decision makers (eg, health care insurers, government programs) with financial constraints must determine if the increased effectiveness of intrauterine device emergency contraception methods are worth the additional costs. We sought to compare the cost-effectiveness of 4 emergency contraception strategies-ulipristal acetate, oral levonorgestrel, copper intrauterine device, and oral levonorgestrel plus same-day levonorgestrel intrauterine device-over 1 year from a US payer perspective. Costs (2017 US dollars) and pregnancies were estimated over 1 year using a Markov model of 1000 women seeking emergency contraception. Every 28-day cycle, the model estimated the predicted number of pregnancy outcomes (ie, live birth, ectopic pregnancy, spontaneous abortion, or induced abortion) resulting from emergency contraception failure and subsequent contraception use. Model inputs were derived from published literature and national sources. An emergency contraception strategy was considered cost-effective if the incremental cost-effectiveness ratio (ie, the cost to prevent 1 additional pregnancy) was less than the weighted average cost of pregnancy outcomes in the United States ($5167). The incremental cost-effectiveness ratios and probability of being the most cost-effective emergency contraception strategy were calculated from 1000 probabilistic model iterations. One-way sensitivity analyses were used to examine uncertainty in the cost of emergency contraception, subsequent contraception, and pregnancy outcomes as well as the model probabilities. In 1000 women

Preference for and efficacy of oral levonorgestrel for emergency contraception with concomitant placement of a levonorgestrel IUD: a prospective cohort study.

PubMed

Turok, David K; Sanders, Jessica N; Thompson, Ivana S; Royer, Pamela A; Eggebroten, Jennifer; Gawron, Lori M

2016-06-01

We assessed intrauterine device (IUD) preference among women presenting for emergency contraception (EC) and the probability of pregnancy among concurrent oral levonorgestrel (LNG) plus LNG 52 mg IUD EC users. We offered women presenting for EC at a single family planning clinic the CuT380A IUD (copper IUD) or oral LNG 1.5 mg plus the LNG 52 mg IUD. Two weeks after IUD insertion, participants reported the results of a self-administered home urine pregnancy test. The primary outcome, EC failure, was defined as pregnancies resulting from intercourse occurring within five days prior to IUD insertion. One hundred eighty-eight women enrolled and provided information regarding their current menstrual cycle and recent unprotected intercourse. Sixty-seven (36%) chose the copper IUD and 121 (64%) chose oral LNG plus the LNG IUD. The probability of pregnancy two weeks after oral LNG plus LNG IUD EC use was 0.9% (95% CI 0.0-5.1%). The only positive pregnancy test after treatment occurred in a woman who received oral LNG plus the LNG IUD and who had reported multiple episodes of unprotected intercourse including an episode more than 5 days prior to treatment. Study participants seeking EC who desired an IUD preferentially chose oral LNG 1.5 mg with the LNG 52 mg IUD over the copper IUD. Neither group had EC treatment failures. Including the option of oral LNG 1.5 mg with concomitant insertion of the LNG 52 mg IUD in EC counseling may increase the number of EC users who opt to initiate highly effective reversible contraception. Consideration should be given to LNG IUD insertion with concomitant use of oral LNG 1.5 mg for EC. Use of this combination may increase the number of women initiating highly effective contraception at the time of their EC visit. Copyright © 2016 Elsevier Inc. All rights reserved.

Oral contraceptive discontinuation and its aftermath in 19 developing countries.

PubMed

Ali, Mohamed M; Cleland, John

2010-01-01

The purpose of the article was to document oral contraceptive (OC) discontinuation and switching in a large number of low- and middle-income countries, and to assess the effects of women's education and reason for use (spacing vs. limitation). An attempt was made to explain intercountry variations. Calendar data from 19 Demographic and Health Surveys conducted between 1999 and 2005 were used. Data were analyzed by single- and multiple-decrement life tables and by Cox proportional hazard model. The probability of stopping OC use within 12 months for reasons that implied dissatisfaction with the method ranged from 15% in Indonesia to over 40% in Bolivia and Peru with a median value of 28%. On average, 35% switched to a modern method within 3 months and 16% to a less effective 'traditional' method. Both education and reason for use were strongly related to the probability of switching to a modern method. Discontinuation was lower and switching higher in countries judged to have strong family planning programs. Both discontinuation of use and inadequate switching to alternative methods are major but neglected problems in the family planning services of many developing countries.

The effect of a combination therapy with myo-inositol and a combined oral contraceptive pill versus a combined oral contraceptive pill alone on metabolic, endocrine, and clinical parameters in polycystic ovary syndrome.

PubMed

Minozzi, Massimo; Costantino, Demetrio; Guaraldi, Claudia; Unfer, Vittorio

2011-11-01

Compare the effects of a combined contraceptive pill (OCP) in combination with myo-inositol (MI) on endocrine, metabolic, and clinical parameters in patients with polycystic ovary syndrome (PCOS). One hundred fifty-five patients with PCOS were enrolled in this prospective, open-label clinical study. Patients were assigned to receive oral treatment with OCP alone (estradiol (EE) 30 μg/gestodene 75 μg) or in combination with myo-inositol 4 g/die, for 12 months. OCP plus MI therapy resulted in a higher reduction of FG score compared with OCP alone therapy. The combined therapy (OCP plus MI) significantly decreased hyperinsulinaemia, by positively affecting the fasting insulin and glucose levels and homeostasis model assessment-insulin resistance parameters, while no significant changes were observed in the OCP group. Androgens serum levels decreased in both groups, but significantly more in the combined therapy group. The lipid profile was improved in the combined therapy group, by reducing low-density lipoprotein cholesterol levels and enhancing high-density lipoprotein cholesterol levels. Our data show that a combination of combined contraceptive pill and MI may be more effective in controlling endocrine, metabolic, and clinical profile in patients with PCOS than OCP alone, and may reduce insulin levels and insulin resistance. Hence, combined treatment may become a more effective long-term therapeutic choice for controlling PCOS symptoms.