Caserta, D; Ralli, E; Matteucci, E; Bordi, G; Mallozzi, M; Moscarini, M
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.
Stewart, Mary; Black, Kirsten
Summary The combined oral contraceptive pill is an effective contraceptive method which can also offer other benefits. However, other contraceptive options should be discussed. If the pill is the chosen method, prescribe a pill with the lowest effective dose of oestrogen and progestogen. Pills containing levonorgestrel or norethisterone in combination with ethinyloestradiol 35 microgram or less are considered first-line. They are effective if taken correctly, have a relatively low risk of venous thromboembolism, and are listed on the Pharmaceutical Benefits Scheme. The pill is usually taken in a monthly cycle. Some women may prefer an extended pill regimen with fewer or no inactive pills. PMID:26648603
Kubba, A; Guillebaud, J
With over 60 million users of 'the pill' worldwide, safety and efficacy remain the two most relevant issues to both the consumer and the research scientist. Safety of combined oral contraception (COC) has advanced appreciably. Lessons learned from cohort and case-control studies have been applied to the practical management of oral contraception use, based on screening, selection and regular monitoring of users. Most health risks of COCs appear to be dependent on the dose and potency (or biological impact) of the constituent steroids. While many of the non-contraceptive benefits of COCs are maintained when modern low dose preparations are used, most, if not all, of the adverse effects have been reduced progressively. Moreover the range of modern hormonal contraceptives has widened with the introduction of a new generation of 'selective' progestogens (Desogestrel, Norgestimate and Gestodene), which have minimal androgenicity. User failure of COCs is still high in many countries. The cause is a combination of poor compliance and anxiety about perceived adverse effects. Compliance can be enhanced by improving the quality of instruction in pill use. Fears of adverse effects of COCs may be allayed through education of users and providers, and sympathetic management of side effects.
The benefits of combined oral contraceptives are put into perspective, considering their effectiveness as a contraceptive, actual risks for breast, ovarian, endometrial and cervical cancer, and effects of reproductive and other body systems. Combined oral contraceptives are the best contraceptives available except for injectable progestogens, therefore they an reduce the risk of maternal mortality by at least 5 in nonsmoking western women, or over 100 in developing countries. No data are available on mortality risk of the presumed safer low-dose pills. Pills reduce ectopic pregnancy to virtually nil. They decrease the risk of endometrial cancer, and of ovarian cancer for up to 15 years after use. Although they protect against benign breast disease, both fibrocystic disease and fibroadenoma, which are risk factors for breast cancer, it is unsettled whether pills affect breast cancer incidence. Cervical cancer risk may be slightly higher. Functional ovarian cysts requiring surgery are cut about 10-fold; corpus luteum and follicular cysts are also reduced. Fibroids are decreased in proportion to duration of use. Pelvic inflammatory disease rates fall 50% during use. Chlamydial infections have not fallen in pill users, but it is not known whether sexual activity is a factor. Combined pills cut abnormal uterine bleeding by about half, reduce the incidence of iron deficiency anemia and of premenstrual tension. Seizures related to menses also are controlled. Some studies find a reduction in rheumatoid arthritis. Most of the cardiovascular complications of pills are thought to be dose related. Since today's pills contain approximately the same dose as a whole cycle of the original pills, it is expected that these risks will be greatly reduced, especially with better screening of candidates that is now the rule.
Dragoman, Monica V
The introduction of the birth control pill as an effective, coitally-independent method of contraception was a public health milestone of the last century. Over time, combined oral contraception (COC) formulations and pill-taking regimens have evolved with improved safety and tolerability while maintaining contraceptive efficacy. In addition to protection against pregnancy, use of combined oral contraception confers a number of significant non-contraceptive benefits to users. COC use is also associated with well-studied risks. Common side effects are generally self-limiting and improve with increasing duration of use while serious adverse events, including venous thromboembolism, are rare among healthy COC users. Contraceptive decision-making should include consideration of both the risks and benefits of a given method versus the real consequences of unintended pregnancy.
DOMINGUES, Roberta Santos; FERRAZ, Bruna Fidêncio Rahal; GREGHI, Sebastião Luiz Aguiar; de REZENDE, Maria Lúcia Rubo; PASSANEZI, Euloir; SANT'ANA, Adriana Campos Passanezi
Most studies investigating the impact of oral contraceptives have been performed some years ago, when the level of sexual hormones was greater than the actual formulations. Objective The aim of this study was to evaluate the effects of current combined oral contraceptives (COC) on periodontal tissues, correlating the clinical parameters examined with the total duration of continuous oral contraceptive intake. Material and methods Twenty-five women (19-35 years old) taking combined oral contraceptives for at least 1 year were included in the test group. The control group was composed by 25 patients at the same age range reporting no use of hormone-based contraceptive methods. Clinical parameters investigated included pocket probing depth (PD), clinical attachment level (CAL), sulcular bleeding index (SBI) and plaque index (Pl.I). Data were statistically evaluated by unpaired t test, Pearson's correlation test and Spearman's correlation test. Results The test group showed increased PD (2.228±0.011 x 2.154±0.012; p<0.0001) and SBI (0.229±0.006 x 0.148±0.005, p<0.0001) than controls. No significant differences between groups were found in CAL (0.435±0.01 x 0.412±0.01; p=0.11). The control group showed greater Pl.I than the test group (0.206±0.007 x 0.303±0.008; p<0.0001). No correlation between the duration of oral contraceptive intake, age and periodontal parameters was observed. Conclusions These findings suggest that the use of currently available combined oral contraceptives can influence the periodontal conditions of the patients, independently of the level of plaque accumulation or total duration of medication intake, resulting in increased gingival inflammation. PMID:22666846
Kiley, Jessica; Hammond, Cassing
Millions of women use birth control pills for contraceptive and noncontraceptive reasons. Although there have been reports of rare adverse events, birth control pills do offer well-documented health benefits, including a decrease in the risk of ovarian and endometrial carcinoma. In addition, manufacturers continue to modify birth control pills to reduce side effects and medical risks.
Maclennan, A H
Over 60 million women use highly efficient and safe modern combined oral contraceptives (OCs) every day. A women who takes the oral contraceptive for 5 years before the age of 30 will actually live 12 days longer, although a woman taking the pill for the 1st time for 5 years after the age of 30 will have her life span reduced on the average by 80 days. OC related morbidity and mortality mostly occur in women over 35 who smoke. Combined low dose OCs are safe for women who do not smoke, at least to 45 years of age and probably to the menopause. The prescription of OCs is also safe to the young adolescent. The pill does not interfere with maturation of the hypothalamic-pituitary ovarian axis and does not increase the incidence of amenorrhoea, oligomenorrhoea or infertility in later life. Patients with contraindications to estrogen therapy are excluded from OC use (history of thromboembolism, major heart disease, liver disease, breast cancer). Low-dose (30-35 mcg estrogen-containing monophasic or triphasic) pills are recommended. Combined oral contraceptives contain either ethinyl estradiol (1.7 to 2 times more potent) or mestranol. After absorption the progestagens, norethisterone acetate, ethynodiol diacetate and lynoestrenol are all metabolized to norethisterone. The progestagen-only pill has about a 2% failure rate and poorer cycle control than the combined pill, but it lacks estrogenic, progestagenic and androgenic side effects. This pill is suitable for the lactating mother, for smokers over 35, for hypertensive patients, and for those with a history of thrombosis. The efficacy of the progestagen-only pill is restored in 3 days of pill taking. Postcoital contraception is an alternative: treatment can be given for at least 72 hours after intercourse. The Yuzpe method calls for the patient to take 2 combined oral contraceptive tablets containing levonorgestrel and ethinyl estradiol (Eugynon or Ovral) followed by a further 2 tablets 12 hours later. This regimen
Ellsworth, A J; Leversee, J H
Management of oral contraception requires an understanding of the relationships between the method's effectiveness, noncontraceptive benefits, and hormonal adverse effects. The new multiphasic combinations or OCs containing 35 micrograms of ethinyl estradiol and 0.5-1.0 mg of norethindrone or equivalent result in a maximum combination of efficacy and safety for the patient with minimal annoying problems for the patient and the prescriber. Patient education regarding early warning symptoms of adverse effects, breakthrough bleeding, and lack of withdrawal bleeding adds an additional margin of safety and reduces patient questions and uncertainties.
Oesterheld, Jessica R; Cozza, Kelly; Sandson, Neil B
Nearly 50 years ago, the introduction of Enovid (norethynodrel 10 microg and mestranol 150 microg), which provided convenient and reliable contraception, revolutionized birth control. Reports of interactions between oral contraceptives (OCs) and other drugs began to trickle into the literature. At first, these drug interactions appeared to be random and unrelated. Increased understanding of P450 enzymes and phase II reactions of sulfation and glucuronidation has permitted preliminary categorization and assessment of the clinical relevance of these drug interactions.
Allais, Gianni; Gabellari, Ilaria Castagnoli; De Lorenzo, Cristina; Mana, Ornella; Benedetto, Chiara
Combined oral contraceptives are a safe and highly effective method of birth control, but they can also raise problems of clinical tolerability and/or safety in migraine patients. It is now commonly accepted that, in migraine with aura, the use of combined oral contraceptives is always contraindicated, and that their intake must also be suspended by patients suffering from migraine without aura if aura symptoms appear. The newest combined oral contraceptive formulations are generally well tolerated in migraine without aura, and the majority of migraine without aura sufferers do not show any problems with their use; nevertheless, the last International Classification of Headache Disorders identifies at least two entities evidently related to the use of combined oral contraceptives: exogenous hormone-induced headache and estrogen-withdrawal headache. As regards the safety, even if both migraine and combined oral contraceptive intake are associated with an increased risk of ischemic stroke, migraine without aura per se is not a contraindication for combined oral contraceptive use. Other risk factors (tobacco use, hypertension, hyperlipidemia, obesity and diabetes) must be carefully considered when prescribing combined oral contraceptives in migraine without aura patients, in particular in women aged over 35 years. Furthermore, the exclusion of a hereditary thrombophilia and of alterations of coagulative parameters should precede any decision of combined oral contraceptive prescription in migraine patients.
Stubblefield, P G
Low-dose oral contraceptives differ in the specific progestin component. Our review of available animal and human data revealed differences between the progestins as to their potencies for estrogenic, anti-estrogenic, androgenic and progesterone effects. Ideally, oral contraceptive formulations should have the minimal effective dose, sufficient to prevent pregnancy but with the fewest metabolic changes. The risk of cardiovascular disease may be predicted by changes in the composition and amount of circulating lipoproteins. Progestins with significant androgenic potency can lower high-density lipoprotein2; that is a possible adverse effect. Randomized, blind, comparative trials of the new multiphasic preparations are needed to determine which ones truly cause the fewest metabolic changes that might be of clinical significance.
Allais, Gianni; Gabellari, Ilaria Castagnoli; Airola, Gisella; Borgogno, Paola; Schiapparelli, Paola; Benedetto, Chiara
Although combined oral contraceptives (COCs) are a safe and highly effective method of birth control, they may also give rise to problems of clinical tolerability in migraine patients. Indeed, headache is among the most common side effects reported with the use of COCs, frequently leading to their being discontinued. The latest International Classification of Headache Disorders identified at least two entities evidently related to the use of COCs, i.e., exogenous hormone-induced headache and estrogen-withdrawal headache. As to the former, the newest formulations of COCs are generally well tolerated by migraine without aura patients, but can worsen headache in migraine with aura patients. Headache associated with COCs, generally, tends to improve as their use continues. However, although it is not yet clear if there is an association between headache and the composition of COCs (both in the type and amount of hormones), it has been observed that the incidence of headache during COC use seems greater if migraine is associated with menstrual trigger. The estrogen-withdrawal headache is a headache that generally appears within the first 5 days after cessation of estrogen use and resolves within 3 days, even if in some cases it may appear on the sixth or seventh day after pill suspension and lasts more than 3 days.
Bozdag, Gurkan; Yildiz, Bulent Okan
Combined oral contraceptive pills (OCPs) have been used in women with polycystic ovary syndrome (PCOS) for the treatment of menstrual disorders, acne and hirsutism. Despite years of their use and broad clinical experience, there are still ongoing doubts concerning their implications for the cardiovascular system and carbohydrate metabolism both in the general population and women with PCOS. In the general population, the risk of venous thromboembolism is reported to be increased. However, arterial thrombotic events seem to require concomitant risk factors to appear during administration of OCPs. In terms of carbohydrate metabolism, available data do not consistently suggest an increased risk of impaired glucose tolerance (IGT) or conversion of IGT to type 2 diabetes mellitus, in spite of some subtle fluctuations in glucose and insulin levels. In subgroup analyses of epidemiological studies in the general population, there is no finding indicating an increased risk of cardiovascular disease and related mortality in premenopausal women with PCOS. There is no significant alteration in carbohydrate and lipid metabolism after use of OCP in PCOS either. The absence of further cardiometabolic risk with OCP use in PCOS might suggest some unproven preventive alterations in this patient population.
De Giglio, Laura; Barletta, Valeria T.; Marinelli, Fabiana; Angelis, Floriana De; Gallo, Valentina; Pagano, Veronica A.; Marini, Stefano; Piattella, Maria C.; Tomassini, Valentina; Pantano, Patrizia
Objective: To test the effect of oral contraceptives (OCs) in combination with interferon β (IFN-β) on disease activity in patients with relapsing-remitting multiple sclerosis (RRMS). Methods: One hundred fifty women with RRMS were randomized in a 1:1:1 ratio to receive IFN-β-1a subcutaneously (SC) only (group 1), IFN-β-1a SC plus ethinylstradiol 20 μg and desogestrel 150 μg (group 2), or IFN-β-1a SC plus ethinylestradiol 40 μg and desogestrel 125 μg (group 3). The primary endpoint was the cumulative number of combined unique active (CUA) lesions on brain MRI at week 96. Secondary endpoints included MRI and clinical and safety measures. Results: The estimated number of cumulative CUA lesions at week 96 was 0.98 (95% confidence interval [CI] 0.81–1.14) in group 1, 0.84 (95% CI 0.66–1.02) in group 2, and 0.72 (95% CI 0.53–0.91) in group 3, with a decrease of 14.1% (p = 0.24) and 26.5% (p = 0.04) when comparing group 1 with groups 2 and 3, respectively. The number of patients with no gadolinium-enhancing lesions was greater in group 3 than in group 1 (p = 0.03). No significant differences were detected in other secondary endpoints. IFN-β or OC discontinuations were equally distributed across groups. Conclusions: Our results translate the observations derived from experimental models to patients, supporting the anti-inflammatory effects of OCs with high-dose estrogens, and suggest possible directions for future research. Classification of evidence: This study provides Class II evidence that in women with RRMS, IFN-β plus ethinylstradiol and desogestrel decreases the cumulative number of active brain MRI lesions compared with IFN-β alone. PMID:26140279
Abasiattai, A M; Utuk, M N; Ojeh, S O; Eyo, U E
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.
Estradiol 17-β, which is the natural estrogen in women, offers an alternative to ethinyl-estradiol to be used in combined oral contraceptives. Thanks to its biochemical structure, estradiol has a far lesser impact on the synthesis of hepatic proteins than ethinyl-estradiol, which is likely to result in a better metabolic and vascular profile. However and until lately, the different clinical trials that had investigated estradiol-containing oral contraceptives were limited by bleeding disturbances, with breakthrough and irregular bleeding and higher rates of discontinuation. Development of anti-gonadotropic progestins with a potent endometrial activity is likely to make possible their combination with estradiol in oral contraceptives. The objective of this current review is to provide an overview of the development of combined oral contraceptives containing natural estrogen from the respective biochemical and pharmacological characteristics of ethinyl-estradiol and estradiol.
Shahnazi, Mahnaz; Farshbaf Khalili, Azizeh; Ranjbar Kochaksaraei, Fatemeh; Asghari Jafarabadi, Mohammad; Gaza Banoi, Kamal; Nahaee, Jila; Bayati Payan, Somayeh
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
Sech, Laura A; Mishell, Daniel R
Oral steroid contraception is a popular method of family planning worldwide. Over the past several decades, this method of contraception has changed significantly by decreasing the estrogen dose, changing the progestin component, and reducing the hormone free interval. Despite the popularity of oral steroid contraception, there has been much criticism regarding the associated risks of venous thromboembolism and stroke. Despite these established, yet uncommon risks, oral steroid contraception has many important health benefits. This review highlights the available formulations of oral contraceptives along with their evidence-based associated risks and benefits. Highlights regarding future directions for development of novel oral contraceptives are also addressed.
Stang, A.; Schwingl, P.; Rivera, R.
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
del Marmol, V; Teichmann, A; Gertsen, K
Acne and seborrhea (or facial oiliness) are related androgenic skin disorders which affect a high proportion of women after menarche. They can have a negative effect on psychological well-being and social life. Androgens play an important role in the pathogenesis of acne through the stimulation of sebum secretion, increasing sebaceous gland size and possibly through follicular hyperkeratinization. Conversely, estrogens decrease sebum production by suppressing gonadotropin release and androgen production and increasing sex hormone binding globulin production. One of the treatment options for these conditions is hormonal therapy, especially for women who require contraception. The effect of combined oral contraceptives in androgenic skin disorders depends on their estrogen:progestogen balance and on the antiestrogenic activity of the progestogen component. Improved understanding of what women value about oral contraceptives suggests that the choice of product should be tailored as much as possible to the individual. Several combined oral contraceptives containing new-generation progestogens (e.g. desogestrel, gestodene) or progestational antiandrogens (e.g. cyproterone acetate, chlormadinone acetate) have demonstrated efficacy in the treatment of women with acne, although comparisons between trials are difficult because of differing endpoints. Seborrhea has been less well studied, but the few studies that are available show an improvement in women with this condition using combined oral contraceptives.
Vertkin, A L; Nosova, A V
The paper is devoted to the topical problem of maintaining somatic and psychic health of the women of reproductive age by rational pregnancy planning and prevention of abortions by modern methods of contraception including combined oral hormonal contraception. Unfortunately, this approach is rarely employed in this country (5-6%). Results of retrospective analysis of medical documentation, clinical efficacy and safety of modern combined oral hormonal contraception are presented.
Tricotel, Aurore; Raguideau, Fanny; Collin, Cédric; Zureik, Mahmoud
Purpose To estimate the number of venous thromboembolic events and related-premature mortality (including immediate in-hospital lethality) attributable to the use of combined oral contraceptives in women aged 15 to 49 years-old between 2000 and 2011 in France. Methods French data on sales of combined oral contraceptives and on contraception behaviours from two national surveys conducted in 2000 and 2010 were combined to estimate the number of exposed women according to contraceptives generation and age. Absolute risk of first time venous thromboembolism in non-users of hormonal contraception and increased risk of thromboembolism in users vs. non-users of hormonal contraception were estimated on the basis of literature data. Finally, immediate in-hospital lethality due to pulmonary embolism and premature mortality due to recurrent venous thromboembolism were estimated from the French national database of hospitalisation and literature data. Results In France, more than four million women are daily exposed to combined oral contraceptives. The mean annual number of venous thromboembolic events attributable to their use was 2,529 (778 associated to the use of first- and second-generation contraceptives and 1,751 to the use of third- and fourth-generation contraceptives), corresponding to 20 premature deaths (six with first- and second-generation contraceptives and fourteen with third- and fourth-generation contraceptives), of which there were eight to nine immediate in-hospital deaths. As compared to the use of first- and second-generation contraceptives, exposure to third- and fourth-generation contraceptives led to a mean annual excess of 1,167 venous thromboembolic events and nine premature deaths (including three immediate in-hospital deaths). Conclusions Corrective actions should be considered to limit exposure to third- and fourth-generation contraceptives, and thus optimise the benefit-risk ratio of combined oral contraception. PMID:24751717
Burkman, R T
During the past four decades, oral contraceptives have remained a safe and effective method of birth control. Reductions in the estrogen and progestin dosages have significantly decreased the incidence of cardiovascular complications. The association between oral contraceptives and breast cancer appears to be primarily because of detection bias or possibly a promotional effect. Despite the changes in formulation, the problems related to side effects have not been totally solved. Because compliance and successful use is strongly affected by side effects, improvement in this area is probably the biggest challenge faced by developers of oral contraceptives. It is also clear that there are a growing number of significant noncontraceptive benefits that accrue in oral contraceptive users. Unfortunately, many women do not know about these benefits. Thus, one of the issues that providers need to continue to address is how to provide better information about oral contraceptives and contraception in general to patients.
... Health Gynecology Medical Conditions Nutrition & Fitness Emotional Health PCOS: The Oral Contraceptive Pill Posted under Health Guides . ... of oral contraceptive pills for young women with PCOS? Regular and Lighter Periods: Oral contraceptive pills can ...
Dennerstein, L; Burrows, G
A search of the literature has been carried out to determined how oral contraceptives affect sexuality in women. Some studies featured a high incidence of loss of libido. This could perhaps be attributed to preparations containing progestational compounds. However, no adequate double-blind trial has confirmed this observation. Some psychological and pharmacological aspects of contraceptions are discussed. More research is needed to ascertain why women often lose their sexual interest when taking oral contraceptives.
Burkman, Ronald; Bell, Carrie; Serfaty, David
Since its introduction in 1960, the combined oral contraceptive (COC) pill has become one of the most widely and frequently used methods of contraception worldwide. Although highly effective, early COC formulations were associated with significant adverse effects and unacceptable cardiovascular risk. Improvements in tolerability and safety have been achieved, without compromises in effectiveness, primarily via hormone dosage reductions and the development of several new progestins. Multiphasic COCs and extended-/continuous-cycle COCs have also been introduced, although the clinical advantages of these formulations vs. traditional COCs have yet to be established. Inclusion of natural estrogens such as estradiol valerate and 17β-estradiol with selective progestins in new combinations that maintain good cycle control is the most recent evolutionary step designed to improve COC tolerability and safety. Vigorous research needs to continue to help guarantee that the unmet need for safe and effective contraception is satisfied in future generations.
Mousa, G Y
Migraine is a common complaint in optometric practice. Three cases of migrainous patients taking oral contraceptives are presented in this report. The role of oral contraceptives in triggering a migraine attack and possibly elevating the risk of a stroke in a patient with migraine is discussed. The counseling an optometrist can provide in such cases in discussed.
The COCP is a safe form of contraception for the majority of women. The challenge is to identify the women who have risk factors that make the use of COCP less safe. This approach is summarised by a recent consensus statement from an international conference on evidence based prescribing of COCPs. This states that 'current evidence suggests only two prerequisites for the safe provision of COCPs: a careful personal and family medical history with particular attention to cardiovascular risk factors, and an accurate blood pressure measurement'.
Nappi, Rossella E; Serrani, Marco; Jensen, Jeffrey T
Combined oral contraceptives formulated to include estradiol (E2) have recently become available for the indication of pregnancy prevention. A combined estradiol valerate and dienogest pill (E2V/DNG), designed to be administered using an estrogen step-down and a progestin step-up regimen over 26 days of active treatment followed by 2 days of placebo (26/2-day regimen), has also undergone research to assess the potential for additional noncontraceptive benefits. Randomized, placebo-controlled studies have demonstrated that E2V/DNG is an effective treatment for heavy menstrual bleeding – a reduction in median menstrual blood loss approaching 90% occurs after 6 months of treatment. To date, E2V/DNG is the only oral contraceptive approved for this indication. Comparator studies have also demonstrated a reduction in hormone withdrawal-associated symptoms in users of E2V/DNG compared with a conventional 21/7-day regimen of ethinylestradiol/levonorgestrel. Other potential noncontraceptive benefits associated with E2V/DNG, like improvement in dysmenorrhea, sexual function, and quality of life, are comparable with those associated with other combined oral contraceptives and are discussed further in this review. PMID:25120376
Edgren, R A; Sturtevant, F M
Oral contraceptives are combinations of estrogens and progestogens or, in the case of the mini-pills, progestogens alone. With specific test procedures in laboratory animals or human subjects, it is possible to assign potency evaluations to the components relative to the progestational, estrogenic, or antiestrogenic activities of the progestogen or to the estrogenic potencies of the estrogenic component. It might even be possible to quantify the synergistic effects of the estrogen on the progestational agent. Unfortunately, however, it is impossible now to amalgamate such assay results into single estimates of the potencies of the combinations (either the combination products per se or the combination tablets of sequential products). For example, an over-all estrogenic potency of a combination preparation would involve the integration of contributions form the estrogen itself plus the estrogenic products of metabolism of the progestogen minus the antagonistic effect of the progestational agent, if any. These factors cannot now be quantified independently, much less merged into a single figure of clinical significance. Further, even if it were possible to produce such an estimate, it is unlikely that the evaluation would be meaningful in relation to any putative side effect or adverse reaction, i.e., the alleged thrombogenic effects of oral contraceptives cannot currently be related directly to any measure of potency that will allow prediction of these clinical conditions from laboratory models. Any evaluation of the potential of a given contraceptive to produce a specific side effect will depend upon data generated with specific regard to that adverse reaction and the individual product in question.
Braun, Marina; Elshoff, Jan-Peer; Andreas, Jens-Otto; Müller, Louise Ischen; Horstmann, Rolf
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
On the 50th birthday of the pill, it is appropriate to recall the milestones which have led to its development and evolution during the last five decades. The main contraceptive effect of the pill being inhibition of ovulation, it may be called a small miracle that this drug was developed long before the complex regulation of ovulation and the menstrual cycle was elucidated. Another stumbling block on its way was the hostile climate with regard to contraception that prevailed at the time. Animal experiments on the effect of sex steroids on ovulation, and the synthesis of sex steroids and orally active analogues were the necessary preliminaries. We owe the development of oral contraceptives to a handful of persons: two determined feminists, Margaret Sanger and Katherine McCormick; a biologist, Gregory Pincus; and a gynaecologist, John Rock. Soon after the introduction of the first pills, some nasty and life-threatening side effects emerged, which were due to the high doses of sex steroids. This led to the development of new preparations with reduced oestrogen content, progestins with more specific action, and alternative administration routes. Almost every decade we have witnessed a breakthrough in oral contraception. Social and moral objections to birth control have gradually disappeared and, notwithstanding some pill scares, oral contraceptives are now one of the most used methods of contraception. Finally, all's well that ends well: recent reports have substantiated the multiple noncontraceptive health benefits paving the way for a bright future for this 50-year-old product.
Nappi, Rossella E.; Kaunitz, Andrew M.; Bitzer, Johannes
ABSTRACT Objectives: The clinical utility of extended regimen combined oral contraceptives (COCs) is increasingly being recognised. Our objective was to understand the attitudes of women and clinicians about the use of these regimens. We present the rationale for extended regimen COCs from a historical perspective, and trace their evolution and growing popularity in light of their clinical benefits. We conclude by offering potential strategies for counselling women about extended regimen COC options. Methods: We conducted a MEDLINE search to identify and summarise studies of extended regimen COCs, focusing on attitudes of women and clinicians regarding efficacy, safety/tolerability and fewer scheduled bleeding episodes and other potential benefits. Results: The body of contemporary literature on extended regimen COCs suggests that their contraceptive efficacy is comparable to that of conventional 28-day (i.e., 21/7) regimens. For women seeking contraception that allows infrequent scheduled bleeding episodes, particularly those who suffer from hormone withdrawal symptoms and cyclical symptoms (e.g., headache, mood changes, dysmenorrhoea, heavy menstrual bleeding), extended regimen COCs are an effective and safe option. Although satisfaction with extended regimen COCs in clinical trials is high, misperceptions about continuous hormone use may still limit the widespread acceptance of this approach. Conclusions: Despite the widespread acceptance among clinicians of extended regimen COCs as an effective and safe contraceptive option, these regimens are underused, likely due to a lack of awareness about their availability and utility among women. Improved patient education and counselling regarding the safety and benefits of extended regimen COCs may help women make more informed contraceptive choices. PMID:26572318
Cardiovascular risks attributable to oral contraceptive use may now be subdivided into those that appear to be secondary to the estrogen component, i.e., venous thrombosis, pulmonary embolism, and those linked to the progestin component, i.e., small vessel disease including myocardial infarction and cerebrovascular accident. It appears that venous risk is attributable to subtle changes in clotting factors, while arterial risk may be secondary to changes in glucose and lipid metabolism. In order to determine which women are at greatest risk from oral contraceptive use, Spellacy et al. has developed a risk scoring form that aids in the screening process. After excluding women with an absolute contraindication to pill use, women at greatest risk for cardiovascular disease related to oral contraceptive use are those with a family history of hyperlipidemia, gestational or overt diabetics, hypertensives, and smokers over the age of 35. The gradual reduction by manufacturers of the steroid content of oral contraceptives appears to have lessened the incidence of adverse effects. Our current knowledge of risk factors permits the clinician to reduce exposure to oral contraceptive-related mortality by as much as 86 per cent. As we continue to search for ways to reduce risk among oral contraceptive users, it is important to note that more than 25 per cent of women are still taking formulations containing 50 micrograms of estrogen. It becomes the responsibility of the practicing physician to "step-down" these patients to lower-dose preparations such as the multiphasics. Such preparations also represent optimal therapy for first-time pill users.
Hofmann, Birte; Reinecke, Isabel; Schuett, Barbara; Merz, Martin; Zurth, Christian
Objective: To determine the relative bioavailability of ethinyl estradiol (EE) and gestodene (GSD) after application of a novel transdermal contraceptive patch vs. a standard combined oral contraceptive (COC) pill (study 1), and to evaluate the pharmacokinetics (PK) of EE after application of the EE/GSD patch compared with an EE/norelgestromin (NGMN) patch (study 2). Materials: Participants were healthy, non-obese women aged 18 – 45 years (study 1) or 18 – 35 years (study 2). Compositions of study treatments were as follows: 0.55 mg EE/2.1 mg GSD (EE/GSD patch); 0.02 mg EE/0.075 mg GSD (standard COC); 0.6 mg EE/6 mg NGMN (EE/NGMN patch). Methods: In study 1, which consisted of 3 treatment periods (each followed by 7 patch- or pill-free days), treatments were administered in one of two randomized orders: either P–M–E (EE/GSD patch (P) every 7 days for 28 days → COC (M) once-daily for 21 days → two 7-day patch-wearing periods followed by one 10-day patch-wearing phase (E)), or the same treatments administered in sequence M–P–E. For study 2, participants received either the EE/GSD patch or EE/NGMN patch for seven treatment cycles (one patch per week for 3 weeks followed by a 7-day patch-free interval). Results: In study 1, average daily exposure to EE was similar for treatments P and M; the mean daily area under the concentration-time curve (AUC) ratio of treatment P vs. treatment M for EE was 1.06 (90% confidence interval (CI): 0.964 – 1.16), indicating average daily delivery similar to oral administration of 0.019 – 0.023 mg EE. For unbound GSD, average daily exposure was lower for treatment P vs. treatment M. The mean AUC ratio of treatment P vs. treatment M for unbound GSD was 0.820 (90% CI: 0.760 – 0.885), indicating average daily delivery from the patch of 0.057 – 0.066 mg GSD. Prolonged patch wearing did not result in a distinct decline in GSD and EE serum concentrations. In study 2, AUC at steady state (AUC0–168,ss
Oyelola, O O
Fasting plasma lipid, lipoprotein, and apolipoprotein (apo) profiles were determined in Nigerian women using a low-dose combined oral (Lo-Feminal + Fe) (n = 18), a progestin-only injectable (Depo-Provera) (n = 16) contraceptives and matched controls (n = 18). The mean of plasma total and low-density lipoprotein (LDL) cholesterol, apo B and Lp(a) were significantly higher (p < 0.01) in women using contraceptives than the controls. The mean of total and LDL-cholesterol and apo B were also significantly higher in the oral contraceptive users than those on progestin-only injectables. Furthermore, the mean of cardiovascular disease (CVD) risk indices, total/HDL-cholesterol (p < 0.05) and LDL/HDL-cholesterol (p < 0.01), were significantly higher in women on oral contraceptives than the controls. There were no statistically significant differences between the indices in the women using progestin-only injectables and the controls. Based on this finding, it is concluded that the use of steroidal contraceptives is associated with alterations of lipid and apolipoprotein profiles in Nigerian women and that the use of low-dose combined oral contraceptives may be associated with an increased CVD risk.
Rechberger, Tomasz; Tomaszewski, Jacek; Pieprzowska-Białek, Anna; Kulik-Rechberger, Beata; Skorupski, Paweł
Resistin is a hormone secreted by adipose tissue that could be involved in the development of insulin resistance. Previous studies confirmed that endogenous sex steroids may influence serum resistin concentration in women. The aim of our study was to investigate the influence of combined oral contraceptives containing desogestrel or gestodene on circulating levels of resistin. Fifty-three women were enrolled in the study. Thirteen patients received 20 microg ethinylestradiol/150 microg desogestrel, 15 women were treated with 20 microg ethinylestradiol/75 microg gestodene, 11 with 30 microg ethinylestradiol/150 microg desogestrel and 14 with 30 microg ethinylestradiol/75 microg gestodene. Blood samples for estimation of serum resistin and insulin levels were drawn before administration of oral contraceptive and after 6 cycles of therapy. We found that serum resistin level remained unchanged in women receiving ethinylestradiol/desogestrel and was reduced in women treated with formulations containing gestodene. We conclude that ethinylestradiol combined with desogestrel or gestodene is unlikely to induce insulin resistance through resistin pathway.
Bahamondes, Luis; Lira-Plascencia, Josefina; Martin, Ricardo; Marin, Victor; Makuch, Maria Y
Background Unintended pregnancy is a public health problem and unmet medical need worldwide. It is estimated that in the year 2012, almost 213 million pregnancies occurred, and the global pregnancy rate decreased only slightly from 2008 to 2012. It was also estimated that 85 million pregnancies (40% of all pregnancies) were unintended and that 38% ended in an unintended birth. Objectives To assess knowledge and attitudes of Latin American (LA) obstetricians and gynecologists (OBGYNs) regarding unintended pregnancies and aspects of combined oral contraceptive (COC) use. Methods A survey was conducted during a scientific meeting about contraception in 2014, in which OBGYNs from 12 LA countries who provide attention in contraception were invited to respond to a multiple-choice questionnaire to assess their knowledge and attitudes regarding unplanned pregnancy and some aspects regarding COC use. Results A total of 210 OBGYNs participated in the study. Their knowledge regarding COC failure was low. The participants reported they believed that their patients habitually forgot to take a pill and that their patients did not know what to do in these situations. They were aware of the benefits of COC use; however, they were less prone to prescribe COCs for the purpose of protecting against ovarian and endometrial cancer, and one-quarter of them had doubts about the association between COC use and cancer risk. Conclusion The interviewed LA OBGYNs showed some flaws in terms of knowledge of COC failure rates and the non-contraceptive benefits and risks of COCs. To adequately counsel their patients regarding COC intake, OBGYNs must be updated regarding all aspects of COC use. PMID:25999766
DeRossi, Scott S; Hersh, Elliot V
With the exception of rifampin-like drugs, there is a lack of scientific evidence supporting the ability of commonly prescribed antibiotics, including all those routinely employed in outpatient dentistry, to either reduce blood levels and/or the effectiveness of oral contraceptives. To date, all clinical trials studying the effects of concomitant antibiotic therapy (with the exception of rifampin and rifabutin) have failed to demonstrate an interaction. Like all drugs, oral contraceptives are not 100% effective with the failure rate in the typical United States population reported to be as high as 3%. It is thus possible that the case reports of unintended pregnancies during antibiotic therapy may simply represent the normal failure rate of these drugs. Considering that both drug classes are prescribed frequently to women of childbearing potential, one would expect a much higher rate of oral contraceptive failure in this group of patients if a true drug:drug interaction existed. On the other hand, if the interaction does exist but is a relatively rare event, occurring in, say, 1 in 5000 women, clinical studies such as those described in this article would not detect the interaction. The pharmacokinetic studies of simultaneous antibiotic and oral contraceptive ingestion, and the retrospective studies of pregnancy rates among oral contraceptive users exposed to antibiotics, all suffer from one potential common weakness, i.e., their relatively small sample size. Sample sizes in the pharmacokinetic trials ranged from 7 to 24 participants, whereas the largest retrospective study of pregnancy rates still evaluated less than 800 total contraceptive users. Still, the incidence of such a rare interaction would not differ from the accepted normal failure rate of oral contraceptive therapy. The medico-legal ramifications of what looks like at best a rare interaction remains somewhat "murky." On one hand, we have medico-legal experts advising the profession to exercise caution
Stanczyk, Frank Z; Archer, David F; Bhavnani, Bhagu R
The need to seek improved combined oral contraceptive (COC) efficacy, with fewer health risks and better acceptability, has been ongoing since the introduction of COCs more than 50 years ago. New progestin formulations combined with lower doses of ethinyl estradiol (EE), the predominant estrogenic component of COCs, have reduced the incidence of venous thromboembolism and other negative outcomes of COC treatment. Previous attempts to use endogenous 17β-estradiol (E₂) instead of EE were limited primarily by poor cycle control. The recent introduction of E₂-based formulations has renewed interest to determine if there are potential benefits of using E₂ in COCs. These formulations have been shown to have similar efficacy and cycle control as EE-based COCs. This review provides a brief summary of the pharmacology of EE and E₂, including metabolism, pharmacokinetics and pharmacodynamics, as well as adverse effects of these estrogens.
Igunnu, Adedoyin; Seok, Young-Mi; Olatunji, Lawrence A; Kang, Seol-Hee; Kim, Inkyeom
Clinical studies have shown that the use of combined oral contraceptive in pre-menopausal women is associated with fluid retention. However, the molecular mechanism is still elusive. We hypothesized that combined oral contraceptive (COC) ethinyl estradiol (EE) and norgestrel (N) synergistically activates mineralocorticoid receptor (MR) through histone code modifications. Twelve-week-old female Sprague-Dawley rats were treated with olive oil (control), a combination of 0.1µg EE and 1.0µg N (low COC) or 1.0µg EE and 10.0µg N (high COC) as well as 0.1 or 1.0µg EE and 1.0 or 10.0µg N daily for 6 weeks. Expression of MR target genes in kidney cortex was determined by quantitative real-time polymerase chain reaction. MR was quantified by western blot. Recruitment of MR and RNA polymerase II (Pol II) on promoters of target genes as well as histone code modifications was analyzed by chromatin immunoprecipitation assay. Treatment with COC increased renal cortical expression of MR target genes such as serum and glucocorticoid-regulated kinase 1 (Sgk-1), glucocorticoid-induced leucine zipper (Gilz), epithelial Na(+)channel (Enac) and Na(+)-K(+)-ATPase subunit α1 (Atp1a1). Although COC increased neither serum aldosterone nor MR expression in kidney cortex, it increased recruitment of MR and Pol II in parallel with increased H3Ac and H3K4me3 on the promoter regions of MR target genes. However, treatment with EE or N alone did not affect renal cortical expression of Sgk-1, Gilz, Enac or Atp1a1. These results indicate that COC synergistically activates MR through histone code modifications.
Savabi-Esfahany, M; Fadaei, S; Yousefy, A
We carried out a retrospective cross-sectional study on 500 women in Isfahan who started taking combined oral contraceptives (COCs) during the period 21 March 1995-20 March 1997. The cumulative continuation rate fell from 77% to 12% over 60 months. The most common reason for discontinuation was side-effects. There was a significant correlation between side-effects and cumulative COC continuation rate (P < 0.05). The lowest rate was seen in women reporting nausea or vomiting. Women who are interested in COCs should receive extensive counselling about the possible side-effects and should be helped to find a method of birth control suited to their temperament and physiology.
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.
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
Shearman, R P
The history of the development of oral contraceptives (OCs) has been a progressive reduction in dosage to what is now probably the lowest does that is compatible with the desired therapeutic effect -- to inhibit ovluation. Yet, controversy and argument continue. A table lists the OCs that are available in Australia. Many of these preparations, although having different trade names, have an identical composition. Since the withdrawal of sequential OCs from the Australian market, there are only 2 generic types. These are the progestogen only (mini) OCs, which consist of either 30 mcg of levonorgestrel or 350 mcg of norethisterone given at the same time every day; and the combined OCs, which contain an estrogen and a progestogen. In the last 12 months, some of the older high-dose OCs have been withdrawn, and it seems likely that further withdrawals will follow. Only 2 estrogens are used in the formulation of the OC, but there is a greater variety of progestogens. Ethinyl estradiol is used in most preparations. A small minority of OCs contain mestranol, the 3-methyl ether of ethinyl estradiol. Currently, there are only 4 OC agents that are available in Australia that contain mestranol and 2 of these contain the high doses of 100 mcg. Fundamentally, there are 2 types of progestogens -- those that contain, or are metabolized to, norethisterone and those that contain norgestrel or its close relative, desogestrel. With the exception of the norgestrel group and desogestrel, all other progestins, including norethisterone itself, are effective in vivo after they have been metablized to norethisterone. Mestranol is effective in humans after demethylation to ethinyl estradiol. In the norgesterel group, since d-norgestrel is inert endocrinologically, 250 mcg of levonorgestrel and 500 mcg of dl-norgestrel are equivalent. Levonorgestrel and desogestrel are of approximately equal potency. With the combined OC agents, the overwhelming mechanism of action is by the inhibition of the
Chihal, H J; Peppler, R D; Dickey, R P
This letter is a response to the discussion by Edgren and Sturtevant (125:1029, 1976) on potencies of oral contraceptives (OCs). It is agreed that the results of studies in animal models on OC potencies may not necessarily reflect true potencies in human subjects, however, these animal models do allow the evaluation of the biological effects and interactions of the components of OCs. Data obtained in animal studies are acknowledged to be valuable aids in the study of human diseases. Likewise, mouse uterine response to contraceptive steroids is 1 criterion to be used in evaluating steroid potency. As previously reported, the importance of the mouse uterine response is that the contribution of the progestin component to the total estrogenic potency of the OC is demonstrated.
Langer, A; Devanesan, M; Pelosi, M A
The estrogen and progestin in most oral contraceptives, regardless of amounts, can produce undesirable side effects in any woman. The convenience and effectiveness, however, make oral contraceptives an excellent birth control method for the correctly screened patient. The use of relatively small doses of estrogen combined with a progestin complementary to the estrogenic, progestogenic, and androgenic needs of the patient will reduce the risk of side effects. Above the 50 ug estrogen level there is significantly higher risk of pulmonary embolism, venous thrombosis, and cerebral thrombosis. Hypertension, depression and hepatic disorders are other potential side effects. Less serious complications are breakthrough bleeding, likely caused by low level estrogen dosage and amenorrhea. Progestogenic effects include sustained noncyclic weight gain and amenorrhea. Prescribing these agents necessitates adequate follow-up and willingness to alter the prescription.
Sanfilippo, J S
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
Stegeman, Bernardine H; de Bastos, Marcos; Rosendaal, Frits R; van Hylckama Vlieg, A; Helmerhorst, Frans M; Stijnen, Theo
Objective To provide a comprehensive overview of the risk of venous thrombosis in women using different combined oral contraceptives. Design Systematic review and network meta-analysis. Data sources PubMed, Embase, Web of Science, Cochrane, Cumulative Index to Nursing and Allied Health Literature, Academic Search Premier, and ScienceDirect up to 22 April 2013. Review methods Observational studies that assessed the effect of combined oral contraceptives on venous thrombosis in healthy women. The primary outcome of interest was a fatal or non-fatal first event of venous thrombosis with the main focus on deep venous thrombosis or pulmonary embolism. Publications with at least 10 events in total were eligible. The network meta-analysis was performed using an extension of frequentist random effects models for mixed multiple treatment comparisons. Unadjusted relative risks with 95% confidence intervals were reported. The requirement for crude numbers did not allow adjustment for potential confounding variables. Results 3110 publications were retrieved through a search strategy; 25 publications reporting on 26 studies were included. Incidence of venous thrombosis in non-users from two included cohorts was 1.9 and 3.7 per 10 000 woman years, in line with previously reported incidences of 1-6 per 10 000 woman years. Use of combined oral contraceptives increased the risk of venous thrombosis compared with non-use (relative risk 3.5, 95% confidence interval 2.9 to 4.3). The relative risk of venous thrombosis for combined oral contraceptives with 30-35 µg ethinylestradiol and gestodene, desogestrel, cyproterone acetate, or drospirenone were similar and about 50-80% higher than for combined oral contraceptives with levonorgestrel. A dose related effect of ethinylestradiol was observed for gestodene, desogestrel, and levonorgestrel, with higher doses being associated with higher thrombosis risk. Conclusion All combined oral contraceptives investigated in this analysis were
Nichols, Andrew W; Hetzler, Ronald K; Villanueva, Richard J; Stickley, Christopher D; Kimura, Iris F
This study was designed to investigate the effects of combination oral contraceptive agents (OCAs) on strength and torque production in collegiate women softball and water polo athletes who participated in a 12-week strength development program. A double-blind research design was used to mask subjects to the main outcome of interest. Thirty-one women collegiate softball and water polo players were divided into experimental (OCA users, n = 13), and control (non-OCA users, n = 18) groups. All subjects participated in the same supervised 12-week preseason strength development program. One-repetition maximum bench press (1RMBP), 10-repetition maximum leg extension (10RMLE), isokinetic peak torque bench press (IKBP), and isokinetic peak torque leg extension (IKLE) data were collected at weeks 0 (pre-test), 4, 8, and 12 (post-test). Significant increases in strength and torque production over time were identified regardless of group for 1RMBP, 10RMLE, and IKLE. No significant differences in IKBP torque production occurred during the 12-week strength training program. No significant differences in 1RMBP, 10RMLE, IKBP, or IKLE occurred between the OCA users and the non-OCA users groups. It was concluded that, within the limitations of the study, the use of combination OCAs did not provide sufficient androgenic effect to increase strength gains beyond the stimulus of the training protocol.
Tan, Jerry Kl; Ediriweera, Chemanthi
Acne is a common disorder affecting the majority of adolescents and often extends into adulthood. The central pathophysiological feature of acne is increased androgenic stimulation and/or end-organ sensitivity of pilosebaceous units leading to sebum hypersecretion and infundibular hyperkeratinization. These events lead to Propionibacterium acnes proliferation and subsequent inflammation. Hormonal therapy, including combined oral contraceptives (OCs), can attenuate the proximate androgenic trigger of this sequence. For many women, hormonal therapy is a rational option for acne treatment as it may be useful across the spectrum of severity. Drospirenone (DRSP) is a unique progestin structurally related to spironolactone with progestogenic, antimineralocorticoid, and antiandrogenic properties. It is available in 2 combined OC preparations (30 μg EE/3 mg DRSP; Yasmin(®) in a 21/7 regimen; and 20 μg EE/3 mg DRSP; Yaz(®) in a 24/4 regimen). These preparations are bereft of the fluid retentional side effects typical of other progestins and their safety has been demonstrated in large epidemiological studies in which no increased risk of vascular thromboembolic disease or arrhythmias was observed. In acne, the efficacy of DRSP-containing OCs has been shown in placebo-controlled superiority trials and in active-comparator non-inferiority trials.
Thomas, Robin Lynn; Halvorson, Lisa Marie; Carr, Bruce Richard; Doody, Kathleen Marie; Doody, Kevin John
Background Our study compares the efficacy of the combined contraceptive vaginal ring to oral contraceptive pills (OCPs) for hypothalamic-pituitary-ovarian (HPO) axis suppression in egg donor in vitro fertilization (IVF) cycles. Methods Our retrospective cohort study includes patients from the Center for Assisted Reproduction (CARE) in Bedford, Texas undergoing IVF cycles as egg donors from January 2003 through December 2009. Twenty-five and thirty-nine women were treated with OCPs and the combined contraceptive vaginal ring, respectively. Statistical analyses were performed using the SigmaStat Software package (Systat, Chicago, IL). Data were analyzed by t or Mann-whitney test and Chi-square of Fisher exact test. Statistical significance was set at p<0.05. Results Prior to gonadotropin initiation, endometrial thickness and serum estradiol were 5.6±2.6 mm and 33.6±19.9 pg/ml in the OCP group and 6.0±2.4 mm and 36.6±24.3 pg/ml in the combined contraceptive vaginal ring group, respectively (p=0.49 and p=0.33). Average serum FSH and LH were 1.7±1.9 and 1.7±2.5 mIU/ml in the OCP group and 1.7±1.6 and 1.2±1.4 mIU/ml in the combined contraceptive vaginal ring group, respectively (p=0.45 and p=0.95). No significant differences were found for gonadotropin requirement, peak estradiol, maximal endometrial thickness, number of oocytes retrieved, number of normally fertilized embryos, number of cryopreserved embryos, or live birth rates. Conclusion The combined contraceptive vaginal ring is effective for HPO axis suppression in egg donor IVF cycles and associated with cycle characteristics similar to those observed with OCP treatment. The combined contraceptive vaginal ring may provide an important advantage over OCPs due to improved patient compliance. PMID:24551576
Che, Yan; Liu, Xiaoting; Zhang, Bin; Cheng, Linan
Abstract Oral contraceptives (OCs) following induced abortion offer a reliable method to avoid repeated abortion. However, limited data exist supporting the effective use of OCs postabortion. We conducted this systematic review and meta-analysis in the present study reported immediate administration of OCs or combined OCs postabortion may reduce vaginal bleeding time and amount, shorten the menstruation recovery period, increase endometrial thickness 2 to 3 weeks after abortion, and reduce the risk of complications and unintended pregnancies. A total of 8 major authorized Chinese and English databases were screened from January 1960 to November 2014. Randomized controlled trials in which patients had undergone medical or surgical abortions were included. Chinese studies that met the inclusion criteria were divided into 3 groups: administration of OC postmedical abortion (group I; n = 1712), administration of OC postsurgical abortion (group II; n = 8788), and administration of OC in combination with traditional Chinese medicine postsurgical abortion (group III; n = 19,707). In total, 119 of 6160 publications were included in this analysis. Significant difference was observed in group I for vaginal bleeding time (P = 0.0001), the amount of vaginal bleeding (P = 0.03), and menstruation recovery period (P < 0.00001) compared with the control groups. Group II demonstrated a significant difference in vaginal bleeding time (P < 0.00001), the amount of vaginal bleeding (P = 0.0002), menstruation recovery period (P < 0.00001), and endometrial thickness at 2 (P = 0.003) and 3 (P < 0.00001) weeks postabortion compared with the control group. Similarly, a significant difference was observed in group III for reducing vaginal bleeding time (P < 0.00001) and the amount of vaginal bleeding (P < 0.00001), shortening the menstruation recovery period (P < 0.00001), and increasing endometrial thickness 2 and 3 weeks after surgical abortion (P < 0
Frey, Reiner; Unger, Sigrun; van der Mey, Dorina; Becker, Corina; Saleh, Soundos; Wensing, Georg; Mück, Wolfgang
Female patients requiring treatment for pulmonary arterial hypertension (PAH) are advised to avoid pregnancy because of the high associated mortality rate. Oral contraception is one of the main methods of preventing pregnancy in this context, mandating pharmacokinetic and safety studies for new agents in this setting. Riociguat is a soluble guanylate cyclase stimulator approved for treatment of PAH and inoperable and persistent or recurrent chronic thromboembolic pulmonary hypertension. This single-center, randomized, nonblinded study involving healthy postmenopausal women investigated the effect of riociguat on plasma concentrations of levonorgestrel (0.15 mg) and ethinylestradiol (0.03 mg) in a combined oral contraceptive. Treatment A was a single oral tablet of levonorgestrel-ethinylestradiol. In treatment B, subjects received 2.5 mg riociguat 3 times daily for 12 days. On the eighth day, they also received a single oral tablet of levonorgestrel-ethinylestradiol. Subjects received both regimens in a crossover design. There was no change in area under the plasma concentration-time curves of levonorgestrel or ethinylestradiol or maximum concentration in plasma (C max) of levonorgestrel during combined administration versus levonorgestrel-ethinylestradiol alone. A 20% increase in the C max of ethinylestradiol was noted during coadministration; this is not anticipated to adversely impact the contraceptive efficacy or to require any dose adjustment for ethinylestradiol. Plasma concentrations and exposures of riociguat were within the expected range and were not influenced by coadministration with levonorgestrel-ethinylestradiol. Combined treatment was safe and well tolerated. In conclusion, riociguat did not change the exposure to levonorgestrel or ethinylestradiol relative to oral contraceptive administered alone.
Unger, Sigrun; van der Mey, Dorina; Becker, Corina; Saleh, Soundos; Wensing, Georg; Mück, Wolfgang
Abstract Female patients requiring treatment for pulmonary arterial hypertension (PAH) are advised to avoid pregnancy because of the high associated mortality rate. Oral contraception is one of the main methods of preventing pregnancy in this context, mandating pharmacokinetic and safety studies for new agents in this setting. Riociguat is a soluble guanylate cyclase stimulator approved for treatment of PAH and inoperable and persistent or recurrent chronic thromboembolic pulmonary hypertension. This single-center, randomized, nonblinded study involving healthy postmenopausal women investigated the effect of riociguat on plasma concentrations of levonorgestrel (0.15 mg) and ethinylestradiol (0.03 mg) in a combined oral contraceptive. Treatment A was a single oral tablet of levonorgestrel-ethinylestradiol. In treatment B, subjects received 2.5 mg riociguat 3 times daily for 12 days. On the eighth day, they also received a single oral tablet of levonorgestrel-ethinylestradiol. Subjects received both regimens in a crossover design. There was no change in area under the plasma concentration–time curves of levonorgestrel or ethinylestradiol or maximum concentration in plasma (Cmax) of levonorgestrel during combined administration versus levonorgestrel-ethinylestradiol alone. A 20% increase in the Cmax of ethinylestradiol was noted during coadministration; this is not anticipated to adversely impact the contraceptive efficacy or to require any dose adjustment for ethinylestradiol. Plasma concentrations and exposures of riociguat were within the expected range and were not influenced by coadministration with levonorgestrel-ethinylestradiol. Combined treatment was safe and well tolerated. In conclusion, riociguat did not change the exposure to levonorgestrel or ethinylestradiol relative to oral contraceptive administered alone. PMID:27162633
Author gives a review of the development of Hungarian oral contraceptives from the beginning to the present status. He describes the three main historical phases that means the high-dose combined pills, the low-dose compositions and the most modern two- and three-phasic preparations. Besides, he mentions the monohormonal mini-pills and the so-called postcoital pill, too. He refers to the fact that the Hungarian pharmaceutical research followed truly the international development in oral contraception, too.
Lüdicke, F; Sullivan, H; Spona, J; Elstein, M
An open label, non-comparative study was carried out in 22 women over a total of five cycles. After an untreated cycle, oral administration of 20 microg ethinyl estradiol (EE) with 50 microg gestodene (GST) (tablets taken daily for 21 days with a break of 7 days) was commenced, and three treatment cycles were followed by an untreated follow-up control cycle. The ability of this formulation to inhibit ovulation and suppress ovarian activity was assessed by using hormonal parameters and ultrasound. One ovulation occurred during treatment. Luteinized unruptured follicles were observed in three cases in the second treatment cycle and in one case during the third treatment cycle. Follicle-like structures larger than 13 mm associated with a serum estradiol level of more than 30 pg/mL were noted in 19% of the women in the first treatment cycle. The rate of active follicle-like structures was 43% in the second treatment cycle and 28% in the third treatment cycle. The results were compared with previously reported findings of a preparation containing 20 microg EE and 75 microg GST. With regard to ovarian grading and endogenous hormone secretion, considerably more residual ovarian activity, with all parameters examined, was found in the 20 microg EE and 50 microg GST preparation compared to the 20 microg EE and 75 microg GST preparation. It was concluded that the 20 microg EE and 50 microg GST preparation administered for 21 days does not meet the requirements of a combined oral contraceptive with respect to ovulation inhibition.
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.
The UK's prescription drug regulatory agency warned the public and health care providers about the possible increased risk of venous thromboembolism (VTE) among users of the combined oral contraceptives (OCs) containing desogestrel or gestodene. Data from three large not-yet-published studies served as the basis for the warning. The studies found about a 2-fold increased risk of VTE for these OC users when compared to users of OCs with other progestins. Yet the observational studies are subject to inherent biases (e.g., hospitalized cases and selection bias), which may explain the increased risk. Assuming the increased risk to be true, the risk of VTE is still lower than that linked to pregnancy (30 vs. 60 VTE cases per 100,000). The risk of VTE for users of OCs containing older progestins is about 15 VTE cases and that among healthy, nonpregnant, nonusers is about 4 VTE cases. The mortality risk associated with VTE among users of OCs containing desogestrel or gestodene is 1-1.5 deaths/1 million woman-years. The US Food and Drug Administration has examined the data and has concluded that the risk is not high enough to justify switching to other OCs or stopping use of OCs containing desogestrel or gestodene. It recommends that users of the OCs in question discuss the OCs with their providers and make an informed choice based on the benefits and risks and individual preferences. It might consider changes in labeling, but not pulling the OCs off the market. In Germany, women aged less than 30 were temporarily advised not to begin use of desogestrel- or gestodene-containing OCs. Women using them were advised to continue their use, however. The European Union announced that bias or chance could account for the findings and thus did not recommend changes in prescribing desogestrel- or gestodene-containing OCs.
Farley, T M; Meirik, O; Collins, J
Cardiovascular risks have been a concern since combined oral contraceptives (OCs) were first introduced. In the past four years new, mostly reassuring information on the safety of modern, low oestrogen dose OCs has become available. However, in 1995 the new information showed higher venous thromboembolism (VTE) risk for OCs containing desogestrel and gestodene compared with levonorgestrel- or norethindrone-containing OCs. The controversial responses by national authorities, their scientific and public health merits were hotly debated and many considered the differences in risk small and resulted from bias and/or confounding. We discuss these arguments and conclude they lack empirical support or cannot account for the 2-fold increased risk. The risk of ischaemic stroke and myocardial infarction (MI) associated with low oestrogen dose OCs are very small in women without cardiovascular risk factors, while increased risk of haemorrhagic stroke is confined to women >35 years of age. Applying the most recent risks to models of OC-attributable events and deaths, OC-attributable mortality in women <35 years is estimated to be <3 per million users annually, rising to about 10 per million users annually among smokers. In the context of external cause mortality (about 90 per million women of reproductive age annually in the UK) such risks appear small. Over the age of 35 years, OC-attributable mortality is a more important concern, particularly among smokers. In the absence of any appreciable OC-attributable mortality in young healthy women, the additional VTE risk for third compared with second generation OCs should be considered when women choose which OC to use.
Obreli-Neto, Paulo Roque; Pereira, Leonardo Régis Leira; Guidoni, Camilo Molino; Baldoni, André de Oliveira; Marusic, Srecko; de Lyra-Júnior, Divaldo Pereira; de Almeida, Kelsen Luis; Pazete, Ana Claudia Montolezi; do Nascimento, Janaina Dutra; Kos, Mitja; Girotto, Edmarlon; Cuman, Roberto Kenji Nakamura
Background Combined oral contraceptive (COC) use is the most commonly used reversible method of birth control. The incorrect use of COCs is frequent and one of the most common causes of unintended pregnancies. Community pharmacists (CPs) are in a strategic position to improve COC use because they are the last health professional to interact with patients before drug use. Objective To evaluate the COC dispensing practices of CPs in a developing country. Method A cross-sectional study was conducted in community pharmacies of Assis and Ourinhos microregions, Brazil, between June 1, 2012, and October 30, 2012. Four simulated patients (SPs) (with counseled audio recording) visited community pharmacies with a prescription for Ciclo 21® (a COC containing ethinyl estradiol 30 mcg + levonorgestrel 15 mcg). The audio recording of every SP visit was listened to independently by 3 researchers to evaluate the COC dispensing practice. The percentage of CPs who performed a screening for safe use of COCs (i.e., taking of patients’ medical and family history, and measuring of blood pressure) and provided counseling, as well as the quality of the screening and counseling, were evaluated. Results Of the 185 CPs contacted, 41 (22.2%) agreed to participate in the study and finished the study protocol. Only 3 CPs asked the SP a question (1 question asked by each professional), and all of the questions were closed-ended, viz., “do you smoke?” (n = 2) and “what is your age?” (n = 1). None of the CPs measured the patient’s blood pressure. Six CPs provided counseling when dispensing COCs (drug dosing, 5 CPs; possible adverse effects, 2 CPs), and one CP provided counseling regarding both aspects. Conclusion The CPs evaluated did not dispense COC appropriately and could influence in the occurrence of negatives therapeutic outcomes such as adverse effects and treatment failure. PMID:24324584
Pallavee, P; Samal, Sunita; Samal, Rupal
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.
... 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) ...
Kulier, Regina; Helmerhorst, Frans M; Maitra, Nandita; Gülmezoglu, A Metin
Background The progestogen component of oral contraceptives (OCs) has undergone changes since it was recognized that their chemical structure can influence the spectrum of minor adverse and beneficial effects. Methods The objective of this review was to evaluate currently available low-dose OCs containing ethinylestradiol and different progestogens in terms of contraceptive effectiveness, cycle control, side effects and continuation rates. The Cochrane Controlled Trials Register, MEDLINE and EMBASE databases were searched. Randomized trials reporting clinical outcomes were considered for inclusion and were assessed for methodological quality and validity. Results Twenty–two trials were included in the review. Eighteen were sponsored by pharmaceutical companies and in only 5 there was an attempt for blinding. Most comparisons between different interventions included one to three trials, involving usually less than 500 women. Discontinuation was less with second-generation progestogens compared to first–generation (RR 0.79; 95% CI 0.69–0.91). Cycle control appeared to be better with second-compared to first-generation progestogens for both, mono-and triphasic preparations (RR 0.69; 95% CI 0.52–0.91) and (RR 0.61; 95% CI 0.43–0.85), respectively. Intermenstrual bleeding was less with third- compared to second-generation pills (RR 0.71; 95% CI 0.55–0.91). Contraceptive effectiveness of gestodene (GSD) was comparable to that of levonorgestrel (LNG), and had similar pattern of spotting, breakthrough bleeding and absence of withdrawal bleeding). Drospirenone (DRSP) was similar compared to desogestrel (DSG) regarding contraceptive effectiveness, cycle control and side effects. Conclusion The third- and second-generation progestogens are preferred over first generation in all indices of acceptability. Current evidence suggests that GSD is comparable to LNG in terms of contraceptive effectiveness and for most cycle control indices. GSD is also comparable to DSG
Edgren, R A
Concerns over the safety of oral contraceptives (OCs) have led to numerous empirical studies of the relationship of OC use to normal pregnancy outcomes, pituitary effects, cardiovascular accidents, and cancer. The article reviews some of the results of studies on the effects of OC use on ovarian, uterine, cervical, and breast cancer and on hepatic cancer and melanomas. Reference is made to direct study results rather than to reviews of studies, although it is noted that the critical reviews of Goldzieher and Realini reflect appropriate critiques of the validity of the methods employed in the analysis of cancers as well as cardiovascular risks. Concern is raised for meta-analysis of pooled data. In spite of the 30 years of research on OCs there is no definitive answer to the question of cause and effect. The epidemiological articles reviewed do not meet the standards of critical editorial review boards of experimental journals; confirmation of findings is also lacking. Studies suggesting increased risks as well as those showing positive benefits are questionable. The conclusion reached is that OCs protect against ovarian and uterine cancers and do not cause mammary, cervical, or liver cancer or melanoma. This conclusion is based on inconclusive data. The conclusion on hepatic cancer is that the 3 retrospective case control studies and anecdotal reports are flawed in design, and little confidence can be placed on such a limited number of cases. Malignant melanoma conclusions are that the data are inconsistent and hover around a risk of one for long-term OC-users. There is no increased risk related to OC-use. Ovarian cancer risk seems to be decreased in about 40% of OC-users. Endometrial cancer risk seems to be decreased, except for the sequential contraceptive Oracon which is associated with increased risk. Decreased risk is related to length of usage and continues after stoppage. Cervical carcinoma results appear to confirm the finding that prolonged OC use slightly
Maia, Hugo; Haddad, Clarice; Casoy, Julio
Endometriosis is a chronic disease in which a persistent state of heightened inflammation is maintained by nuclear factor-kappa B (NF-κB) activation. The progestins present in oral contraceptives are potent inhibitors of NF-κB translocation to cell nuclei, while Pycnogenol® (Pinus pinaster) acts by blocking post-translational events. In this study, the effects of Pycnogenol on pain scores were investigated in patients with endometriosis using oral contraceptives containing either gestodene or drospirenone in extended regimens. Pain scores were determined using a visual analog scale before and after 3 months of treatment. Oral contraceptives, used alone (groups 1 and 3) or in association with Pycnogenol (groups 2 and 4), resulted in significant decreases in pain scores after 3 months of treatment; however, this reduction was significantly greater in the groups using oral contraceptives + Pycnogenol (groups 2 and 4) compared with those using oral contraceptives alone (groups 1 and 3). In the groups using oral contraceptives alone, 50% of patients became pain-free by the end of the third month of treatment. These results suggest that Pycnogenol increases the efficacy of oral contraceptives for the treatment of endometriosis-related pain. PMID:24379702
Efird, Jimmy T.; Toland, Amanda E.; Lea, C. Suzanne; Phillips, Christopher J.
The vast majority of cutaneous squamous cell carcinoma (CSCC) will occur in those with fair complexion, tendency to burn, and high ultraviolet radiation (UVR) exposure. Organ transplant recipients also are an important population at great risk for CSCC. An association has been reported between oral contraceptive (OC) use, human papillomavirus virus (HPV) and cervical cancer, and there could be a similar association for CSCC. The cutaneous HPV β-E6 protein, a close cousin of the transformative E6 protein underlying anogenital cancers, has been shown to inhibit apoptosis in response to UVR damage and stimulate morphologic transformation in rodent fibroblast cell lines. Furthermore, OC use has been shown to enhance HPV transcription and may contribute to CSCC risk through this pathway. PMID:21499554
Rachev, E; Damianov, L; Kolarov, G; Novachkov, V; Ivanov, S
The authors review the effect of the oral contraceptive Mercilon on menstrual cycle, contraceptive efficacy, lipid profile, safety profile and adverse effects in a group of 32 women, included in the survey. The results of the trial show excellent contraceptive effect with Pearl Index of 0.00 and good control over the menstrual cycle. No negative or unfavorable effects were seen on the lipid profile as well as on the liver kidney and coangulant system function. Minor side effects were seen in only 5% of the patients.
Oral contraceptives can cause liver damage and jaundice but this is very rare in women in the United Kingdom. The drugs are contraindicated where there is a history of recurrent intrahepatic cholestasis of pregnancy and acute or chronic disturbance of liver function which can be congenital or acquired. It is not yet known whether the oestrogenic or progestogenic components of oral contraceptives cause the hepatic abnormalities. The available data suggest that neither oestrogens nor progestogens in low doses impair hepatic excretory processes. The full implications of the continued administration of oestrogens and progestogens for many years on liver proteins are not yet known.
van Heusden, A M; Fauser, B C J M
Steroid drugs with contraceptive properties have been available in the clinical setting for over four decades and are still subject to improvement. Estrogens, progestins and anti-progestins have been used alone or in various combinations, regimens and routes of administration to favour the balance between efficacy and undesirable effects. One of the most important changes in this respect is the gradual lowering of steroid dosage in commercially available contraceptives. Current steroid contraceptive pills still achieve the goal of suppression of pituitary-ovarian activity, but the margins for error are minimal. In this review the available data on modes of action and the effects on suppressing pituitary-ovarian activity by different forms of oral contraception are reassessed. Although pregnancy rates provide a crude measure of contraceptive efficacy, no benchmark for pituitary-ovarian inhibition is available to test the suppressive potential of contraceptive drugs. Consequently, many studies provide incomplete and/or incomparable results. For the further study of those forms of steroid contraception that rely predominantly on suppression of ovarian activity, prevention of dominant follicles selection should be the objective.
Tan, J K; Degreef, H
Oral contraceptives (OCs) can reduce acne by lowering the production of adrenal and ovarian androgens, by inhibiting 5-alpha-reductase, which in turn, reduces the levels of dihydrotestosterone, and by stimulating sex hormone binding globulin (SHBG), thus reducing the levels of free testosterone. In newer OCs, such as Tricyclen and Diane-35, the progestin component is minimally androgenic and anti-androgenic respectively, thereby enhancing the favorable profile of these products in the treatment of hyperandrogenic disorders, including acne. The efficacy of these agents and their long-term safety profile supports their use in various grades of acne in females: * As adjunctive therapy to topical agents for women with mild non-scarring acne desiring oral contraception * As primary therapy for patients with moderate non-scarring acne in combination with topical therapy and systemic antibiotics * As one of two preferred methods of contraception in patients with scarring and severe inflammatory acne being treated with systemic isotretinoin.
Cremer, Miriam; Phan-Weston, Scarlett; Jacobs, Adam
Traditional forms of oral contraception contain 21 days of hormone-containing pills and 7 days of placebo during the hormone-free interval (HFI). Since 2003, the Food and Drug Administration has approved 24/4, 84/7, and 365-day regimens. These regimens shorten the HFI in an attempt to decrease bleeding and menstrual-associated side effects. Safety and efficacy of these regimens is comparable with traditional 21/7 dosing. Extended regimens are associated with high patient satisfaction. Bleeding patterns are similar or shorter in women using extended regimens, along with improvement in menstrual symptoms. One of the new formulations contains the new progestin drospirenone, which has antimineralocorticoid and antiandrogenic properties. This review summarizes the data about new formulations of oral contraception available in the United Sates and also provides a summary of the current literature on drospirenone.
Johnson, K H; Millard, P S
The Collaborative Group on Hormonal Factors in Breast Cancer conducted a meta-analysis of data from 10 cohort and 44 case-control studies of the association between combined oral contraceptive (OC) use and breast cancer. 53,297 women with breast cancer and 100,239 women with no breast cancer from 25 countries worldwide were studied. Current OC users faced a 24% increased risk of developing breast cancer (confidence interval = 1.15-1.33). This risk fell steadily after cessation and reached 0 at 10 years and thereafter. Use of OCs with higher doses were associated with a greater risk of breast cancer than medium or low-dose OCs. The number of excess cancers in women while using OCs and up to 10 years after OC cessation stood at 0.5/10,000 women 16-19 years old, 1.5/10,000 women 20-24 years old, and 4.7/10,000 women 25-29 years old. The elevated risk of developing breast cancer did not differ by country of origin, ethnic background, reproductive history, or family history of breast cancer. OC users had less clinically advanced breast cancer than never-users who had breast cancer. This finding plus the moderate reduced risk of breast cancer more than 10 years after OC cessation suggest that OCs may effect earlier diagnosis of existing breast cancer instead of causing new breast cancers. The findings of this meta-analysis along with a plausible biologic mechanism (estrogen stimulates breast cancer cells) suggest a causal relationship between OC use and breast cancer. They also indicate that the risk is small, decreases with time, and is lower among low-dose OC users. It is reassuring that the breast cancers found among OC users is less clinically advanced than those found in never-users.
A review of the available literature suggests that adolescent lack of compliance with oral contraceptives (OCs) is a multifactorial problem that requires a multifactorial solution. Because of their lack of experience with contraception, higher frequency of intercourse, higher intrinsic fertility, and pattern of frequent stopping or switching of methods, adolescents experience higher OC failure rates than do adult women. Adolescents also are more likely to forget to take the pill or to discontinue due to side effects, without consulting their physician. A survey of European young women identified contraceptive protection without weight gain as the most necessary change in OCs. Adolescents must be counseled not to miss a single pill, observe the pill-free interval, take phasic formulations in the right order, and use a back-up method in case of diarrhea and vomiting or when certain medications (e.g., antibiotics and anti-epileptics) are used concurrently, and be informed of steps to take in the event of side effects and unprotected intercourse. The quality of the counseling appears to be more important to compliance than the quantity of information provided. Pharmacists should complete the counseling initiated by the physician and explain prescription use. The most significant predictor of consistent OC use is the adolescent's motivation.
Multinational, multicentre, randomised, open-label study evaluating the impact of a 91-day extended regimen combined oral contraceptive, compared with two 28-day traditional combined oral contraceptives, on haemostatic parameters in healthy women
Paoletti, Anna Maria; Volpe, Annibale; Chiovato, Luca; Howard, Brandon; Weiss, Herman; Ricciotti, Nancy
Objectives To evaluate the impact of a 91-day extended regimen combined oral contraceptive (150 μg levonorgestrel [LNG]/30 μg ethinylestradiol [EE] for 84 days, followed by 10 μg EE for seven days [Treatment 1]) compared with two traditional 21/7 regimens (21 days 150 μg LNG/30 μg EE [Treatment 2] or 150 μg desogestrel [DSG]/30 μg EE [Treatment 3], both with seven days’ hormone free), on several coagulation factors and thrombin formation markers. Methods Randomised, open-label, parallel-group comparative study involving healthy women (18–40 years). The primary endpoint was change from baseline in prothrombin fragment 1 + 2 (F1 + 2) levels over six months. Results A total of 187 subjects were included in the primary analysis. In all groups, mean F1 + 2 values were elevated after six months of treatment. Changes were comparable between Treatments 1 and 2 (least squares mean change: 170 pmol/L and 158 pmol/L, respectively) but noticeably larger after Treatment 3 (least squares mean change: 592 pmol/L). The haemostatic effects of Treatment 1 were comparable to those of Treatment 2 and noninferior to those of Treatment 3 (lower limit of 95% confidence interval [− 18.3 pmol/L] > − 130 pmol/L). Conclusions The LNG/EE regimens had similar effects on F1 + 2. Noninferiority was demonstrated between extended regimen LNG/EE and DSG/EE. PMID:24923685
Aldrighi, José Mendes; De Campos, Luis Salvoni Carneiro; Eluf Gebara, Otávio Celso; Petta, Carlos Alberto; Bahamondes, Luis
The effects of a combined oral contraceptive (COC) containing 20 microg ethinyl estradiol (EE) and 75 microg gestodene (GSD) on prothrombin activity (PA), activated partial thromboplastin time (APTT), thrombin time (TT), platelet number, fibrinogen, antithrombin III (ATIII), protein C, protein S and D-dimer were evaluated over 6 months in 23 young, healthy women. Laboratory assessments were performed prior to initiation of COC use (pretreatment) and after 3 and 6 months of use. Results showed no significant changes in fibrinogen, protein C, ATIII or D-dimer during COC use, compared with pretreatment values. The increase in platelet count, decreases in protein S level, PA and APTT, and the prolongation of TT were significant. In conclusion, the use of a COC containing 20 microg EE and 75 microg GSD did not cause any significant changes in the hemostatic parameters studied that could be suggestive of a higher prothrombotic risk. Further studies with a larger sample size are necessary in order to obtain conclusive data.
Suchon, Pierre; Al Frouh, Fadi; Henneuse, Agathe; Ibrahim, Manal; Brunet, Dominique; Barthet, Marie-Christine; Aillaud, Marie-Françoise; Venton, Geoffroy; Alessi, Marie-Christine; Trégouët, David-Alexandre; Morange, Pierre-Emmanuel
Identifying women at risk of venous thromboembolism (VTE) is a major public health issue. The objective of this study was to identify environmental and genetic determinants of VTE risk in a large sample of women under combined oral contraceptives (COC). A total of 968 women who had had one event of VTE during COC use were compared to 874 women under COC but with no personal history of VTE. Clinical data were collected and a systematic thrombophilia screening was performed together with ABO blood group assessment. After adjusting for age, family history, and type and duration of COC use, main environmental determinants of VTE were smoking (odds ratio [OR] =1.65, 95% confidence interval [1.30-2.10]) and a body mass index higher than 35 kg.m⁻² (OR=3.46 [1.81-7.03]). In addition, severe inherited thrombophilia (OR=2.13 [1.32-3.51]) and non-O blood groups (OR=1.98 [1.57-2.49]) were strong genetic risk factors for VTE. Family history poorly predicted thrombophilia as its prevalence was similar in patients with or without first degree family history of VTE (29.3% vs 23.9%, p=0.09). In conclusion, this study confirms the influence of smoking and obesity and shows for the first time the impact of ABO blood group on the risk of VTE in women under COC. It also confirms the inaccuracy of the family history of VTE to detect inherited thrombophilia.
Sriprasert, Intira; Suerungruang, Suparerk; Athilarp, Porntip; Matanasarawoot, Anuchart; Teekachunhatean, Supanimit
This open-label randomized controlled trial was designed to compare the efficacy of acupuncture and combined oral contraceptive (COC) pill in treating moderate-to-severe primary dysmenorrhea. Fifty-two participants were randomly assigned to receive either acupuncture (n = 27) or COC (n = 25) for three menstrual cycles. Mefenamic acid was prescribed as a recue analgesic drug with both groups. The statistical approach used for efficacy and safety assessments was intention-to-treat analysis. By the end of the study, both treatments had resulted in significant improvement over baselines in all outcomes, that is, maximal dysmenorrhea pain scores, days suffering from dysmenorrhea, amount of rescue analgesic used, and quality of life assessed by SF-36 questionnaire. Over the three treatment cycles, COC caused greater reduction in maximal pain scores than acupuncture, while improvements in the remaining outcomes were comparable. Responders were defined as participants whose maximal dysmenorrhea pain scores decreased at least 33% below their baseline. Response rates following both interventions at the end of the study were not statistically different. Acupuncture commonly caused minimal local side effects but did not cause any hormone-related side effects as did COC. In conclusion, acupuncture is an alternative option for relieving dysmenorrhea, especially when COC is not a favorable choice. PMID:26346199
Meier, Christoph R
Oral contraceptives (OC) are either composed of a combination of an estrogen derivative (usually ethinly estradiol) and a progestogen, or they contain a progestogen only. OC are characterized by a high effectiveness and have a low failure rate if taken correctly. Most women tolerate OC relatively well, but adverse effects do occur which are driven by the estrogen dose as well as by the type of progestogen. The most frequently reported adverse effects are nausea or vomiting, breast tenderness, headache or inbalanced mood, but these unwanted side effects are often transient. The fear of weight gain of many OC users is not necessarily supported by data from studies which report relatively little differences in body mass index on average during OC use. Nevertheless, substantial weight gain can occur in individual women. The widely discussed fear of breast cancer is also not justified, and the risk of developing ovarian or endometrial cancer is reduced for women who use OC on a regular basis. Venous thromboembolism (VTE) is the adverse effect with the greatest potential for serious harm if pulmonary embolism develops. This rare, but potentially dangerous adverse effect of OC has been discussed emotionally for many years and keeps attracting a lot of public interest. VTE is rare in young women, but the VTE risk is increased two- to sixfold for OC users as compared to non-users. The VTE risk increases with increasing estrogen dose, is highest in the first year of use, and is higher for OC from the third generation (containing desogestrel, gestodene or norgestimate) than for OC from the second generation (containing levonorgestrel) or than for the progestogen-only pill. According to most studies, OC containing the progestogens drospirenone or cyproterone acetate are similar with regard to VTE risks than OC from the third generation. Individual genetic susceptibility affecting the clotting system plays a major role in the risk of developing VTE in combination with OC, and
Bamgboye, E A; Ladipo, O A
The demographic transition in Nigeria is gradually moving towards the second stage. There is clear evidence of a declining mortality but the fertility rate remains exceptionally high. A realistic approach towards reducing fertility rate is the use of oral contraceptive. This study assesses the distribution system of oral contraceptive in Ibadan, the second largest city in Nigeria. The findings revealed that the people are aware of modern oral contraceptives as they purchase them freely at chemist shops. But effective distribution is hampered by existing channels and high costs. A local source recommended is the proprietary medicine stores, often at convenient locations to the potential users of contraceptives. The current cost which is between $1.3 and $19.5 per couple-years of protection is exorbitant, consuming 0.5-7.8% of the gross annual income of the average individual. Therefore, the government should subsidize the prices of oral contraceptives, to facilitate freedom from the tyranny of excessive fertility.
Coupland, Carol; Hippisley-Cox, Julia
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
Hinderaker, Katie; Allen, Alicia M; Tosun, Nicole; al'Absi, Mustafa; Hatsukami, Dorothy; Allen, Sharon S
Although an estimated 25% of premenopausal smokers report using oral contraceptives (OC), little is known about how OC use may influence smoking cessation. The purpose of this study was to examine the difference in smoking-related symptomatology during acute smoking abstinence between women on a standardized combination OC (Tri-Sprintec(™)) compared to women not on OCs (no-OC). Participants were women aged 18-40 who smoked ≥5 cigarettes/day and reported regular menstrual cycles. Using a controlled cross-over design, participants completed two six-day testing weeks: Low Progesterone Week (LPW; Follicular (F) phase in no-OC or 1st week of pills in OC) and High Progesterone Week (HPW; Luteal (L) phase in no-OC or 3rd week of pills in OC). Each testing week included daily assessment of symptomatology and biochemical confirmation of smoking status. During smoking abstinence, the OC group (n=14) reported significantly lower levels of positive affect (21.56±7.12 vs. 24.57±6.46; β=3.63, p=0.0323) than the no-OC group (n=28). Further significant interactions between group and testing week were observed as follows: Smoking satisfaction was higher during LPW in the OC group (LPW: 4.29±1.30 vs. HPW: 4.10±1.37) but higher during HPW in the no-OC group (LPW: 3.91±1.30 vs. HPW: 4.23±1.30; β=-0.5499, p<0.0001). Similar interactions were noted in negative affect and psychological reward of smoking. These results suggest that women on OCs may have different patterns of smoking-related symptomatology during short-term smoking abstinence as compared to women not on OCs. Additional work is needed to examine how this may affect smoking cessation efforts.
Olatunji, Lawrence A; Olaniyi, Kehinde S; Usman, Taofeek O; Abolarinwa, Bilikis A; Achile, Caleb J; Kim, In-Kyeom
Combined oral contraceptive (COC) use or inhibition of nitric oxide (NO) synthesis has been shown to cause hypertension and insulin resistance. However, the concomitant effects of COC and NO deficiency on the heart and glucose regulation are not well known. We therefore hypothesized that COC treatment during NO deficiency would lead to the development of cardiac hypertrophy that is associated with aggravated glucose deregulation, pro-inflammatory and pro-fibrotic biomarkers. Eight-week-old female Wistar rats were randomly allotted into control, NO deficient (N(G)-nitro-l-arginine methyl ester: L-NAME; 20.0mg/kg b.w.), COC-treated (1.0μg ethinylestradiol+5.0μg levonorgestrel, p.o) and L-NAME+COC-treated groups. The animals were treated daily for 6 weeks. Systolic blood pressure was estimated by tail-cuff plethysmography, insulin resistance (IR) and β-cell function were estimated by homeostatic model of assessment (HOMA-IR and HOMA-β). Pro-inflammatory (C-reactive protein; CRP and uric acid) and pro-fibrotic (plasminogen activator inhibitor-1; PAI-1) biomarkers were estimated in the plasma. Cardiac histological examination was also done. Results show that COC or L-NAME treatments led to increased blood pressure, HOMA-IR, impaired β-cell function, PAI-1, CRP and uric acid, without significant effect on cardiac mass. L-NAME+COC-treated group had significantly higher blood pressure, HOMA-IR, impaired β-cell function, PAI-1, CRP and cardiac mass than COC- or L-NAME-treated groups. Histological examination validated that COC use during NO deficiency causes cardiac hypertrophy. The present study demonstrates that COC treatment and NO deficiency synergistically causes cardiac hypertrophy that is associated with aggravated glucose deregulation, atherogenic dyslipidemia, pro-inflammatory and pro-fibrotic markers.
Agarwal, N; Gupta, M; Kriplani, A; Bhatla, N; Singh, N
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.
Vinogradova, Yana; Coupland, Carol; Hippisley-Cox, Julia
Introduction Many studies have found an increased risk of venous thromboembolism (VTE) associated with the use of combined hormonal contraceptives, but various methodologies have been used in the study design relating to definition of VTE event and the selection of appropriate cases for analysis. This study will focus on common oral hormonal contraceptives, including compositions with cyproterone because of their contraceptive effect and will perform a number of sensitivity analyses to compare findings with previous studies. Methods and analysis 2 nested case–control studies will be based on the general population using records from UK general practices within the QResearch and Clinical Practice Research Datalink databases. Cases will be female patients aged 15–49 with primary VTE diagnosed between 2001 and 2013. Each case will be matched by age, year of birth and practice to five female controls, who are alive and registered with the practice at the time of diagnosis of the case (index date). Exposure to different hormonal contraceptives will be defined as at least one prescription for that contraceptive in the year before the index date. The effects of duration and the length of any gap since last use will also be investigated. Conditional logistic regression will be applied to calculate ORs adjusted for smoking, ethnicity, comorbidities and use of other medications. Possible indications for prescribing hormonal contraceptives, such as menstrual disorders, acne or hirsutism will be included in the analyses as confounding factors. A number of sensitivity analyses will be carried out. Ethics and dissemination The initial protocol has been reviewed and approved by ISAC (Independent Scientific Advisory Committee) for Medicine and Healthcare Products Regulatory Agency Database Research. The project has also been reviewed by QResearch and meets the requirements of the Trent Research Ethics Committee. The results will be published in a peer-reviewed journal. PMID
Oh, Hea Young; Kim, Mi Kyung; Seo, Sang-Soo; Lee, Jae-Kwan
Background Cigarette smoking and oral contraceptive (OC) use have been associated with cervical neoplasia, and the combination of smoking and OC use could influence cervical carcinogenesis. We aimed to assess the joint effect of smoking and OC use on the risk of cervical intraepithelial neoplasia (CIN). Methods From a cohort of human papillomavirus-positive subjects recruited from 6 hospitals in Korea from March 2006 to November 2012, a total of 678 subjects (411 control, 133 CIN 1, and 134 CIN 2 or 3 cases) were selected for this study (mean age, 43 years). The risk of CIN associated with smoking and OC use on additive and multiplicative scales was estimated via multinomial logistic regression after adjustment for potential confounding factors. The relative excess risk due to interaction (RERI) and the synergy index (S) were used to evaluate the additive interaction. Results OC users (odds ratio [OR] 1.98; 95% confidence interval [CI], 1.07–3.69) and long-term OC use (≥20 months; OR 2.71; 95% CI, 1.11–6.59) had a higher risk of CIN 2/3, but had no association with CIN 1, compared to non-OC users. Smokers and heavy smoking (≥8 cigarettes/day) were not associated with any CIN grade. Combined smoking and OC use (OR 4.91; 95% CI, 1.68–14.4; RERI/S, 3.77/27.4; P for multiplicative interaction = 0.003) and combined heavy smoking and long-term OC use (OR 11.5; 95% CI, 1.88–70.4; RERI/S, 9.93/18.8; P for multiplicative interaction = 0.009) had a higher risk of CIN 2/3 but had no association with CIN 1 compared to combined non-smoking and non-OC use. Conclusions OC use and smoking acted synergistically to increase the risk of CIN 2 or 3 in Korean women. PMID:26441210
Suvarna, Yashasvi; Maity, Nivedita; Kalra, Pramila; Shivamurthy, MC
Objective The 2013 Endocrine Society guidelines state that hormonal contraceptives should be used for treating both menstrual irregularity and hirsutism in patients with polycystic ovary syndrome (PCOS). Metformin should be reserved for the treatment of women presenting with only menstrual irregularity because it has limited benefits in treating hyperandrogenism associated with PCOS. A high prevalence of insulin resistance is noted among the South Asians, and these guidelines may not hold good for this population. Thus, this study was conducted to investigate and compare the effects of metformin and an oral contraceptive containing drospirenone on menstrual pattern, body mass index, serum testosterone levels, and dehydroepiandrosterone sulfate (DHEAS) levels at baseline to 6 months of therapy in the treatment groups. Material and Methods This was a prospective observational study that was conducted over a year in patients visiting the Endocrinology outpatient department at a tertiary care center in a south Indian city. Forty-six subjects diagnosed with PCOS as per the Rotterdam criteria were included. They received either metformin twice daily or an oral contraceptive containing drospirenone once daily as a monthly regimen for 6 months. Results Metformin regularized menstrual cycles in 72% of patients who were followed up at 6 months. No significant difference was observed between the two treatment groups with respect to decreasing the body mass index, serum testosterone levels, and DHEAS levels (p=0.40, p=0.65, and p=0.22, respectively). Conclusion Metformin is effective in regularizing menstrual cycles, decreasing body mass index, and treating hyperandrogenism in Indian women diagnosed with PCOS. PMID:27026772
Montes, M B; Ferreira, A C; Fenólio, J C; Franceschini, S A; Toloi, M R
Many literature studies have shown that long-term use of oral contraceptives (OC) is associated with lack of protection of the epithelium of the uterine cervix. Forty-five patients, from 18 to 35 years old, users of two contraceptive formulations, of different estrogenic concentration, took part in this study as volunteers to evaluate the predisposition of the cervix to pathologies. The results found before OC use were 11% of Chlamydia trachomatis infection and 13% of HPV infection. These pathologies were correctly treated and after 5 months of OC use we found total remission of Chlamydia trachomatis infection and 4% of persistent HPV infection. These data lead us to conclude that the OC studied here interfered very little with the presented pathologic results. The risk factors that we considered relevant were: 1) age group (the patients that presented HPV and C. trachomatis infections were young university students); 2) lifestyle (most patients certified that they did not combine the use of barrier contraceptives with the use of OC); 3) multiple sexual partners; 4) low socioeconomic condition.
Kapitza, Christoph; Nosek, Leszek; Jensen, Lene; Hartvig, Helle; Jensen, Christine B; Flint, Anne
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
Reports concerning the interaction between steroidal contraceptives (the combined pill) and vitamins indicate that in users the mean serum-vitamin-A level is raised and the mean serum-vitamin-B2 (riboflavine), vitamin-B6 (pyridoxine), vitamine-C, folic-acid, and vitamin-B12 levels are reduced. Other vitamins have been insufficiently studied for comment. Biochemical evidence of co-enzyme deficiency has been reported for vitamin B2, vitamin B6, and folic acid. Clinical effects due to vitamin deficiency have been described for vitamin B6--namely, depression and impaired glucose tolerance. Folic-acid deficiency with megaloblastic anaemia has been reported in only 21 cases.
Prasad, R N; Koh, S C; Viegas, O A; Ratnam, S S
We studied 67 healthy women who were randomly allocated to receive third generation gestodene (Gynera) or second generation levonorgestrel (Microgynon 30) combination of low-dose estrogen oral contraceptives (OCs) for their hemostatic effects over 2 years. Hemostatic changes were apparent within 3 months of OC use. Hematocrit (Hct) was not affected, but hemoglobin (Hb) concentration decreased by 18 months. Shortened prothrombin time (PT) and activated plasma thromboplastin time (APTT) were associated with elevated fibrinogen within the 12-month use of both OCs. Factor VII was reduced only in Micro 30 during the 18 months of use. Enhanced thrombin-antithrombin (TAT)-complex level was seen at 18 months of Gynera use. Prothrombin fragment1+2 (F1+2) rise was seen at 3 months with Micro 30. Reduced antithrombin III (ATIII) activity was seen at 18 months with Gynera and at 24 months with Micro 30. Increased protein C activity was seen at 3 months and reduced protein S occurred at 18 months of Gynera use. Tissue plasminogen activator (t-PA) activity was enhanced for 6 months in both OCs with raised D-dimer levels for 12 months with Gynera and 6 months with Micro 30. Decreased t-PA antigen was seen at 18 months and decreased urokinaselike plasminogen activator (u-PA) antigen occurred throughout the 24 months of both OCs use. Enhanced u-PA activity was only seen in Gynera users. Elevated plasminogen levels were apparent throughout both OCs use. PAI-1 levels were significantly decreased with Micro 30. With Gynera, the decreased PAI-1 activity was seen only at 18 months and PAI-1 antigen at 12 months. No change in platelets and von Willebrand factor (vWF) were seen in long-term OC use except that beta-thromboglobulin (beta-TG) showed decreased trends reaching statistical significance by 18 and 24 months of Micro 30 use and by 24 months of Gynera use. A further significant decrease in beta-TG, u-PA antigen, ATIII, and protein S levels were seen 3 months after pill stoppage
Walker, A M
Research on the relationship between venous thromboembolism and the progestagen content of combined oral contraceptives has pointed to an increase in risk associated with products containing desogestrel and gestodene. Although many biases must have been at play in these nonexperimental studies, the errors that have been suggested and examined are not of a sufficient magnitude to account for the observed results. The most plausible explanation of the available data is that combined oral contraceptives containing desogestrel and gestodene carry a very small risk of venous thromboembolism, which exceeds the even smaller risk carried by products containing levonorgestrel. The position of norgestimate is uncertain.
Golobof, Alexandra; Kiley, Jessica
Millions of women in the United States and abroad use oral contraceptive pills. These popular contraceptives are the most common reversible birth control method in the United States, and a wide variety of pills are available for prescription. Oral contraceptives provide safe and effective protection against pregnancy and offer several noncontraceptive benefits. Over the years, advances in the laboratory and knowledge gained through epidemiologic data promoted the development of new contraceptive preparations. Generations of oral contraceptives emerged over time, containing lower doses of estrogens and new and novel progestins. The current review discusses the clinical characteristics of oral contraceptives, with emphasis on basic pharmacology and the evolution of various contraceptive formulations and regimens.
Feldblum, P J; Burton, N; Rosenberg, M J
Oral contraceptive use has been shown to protect against gonococcal pelvic inflammatory disease (PID), but the effect on chlamydial PID is uncertain. Chlamydia infection is rising in incidence and has become the major cause of PID in many areas. PID may cause infertility, impairing the future reproduction of women. Previous studies on oral contraceptives and PID relied on hospitalized women, which may have biased the sample to include mainly gonococcal PID. Several studies show increased risk of endocervical chlamydia infection in users of oral contraceptives. The postulated mechanism is cervical ectopy, exposing more squamous epithelium to the organisms. Nevertheless, there is evidence indicating that despite the increased incidence of endocervical infection, oral contraceptives may inhibit the organisms from ascending, thus still offering a protective affect against both gonococcal and chlamydial PID. Future research must focus on the prevalence of chlamydia infection in Africa, and the natural history of the illness. The effect of different types of oral contraceptives on chlamydia infection must be evaluated.
Keder, Lisa M
Oral contraceptive pills were first approved by the Food and Drug Administration 50 years ago. Discovery of the physiology of reproduction and demonstration of the ability to inhibit ovulation with ovarian extracts laid the early groundwork for the development of contraceptives. Later, characterization of the hormones controlling ovulation and synthesis of progestins allowed production of oral contraceptives. Modern estrogen and progestin pills have undergone significant changes since their initial introduction. New formulations have been developed, doses have been lowered, and extended use introduced. The Food and Drug Administration has recently approved a new oral contraceptive containing estradiol valerate and dienogest. This pill contains an orally active estradiol in combination with a progestin with strong endometrial activity. The decreasing estrogen dose combined with an increasing progestin dose decreases the risk of break through bleeding when compared to previous estradiol valerate formulations. The contraceptive efficacy and a tolerability of this new pill are similar to currently marketed low dose combined estrogen-progestin oral contraceptives.
Zimmerman, Y.; Eijkemans, M.J.C.; Coelingh Bennink, H.J.T.; Blankenstein, M.A.; Fauser, B.C.J.M.
BACKGROUND Combined oral contraceptives (COCs) reduce levels of androgen, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Although this suppressive effect has been investigated by numerous studies over many years, to our knowledge no systematic review concerning this issue had been performed. This systematic review and meta-analysis was performed to evaluate the effect of COCs on concentrations of total T, free T and SHBG in healthy women and to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T and free T. METHODS A review of the literature was performed using database searches (MEDLINE, EMBASE and the Cochrane Central Register of Clinical Trials) and all publications (from inception date until July 2012) investigating the effect of COCs on androgen levels in healthy women were considered eligible for selection. Three reviewers were involved in study selection, data extraction and critical appraisal. For the meta-analysis, data on total T, free T and SHBG were extracted and combined using random effects analysis. Additional subgroup analyses were performed to evaluate differences between the various types of COCs (e.g. estrogen dose, type of progestin) and the assays used to assess total T or free T. RESULTS A total of 151 records were identified by systematic review and 42 studies with a total of 1495 healthy young women (age range: 18–40 years) were included in the meta-analysis. All included studies were experimental studies and 21 were non-comparative. Pooling of the results derived from all the included papers showed that total T levels significantly decreased during COC use [mean difference (MD) (95% confidence interval, CI) −0.49 nmol/l (−0.55, −0.42); P < 0.001]. Significantly lower levels of free T were also found [relative change (95% CI) 0.39 (0.35, 0.43); P < 0
Elomaa, K; Ranta, S; Tuominen, J; Lähteenmäki, P
Using steady-state conditions we aimed to test if administration of oral activated charcoal affects the bioavailability of norethisterone acetate (NET Ac) and gestodene (GEST) by inhibiting their enterohepatic recirculation. Thirteen volunteers received, in a randomized order, Minulet (75 microg GEST and 30 microg ethinylestradiol [EE(2)]) and Econ/30 (1 mg NET Ac and 30 microg EE(2)), each for 4 months. Serum GEST and norethisterone (NET) levels were evaluated with respect to C(max,) t(max) and 24-h area under the curve (AUC(0-24h)) in the middle of the control (3rd) cycle and the charcoal treatment (4th) cycle during both pill treatments. No statistically significant difference was seen in any of the aforementioned variables between the control and charcoal treatment cycles of either pill. Neither was a difference seen in the bioavailability of GEST and NET as evaluated by the ratios of two 24-h AUCs calculated in the control and charcoal cycles of each pill treatment (p = 0.29). The results suggest that enterohepatic circulation of GEST and NET is not of clinical importance. We conclude that women on oral contraceptives can take activated charcoal for the treatment of diarrhea when administered 3 h after and at least 12 h before pill intake.
Upreti, V V; Hsiang, C B; Li, L; Xu, X; LaCreta, F P; Boulton, D W
Saxagliptin (Onglyza™) is a dipeptidyl peptidase-4 (DPP4) inhibitor for treating type 2 diabetes mellitus. This open-label, randomized, two-way crossover study in 20 healthy female subjects investigated the effect of saxagliptin on the pharmacokinetics (PK) of the active components of a combined oral contraceptive (COC). Subjects received either COC (Ortho-Cyclen(®)) once daily (QD) for 21 days, then 5 mg saxagliptin QD + COC QD for 21 days, or vice versa. Coadministration of saxagliptin and COC did not alter the steady-state PK of the primary active oestrogen (ethinyl estradiol) or progestin (norelgestromin) COC components. The area under the concentration-time curve (AUC) and peak plasma concentration (Cmax) of an active metabolite of norelgestromin (norgestrel) were increased by 13 and 17%, respectively, a magnitude that was not considered clinically meaningful. Coadministration of saxagliptin and COC in this study was generally well-tolerated. Saxagliptin can be co-prescribed with an oestrogen/progestin combination for women taking oral contraceptive.
Ruan, Xiangyan; Mueck, Alfred O
Women at middle age have decreased fertility and their pregnancies are higher risk. Combined oral contraceptives (COC) are effective but confer increased risk of age-related diseases, especially cardiovascular diseases. These risks are lower, however, with progestogen-only pills (POP). Therefore, other than the levonorgestrel intrauterine device (LNG-IUD), POP are usually the first choice, even though they do often lead to bleeding problems, which are already frequent in the perimenopause. However, the main risk of COC, venous thromboembolism, seems not to be relevant in (non-hospitalized) Chinese women and perhaps also other Asian women. COC may therefore be in fact a better choice than POP for these groups. In contrast to POP and IUDs, they have a variety of benefits especially important for middle-aged women, including a large decrease of the risk of ovarian, endometrial and colorectal cancer, an improvement in bleeding irregularities, a reduction of climacteric symptoms and some protection against bone loss. Further research is needed into individualized and safe contraception that takes into account ethnicity, as well as other factors.
Villegas-Salas, E; Ponce de León, R; Juárez-Perez, M A; Grubb, G S
Analogous to recommendations for treatment of side effects of early pregnancy and premenstrual syndrome, use of vitamin B6 has been recommended for the treatment of side effects of oral contraceptive (OC) use. A randomized, triple-blinded controlled trial of 124 women was done to evaluate the effect of taking 150 mg of vitamin B6 daily for 30 days on the severity of nausea, headache, vomiting, dizziness, depression, and irritability associated with the initiation of low-dose (30 micrograms norgestrel and 30 micrograms ethinyl estradiol) OG use. The severity of the symptoms was measured on a scale from 0 to 3 (not present to severe), and was evaluated at one month after admission. The two treatment groups (vitamin B, and placebo) had comparable baseline characteristics. From admission to follow up, there was a decrease in the severity of all symptoms in both groups. There was no statistically significant difference in the reductions found in the vitamin B6 and the placebo groups, although reductions in the severity of headache and dizziness were greater in the B6 group. The decrease in the severity of all OC side effects can be explained more by a placebo effect than by a marginal pharmacological effect of the vitamin B6.
Kapitza, Christoph; Nosek, Leszek; Jensen, Lene; Hartvig, Helle; Jensen, Christine B; Flint, Anne
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.
Tanis, Bea C; Rosendaal, Frits R
Since the introduction of oral contraceptives, their use has been associated with an increased risk of both venous and arterial thrombosis. Pulmonary embolism, myocardial infarction, and stroke are serious disorders with a considerable risk of mortality. Because worldwide over 100 million women use oral contraceptives, issues of drug safety are of great importance. The risk of venous thrombosis during low-dose oral contraceptive use is three- to sixfold increased compared with that of nonusers. The association is not only attributed to the estrogen component of the pill: the risk is twice as high for desogestrel and gestodene (third generation) containing oral contraceptives as for levonorgestrel (second generation) containing oral contraceptives. The risk of venous thrombosis is highest in the first year of use and in women with genetic or acquired risk factors for thrombosis. Both venous or arterial thrombosis are unrelated to duration of use or past use of combined oral contraceptives. The risk of myocardial infarction and stroke during low-dose oral contraceptive use is two- to fivefold increased relative to that of nonusers. The risk of arterial thrombosis induced by oral contraceptive use is more pronounced in smokers and women with hypertension, diabetes, and hypercholesterolemia. All types of thrombosis have strongly age-dependent incidences, and therefore in absolute figures the risks and effects of risk factors increase with age. The lowering of the estrogen dose in combined oral contraceptives from 50 microg to 20-30 microg in the last decade did not clearly reduce the risk of venous thrombosis, myocardial infarction, stroke, or peripheral arterial disease. For stroke and peripheral arterial disease no difference in risk was found between second and third generation oral contraceptives. For myocardial infarction study results are conflicting, and a small benefit of third- over second-generation oral contraceptives cannot be ruled out. However, this is
Wingrave, S J
The longterm prospective study of health effects of oral contraceptives (OCs) conducted by the Royal College of General Practitioners compared 23,000 OC users with 23,000 controls matched for age and marital status. As of 1981, 55 deaths attributable to circulatory problems had occurred in ever-users of OCs, ciompared to 10 in controls, giving a relative risk of 4.2 for OC users. No relation was found between duration of use and mortality risk among users, although mortality risks were greater at all durations of use than for nonusers. Parity was related to mortality risk among users but not among controls. The most significant factors affecting the relation between pill use and circulatory risk were age and smoking. Among users who smoked, the risk ratios were 3.4 for those aged 25-34, 4.2 for those aged 35-44, 7.4 for those aged 45 and over, and 5.1 for the entire group. Among nonsmoking pill users, the ratios were 1.6 for those aged 25-34, 3.3 for those aged 35-44, 4.6 for those 45 and over, and 3.2 for the total sample. Among smokers, the rates of excess deaths were 1 in 10,000 for users aged 15-34, 1 in 2000 for those aged 35-44, and 1 in550 for those aged 45 and over. Among nonsmokers, the rates were 1 in 50,000 users for those aged 25-34, 1 in 6700 for those aged 35-44, and 1 in 2500 for those aged 45 and over. The majority of deaths were attributed to ischemic cardiac problems and to sub-arachnoid hemorrhages, and risks appeared to be elevated in former as well as current users. The total incidence of circulatory effects in former users appears to be elevated only for cerebrovascular disorders, but the suggestion of residual effects requires further study before conclusions can be drawn. Smokers who developed cardiovascular or cerebrovascular problems were at 2-3 times greater risk of dying than were other women. The percentages of fatal cases of ischemic heart and cerebrovascular diseases were 22.8% among ever-users who smoked, 10.9% among controls who
Bradstreet, Thomas E.; Panebianco, Deborah L.
This article focuses on a two treatment, two period, two treatment sequence crossover drug interaction study of a new drug and a standard oral contraceptive therapy. Both normal theory and distribution-free statistical analyses are provided along with a notable amount of graphical insight into the dataset. For one of the variables, the decision on…
Pangrazzi, J; Roncaglioni, M C; Donati, M B
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.
Krasznai, Zsuzsa; Tóth, Péter
Oral hormonal contraceptives are the safest methods for young patients to avoid unwanted pregnancy. They are well accepted and have certain beneficial effects; however, physicians should pay attention to risk factors even when applied in young age. Obesity, dyslipidemia, smoking and oral contraceptive pills alone or in combination may lead to serious adverse events. Authors present a young woman who developed acute myocardial infarction in association with several unconsidered risk factors including the use of contraceptive pills.
Dalichampt, Marie; Raguideau, Fanny; Ricordeau, Philippe; Blotière, Pierre-Olivier; Rudant, Jérémie; Alla, François; Zureik, Mahmoud
Objective To assess the risk of pulmonary embolism, ischaemic stroke, and myocardial infarction associated with combined oral contraceptives according to dose of oestrogen (ethinylestradiol) and progestogen. Design Observational cohort study. Setting Data from the French national health insurance database linked with data from the French national hospital discharge database. Participants 4 945 088 women aged 15-49 years, living in France, with at least one reimbursement for oral contraceptives and no previous hospital admission for cancer, pulmonary embolism, ischaemic stroke, or myocardial infarction, between July 2010 and September 2012. Main outcome measures Relative and absolute risks of first pulmonary embolism, ischaemic stroke, and myocardial infarction. Results The cohort generated 5 443 916 women years of oral contraceptive use, and 3253 events were observed: 1800 pulmonary embolisms (33 per 100 000 women years), 1046 ischaemic strokes (19 per 100 000 women years), and 407 myocardial infarctions (7 per 100 000 women years). After adjustment for progestogen and risk factors, the relative risks for women using low dose oestrogen (20 µg v 30-40 µg) were 0.75 (95% confidence interval 0.67 to 0.85) for pulmonary embolism, 0.82 (0.70 to 0.96) for ischaemic stroke, and 0.56 (0.39 to 0.79) for myocardial infarction. After adjustment for oestrogen dose and risk factors, desogestrel and gestodene were associated with statistically significantly higher relative risks for pulmonary embolism (2.16, 1.93 to 2.41 and 1.63, 1.34 to 1.97, respectively) compared with levonorgestrel. Levonorgestrel combined with 20 µg oestrogen was associated with a statistically significantly lower risk than levonorgestrel with 30-40 µg oestrogen for each of the three serious adverse events. Conclusions For the same dose of oestrogen, desogestrel and gestodene were associated with statistically significantly higher risks of pulmonary embolism but not arterial
Pretell-Zárate, Eduardo A
Emergency oral contraception is part of the sexual and reproductive rights of women. In 2001, this health policy was incorporated into the Rules of the National Family Planning Program of the Ministry of Health, primarily to prevent unwanted pregnancy and its serious consequences, induced abortion and the high associated maternal mortality rate, which are major public health problems. Scientific research has confirmed that the main mechanism of action of levonorgestrel, component of emergency oral contraception (EOC) is to inhibit or delay ovulation, preventing fertilization of the egg; additionally, it increases the thickening of the cervical mucus, making the sperm migration more difficult. No study has found endometrial abnormalities that may interfere with the implantation of the fertilized egg or embryo development of an implanted egg. However, despite the support of medical science and legal backing, the EOC is available only to users with economic resources, but its use has not been fully implemented in public sector services, due to obstacles created by groups opposed to contraception under claim of an alleged abortive effect that has already been ruled out scientifically. This article describes the administrative experience and legal confrontations between groups of power that prevent the proper implementation of an emergency contraception policy in Peru.
Winkler, U H
In some studies third-generation oral contraceptives have been reported to be associated with a higher risk of venous thromboembolism than are second-generation oral contraceptives, whereas recent, more refined studies have not confirmed this. The reasons for the alleged differences are under discussion, and differential effects on hemostasis have been proposed. Eighteen studies comparing second- and third-generation oral contraceptives with respect to their effects on hemostasis were analyzed. Significant changes from baseline were reported for many variables with both second- and third-generation oral contraceptives without significant between-group differences. Also, in a combined analysis of nonsignificant changes, no consistent pattern of change emerged for any marker, with the exception of higher factor VII levels associated with third-generation oral contraceptives. However, factor VII is not related to venous thromboembolism risk. In addition, 1 cross-sectional study with an unvalidated assay reported a higher ratio of activated protein C sensitivity with third-generation oral contraceptives. Only 2 components of the hemostatic system (factor VII and activated protein C sensitivity ratio) emerged as potentially differentially affected by second- and third-generation oral contraceptives; the association with venous thromboembolism risk is questionable in the former case and unknown in the latter.
Foster, M. E.; Powell, D. E. B.
The fact that oral contraceptives may predispose to thrombosis is not disputed, although its frequency is still debated. Any reliable assessment of the prevalence of this complication must in the main depend on careful statistical studies of well controlled groups, because the isolated case may well be coincidental when conditions such as coronary thrombosis, cerebral thrombosis, and pulmonary embolism are not extreme rarities in adult women. However, occasionally the clinical and pathological findings are so striking that they afford compelling evidence. The patient to be described presented with clinical features of pancreatitis that did not initially suggest an association with oral contraception. A hitherto undescribed state of multiple infarcts was found at post-mortem. This also illustrates the way in which the official figures for thrombotic complications can be underestimated. ImagesFig. 1 PMID:1197171
Winkelman, R K
A generalized erythema nodosum developed in a 17 year old girl receiving oral contraceptive therapy, which was immediately discontinued. The erythema failed to respond to tetracycline, potassium iodide or prednisone therapy (partially successful), and recurred 6 times, usually just before menstruation. The recommended therapy is bed rest, salicylates and 10 cm roller elastic bandages. No medication can help in the face of unrestricted physical activity.
Hansen, Thomas; Skjeldestad, Finn Egil
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…
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
Fruzzetti, F; Perini, D; Spirito, N; Manca, R
The venous thromboembolism (VTE) is a rare event during childbearing age and during the assumption of combined oral contraceptive. The absolute risk of VTE in users of combined oral contraceptives is 20-30 per 100000 women years. A number of case-control studies published in recent years have shown an apparent increase in the risk of VTE among users of oral contraceptives (OCs) containing desogestrel, gestodene, drospirenone and cyproterone, relative to the use of levonorgestrel. The data derived from these recent studies is of borderline statistical significance because any important factors are not considered to evaluate the real correlation between the assumption of OCs and risk of venous thromboembolism. Among the factors that should be considered, there are: EE dose, duration of use, coexistance of other risk factors of venous thromboembolism (age, BMI, familiarity, surgical interventions) and other prescription bias. The lack of these factors is likely to contribute to the increased risk of venous thromboembolism observed in users of third-generation OCs when compared to that in users of second-generation OCs. To date, because of the inadequacy of epidemiological studies, the data about the correlation between OCs and TVE, are not conclusive and it will be necessary to carry out other studies to clarify this debating point, definitively.
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
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
Overgaard, K; Hauch, O; Lidegaard, O
Ever since 1961, there has been discussion on possible thromboembolic effects from the use of oral contraceptives. The purpose of this Danish study was to determine if birth-control pill users did have an increased risk of venous thromboembolic disease (VTD), including deep venous thrombosis and pulmonary embolism. In previous research, morbidity from VTD has been found to show a great variance, as high as 1/330 woman years in 1 study to as low as 1/5,000 woman years in another. In these studies no significant difference was found between users and non-users of oral contraceptives. Only in 1 study was there found to be increased morbidity from VTD among pill users: 1/5,200 woman years, compared with 1/35,000 woman years for non-pill users. As a possible explanation of the pill's effect, several studies have demonstrated a rise in certain coagulation factors, increased fibrinogen and lowered antithrombin III. In the present study, medical records of all women aged 34 or under who had been referred to a Copenhagen hospital between 1981 and 1983 for treatment of phlebographic-or lungescintographic-confirmed VTD were investigated. After controlling for exclusion factors, there remained 35 test subjects between the ages of 16 and 34 (median age 22). Of the 22 cases of known etiology, 16 suffered from iatrogenic VTD. Of 13 women who suffered from VTD of unknown etiology, 69% were pill users, compared with only 29% (a significant difference) in a background-population interview study conducted in Denmark during 1983. With a known disposition to VTD, oral-contraceptive usage meant a relative risk of 0.9 for developing the disease, which figure conforms well with other cited research (in which the risk factor varied from 0.4 to 3.8).
Dominguez, Celia E
Oral contraceptives (OCs) are the most widely used form of reversible birth control in the United States. However, incorrect and/or inconsistent use may result in increased failure rates and unintended pregnancies, which present a significant cost burden to the health care system and HMOs. One of the best mechanisms to improve outcomes is through high-quality clinician-patient communication. Managed care organizations may benefit from encouraging their providers to counsel and educate patients on the proper use of OCs, as this may reduce unnecessary follow-up visits, lower the number of unintended pregnancies, and increase patient satisfaction with their health care.
van Heusden, A M; Fauser, B C
This study was performed to evaluate pituitary-ovarian recovery in the pill-free interval during use of three low-dose combined oral contraceptives (COC). Either the estrogen component or the progestin component was comparable in the study groups, to evaluate their relative influence. Serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2) levels were measured and follicle number and size estimated by transvaginal sonography daily during the 7-day pill-free interval in 44 healthy volunteers using three different low-dose oral contraceptives. Healthy volunteers were enrolled using 20 micrograms ethinyl estradiol (EE) + 75 micrograms gestodene (GSD) (Harmonet, Wyeth-Lederle; n = 15), 20 micrograms EE + 150 micrograms desogestrel (DSG) (Mercilon, Organon n = 17), or 30 micrograms EE + 150 micrograms DSG (Marvelon, Organon, n = 12) given according to the usual regimen of one tablet daily during 3 weeks and 1 week pill-free interval. No ovulations were observed. Pituitary hormones were not statistically significantly different at the beginning of the pill-free interval between the study groups. FSH concentrations were significantly higher at the end of the pill-free interval in the 30 micrograms EE group compared with both 20 micrograms EE groups (7.0 [0.6-12.4] IU/L vs 4.9 [1.4-6.1] IU/L and 4.5 [2.4-7.4] IU/L; p = 0.001). In both 20 micrograms EE groups, a single persistent follicle (24 and 28 mm) was present in one subject. Follicle diameters were statistically significantly smaller at the beginning and at the end of the pill-free period in the 30 micrograms EE group compared with both 20 micrograms EE study groups. Dominant follicles (defined as follicle diameter > or = 10 mm) were observed at the end of the pill-free interval in both 20 micrograms EE groups (in 27% and 18% of women, respectively) but not in the 30 micrograms EE group. Finally, the area-under-the-curve for E2 was statistically significantly lower in the 30 micrograms
Wiener, Alane L.; And Others
Although investigations of the physiological effects of oral contraceptives suggest that affective changes may accompany their use, empirical documentation of these effects has not been consistent. This study examined physiological and affective changes accompanying use of a low-dosage oral contraceptive while controlling for possible expectancy…
Ball, A P; McKee, P A
Factors affecting fibrin formation and dissolution were compared for 15 women taking combined oral contraceptives and 15 women using nonpharmacological methods of birth control. The two groups were matched for age, body weight, time of blood collection, and day in menstrual cycle; none of the women was receiving other drugs known to affect the blood coagulation or fibrinolytic parameters measured in this study. Fibrinogen concentrations tended to be higher in the experimental group; the degree of fibrinogen degradation, number of fibrin cross-links, and levels of factor XIII and plasminogen were the same for both group. There were significant reductions in antithrombin activity, the euglobulin lysis time, and fibrinolytic inhibitor level in women using oral contraceptives. An estrogen dose effect was suggested for fibrinogen concentration and the degree of antithrombin activity. The increased fibrinolytic activity and decreased fibrinolytic inhibitor levels are consistent with in vitro observations that antithrombin also inhibits plasmin activity. Thus while oral contraceptive-induced depression of antithrombin III could possibly predispose to thrombosis by diminishing the inhibition of the serine protease clotting factors, the concomitant decreased level of plasmin inhibition might balance the system by favoring thrombolysis as well as the digestion and inactivation of certain clotting factors by plasmin.
Bakir, R; Hilliquin, P
This work reviews lipoprotein metabolism and relationships to atherosclerosis, examines the nature of arterial accidents and lipid modifications that occur with oral contraceptive (OC) use, and assesses the practical consequences for OC prescription. Cholesterol, triglycerides, and phospholipids are not soluble in aqueous milieus, and their transport in plasma is provided by macromolecules comprising a protein part and a lipid part. 5 types of these lipoproteins are distinguished by their relative richness in lipids and protein and by the nature of their proteins. The chylomicrons carry exogenous triglycerides to the peripheral tissues and cholesterol of dietary origin to the liver. Very low density lipoprotein (VLDL) cholesterol is secreted by the liver and transports triglycerides and cholesterol of endogenous origin. Low denisty lipoprotein (LDL) cholesterol originates in the degradation of VLDL cholesterol and transports cholesterol to the cells. High density lipoprotein (HDL) cholesterol is secreted by the liver and intestines or formed in the course of degradation of chylomicrons and VLDL cholesterol. Its role is to carry excess cholesterol in the peripheral tissues to the liver for elimination in the bile. Cholesterol thus follows 2 different pathways in the body: a path from the liver to the peripheral cells, whose markers are LDL and VLDL cholesterol and the plasma apoprotein B, and a path of return of excess cholesterol from the tissues and especially the arteries to the liver, marked by HDL cholesterol and the plasma apoprotein A. Only a proper balance between the 2 flows can prevent an excess of cholesterol in the arteries and the consequent constitution of atherosclerotic lesions. LDL and to a lesser extent VLDL cholesterol are strongly and positively correlated to atherogenic risk, while HDL cholesterol is negatively correlated to risk, independently of other risk factors. Arterial accidents occurring with OC use do not seem to be atheromatous in
Chihal, H J; Peppler, R D; Dickey, R P
The estrogen potencies of 9 oral contraceptive pills, Enovid-E, Enovid-5, Ovulen, Demulen, Norinyl+80, Norinyl+50, Ovral, Norlestrin 1 mg. and Norlestrin 2.5 mg., were determined by bioassay. Relative estrogen potency was determined by analysis of variance. Enovid-5, the most estrogenic compound, had a potency of 4.88 compared to ethinyl estradiol, 50 mcg. equal 1.00; Ovral, the least estrogenic compound, had a potency of 0.81, a sixfold difference. Estrogen potencies at a fractional dose of 0.00155 correlate with reports of the incidence of minor side effects and thromboembolic disease. The effect of progestins on estrogen potency was purely additive (norgestrel and norethynodrel), purely antagonistic, or additive at low concentrations and antagonistic at high concentrations (norethindrone, norethindrone acetate, and ethynodiol diacetate). These results suggest that pills with a greater margin of safety might be developed by utilizing greater ratios of progestin to estrogen. In addition, differences in relative estrogen potency of oral contraceptive pills may be used as a basis for better clinical selection.
Wiegratz, I; Stahlberg, S; Manthey, T; Sänger, N; Mittmann, K; Palombo-Kinne, E; Mellinger, U; Lange, E; Kuhl, H
The effects of extended regimens of combined oral contraceptives (COCs) on carbohydrate metabolism are largely unknown. The present study compared the effects of a COC containing 30 microg ethinylestradiol and 2 mg dienogest (EE/DNG) in conventional and extended-cycle regimen over 1 year. Parameters of carbohydrate metabolism were measured in 59 women treated with EE/DNG either conventionally (13 cycles of 21+7 days) or in extended-cycle regimen (4 cycles of 84+7 days). Blood samples were taken in a control cycle, and at 3 and 12 months of treatment. The mean levels of HbA1c and fasting glucose levels remained stable in both conventional and extended-regimen of EE/DNG. The mean levels of fasting insulin and C-peptide underwent comparable increases in both regimens, suggesting a similar readjustment of glucose metabolism via slightly increased insulin secretion. For both regimens, the response to the oral glucose tolerance test (OGTT) showed a slightly impaired glucose tolerance and insulin resistance at 3 months. These changes improved or returned to baseline at 12 months. Accordingly, the mean index for insulin resistance (homeostasis model assessment of insulin resistance, HOMA-IR) increased and the mean insulin sensitivity index [ISI (composite)] decreased modestly in both groups. The present study demonstrates that there are no statistically significant differences between the effects of conventional and extended-cycle treatment on carbohydrate metabolism over 1 year of treatment. In general, the effects of both regimens were moderate and mostly transient.
Oral contraceptive (OC) labeling disclosure of possible benefits from use of the products, was recommended by the U.S. Food and Drug Administration's (FDA) Fertility and Maternal Health Drugs Advisory Committee at its February 11 meeting. Committee member Howard Orr, Centers for Disease Control, noting the emphasis on cautionary and warning statements contained in current OC labeling maintained: "Women should make informed decisions and this is the other half. The package insert must include the benefits information." The recommendation by the committee represents a shift in the approach to what constitutes proper labeling for OC products. Since first approved, the drugs have never carried a discussion of benefits on their labels. "A number of additional benefits from OCs--other than contraception--have emerged from the large number of studies recorded in the literature on OC use," Ron Nelson, White Memorial Medical Center, stated. "Studies cited a more regular and lighter menstrual flow, resulting in less blood loss and lower iron deficiency and anemia in contraceptive pill users, and dysmenorrhea and premenstrual tension have been sifnificantly reduced." "Ovarian cysts and pelvic inflammatory disease occurred less frequently in pill users than in controls," Nelson continued, "and the incidence of fibrocystic disease of the breast were less. There are some instances where OCs may incur protection against the development of ovarian cancer, endometrial cancer, and rheumatoid arthritis." Orr added: "I think there are 2 good studies that show almost a total elimination of ectopic pregnancy with women who took the pill. Given that now there's an epidemic of the disease going around, I think it's worth adding." The committee was asked by FDA last November to recommend changes in the current physician and patient OC labeling. FDA's Solomon Sobel, MD, Endocrine and Metabolic Drugs Division, told the committee that an agency subcommittee would review the recommendations
Rosenberg, M J; Burnhill, M S; Waugh, M S; Grimes, D A; Hillard, P J
Compliance difficulties are more common among oral contraceptive (OC) users than generally appreciated by clinicians, in part because unintended pregnancy is a relatively infrequent consequence and in part because more common manifestations such as spotting and bleeding may not be recognized as resulting from poor compliance. While improving compliance is a shared responsibility of patients, clinicians, and manufacturers, the clinician is the focal point for these efforts. Counseling must be individualized, which requires knowledge of factors that predict compliance and an understanding of the patient's decision-making process as it relates to medications. Most OC compliance research has focused on adolescents, where predictors of poor compliance include multiple sex partners, low evaluation of personal health, degree of concern about pregnancy, and previous abortion. Good compliance has been linked with patient satisfaction with the clinician, the absence of certain side effects, establishing a regular daily routine to take OCs, and reading information distributed with OC packaging.
Zichella, L; Sbrignadello, C; Tomassini, A; Di Lieto, A; Montoneri, C; Zarbo, G; Mancone, M; Pietrobattista, P; Bertoli, G; Perrone, G
Cycle control and tolerability of two monophasic oral contraceptive pills containing 30 microg ethinyl estradiol (EE) with either 150 microg desogestrel (DSG) or 75 microg gestodene (GSD) were compared in women starting oral contraception. A minimum of 200 healthy women at risk for pregnancy were to be treated for a total of 6 cycles per patient in a prospective, randomized open parallel-group multicenter trial. Two hundred and forty-one subjects were randomized, 115 to DSG/EE and 126 to GSD/EE. Compliance to the study preparation was high (around 95%) in both groups and no pregnancies occurred during the study. Cycle control was excellent; there were no differences between the two groups with regard to incidence of spotting and breakthrough bleeding or duration and intensity of withdrawal bleeding. Side-effects were mild and in general comparable in the two groups. Both at baseline and during treatment, a higher proportion of women taking GSD/EE complained about breast tenderness. This resulted in more early withdrawals because of breast tenderness in the GSD/EE group. It was concluded that monophasic DSG/EE and GSD/EE are equally effective, have similar cycle control and both are generally well tolerated.
Sawyer, Robin G.; Beck, Kenneth H.
Results are reported from a study which examined attitudes, experiences, and concerns of college women (N=237) regarding oral contraception. Implications of the findings for health educators are discussed. (IAH)
Barton, Matthias; Dubey, Raghvendra K; Traupe, Tobias
Oral contraceptives containing synthetic oestrogens have been used successfully as birth control for > 40 years and are currently prescribed to > 100 million women worldwide. Several new progestins have been introduced and the third generation of progestins has now been available for two decades. Oral contraceptives are prescribed over a prolonged period of time and therefore substantially impact on hormonal, metabolic and plasmatic functions. Oral contraceptives increase the risk for venous thrombosis and pulmonary embolism, particularly if associated with confounding factors, such as genetic predisposition, smoking, hypertension or obesity. The risk of developing coronary artery disease is also increased in users with cardiovascular risk factors. This article discusses mechanistic and clinical issues and reviews the need for novel approaches targeting the considerable side effects in order to reduce cardiovascular morbidity in women using oral contraceptives.
Edgren, R A
Considerable research evidence now exists to suggest that the risks of oral contraceptive (OC) use were seriously overestimated in earlier work. Because experimentation in medicine is never possible in the rigorous sense in which it is employed in basic sciences, other sources of information must be substituted. Information on the dangers of OC use has come from anecdotal reports, retrospective case control studies, prospective cohort studies, and statistical analyses of deaths, each source being associated with specific problems of interpretation. Recent findings of the Royal College of General Practitioners, the Walnut Creek Study, and the Oxford Study have suggested a lowered incidence of malignant neoplasms in OC than in IUD or diaphragm users; a reduced incidence of breast cancer although the relationship did not consistently achieve statistical significance, and a reduced incidence of ovarian and endometrial cancer. The risks of cervical cancer among OC users appeared slightly higher but disappeared when sexual behavior was controlled. Despite much concern with the possibility of postpill amenorrhea and perhaps sterility among women discontinuing OC use, it now appears that after 2 years there is no difference in the fertility of women who have discontinued use of OCs, IUDs, or diaphragms. Use of OCs as a contraceptive before pregnancy does not appear to be associated with fetal malformations, spontaneous abortion, or perinatal mortality, and the inadvertent use of OCs in early pregnancy is apparently associated with only a very slight risk of anomalies. Recent studies of cardiovascular disease risks indicate that the relative risks of cardiovascular disease among OC users have been greatly exaggerated, especially when smoking is taken into account. Various studies of mortality data have failed to establish a link between OC use and excess mortality from cardiovascular disease.
Stanczyk, Frank Z; Archer, David F
Combined progestin-estrogen pills are an established and reliable contraceptive option used by women worldwide. Combined oral contraceptives (COCs) containing the progestins--gestodene, desogestrel or norgestimate--were developed to minimize androgenic side effects and are considered an effective, well-tolerated contraceptive option. Gestodene achieves contraceptive efficacy with the lowest dose of any progestin in a COC, and has an established and favorable short- and long-term tolerability profile. In this review we present an overview of the pharmacology, potency and tolerability of gestodene.
Bressler, R; Durand, J L
Reports regarding the question of whether oral contraceptive (OC) use enhances the risk of cancer or one of several serious cardiovascular disorders, i.e., thromboembolic disease, stroke, and myocardial infarction are reviewed. In 1974 the Royal College of General Practitioners (RCGP) issued an interim report of a large prospective study involving 46,000 women. The study found a 5-fold increase in the risk of deep venous thrombosis among women taking OCs. Laboratory studies have tried to establish a direct causal relationship between OC use and altered hemostatis. In review of these studies, Bingel and Benoit reported an increased incidence of thromboembolism in OC users with blood group A. Other hemostatic alterations in OC users were also noted. Other investigators have examined the effect of OCs on antithrombin 3. In 1 study, the inhibitory activity of antithrombin 3 on factor X was significantly reduced among 57 women using the combined OCs, but there was no substantial difference in the quantity of antithrombin 3 in these women as compared with 48 women in the control group. In 1 retrospective case control study of 60 surgical patients with complications of pulmonary embolism or venous thrombosis, the risk of postoperative thromboembolism was 6.7 times greater in OC users than in 97 well matched surgical controls. The RCGP study showed that the risk of cerebrovascular disease in women using OCs was 4 times greater than in nonusers. This finding was substantiated by the Boston-based Collaborative Group for the Study of Stroke in Young Women, which observed a 2-fold increase in risk for all types of stroke among OC users. Several studies have demonstrated that serum lipids are higher in women who use OCs than in those who do not, with estrogen being implicated as the cause of the elevation. Other studies have attempted to link serum lipid elevations to myocardial infarction, but the association is unclear. Both epidemiological and laboratory studies have
Gibson, J; McGowan, D A
This paper considers the possible interactions between oral contraceptive pills and antibiotics, in the context of modern dental practice. A review of the literature on such interactions leads to the conclusion that current national guidelines on the use of alternative contraceptive measures during a course of broad spectrum antibiotics in women also using the oral contraceptive pill should be emphasised and encouraged as part of good clinical practice. A patient information leaflet may be considered as a useful way of presenting such advice to female patients.
Flowers, C E; Griffith, S F
Facts about oral contraceptives and their use are provided for the practcing generalist and specialist. Identification of oral contraceptives is given in chart form including company, name, contents, pill color, number in pack and special markings. Section 2 entitled "facts that may be helpful in prescribing or changing the prescription of oral contraceptives" includes potency of progestins and estrogens and symptoms indicating excessive or deficient progestin and estrogen activity. Contraindications such as migraine headaches, epilepsy, hepatic disease, renal disease and hypertension are among the reasons for obtaining a complete family history prior to prescription of oral contraceptives. This information provides the basis for choice of contraception tailored to the individual. A 100 pound 17 year old with a normal menstrual history and with adequate estrogen production would be safest with a medication low in estrogen and progestin. An older heavier woman with prolonged menstruation and cramps would require a pill which is potent in progestins since these are excellent for causing endometrium regression and vascular reduction. Length of time on oral c ontraceptives depends upon the patient's general health. If responding well to contraceptives the patient should continue to use them because 1) the body is programmed for lengthy periods of ovulation suppression; 2) the patient becomes accustomed to infertility and 3) too many unplanned pregnancies occur during rest intervals. Complaints of nausea, migraine headaches, change in libido, chloasma or thrombophlebitis determine the termination of the drug.
... comparing the effectiveness of oral contraceptives to other methods of contraception. (4) A boxed warning... indications in addition to contraception that are identified in the professional labeling for the drug...
... comparing the effectiveness of oral contraceptives to other methods of contraception. (4) A boxed warning... indications in addition to contraception that are identified in the professional labeling for the drug...
... comparing the effectiveness of oral contraceptives to other methods of contraception. (4) A boxed warning... indications in addition to contraception that are identified in the professional labeling for the drug...
Patthi, Basavaraj; Singla, Ashish; Gupta, Ritu; Dhama, Kuldeep; Niraj, Lav Kumar; Kumar, Jishnu Krishna; Prasad, Monika
Introduction Oral contraceptives are one of the risk factors for gingival disease. Oral contraceptives can affect the proliferation of cell, growth and differentiation of tissues in the periodontium. Nowadays recent research has suggested that the newer generation oral contraceptives have less influence on gingival diseases. Aim The purpose of this study was to systematically review the effect of oral contraceptives on periodontium. Materials and Methods A literature review was performed; PubMed, PubMed Central and Cochrane Library, Embase, Google Scholar were searched from 1970 up to December 2015 to identify appropriate studies. Results Out of the total 94 titles appeared 13 articles fulfilled the criteria and were selected for the review. Two articles which were hand searched and one article which was through e-mail was also included. The hormones progesterone and estrogen have direct impact on immune system of the body and thus, affect the pattern and rate of collagen production in the gingiva. Furthermore, the review also shows that longer duration usage of oral contraceptive could lead to poorer oral hygiene status, gingival inflammation and increased susceptibility to periodontal disease. Conclusion There are relatively few studies evaluating the effect of oral contraceptives on periodontium. It was found that oral contraceptives have a marked effect on periodontium. The gingival changes after use of oral contraceptives are pronounced in the first few months and with the passage of time these changes get enhanced. PMID:28050520
Harper, Julie C
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.
de Melo, Nilson Roberto
Although combined oral contraceptives (COCs) are commonly used and highly effective in preventing pregnancy, they may not be suitable for some women. COC use is associated with increased rates of cardiovascular events and is not recommended in nonbreastfeeding women in the immediate postpartum period or in breastfeeding women during the initial 6 months of breastfeeding. Moreover, estrogen-related adverse effects, such as headache, are common. Estrogen-free progestin-only pills (POPs) are a valuable option in women who prefer to take an oral hormonal contraceptive, but are ineligible for, or choose not to use, COCs. Although some POPs have been associated with lower contraceptive effectiveness than COCs, the POP containing desogestrel has shown similar contraceptive effectiveness to COCs. The most commonly reported complaints in women using all POPs are bleeding problems. Counseling women interested in using POPs about the variable bleeding patterns associated with this method may improve compliance and acceptance.
Koulianos, G T
Combination oral contraceptives (OCs) (those that contain estrogen and progestin) are widely used in the treatment of acne because they modify an excessively androgenic hormonal environment and can decrease lesions. Dermatologists' knowledge of the most appropriate OC may be hampered by an incomplete understanding of these agents, misleading promotion, and confusion surrounding the new generation of OCs. Despite reports attributing significance to the degree of androgenicity of the progestin components of OCs, in vitro and animal bioassays of androgenicity have little clinical relevance. Because all of today's low-dose combination OCs are estrogen dominant, they are equally beneficial in women with androgenic conditions such as acne. Use of the OC containing the lowest dose of each hormone, consistent with the patient's needs, can enhance compliance by preventing or limiting common early-cycle side effects (e.g., nausea/vomiting, breast tenderness, weight gain, headache), while providing acne improvement.
Orme, M L; Back, D J
Oral contraceptive steroids may undergo enterohepatic circulation, but it is relevant for only estrogens, because these compounds can be directly conjugated in the liver. Animal studies show convincing evidence of the importance of the enterohepatic circulation, but studies in humans are much less convincing. The importance of the route and the rate of metabolism of ethinyl estradiol are reviewed. Some antibiotics have been reported anecdotally to reduce the efficacy of oral contraceptive steroids, but controlled studies have not confirmed this observation. Although gut flora are altered by oral antibiotics, the blood levels of ethinyl estradiol are not reduced, and one antibiotic at least (cotrimoxazole) enhances the activity of ethinyl estradiol.
(1) Intrauterine devices (IUDs) are placed in the uterine cavity with the objective of providing long-term contraception, mainly by preventing fertilisation. The best-known IUDs contain copper, but there is also an IUD delivering levonorgestrel, a progestin; (2) How effective are these devices, and what are their adverse effects? To answer these questions, we analysed the literature using the standard Prescrire methodology; (3) T-shaped copper IUDs, with a copper surface area of 380 mm2 on 3 arms, and the levonorgestrel-releasing device, have similar contraceptive efficacy as combined oral contraceptives that are used correctly. In contrast, IUDs are more effective than oral contraception used incorrectly; (4) Among IUD users, there are on average about 6 pregnancies per 1000 woman-years. There is less experience with the levonorgestrel IUD which seems to be at least as effective as copper IUDs; (5) The rare intrauterine pregnancies that occur in women using an IUD generally end in miscarriage. About 25% of these pregnancies end in a live birth if the device is left in place, compared to about 90% if the device is removed; (6) Ectopic pregnancies are rarer in IUD users than in women who do not use contraception. However, about one in 20 pregnancies that occur in women using an IUD is ectopic; (7) The IUD is expelled in about 5% to 10% of cases within 5 years, and expulsion recurs in about 30% of these women; (8) Problems such as difficult insertion, pain, bleeding and syncope are reported in less than 1.5% of cases overall; (9) Uterine perforation during insertion is rare, occurring in 0.6 to 16 cases per 1000 insertions, regardless of the type of IUD. The risk of perforation is higher when the IUD is inserted less than 4 to 6 weeks after delivery or elective abortion; (10) During the first 3 months after insertion, the risk of pelvic infection is slightly higher than in the general population, especially in women with pre-existing asymptomatic Chlamydia
Cottingham, J; Hunter, D
OBJECTIVES--Chlamydia trachomatis is now recognised as a major sexually transmitted disease; oral contraceptive use is rapidly increasing particularly in developing countries. There are thus important public health implications of the many reports that isolation of C trachomatis is more frequent among users of oral contraceptives. The aim of this analysis was to assess the strength and consistency of this association by summarising published studies between 1972 and 1990. DESIGN--Studies identified were grouped according to whether they were prospective or case-control studies. Data were extracted and pooled estimates of the unadjusted odds ratios were made for all studies, as well as for sub-groups defined by an index of study quality, background prevalence of C trachomatis, and the contraceptive comparison being made. LOCATION--Studies in the analysis were mainly conducted in Europe and North America; the meta-analysis was done at the Harvard School of Public Health, Boston, MA, USA. RESULTS--The pooled estimated unadjusted odds ratio for 29 case-control studies examined was 1.93 (95% CI, 1.77-2.11), indicating an almost twofold increased risk of chlamydial infection for oral contraceptive users. Neither study quality nor prevalence of C trachomatis modified this risk. When compared to the use of barrier contraceptives, however, the risk of infection for women using oral contraceptives increased to 2.91 (95% CI, 1.86-4.55). The pooled estimated protective effect of barrier methods in these studies was 0.34 (95% CI, 0.22-0.54). CONCLUSIONS--Cross-study comparisons of the relationship between oral contraceptive use and chlamydial infection are limited by the design and analysis of many component studies which did not control for confounding factors such as sexual behaviour and age. The almost twofold risk of increased chlamydial infection for oral contraceptive users, supported by the findings of two prospective studies, however, points to the importance of
Cramer, D W; Hutchison, G B; Welch, W R; Scully, R E; Knapp, R C
We investigated the relation between epithelial ovarian cancer and the use of oral contraceptives in a case-control study of 144 white women under the age of 60 who had ovarian cancer and 139 white women under 60 who were selected from the general population. We observed a decreased risk for ovarian cancer associated with the use of oral contraceptives in subjects 40 through 59 years of age at the time of the study. The relative risk, adjusted for parity, was 0.11, with 95 per cent confidence limits of 0.04 to 0.33. In contrast to the findings in older women, a decreased risk for ovarian cancer associated with oral-contraceptive use was not found in women under 40. In this group, the adjusted relative risk associated with any use of oral contraceptives was 1.98, with 95 per cent confidence limits of 0.74 to 5.27. The lowest risk for ovarian cancer associated with the use of oral contraceptives was observed in older parous subjects and in women who had discontinued use more than 10 years previously.
Pearson, Jacob; Maslen, Cheryl; Edelman, Alison
Oral contraceptives have been in wide use for more than 50 years. Levonorgestrel, a commonly employed progestin component of combined oral contraceptives, was implicated in drug–drug interactions mediated via CYP2C9. Although in vitro studies refuted this interaction, there are no confirmatory in vivo studies. In the current study, we examined the phenotypic status of CYP2C9 using low-dose (125 mg) tolbutamide before and after oral contraceptive use in reproductive age women. Blood was collected 24 hours after the tolbutamide oral dose was administered, plasma was isolated, and tolbutamide concentration (C24) was measured using liquid chromatography–mass spectrometry. The natural logarithm of tolbutamide C24, a metric for CYP2C9 phenotype, was found to be equivalent (within 80%–125% equivalency boundaries) before and after oral contraceptive use. In conclusion, levonorgestrel-containing oral contraceptives, the most commonly used form of oral contraception, do not affect the status of the CYP2C9 enzyme. This suggests that it is safe to coadminister levonorgestrel-containing oral contraceptives and CYP2C9 substrates, which include a wide array of drugs. PMID:24368832
Cherala, Ganesh; Pearson, Jacob; Maslen, Cheryl; Edelman, Alison
Oral contraceptives have been in wide use for more than 50 years. Levonorgestrel, a commonly employed progestin component of combined oral contraceptives, was implicated in drug-drug interactions mediated via CYP2C9. Although in vitro studies refuted this interaction, there are no confirmatory in vivo studies. In the current study, we examined the phenotypic status of CYP2C9 using low-dose (125 mg) tolbutamide before and after oral contraceptive use in reproductive age women. Blood was collected 24 hours after the tolbutamide oral dose was administered, plasma was isolated, and tolbutamide concentration (C24) was measured using liquid chromatography-mass spectrometry. The natural logarithm of tolbutamide C24, a metric for CYP2C9 phenotype, was found to be equivalent (within 80%-125% equivalency boundaries) before and after oral contraceptive use. In conclusion, levonorgestrel-containing oral contraceptives, the most commonly used form of oral contraception, do not affect the status of the CYP2C9 enzyme. This suggests that it is safe to co-administer levonorgestrel-containing oral contraceptives and CYP2C9 substrates, which include a wide array of drugs.
Lemay, André; Poulin, Yves
Although acne is seldom associated with high serum levels of androgens, it has been shown that female acne patients have definite increases in ovarian and adrenal androgen levels when compared to appropriate controls. As shown in several pilot and in multiple open and comparative studies, oral contraceptives (OCs) are effective in causing a significant regression of mild to moderate acne. These results have been confirmed by multicentre randomized trials where low-dose OCs did not cause side effects different from those of the placebo-controlled group. The beneficial effect of OCs is related to a decrease in ovarian and adrenal androgen precursors; to an increase in sex hormone-binding globulin (SHBG), which limits free testosterone; and to a decrease in 3a-androstenediol glucuronide conjugate, the catabolite of dihydrotestosterone (DHT) formed in peripheral tissues. The estrogen-progestin combination containing cyproterone acetate (CPA) is particularly effective in treating acne, since this progestin also has a direct peripheral anti-androgenic action in blocking the androgen receptor. Only two open studies and one randomized study on small numbers of patients have reported some efficacy of spironolactone used alone or in combination with an OC in the treatment of acne. The new non-steroidal anti-androgens flutamide and finasteride are being evaluated for the treatment of hirsutism. Oral antibiotics are prescribed to patients with inflammatory lesions, where they are effective in decreasing the activity of microbes, the activity of microbial enzymes, and leukocyte chemotaxis. Concomitant intake of an OC and an antibiotic usually prescribed for acne does not impair the contraceptive efficacy of the OC. A second effective contraceptive method should be used whenever there would be decreased absorption or efficacy of the OC (digestive problems, breakthrough bleeding), lack of compliance and use of a type or dose of antibiotic different from that usually prescribed
Poulter, N R
This commentary addresses the New Zealand study (case report) of a fatal pulmonary embolism (PE) associated with oral contraceptive (OC) use by L. Parkin and colleagues. The study significantly adds to the knowledge on the relationship between fatal PE and OC use, because most of the evidence up to now has related to nonfatal venous thromboembolic events (VTE). Several areas of the study, however, are criticized. These include the method used, definition, and the adjustment of data. However, these criticisms have been offered explanations in this commentary. It is noted that data from the study indicated that OCs containing desogestrel or gestodene are associated with higher risks of fatal PE than are those containing levonorgestrel. This is consistent with most previous studies comparing the effects of second-generation progestogens on VTE. Overall, data support previous pragmatic recommendations that second-generation pills, which contain levonorgestrel, are the combined OCs of choice.
Reid, Robert L
Post-marketing surveillance of combined oral contraceptives (COCs) for rare complications such as venous thromboembolism (VTE) presents unique challenges. Prospective studies, which are costly and time consuming, have to date been undertaken by only a few contraceptive manufacturers willing to commit to full evaluation of product safety. Often such studies are conducted with the approval of regulatory authorities as a precondition for marketing. Alternatively, independent investigators with access to large databases have conducted retrospective studies to compare the incidence of VTE between new and older products. Such studies, however, run the risk of erroneous conclusions if they cannot ensure comparable risk profiles for users of these different products. Often database studies are unable to access information on important confounders, and medical records may not be available to validate the actual diagnosis of VTE. "Pill scares" generated following publication and media dissemination of worrisome findings, when the conclusions are in doubt and not corroborated by stronger prospective study designs, are frequently damaging to public health. From a review of recent publications on the VTE risk with drospirenone-containing COCs, it can be concluded that the best quality evidence does not support a difference in risk between users of COCs containing drospirenone and those of COCs containing levonorgestrel.
Hellwig, Kerstin; Chen, Lie H.; Stancyzk, Frank Z.; Langer-Gould, Annette M.
Background The incidence of multiple sclerosis (MS) is rising in women. Objective To determine whether the use of combined oral contraceptives (COCs) are associated with MS risk and whether this varies by progestin content. Methods We conducted a nested case-control study of females ages 14–48 years with incident MS or clinically isolated syndrome (CIS) 2008–2011 from the membership of Kaiser Permanente Southern California. Controls were matched on age, race/ethnicity and membership characteristics. COC use up to ten years prior to symptom onset was obtained from the complete electronic health record. Results We identified 400 women with incident MS/CIS and 3904 matched controls. Forty- percent of cases and 32% of controls had used COCs prior to symptom onset. The use of COCs was associated with a slightly increased risk of MS/CIS (adjusted OR = 1.52, 95%CI = 1.21–1.91; p<0.001). This risk did not vary by duration of COC use. The association varied by progestin content being more pronounced for levenorgestrol (adjusted OR = 1.75, 95%CI = 1.29–2.37; p<0.001) than norethindrone (adjusted OR = 1.57, 95%CI = 1.16–2.12; p = 0.003) and absent for the newest progestin, drospirenone (p = 0.95). Conclusions Our findings should be interpreted cautiously. While the use of some combination oral contraceptives may contribute to the rising incidence of MS in women, an unmeasured confounder associated with the modern woman’s lifestyle is a more likely explanation for this weak association. PMID:26950301
Thorneycroft, I H
Comparing the degree of cycle control provided by various oral contraceptives is problematic. The inherent limitations, small demonstrated differences, and differing methods of data presentation characteristic of these trials support the conclusion that it is almost impossible to compare the bleeding patterns of one preparation with those of another. Chlamydial infection, smoking, and inconsistency of use are factors that have significant effects on rates of spotting and breakthrough bleeding. Clinicians must alert patients to the possibility of intermenstrual bleeding and educate them with regard to the importance of continued, consistent oral contraceptive use to minimize those problems among pill users in their practices.
In the introduction the author points out the importance, mechanism and consequence of interactions between oral contraceptives and other drugs. The interactions between certain drugs with different pharmacological action and the contraceptive tablets which decrease or increase the contraceptive effect as well as the drugs whose effect may be influenced by the contraceptive tablets have been discussed. Cases in which only a few data refer to, or no clinical proof supports interaction, are also mentioned. According to interactions observed until present in women taking Anteovin, the recommended measures to be taken in these cases have been described. Finally it has been emphasized that the knowledge of interactions between drugs is just as important in family planning counselling as is when prescribing other drug treatments.
Lewis, M A
Recent discussions have centered on the small apparent risk increase for venous thromboembolism found with newer oral contraceptives (third-generation oral contraceptives containing the progestins desogestrel and gestodene) compared with older oral contraceptives (second-generation). This article reviews the studies addressing the association between oral contraceptive use and thromboembolic conditions affecting the arterial system, ischemic stroke, and myocardial infarction. Differences are found between a US database study, which showed no risk of ischemic stroke or myocardial infarction associated with low-dose oral contraceptive use, and the European studies, which showed oral contraceptive use in general to be associated with increased risks of ischemic stroke and myocardial infarction. The European studies showed no difference between oral contraceptive generations with respect to the occurrence of ischemic stroke; however, the risk of myocardial infarction associated with oral contraceptive use was consistently lower for third- than for second-generation oral contraceptives. Although there seems to be no differential risk of ischemic stroke associated with oral contraceptive generations, third-generation oral contraceptives appear to be consistently associated with no excess risk of myocardial infarction. In all instances, however, cardiovascular risk factors other than oral contraceptive use play the predominant role in the occurrence of ischemic stroke and myocardial infarction.
La, Filipa M. B.; Sundberg, Johan; Howard, David M.; Sa-Couto, Pedro; Freitas, Adelaide
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…
Pfrunder, Arabelle; Schiesser, Monika; Gerber, Simone; Haschke, Manuel; Bitzer, Johannes; Drewe, Juergen
Aims Breakthrough bleeding or even unwanted pregnancies have been reported in women during concomitant therapy with oral contraceptives and St John's wort extract. The aim of the present study was to investigate the effects of St John's wort extract on oral contraceptive therapy with respect to ovarian activity, breakthrough bleeding episodes and the pharmacokinetics of ethinyloestradiol and 3-ketodesogestrel. Methods Eighteen healthy females were treated with a low-dose oral contraceptive (0.02 mg ethinyloestradiol, 0.150 mg desogestrel) alone (control cycle) or combined with 300 mg St John's wort extract given twice daily (cycle A) or three times daily (cycle B). Ovarian activity was assessed by measuring follicle maturation and serum oestradiol and progesterone concentrations. The number of breakthrough bleeding episodes and the pharmacokinetics of ethinyloestradiol and 3-ketodesogestrel were assessed under steady-state conditions. Results During concomitant administration of low-dose oral contraceptive and St John's wort, there was no significant change in follicle maturation, serum oestradiol or progesterone concentrations when compared with oral contraceptive treatment alone. However, significantly more subjects reported intracyclic bleeding during cycles A (13/17 (77%), P < 0.015) and cycle B (15/17 (88%), P < 0.001) than with oral contraceptives alone (6/17 (35%)). The AUC(0,24 h) and Cmax of ethinyloestradiol remained unchanged during all study cycles, whereas the AUC(0,24 h) and Cmax of 3-ketodesogestrel decreased significantly from 31.2 ng ml−1 h to 17.7 ng ml−1 h (43.9%; 95% confidence interval (CI) −49.3, −38.5, P = 0.001) and from 3.6 ng ml −1 to 3.0 ng ml −1(17.8%; CI −29.9, −5.7, P = 0.005), respectively, during cycle A and by 41.7% (CI −47.9, −35.6; P = 0.001) and by 22.8% (CI −31.2, −13.3; P < 0.001) during cycle B respectively, compared with the control cycle. Conclusions There was no evidence of ovulation during low
that a history of stress fractures, lower bone mass, lower dietary calcium intake, younger chronological age, younger age at menarche, and possibly a... history of irregular menstrual periods were associated with an increased risk. 15. SUBJECT TERMS bone mass, oral contraceptives, physical activity...year decrease). Although not statistically significant, a history of irregular menstrual periods was also associated with increased rate of stress
Gorham-Rowan, Mary; Fowler, Linda
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…
Zapata, Lauren B.; Steenland, Maria W.; Brahmi, Dalia; Marchbanks, Polly A.; Curtis, Kathryn M.
surrogate measures of pregnancy risk and ranged in quality. For studies providing indirect evidence on the effects of missed CHCs, it is unclear how differences in surrogate measures correspond to pregnancy risk. Fewer studies examined the transdermal patch and vaginal ring than combined oral contraceptives. PMID:23083527
Kaunitz, A M
The most recent statistical evidence confirms a protective effect of oral contraceptive use against ovarian and endometrial cancers. Studies of the association between oral contraceptive use and cervical cancer continue to be hampered by confounding factors; however, results suggest that the overall risk of invasive cervical neoplasia is not increased. Although the association between oral contraceptive use and breast cancer remains controversial, existing data strongly suggest that overall risk of breast cancer is not increased by the use of oral contraceptives. In most candidates for oral contraceptive use, the benefits greatly outweigh the risks.
Tworoger, Shelley S; Fairfield, Kathleen M; Colditz, Graham A; Rosner, Bernard A; Hankinson, Susan E
Although oral contraceptives are protective for ovarian cancer, it is unclear how long this protection persists. The authors prospectively assessed this question as well as associations of other, less studied contraceptive methods (tubal ligation, rhythm method, diaphragm, condoms, intrauterine device, foam, spousal vasectomy) and infertility with ovarian cancer risk among 107,900 participants in the US Nurses' Health Study. During 28 years of follow-up (1976-2004), 612 cases of invasive epithelial ovarian cancer were confirmed. Duration of oral contraceptive use was inversely associated with risk (p-trend = 0.02), but no clear trend was observed for years since last use. However, for women using oral contraceptives for >5 years, the rate ratio for ovarian cancer for
Scott, J A; Brenner, P F; Kletzky, O A; Mishell, D R
In order to determine whether certain factors influence the direct pituitary suppressive effect of contraceptive steroid, 50 subjects who had used various formulations of oral contraceptive steroids for periods of time ranging from one to nine years were stimulated with 50 microgram of gonadotropin-releasing hormone (GnRH) during the last week of oral contraceptive ingestion. The response of lutinizing hormone (LH) and follicle-stimulating hormone (FSH) was compared to the results obtained in nine control subjects with regard to: (1) age of subject. (2) type of contraceptive formulation used, and (3) length of use. Prestimulation levels of LH and FSH, respectively, were significantly decreased in 37 (74 per cent) and 42 (84 per cent) of the subjects. Following GnRH stimulation, peak responses of serum LH and FSH, respectively, were also significantly lower than those in the control subjects in 40 (80 per cent) and 45 (90 per cent of the subjects. The degree of suppression of pituitary gonadotropins, both before and after GnRH administration was significantly correlated with the type of steroid formulation used, being greatest with a combination of d-norgestrel and ethinyl estradiol. No correlation was found with length of use of oral contraceptives or age of the subjects.
The effects of oral contraceptives and estrogen replacement drugs on blood lipids that affect cardiovascular disease (atherogenic effects) are reviewed by comparing their androgenicity and progestin potency. Although early oral contraceptives with high doses of estrogen were indicted for increasing risk of thromboembolic disorders and heart attacks, today's pills low in estrogen still bear the same risk for cardiovascular events. A brief explanation of the lipoproteins is presented, emphasizing the importance of High Density Lipoprotein (HDL) in protecting against heart disease and stroke. Menstruating women have naturally high HDL. The estrogen in oral contraceptives and postmenopausal estrogen replacements increases HDL as much as 30%, while decreasing LDL, the component carrying most of the cholesterol. It seems that the progestin in oral contraceptives will lower HDL, and studies show that this action is related to androgenicity and dose of the progestin. Progestins such as levonorgestrel and norgestrel are more androgenic, while norethynodrel, ethynodiol diacetate and norethindrone are less so. When used in combination with estrogens, progestins are less androgenic, but when used alone, the androgenic and atherogenic effects dominate. The lower the estrogen dose in the combination, say around 20-35 mcg ethinyl estradiol, the more atherogenic the progestin. These actions are confirmed theoretically by measurements of sex hormone binding globulin, a blood protein that reflects estrogen activity, as well as by epidemiologic studies in Sweden and Great Britain, where rates of heart attack and stroke in pill users remain as high as they were when pills contained high doses of estrogen.
Maharry, J M
At the Presbyterian Intercommunity Hospital, Whittier, California, 120 cases of pulmonary emboli occurred from 1959 through 1968. During this time there were 124,000 admissions and more than 20,000 live births. 51 of the pulmonary embolic cases were female; 25 were of childbearing age. 10 of these showed relationship to the use of oral contraceptives. 6 of them received oral contraceptives after pulmonary embolism without apparent aggravation or recurrence of thromboembolic disease. 2 of the 10 were taking birth control pills at the time they underwent hysterectomy. A pulmonary embolus followed each operation. 2 more were taking the pills and experienced pulmonary embolism without evidence of any predisposing cause. Short case summaries of the 10 are given, all of whom are living and well. Improvement of diagnosis by lung scanning shows that pulmonary embolism is more prevalent and less serious than previously believed. As thrombotic disease is considered a recurring disorder, its relationship to steroid contraceptives has not been totally substantiated. It is concluded that a history of such disease does not necessarily contraindicate the use of oral contraceptives. Following discussion, the author quotes an FDA claim that women who take birth control pills develop thrombo-phlebitis 3 times as frequently as women who do not. He notes that, even according to these Food and Drug Administration statistics, a woman could take the pills for 30 years without as much danger from thrombo-phlebitis as from a single pregnancy.
Shulman, Lee P
Discussion of effective birth control methods can be a challenging process for clinicians because the adoption and consistent use of contraception may be influenced by patients' fears, myths, and misperceptions. Over the years, new progestins have been included in combination contraceptives or are used alone to provide effective contraception as well as to decrease androgenic side effects and ameliorate the symptoms of premenstrual dysphoric disorder. Alternative delivery systems and regimens have also been introduced to improve tolerability and continuance and convenience of use. This is a review of estrogen and progestin combinations and their effects.
Mild thrombophilias include heterozygous forms of Factor V Leiden and prothrombin G20210A mutation and high levels of factor VIII. These defects are responsible for only a moderate increase of venous thromboembolism (VTE) risk compared with strong thrombophilias (antithrombin III, protein C and protein S deficiencies and homozygous forms of factor V Leiden and G20210A prothrombin mutation). Combined oral contraceptives increase the VTE risk in women in a fertile age, and in a far more important way in thrombophilia carrier women. Universal screening of thrombophilia test before the use of combined oral contraceptives is not recommended. However, selective VTE-history based screening is associated with a better cost-effectiveness, especially in asymptomatic relatives of carriers of strong thrombophilia. Currently, combined oral contraceptives are discouraged in women with any thrombophilic defects. The VTE risk is higher during pregnancy and postpartum period compared to hormonal contraceptive use period in women with mil thrombophilia. For this reason, a careful election of an alternative birth control method is necessary in these women.
Kaminski, Pawel; Szpotanska-Sikorska, Monika; Wielgos, Miroslaw
The use of combined oral contraceptives (COCs) is associated with approximately 2-fold and over 4-fold increased relative risks of arterial and venous thromboembolic events, respectively. The highest risk of venous thromboembolism occurs in the first year of use (OR: 4.17) and is reduced to 2.76 over baseline risk after 4 years of therapy. The risk of myocardial infarction does not correlate to the length of therapy and disappears after treatment termination. Most of women, using COCs, have low absolute cardiovascular risks and benefits outweigh the risk associated with this method of birth control. However, in some cases, COCs may be contraindicated due to excessively increased cardiovascular risks. Current users of COCs, older than 35 years, appear to show an estimated 2.5-fold and 10-fold increased risk of venous thromboembolism in comparison to younger than 35 years COCs non-users and users, respectively. COCs users, who are current smokers, have 10-fold increased risk of myocardial infarction, whereas the risk of stroke increases nearly 3-fold. The presence of poorly controlled hypertension is associated with approximately 3-fold increased risks of myocardial infarction and ischemic stroke, while the risk of haemorrhagic stroke rises 15-fold. In women suffering from hypertension, discontinuation of COCs may improve blood pressure control. Women, who had their blood pressure measured before COCs use, have 2-2.5-fold decreased risk of myocardial infarction and ischaemic stroke. In women with multiple cardiovascular risk factors the use of progestogen-only contraceptives (POCs) should be considered. POC therapy is associated with substantially less risk of cardiovascular events than COCs.
[A clinical case of young, oral combined contraceptive using women, heterozygous carrier of the Factor V (Leiden) which revealed thrombosis of the left internal jugular vein and brain ischemia with cerebral infarction and ischemic stroke].
Kovachev, S; Ramshev, K; Ramsheva, Z; Ivanov, A; Ganovska, A
Thrombophilia is associated with increased risks of venous thrombosis in women taking oral contraceptive preparations. Universal thrombophilia screening in women prior to prescribing oral contraceptive preparations is not supported by current evidence. The case is presented of a 23 year-old women with a personal history of interruption and on the same day started with oral contraceptive (0.03 microg ethynil estradiol - 0.075 microg gestodene), which due on a 18 pill/day to acute headache, increasing vomiting and speaking defects. Physical/neurologic/gynecologic examinations observed a normal status. The MRI and CT revealed thrombosis of the left internal jugular vein and brain ischemia with cerebral infarction and ischemic stroke. The acute therapy of thrombotic findings was accompanied with many tests. The thrombophilia PCR-Real time - test finds heterozygous carrier of the Factor V (Leiden). This case shows the need of large prospective studies that should be undertaken to refine the risks and establish the associations of thrombophilias with venous thrombosis among contraceptive users. The key to a prompt diagnosis is to know the risk factors. The relative value of a thrombophilia screening programme before contraceptive using needs to be established.
Shojania, A. M.
Women who use oral contraceptives have impaired folate metabolism as shown by slightly but significantly lower levels of folate in the serum and the erythrocytes and an increased urinary excretion of formiminoglutamic acid. The vitamin B12 level in their serum is also significantly lower than that of control groups. However, there is no evidence of tissue depletion of vitamin B12 associated with the use of oral contraceptives. The causes and clinical significance of the impairment of folate and vitamin B12 metabolism in these women is discussed in this review of the literature. Clinicians are advised to ensure that women who shop taking "the pill" because they wish to conceive have adequate folate stores before becoming pregnant. PMID:7037144
Farmer, R D; Todd, J C; Lewis, M A; MacRae, K D; Williams, T J
This study investigated the risk of venous thromboembolic disease (VTE) between second and third generation combined oral contraceptives, using the German MediPlus database of patient records. Women studied included 42 patients between the ages of 18 and 49 years, with a diagnosis of VTE treated with an anticoagulant, who were exposed to an oral contraceptive (OC). Four controls per patient (168), matched by year of birth and exposure to an OC on the even day, were identified. More women were users of second generation than third generation OC, and none were using progestogen-only pills. There was no significant difference between patients and control subjects with respect to the type of OC used on the event day (unadjusted odds ratio for third versus second generation users was 0.77; 95% confidence interval [CI] 0.38-1.57). There was no significant age difference between second and third generation users among patients or control subjects. Between January 1 and the event date, there was no significant difference between the patients and control subjects in terms of the number of oral contraceptive prescriptions, number of consultations for psychotherapeutic complaints, or mixed physical and psychotherapeutic consultations; however, patients did demonstrate significantly more consultations for purely physical complaints compared with control subjects (p < 0.0001). There were no significant consultation differences between patients with pulmonary emboli (n = 6) and other VTE patients (n = 36). No significant differences with respect to VTE risk between users of second and third generation oral contraceptives were found in this study. Consultations (physical) for patients were higher than for control subjects before the VTE event. If consultation rate relates to the general health status of a person, this might indicate that VTE risk is higher among women of poorer health, but that this is not related to the type of progestogen in the oral contraceptive that they use.
41(61. 785-791. Bancroft, J, & Rennie, D. (1993). The impact of oral contraceptives on the experience of perimenstrual mood, clumsiness, food craving ...Confusion 10. Cramps - uterine or pelvic 11. Craving for specific foods or tastes* 12. Craving for alcohol 13. Decreased appetite 14. Decreased food ...evaluated separately from non-users. A questionnaire and modified Keye calendar were used to prospectively collect data. They found that negative
found that a history of stress fractures, lower bone mass, lower dietary calcium intake, younger chronological age, younger age at menarche, and...possibly a history of irregular menstrual periods were associated with an increased risk. Another manuscript, “The effect of oral contraceptives on body...spine bone density, age, and stress fracture history in Cox proportional hazards models, we found that only intakes of skim milk and total dairy milk
Barron, A L; Pasley, J N; Rank, R G; White, H J; Mrak, R E
Female guinea pigs were given daily doses of a combination of oral contraceptive (OC) agents, consisting of mestranol and norethynodrel suspended in sesame oil or distilled H2O, and were infected in the genital tract with the chlamydial agent of guinea pig inclusion conjunctivitis (GPIC). Counts of chlamydial inclusions in cells of vaginal smears collected during infection, showed prolongation and enhancement of infection in OC-treated animals as compared with controls. Appearance of IgG and IgA antibodies to GPIC in genital secretions, as determined by enzyme-linked immunosorbent assay (ELISA), was also delayed in OC-treated animals as compared with controls. OC-treated infected animals were killed on days 15 and 43, and gross pathological evidence for ascending infection culminating in salpingitis was found in all of five and four of five animals, respectively. On the other hand, among untreated infected controls on each sacrifice day, only one of five animals had any evidence for ascending infection. Chlamydiae were detected by light and electron microscopy in fallopian tube tissue collected on day 15 following OC-treatment but not in tissue from control animals.
Stachenfeld, N S; Silva, C; Keefe, D L; Kokoszka, C A; Nadel, E R
To test the hypothesis that estrogen reduces the operating point for osmoregulation of arginine vasopressin (AVP), thirst, and body water balance, we studied nine women (25 +/- 1 yr) during 150 min of dehydrating exercise followed by 180 min of ad libitum rehydration. Subjects were tested six different times, during the early-follicular (twice) and midluteal (twice) menstrual phases and after 4 wk of combined [estradiol-norethindrone (progestin), OC E + P] and 4 wk of norethindrone (progestin only, OC P) oral contraceptive administration, in a randomized crossover design. Basal plasma osmolality (P(osm)) was lower in the luteal phase (281 +/- 1 mosmol/kgH(2)O, combined means, P < 0.05), OC E + P (281 +/- 1 mosmol/kgH(2)O, P < 0.05), and OC P (282 +/- 1 mosmol/kgH(2)O, P < 0. 05) than in the follicular phase (286 +/- 1 mosmol/kgH(2)O, combined means). High plasma estradiol concentration lowered the P(osm) threshold for AVP release during the luteal phase and during OC E + P [x-intercepts, 282 +/- 2, 278 +/- 2, 276 +/- 2, and 280 +/- 2 mosmol/kgH(2)O, for follicular, luteal (combined means), OC E + P, and OC P, respectively; P < 0.05, luteal phase and OC E + P vs. follicular phase] during exercise dehydration, and 17beta-estradiol administration lowered the P(osm) threshold for thirst stimulation [x-intercepts, 280 +/- 2, 279 +/- 2, 276 +/- 2, and 280 +/- 2 mosmol/kgH(2)O for follicular, luteal, OC E + P, and OC P, respectively; P < 0.05, OC E + P vs. follicular phase], without affecting body fluid balance. When plasma 17beta-estradiol concentration was high, P(osm) was low throughout rest, exercise, and rehydration, but plasma arginine vasopressin concentration, thirst, and body fluid retention were unchanged, indicating a lowering of the osmotic operating point for body fluid regulation.
Eilers, G M; Swanson, T K
In Wisconsin, 115 Norplant users and 148 oral contraceptive (OC) users, all of whom attended the university-administered family medicine residency training clinic in Eau Claire between May, 1991, and February, 1993, returned questionnaires as part of a study to examine satisfaction with their chosen contraceptive and its benefits and side effects. Most women were satisfied with their contraceptive method (60% for Norplant users and 72% for OC users). OC users were more likely to use their method again than were Norplant users (88% vs. 63%; p .001). Even though most women would recommend their method to a friend, OC users were more likely to do so than Norplant users (97% vs. 74%; p .001). Irregular bleeding was more common among Norplant users than among OC users (73% vs. 34%; p .001). OC users were more likely to feel that OCs caused less bleeding and less cramping than did Norplant users (72% vs. 30% and 60% vs. 30%, respectively; p .001). They were less likely to complain of acne (7% vs. 29%; p .001), weight gain (33% vs. 49%; p .04), and bleeding irregularities (8% vs. 60%; p .001) than Norplant users. Overall, both Norplant and OC users were satisfied with their current contraceptive method, but satisfaction was lower and side effects were more common among Norplant users.
Bonenberger, Martina; Groschwitz, Rebecca C; Kumpfmueller, Daniela; Groen, Georg; Plener, Paul L; Abler, Birgit
Mating preferences in phases of the natural menstrual cycle with a low probability to conceive have been associated with lower interest in characteristics promising genetic benefits but increased search for safety and future security. We hypothesized that this effect would also be evident under oral contraception and may therefore alter neural processing of monetary rewards as a proxy for potential safety. Our aim was to assess the activation of reward-related brain areas using a monetary incentive task in women with functional MRI (fMRI). We compared fMRI activation of 12 young women taking oral contraceptives with 12 women with a natural hormonal cycle in their follicular phase during the expectation of monetary rewards. Women under hormonal contraception who have already shown decreased anterior insula activation upon erotic stimulation in a previous study of the same sample now showed enhanced activation during monetary reward expectation in the anterior insula/inferior lateral prefrontal cortex (t=2.84; P<0.05) relative to young normal cycling women in the follicular phase. Our finding supports the notion that the switch in mating preferences related to different hormonal states in women is mirrored by a switch in the stimulus-dependent excitability of reward-related brain regions. Beyond highlighting hormonal effects on reward processing, our data underline the importance of monitoring hormonal states in fMRI research in women.
Ringrose, C. A. Douglas
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
Younus, Iyan; Reddy, Doodipala Samba
Contraceptive management is critical in women with epilepsy. Although oral contraceptives (OCs) are widely used by many women with epilepsy, little is known about their impact on epileptic seizures and epileptogenesis. Ethinyl estradiol (EE) is the primary component of OC pills. In this study, we investigated the pharmacological effect of EE on epileptogenesis and kindled seizures in female mice using the hippocampus kindling model. Animals were stimulated daily with or without EE until generalized stage 5 seizures were elicited. EE treatment significantly accelerated the rate of epileptogenesis. In acute studies, EE caused a significant decrease in the afterdischarge threshold and increased the incidence and severity of seizures in fully-kindled mice. In chronic studies, EE treatment caused a greater susceptibility to kindled seizures. Collectively, these results are consistent with moderate proconvulsant-like activity of EE. Such excitatory effects may affect seizure risk in women with epilepsy taking OC pills.
Agnew, Mary K; Asa, Cheryl S; Clyde, Victoria L; Keller, Dominique L; Meinelt, Audra
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.
Benagiano, Giuseppe; Carrara, Sabina; Filippi, Valentina
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
Woods, Jennifer L.; Shew, Marcia L.; Tu, Wanzhu; Ofner, Susan; Ott, Mary A.; Fortenberry, J. Dennis
Purpose Imperfect oral contraceptive pill (OCP) regimen adherence may impair contraceptive effectiveness. The purpose of this study was to describe daily adherence patterns of OCP use, to analyze OCP protection on an event level basis, and to examine pill-taking and condom use during method transitions. Methods Women (n = 123, ages 14–17 years) completed quarterly interviews to classify OCP method choice into four categories: stable, initiated, stopped, and discordant use. Within each OCP category, daily diaries were used to assess occurrence of coitus, condom use, and patterns of day-to-day OCP use (i.e., consecutive days of OCP use reported with no more than two consecutive days of nonuse). A coital event was OCP protected if pills were used on both the day of the coitus and the day preceding. Results There were 123 participants who reported at least some OCP use in 210 diary periods (average diary length = 75.5 days). Fifty-three participants categorized as stable users reported 87 diary periods: the average interval of consecutive OCP use in this group was 32.5 days. Among stable users, only 45% of coital events were associated with both OCP and condom use. Over one-fifth of coital events in all groups were protected by no method of contraception. Conclusion Dual use of OCP and barrier contraception remains an elusive goal. The time during OCP adoption or discontinuation is often unprotected by condoms. However, concurrent missed pills and condom nonuse increase pregnancy and infection risk even among stable OCP users. Understanding motivation for method usage may improve education and prevention techniques. PMID:16919800
Sabers, Anne; Christensen, Jacob
The effect on clearance of levetiracetam (LEV) was estimated in women with epilepsy of childbearing potential using oral contraceptives (OCs). The estimated clearance (plasma concentration/daily dose) was 39 nmol/L/mg (range 14-88 nmol/L/mg) among women who did not use OC (n=30) and 38 nmol/L/mg (range 18-103 nmol/L/mg) among OC users (n=23) (p=0.8). In conclusion, combing LEV and OCs seems safe from a pharmacokinetic perspective.
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.
Satoh, P S; Fleming, W E; Johnston, K A; Ozmun, J M
On the assumption that the number of E-rosettable lymphocytes (active T lymphocytes) is an index of cell-mediated immunity, rosette assays were performed at early cycle and at midcycle for 6 women taking oral contraceptives (OCs) for 1-4 years. OC subjects at midcycle had 21.4% active rosette-forming lymphocytes as compared with 14.1% in controls (p less than .05). The 2 youngest subjects had higher values during the early cycle. These results imply the possibility of hormonal regulation of human T-cell activity.
Gardyn, J; Mittelman, M; Zlotnik, J; Sela, B A; Cohen, A M
Serum vitamin B(12) radioimmunoassays may give falsely low results in patients with folate deficiency, multiple myeloma, megadose of vitamin C and following radioisotope organ scan. We evaluated 10 consecutive healthy women on oral contraceptives (OC) who had falsely low vitamin B(12) levels, as reflected by normal urine methylmalonic acid and plasma homocysteine. After 1-month cessation of OCs, vitamin B(12) returned to the normal range in all women. Transcobalamin I (TCI) blood level was decreased in 60% of patients. OCs may cause temporary low vitamin B(12) blood levels of no clinical significance that can be associated with low TCI levels
Combined hormonal contraceptives [combined oral contraceptives (COCs)] have been available for over 50 years and the impact of this invention may not be overestimated. Today over 100 million women are current users and in Western Europe and the United States approximately 80% of women of fertile ages can be considered as ever-users. Over the years several drawbacks have been identified and media alarms on risks are frequently presented, resulting in suboptimal compliance and low compliance and continuation rates. Poor compliance and discontinuation is a big problem and is not generally identified by prescribers. During ideal use COCs offer very good protection against unwanted pregnancies, however there is a big problem with compliance and continuation and thus the ‘real-life’ efficacy is much lower. Reasons for poor compliance include side effects and fear of side effects and it is crucial that the prescriber gives the individual woman thorough and balanced information on the benefits and risks. Most well known is the increased risk of venous thromboembolism, but also an elevated risk of arterial thrombosis and several types of cancer has been reported. The risk estimates are low but according to the large number of users a substantial number of extra cases will occur. However, use of COCs also offers several additional health benefits with significant impact on morbidity and quality of life. COC use is associated with a substantial decrease in the risk of ovarian cancer, endometrial cancer and colorectal cancer. Moreover, COCs are a major option of treatment for women suffering from heavy menstrual bleeding and dysmenorrhea as well as hirsutism and acne vulgaris. The net effect of the additional health effects of COC- use may very well be positive, i.e. a slight increase in life expectancy. PMID:25360241
Heijboer, Annemieke C; Zimmerman, Yvette; de Boer, Theo; Coelingh Bennink, Herjan; Blankenstein, Marinus A
Total testosterone is considered to be decreased during the use of combined oral contraceptives. There is, however, considerable concern about the quality of testosterone assays, especially at low levels. We aimed to confirm testosterone levels measured by direct radioimmunoassay in a recent clinical trial with a state-of-the-art LC-MSMS method. Surplus specimens with known testosterone levels collected during the study (Clinical Trial Registration number ISRCTN06414473) were reanalyzed with an LC-MSMS method. This method was compared to another LC-MSMS method that had shown to concur excellently to a reference method. Follow-up experiments were designed to explain the results. In contrast to our expectation, LC-MSMS measurements did not corroborate the data obtained by radioimmunoassay. Subsequent experiments showed that this could be attributed to a strong dependency of the radioimmunoassay on SHBG. Testosterone results (n = 198) obtained by direct radioimmunoassay showed a negative correlation to SHBG levels (r = -0.676; p<0.001). By contrast, testosterone results obtained by LC-MSMS were not related to SHBG (r = 0.100; NS). In conclusion, our results indicate that total testosterone measurements during oral contraceptive use are unreliable when performed with assays sensitive to the SHBG concentration. The discrepancy with the literature can most likely be explained by the sensitivity of the immunoassay used to SHBG. Given the sharp increase in SHBG during the use of many oral contraceptives, total testosterone may not decrease, whereas its bioavailability, estimated by free testosterone levels, will be diminished. Studies aiming at restoration of testosterone homeostasis during oral contraception need to take this into account.
Cheslack-Postava, Keely; Keyes, Katherine M.; Lowe, Sarah R.; Koenen, Karestan C.
Purpose Examine the association between oral contraceptive use (any current use, duration and type) and major depression disorder (MDD), generalized anxiety disorder (GAD), and panic disorder (PD) in a nationally representative sample of women in the United States. Methods 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 sub-threshold 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. Results Women using oral contraceptives had a lower past-year prevalence of all disorders assessed, other than sub-threshold MDD. When adjusted for confounders, women using oral contraceptives in the past year had significantly lower odds of sub-threshold PD, compared to former users (OR=0.34, 95% C.I. 0.14–0.84). Effects estimates were strongest for monophasic (versus multiphasic) oral contraceptive users. Conclusions 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. PMID:25113319
Naz, F; Jyoti, S; Akhtar, N; Afzal, M; Siddique, Y H
Oral contraceptives (OCs) are the most popular type of birth control pills. The study was designed to examine the biochemical changes which occur due to the use of oral contraceptive pills (OCs). The study was based on the questionnaire for having the information of any reproductive history fasting, age, health, nature of menstrual cycle, bleeding, disease etc and blood profiling for biochemical analysis of the women includes high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG). Lipid profiling was carried out by using a commercially available diagnostic test kits. SPSS was used to analyze the data. The results showed statistically significant differences among users of OCs compared to non-users. Total cholesterol (242.92 +/- 2.842 mg dL(-1)), HDL-C (58.65 +/- 1.098 mg dL(-1)), LDL-C (115.84 +/- 1.266 mg dL(-1)) and triglycerides (105.56 +/- 2.341 mg dL(-1)) were significantly higher compared to the non-users (Total cholesterol 218.49 +/- 1.762, HDL-C 48.17 +/- 0.543, LDL-C 100.321 +/- 0.951 and triglycerides 83.77 +/- 2.299 mg dL(-1)). The result suggests that OCs increase the level of high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG).
Sirakov, M; Tomova, E
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).
Jacobsen, Lisbeth V; Vouis, Jan; Hindsberger, Charlotte; Zdravkovic, Milan
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.
Micks, Elizabeth; Jensen, Jeffrey T
Estradiol valerate and dienogest have been combined to create a novel four-phasic oral contraceptive pill effective for both pregnancy prevention and treatment of heavy menstrual bleeding. This formulation represents the only oral contraceptive pill available in the USA containing an estrogen component that is biologically active as the endogenous estrogen 17β-estradiol. This medication was developed out of efforts to replace the most common estrogen in contraceptive pills, ethinyl estradiol, which is known to be a potent inducer of hepatic protein synthesis. Estradiol valerate has been available since the 1970s in oral and injectable forms indicated for the treatment of menopausal climacteric symptoms. Dienogest has been used in other oral contraceptive pills for over 10 years. Previous attempts to develop an oral contraceptive pill with natural estradiol or estradiol valerate were unsuccessful due to poor cycle control. A novel dynamic-dosing regimen was devised to improve the bleeding pattern. This medication has been shown in several clinical trials to have good contraceptive efficacy and cycle control. Recent studies have also demonstrated that this medication is effective for the treatment of heavy menstrual bleeding. However, compared with other oral contraceptive pills, this medication is associated with a higher frequency of absent withdrawal bleeding. Furthermore, the dynamic dosing regimen requires relatively complex instructions for users who miss pills.
This review of the general effects of oral contraceptives includes mode of action, criteria for severity of side effects, discussion of the most important side effects, and possible drug interactions; each topic is outlined in tables. Pills work by inhibiting ovulation, altering cervical mucus, and suppressing the endometrium. Criteria for severity of side effects are 1) increased incidence in the population, 2) change in the woman's current or future life bearing on her health or 3) that of her offspring, and 4) irreversible changes. Accordingly, the most important probelms are amenorrhea or "oversuppression syndrome," more common in nulliparas and those taking depot contraceptives; abortion due to severe malformation of the embryo within 6 months of stopping the pill; hyperplasia of the cervix or breast fibrosis; and thromboembolism, particularly postoperative. Tables for choosing the type of pill to suit the patient, brands available in Canada, and doses, are provided. Drug interations may involve modification of absorption, augmentation of hormone-protein linkage, and changes in liver metabolism.
Effects of a combined oral contraceptive containing oestradiol valerate/dienogest on hormone withdrawal-associated symptoms: results from the multicentre, randomised, double-blind, active-controlled HARMONY II study.
Macìas, G; Merki-Feld, G S; Parke, S; Mellinger, U; Serrani, M
The objective of this multicentre, randomised, double-blind study was to compare a combined oral contraceptive (COC) containing oestradiol valerate/dienogest (E2V/DNG) administered in a dynamic dosing regimen with a monophasic COC containing ethinyloestradiol/levonorgestrel (EE/LNG), with regard to their ability to reduce the frequency and intensity of headache and pelvic pain in women with hormone withdrawal-associated symptoms (HWAS). Women aged 18-50 years received E2V/DNG in an oestrogen step-down and progestin step-up regimen (26/2 regimen; n = 223) or EE 20 μg/LNG 100 μg (21/7 regimen; n = 218) over six cycles. Headache and pelvic pain were assessed using a visual analogue scale (VAS) during cycle days 22-28. Rescue medication use was also assessed. E2V/DNG was superior to EE/LNG with regard to reducing the frequency and intensity of headache and pelvic pain from baseline to cycle 6 (change from baseline in the average of the three highest VAS values [mean ± standard deviation]: 47.7 ± 29.4 vs 34.5 ± 25.7 mm, respectively; p < 0.0001). The use of rescue medication was also significantly reduced with E2V/DNG compared with EE/LNG (p < 0.05). E2V/DNG may be a good option for women who experience HWAS with traditional 21/7-day regimen COCs.
Gimes, G; Valent, S
In order to reduce the side-effects (blood-lipid alterations, androgen effects etc.) new gestogens were introduced, while the ethinyl-estradiol component of the pill was unchanged. Authors report about clinical trial on monophasic oral contraceptive containing 0.030 mg ethinyl-estradiol and 0.075 mg gestodene. In a follow up of 92 women, in 1740 cycles no pregnancy and no cardivascular or thromboembolic complication was observed. The frequency of bleeding disorders was below 10% already in the first cycle. The quantity of withdrawal bleeding, as well the frequency of breakthrough bleeding and spotting decreased during the treatment. Significant alteration in body weight or blood pressure did not occur. Femoden containing third generation gestogen has an excellent cycle control and good patient compliance.
Rantanen, Kirsi; Tatlisumak, Turgut
Stroke is a devastating disease affecting millions of people worldwide every year. Female stroke victims have higher mortality rates and they do not re-cover as well as men. Women's longevity and different vascular risk factor burden like a larger prevalence of atrial fibrillation play a role. Women also have unique risk factors such as oral contraception, pregnancy, estrogen decrease after the menopause and hormone replacement therapy, which should all be evaluated and taken into consideration in treatment decisions both in the acute phase of stroke and in secondary prevention. In this review, the evidence regarding these hormonal aspects and the risk of stroke in women are evaluated. The relevant guidelines are studied and research gaps identified. Future topics for research are recommended and current treatment possibilities and their risks discussed.
Background Over 100 million women worldwide are using oral contraceptives pills (OCP) and mood changes were being as the primary reason for OCP discontinuation. The purpose of this study was to determine the prevalence and predicting factors of mood changes in oral contraceptive pills users. Methods This was a cross-sectional study of 500 women aged 15–49 years old using low dose (LD) pills attending family planning centers in Ahwaz, Iran. Data were collected via face-to-face interviews using a structured questionnaire including items on demographic, self-efficacy and mood change. Both univarate and multiple logistic regression analyses were performed to assess the relationship between reported mood change and the independent variables. Results In all 406 women reported that they did experience OCP side effects. Of these, 37.7% of women (n =153) reported mood changes due to OCP use. The results of multiple logistic regression revealed that place of living (OR =2.57, 95% CI = 1.06-6.20, p =0.03), not receiving information on OCP side effects (OR =1.80, 95% CI = 1.15-2.80, p =0.009), and lower self-efficacy (OR = 0.87, 95% CI = 0.80-0.94, p =0.001) were significant predictors of mood changes. Conclusion The findings from this study indicated that the prevalence of reported mood changes due to OCP use among Iranian women appeared to be consistent with other studies. In addition the findings showed that receiving information on OCP side effects from health care workers and self-efficacy were important predicting factors for mood changes. Indeed implementing educational programs and improving self-efficacy among women are recommended. PMID:24015872
Zahradnik, H P; Goldberg, J; Andreas, J O
The aim of this open, noncontrolled phase III study was the assessment of the contraceptive efficacy and the evaluation of the safety of long-term use of Belara (30 micrograms ethinyl estradiol plus 2 mg chlormadinone acetate). Furthermore, cycle stability during administration of Belara and the influence of Belara on acne and seborrhea as clinical signs of androgenization were observed. Belara was taken by 1655 women for a total of 22,337 cycles. For the theoretical Pearl index, a value of 0.269 (95% CI [0.109, 0.600]) was calculated. In 1655 of 22,337 cycles (7.4%), no withdrawal bleeding was documented, whereas in 2565 of 22,308 cycles (11.5%), spottings and, in 786 of 22,308 cycles (3.5%), breakthrough bleeding occurred. After the intake of Belara for 12 cycles, acne on the face/neck improved in 64.1% of the women (209 of 326). In 53.4% of the women (175 of 326), acne disappeared completely. Seborrhea improved after 12 cycles in 89 of 131 women (67.9%), of whom 76 women (58.0%) were completely cured. Sixty-two serious adverse events (SAE) occurred in 59 of 1655 women. Accidents and injuries of the musculoskeletal system were the SAE with the highest incidence (0.66%). Two cases of deep venous thrombosis, one pulmonary embolism, and two cases of visual disturbances were observed. Only for the two cases of deep venous thrombosis could a relation to Belara be assumed. Of the adverse events commonly reported for oral contraceptives, headache was observed for the first time under study medication in 37.4%, nausea in 23.1%, breast tenderness in 21.7%, and vaginal discharge in 19.4% of the women. The frequency of adverse events decreased with longer duration of a drug consisting of intake of Belara. In conclusion, Belara can be described as an effective and safe oral contraceptive with marked antiandrogenic properties.
Schorer, A E; Gerrard, J M; White, J G; Krivit, W
The ability of platelet microsomes to generate platelet aggregating activity on addition of arachidonic acid was evaluated in women taking oral contraceptives and in controls taking no medication but matched for age, sex, and family history. Oral contraceptive users generated significantly more platelet aggregating activity per 100 ug of platelet microsomal protein than controls. Variation in generation of platelet aggregating activity during the menstrual cycle was also observed with highest activity during the third week. These studies show an altered balance of platelet prostaglandin and thromboxane synthesis in oral contraceptive users which may contribute to their increased incidence of thromboembolic phenomena.
Oh, M K; Feinstein, R A; Soileau, E J; Cloud, G A; Pass, R F
This study examines the relationship between oral contraceptive use and Chlamydia trachomatis cervical infection in women less than 19 years of age. The clinical and epidemiologic data of 73 (19.4% prevalence rate) girls with chlamydial infection were analyzed, with special attention given to contraceptive use. The findings were compared with data from 303 girls who were chlamydia negative to assess the relationship between oral contraceptive use and C. trachomatis infection. Use of an oral contraceptive for 6 months or longer was associated with chlamydial infection (p = 0.005; odds ratio = 2.41; 95% confidence interval 1.53-3.29). Oral contraceptive use was not associated with an increased rate of Neisseria gonorrhoeae or Trichomonas vaginalis infection. Association of oral contraceptive use with chlamydial infection remained significant after adjustments were made for confounding variables in a logistic regression process (p = 0.013). This study suggests that oral contraceptive use may promote chlamydial infection of the cervix or enhance the detection of the C. trachomatis from the cervix in this population.
Corrêa, Daniele Aparecida Silva; Felisbino-Mendes, Mariana Santos; Mendes, Mayara Santos; Malta, Deborah Carvalho; Velasquez-Melendez, Gustavo
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
Kalkhoff, R K
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.
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. PMID:25688096
Derman, R J
Although a prospective, longitudinal study on the long-term cardiovascular effects of oral contraceptives has yet to be performed, available data are useful in determining a safe course of action while physicians await definitive answers. Exogenous sex steroids produce important effects on lipid metabolism. Early intervention against cholesterol is important in reducing cardiovascular risk. Current users of high-dose formulations, particularly older women who smoke, are at greatest risk for cardiovascular complications, especially myocardial infarction. Low-dose oral contraceptives have more modest effects on lipid metabolism, but important differences in the potency of progestins remain. Fortunately, recent studies among users of lower-dose oral contraceptive formulations fail to show an increase in cardiovascular morbidity and mortality. Nonetheless, prudent physicians will avoid oral contraceptives that may adversely affect lipoprotein metabolism, such as those containing progestins with high androgenic and antiestrogenic potency.
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.
Bennell, K.; White, S.; Crossley, K.
OBJECTIVES: To determine the effects of the oral contraceptive pill (OCP) on skeletal health, soft tissue injury, and performance in female athletes. METHODS: A literature review was performed using literature retrieval methods to locate relevant studies. RESULTS: Most female athletes primarily choose to use the OCP for contraceptive purposes, but cycle manipulation and control of premenstrual symptoms are secondary advantages of its use. The effect of the OCP on bone density in normally menstruating women is unclear, with some studies reporting no effect, others a positive effect, and some even a negative effect. The OCP is often prescribed for the treatment of menstrual disturbances in female athletes, and improvements in bone density may result. Whether the OCP influences the risk of stress fracture and soft tissue injuries is not clear from research to date. Effects of the OCP on performance are particularly relevant for elite sportswomen. Although a reduction in Vo2MAX has been reported in some studies, this may not necessarily translate to impaired performance in the field. Moreover, some studies claim that the OCP may well enhance performance by reducing premenstrual symptoms and menstrual blood loss. A fear of weight gain with the use of the OCP is not well founded, as population studies report no effect on weight, particularly with the lower dose pills currently available. CONCLUSIONS: Overall, the advantages of the pill for sportswomen would appear to outweigh any potential disadvantages. Nevertheless, there is individual variation in response to the OCP and these should be taken into account and monitored in the clinical situation. Women should be counselled as to the range of potential benefits and disadvantages in order to make an informed decision based on individual circumstances. PMID:10450476
Gaspard, U; Lambotte, R
A brief review of the literature is the basis for this discussion of residual effects of oral contraceptives (OCs) on fertility and the quality of ovulation after pill use is terminated. A 1982 study of the delay to conception attempted to avoid methological difficulties of earlier studies by comparing previous contraceptive usage among 7000 women hospitalized for childbirth. The analysis showed that the monthly percentage of pregnancies after OC use was significantly decreased for the 1st 3 months compared to levels in former IUD and diaphragm users. 13 months after OCs, 24.8% of OC users still had not conceived, compared to 12.4% if IUD and 8.5% of diaphragm users. Post-pill amenorrhea of longer than 6 months occurs in about 1% of cases. It is now agreed that post-pill amenorrhea is rare, nonspecific, and of multifactorial etiology. The previous existence of menstrual irregularity, stress, psychological troubles, malnutrition, and anorexia are particularly significant. OC use seems to mask the natural occurrence of secondary amenorrhea rather than to cause it. The most careful of available studies document that, although OC use may because of its estrogen content reveal an unsuspected prolactinemia, there is no increase in prolactinemia among OC users. A consensus exists that, excluding patients developing amenorrhea due to ovarian insufficiency, post-pill amenorrhea responds to ovulation inducing treatment exactly as do amenorrheas with no history of pill use. In cases of conception after failure of OCs and continued treatment with OCs, the aging of sperm or hypermaturation of ova at the time of fertilization is accompanied by a very slight increase in the proportion of male fetuses. The teratogenic risk appears to be negligable among former OC users and perhaps slightly greater if OCs, hormonal tests, or supplementary hormonal therapy are continued during pregnancy. The increased risk is not even seen in many studies and does not appear to indicate pregnancy
Amory, John K; Kalhorn, Thomas F; Page, Stephanie T
Oral administration of testosterone enanthate (TE) and dutasteride increases serum testosterone and might be useful for male hormonal contraception. To ascertain the contraceptive potential of oral TE and dutasteride by determining the degree of gonadotropin suppression mediated by 4 weeks of oral TE plus dutasteride, 20 healthy young men were randomly assigned to 4 weeks of either 400 mg oral TE twice daily or 800 mg oral TE once daily in a double-blinded, controlled fashion at a single site. All men received 0.5 mg dutasteride daily. Blood for measurement of serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, dihydrotesterone (DHT), and estradiol was obtained prior to treatment, weekly during treatment, and 1, 2, 4, 8, 12, 13, 14, 16, 20, and 24 hours after the morning dose on the last day of treatment. FSH was significantly suppressed throughout treatment with 800 mg TE once daily and after 4 weeks of treatment with 400 mg TE twice daily. LH was significantly suppressed after 2 weeks of treatment with 800 mg TE, but not with 400 mg TE. Serum DHT was suppressed and serum estradiol increased during treatment in both groups. High-density lipoprotein cholesterol was suppresed during treatment, but liver function tests, hematocrit, creatinine, mood, and sexual function were unaffected. The administration of 800 mg oral TE daily combined with dutasteride for 28 days significantly suppresses gonadotropins without untoward side effects and might have utility as part of a male hormonal contraceptive regimen.
Mårdh, P A; Hogg, B
Tubal factor infertility is often diagnosed without any documented history of pelvic inflammatory disease. Chlamydial infection is one of the most common causes of pelvic inflammatory disease and likely also of infertility and ectopic pregnancy. Oral contraceptives may alter the course of chlamydial infections which may mask the clinical expression of the disease. This paper considers a number of unresolved matters related to oral contraceptive use and its possible influence on the epidemiology and course of chlamydial pelvic inflammatory disease.
Baerwald, Angela R.; Pierson, Roger A.
Over the past 40 years, alterations to the composition of oral contraceptives (OCs) have been made in attempts to reduce adverse effects and to improve patient compliance while maintaining contraceptive efficacy. However, there is growing evidence to indicate that reducing the estrogen dose to minimize adverse effects may have compromised the degree of hypothalamo-pituitary-ovarian suppression, particularly during the hormone-free interval (HFI) or following missed doses. Follicle development during OC use appears to occur in association with a loss of endocrine suppression during the HFI. This information provides a rationale for reducing or eliminating the HFI in OC regimens. There is also evidence for an increased risk of follicle development and ovulation in women who use delayed OC initiation schemes, such as the “Sunday Start” method. It is not currently known why some follicles ovulate during OC use while others regress or form anovulatory follicle cysts. Continued research about follicle development during OC use would provide insight into understanding the precise mechanisms of action underlying combined OCs, as well as those of continuous OC formulations and emergency contraceptive regimens. PMID:14715122
Wilde, M I; Balfour, J A
The newer progestogens gestodene, desogestrel and norgestimate were developed in an attempt to produce agents with more selective progestational activity that would improve cycle control and minimise metabolic changes and adverse events while effectively preventing pregnancy. In clinical practice, gestodene is combined with ethinylestradiol in monophasic or triphasic combined oral contraceptive preparations. The drug has pharmacokinetic advantages over the other new progestogens in that it is active per se (the others are prodrugs) and has high bioavailability (approximately 100%). The ability of gestodene-containing oral contraceptives to inhibit ovulation is similar to that of preparations containing other progestogens although the required dosage is lower. In common with oral contraceptives containing desogestrel or norgestimate, and in contrast with those containing levonorgestrel, gestodene-containing preparations are associated with neutral or positive changes in lipid and carbohydrate metabolism. The effects of gestodene preparations on coagulation parameters, like those of desogestrel and levonorgestrel, are balanced by changes in the fibrinolytic system. Although the impact of these changes on clinical cardiovascular end-points has not been determined, the altered lipid profile is not likely to have significant clinical relevance because of the predominantly thrombogenic nature of cardiovascular disease in oral contraceptive users. Pregnancy rates and Pearl Indices with gestodene-containing preparations are low and similar to those with preparations containing other progestogens. Most pregnancies are attributable to user failure. Cycle control appears to be better with gestodene preparations than with levonorgestrel preparations, and available data suggest that cycle control may also be better with monophasic gestodene/ethinylestradiol than with monophasic desogestrel- or norgestimate-containing preparations, and better with triphasic gestodene- than with
Comparison of Drospirenone- with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders: A Prospective Randomized Control Trial
Wang, Qiu-Yi; Song, Yong; Huang, Wei; Xiao, Li; Wang, Qiu-Shi; Feng, Gui-Mei
Background: While combined oral contraceptives (COCs) are commonly used to treat polycystic ovary syndrome (PCOS), comparative data regarding metabolic effects of different progestogens on this patient population are missing. This study aimed to compare the different effects of drospirenone (DRP)-containing COCs with cyproterone acetate (CPA)-containing COCs, combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders. Methods: Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial. Participants were randomized into two groups such as DRP-containing COCs, and CPA-containing COCs. Participants took COCs cyclically for 6 months, combined with metformin administration (1.5 g/d) and lifestyle modifications (diet and exercise). Clinical measures and biochemical and hormone profiles were compared. Comparisons for continuous variables were evaluated with paired and unpaired Student's t-tests. The Wilcoxon signed rank test was used when the data were not normally distributed. Analysis of covariance was used to control for age, body mass index (BMI), and baseline data of each analyzed parameter when compared between the two groups. Results: A total of 68 patients have completed the study. The combination regimen of COCs, metformin, and lifestyle modifications in these patients resulted in a significant decrease in BMI, acne, and hirsutism scores when compared to baseline levels in both groups (P < 0.05). Blood pressure (BP) was significantly different in the CPA group when compared to baseline (75.14 ± 6.77 mmHg vs. 80.70 ± 5.60 mmHg, P < 0.01), and after 6 months of treatment, only the change in systolic BP was significantly different between the two groups (4.00 [–6.00, 13.00] mmHg vs. –3.50 [–13.00, 9.00] mmHg, P = 0.009). Fasting glucose, fasting insulin, and homeostasis model assessment-insulin resistance decreased significantly
Bakas, Panagiotis; Hassiakos, Dimitrios; Grigoriadis, Charalampos; Vlahos, Nikolaos F; Liapis, Angelos; Creatsas, George
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.
Aminzadeh, Atousa; Sabeti Sanat, Ali; Nik Akhtar, Saeed
Background 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. Objectives 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. Methods 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. Results 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). Conclusions 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. PMID:28184328
Washington, A E; Gove, S; Schachter, J; Sweet, R L
Management of pelvic inflammatory disease (PID) and decisions about contraception are being influenced by reports that oral contraceptives decrease the risk of PID. To evaluate the validity of this association, we have examined published epidemiologic evidence and reviewed relevant information from other disciplines. Current information does not permit the generalization that oral contraceptives protect against all forms of PID. Most studies conducted (1) have been limited to hospitalized women, who represent less than 25% of all PID cases and are likely to have relatively severe forms of the disease, and (2) have failed to distinguish between gonococcal and nongonococcal PID. While oral contraceptives may provide some protection against gonococcal PID, no basis exists for assuming similar protection is provided against chlamydial PID. In fact, epidemiologic and biologic evidence suggests that infection with Chlamydia trachomatis, the leading cause of nongonococcal PID, is enhanced by oral contraceptives. We judge the conclusion that oral contraceptives protect against all PID to be premature, and urge caution in its application in health policy and clinical decisions.
Allais, G; De Lorenzo, C; Mana, O; Benedetto, C
Oral contraceptives (OCs) are a safe and highly effective method of birth control, but can also be associated with some risks, mainly a potential thrombotic risk. OCs may condition the course of headache and sometimes start it, but their influence on the clinical evolution of migraine is not easily assessable. The last Classification of Headache Disorders of the International Headache Society clearly identifies an "exogenous hormone-induced headache" that could be triggered by intake of OCs. Old high-dose OCs could effectively worsen headache in a significant proportion of patients, but the newest formulations influence headache course to a lesser extent. In any case, while an increase in migraine frequency or intensity do not oblige the cessation of OCs, experiencing a migraine aura for the first time, or even a clear worsening of a preexistent aura suggest discontinuation of OCs. Even if both migraine and OCs intake are associated with an increased risk of ischaemic stroke, migraine per se is not a contraindication for OCs use; however, patients suffering from migraine with aura generally show a greater thrombotic risk than women with migraine without aura. Other risk factors (patient's age, tobacco use, hypertension, hyperlipidaemia, obesity and diabetes) must be carefully considered when prescribing OCs in migraine patients. Furthermore, all OCs, even those with low oestrogen content, are a major risk for venous thrombosis, particularly in women with hereditary thrombophilia. A thorough laboratory control of the genetics of prothrombotic factors and coagulative parameters should precede any decision of OCs prescription in migraine patients.
Lassi, Zohra S; Bhutta, Zulfiqar A
Folate is a generic term for a water-soluble B-complex vitamin which plays an important role in protein synthesis and metabolism and other processes related to cell multiplication and tissue growth. Pregnant and lactating women are at increased risk of folic acid deficiency because generally their dietary folate is insufficient to meet their physiological requirements and the metabolic demands of the growing fetus. The evidence pertaining to the reduction of the risk of neural tube defects (NTDs) due to folate is so compelling that supplementation with 400 μg of folic acid to all women trying to conceive until 12 weeks of pregnancy has been recommended by every relevant authority. A recent Cochrane review has also found protective effects of folate supplementation in occurrence and reoccurrence of NTDs. Despite food fortification and targeted public health campaigns promoting folic acid supplementation, 4,300,000 new cases occur each year worldwide resulting in an estimated 41,000 deaths and 2.3 million disability-adjusted life years (DALYS). This article will review the burden and risk factors of NTDS, and the role of folate in preventing NTDs. It will also describe different modes of supplementing folate and the newer evidence of the effectiveness of adding folate in oral contraceptives for raising serum and red blood cell folate levels. PMID:22570577
Mitra, P K; Roychadhuri, J
A low dose oral contraceptive (OC) containing 0.3 mg norgestrel and 0.03 mg ethinyl estradiol was given for conception control in 10 cases, for dysfunction and uterine bleeding (DUB) in 10 cases, for dysmenorrhea in 5 cases, and for endometriosis in 5 cases. Prior to treatment and subsequently the endometrium was studied by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Post therapeutic TEM indicated marked shrinkage of mitochondria, subnuclear lipid deposition, and loss of nuclear nests in the conception control and dysmenorrhea groups. In the DUB group the epithelial cells and mitochondria became stunted, Golgi-complexes developed, lysosomes appeared, and lipid deposition took place. Significant epithelial and stromal changes also occurred in the endometriosis group with increased of intracellular lipid and hugh enlargement of cell size without abnormal structural alteration. SEM showed stunted isolated cilia, small openings at cell apices, and clear-cut gland openings in the conception control and dysmenorrhea groups. In the DUB group rounded shrunken epithelium with scanty ciliation and prominent microvilli, whereas in the endometriosis group after 6 months total epithelial regression and atrophy was evident. OC therapy may help prevent endometrial carcinoma by inducing regression of subcellular organelles.
Berg, G; Kohlmeier, L; Brenner, H
High serum copper concentration--a well-known effect of oral contraceptive (OC) use--has been linked to increased mortality from cardiovascular disease. The influence of OCs containing newer progestins has not been investigated, however. This concern was addressed in a 1987-88 cross-sectional epidemiologic study of 610 nonpregnant, nonlactating West German women 18-44 years of age. 195 women (32.1%) were current OC users, but only 152 of these women were able to cite the name of the formulation they were taking. In 70% of cases, the OC contained less than 45 mcg of ethylestradiol (median dose, 32.4 mcg). The most common progestin components were desogestrel (41%) and levonorgestrel (30%). Mean serum copper concentration was higher among users of all types of OCs than among non-users, but this concentration varied more strongly according to the OC's progestin compound than its estrogen content. The greatest increase in serum copper (55% compared with non-users) was recorded in users of OCs containing anti-androgen progestins, followed by desogestrel (46%), norethisterone/lynestrenol (42%), and levonorgestrel (34%). The increase in serum copper was more pronounced in women taking OCs containing 45 mcg or less of ethylestradiol than in users of OCs with a high estrogen dose. In the regression models, the different progestin compounds alone explained 28% of the total variance in serum copper concentration. Further investigation of OC-induced increases in serum copper concentration and their impact on cardiovascular risk are warranted.
Roe, D A; Bogusz, S; Sheu, J; McCormick, D B
Riboflavin depletion has been identified in women on oral contraceptives (OC) but change in riboflavin nutriture has not been consistently demonstrated in all OC user groups studied. Discrepant findings in reports have been attributed to differences of pill formulation or riboflavin intake. Aims of this study were to compare the riboflavin requirements of healthy OC users and nonusers on diets prepared in a metabolic unit. A single daily menu and meal pattern was used. The basic diet providing riboflavin at a level of 0.6 mg/1000 kcal was used in the period of acclimation and period 1. In periods 2 and 3, the riboflavin content of the diet was increased to 0.8 and 1.0 mg/1000 kcal, respectively. The riboflavin status of subjects was monitored by erythrocyte glutathione reductase assay and urinary riboflavin excretion. Eight women on OC and 10 nonusers participated. Erythrocyte glutathione reductase assay values and urinary riboflavin excretion showed intersubject and interperiod differences but no significant group differences (OC versus non-OC) in erythrocyte glutathione reductase values or in urinary riboflavin per g creatinine. It was concluded that when dietary intake is controlled, OC do not significantly influence riboflavin status. Riboflavin needs were related to energy requirements of the subjects.
Potts, M; Denny, C
The idea of making oral contraceptives available without prescription has a long history, and has been recently revived in the US and the UK. High dose oral contraceptives have generally been replaced by low dose formulations and, subsequently, most cardiovascular risks have been reduced and a protection against ovarian and uterine cancers has been consistently demonstrated. Oral contraceptive compliance, however, continues to be a problem, but there is no reason to assume that wise practice would be any more or less if oral contraceptives were available over-the-counter (OTC). Some countries have introduced alternatives to prescription-only oral contraceptives, whereby nurses, midwives, social workers and/or pharmacists are incorporated into the distribution process. This article concludes that the balance of risks and benefits is in favour of OTC access for oral contraceptives.
Jankowski, Catherine M; Ben-Ezra, Vic; Gozansky, Wendolyn S; Scheaffer, Suzanne E
Some of the effects of oral contraceptives (OCs) to alter glucoregulation may be ameliorated by exercise. To test this premise, the effects of acute aerobic exercise on postprandial glucose, insulin, and C-peptide responses (area under the curve [AUC]) were measured in 8 users of low-dose estrogen and progestin OCs (OC(+)) and 10 women not using OCs (OC(-)). They completed 2 randomly ordered intervention trials: (1) aerobic exercise on 3 consecutive days with a 2.5-hour, 75-g oral glucose tolerance test (OGTT) on day 4, and (2) no exercise for 3 days prior to the OGTT (control trial). The exercise was 50 minutes of treadmill walking at 70% (.-)VO(2max). The groups were similar in age (27 +/- 3 years), waist-to-hip ratio (0.74 +/- 0.01), and cardiorespiratory fitness (32.5 +/- 1.6 mL x kg body mass(-1) x min(-1)). Fasting plasma glucose, C-peptide, and insulin levels were similar (P >.05) between groups in the control trial. In both trials, glucose(AUC) was significantly greater (13%, P <.05) in OC(+). Exercise resulted in a significant (P <.05) decrease in fasting plasma glucose and insulin, insulin(AUC), glucose(AUC) x insulin(AUC), and C-peptide(AUC) in both groups, suggesting enhanced insulin action and/or reduced pancreatic insulin secretion. Hepatic insulin extraction ([C-peptide(AUC) - insulin(AUC)())]/C-peptide(AUC)) was increased following exercise only in OC(+). Thus, insulin action was enhanced in response to exercise in young sedentary women independent of OC use. The mechanisms for the acute exercise effect on insulin action may be different in OC users compared with normally menstruating women.
Luna, B G; Scavone, J M; Greenblatt, D J
Thirteen women chronically using low-dose estrogen-containing oral contraceptives (50 micrograms or less of ethinyl estradiol or its equivalent for a minimum of 3 months) and 12 age-matched drug-free control women received a single 25 mg oral dose of doxylamine succinate in the fasting state. Ten women taking oral contraceptives and ten controls received a single 50 mg oral dose of diphenhydramine hydrochloride. Multiple plasma samples drawn during 30 hours following the dose of doxylamine, and 12 hours after diphenhydramine dosage, were analyzed by gas chromatography using nitrogen-phosphorus detection. Mean pharmacokinetic variables for doxylamine in control and oral contraceptive groups were: peak plasma concentration, 103 vs 100 ng/ml; time of peak, 2.40 vs 1.87 hours after dosage, elimination half-life, 10.1 vs 10.2 hours; and total clearance, 3.70 vs 3.88 ml/min/kg. Mean pharmacokinetic variables for diphenhydramine in control and oral contraceptive groups were: peak plasma concentration, 63.7 vs 73.8 ng/ml; time of peak, 2.7 vs 2.2 hours after dosage; elimination half-life, 6.0 vs 5.1 hours; and total clearance, 21.8 vs 25.5 ml/min/kg. None of these differences were statistically significant. Thus, low-dose estrogen-containing oral contraceptives do not significantly influence the pharmacokinetics of the antihistamines doxylamine or diphenhydramine.
The efficacy, cycle control, subjective complaints, and safety of monophasic preparations of the oral contraceptives containing gestodene 75 mcg plus ethinyl estradiol 30 mcg versus desogestrel 150 mcg plus ethinyl estradiol 30 mcg were compared in a 6-cycle, open-label, parallel, randomized, multicenter phase IV clinical study in Latin America. Of a total of 176 women in each group, 163 in the gestodene group and 160 in the desogestrel group completed 6 cycles, providing data for 1,015 and 1,006 cycles, respectively. Subject compliance was excellent; pills were missed during only 6.9% of the cycles in each group. No woman became pregnant during the study. Gestodene group exhibited significantly better cycle control as evidenced by the lower incidence of breakthrough bleeding and spotting. Spotting in some cycles was reported by 11.9% of women taking the gestodene-combination compared with 21% of women taking the desogestrel-combination. Based on number of women, 86.4% of the gestodene group reported all cycles were normal (no BTB) compared with 76.7% of the desogestrel group. Also, the women in the gestodene group reported a significantly lower incidence of nuisance side effects during treatment cycles. No amenorrhea was observed for either group. There were no clinically significant differences between groups with respect to body weight, blood pressure, or laboratory evaluations. Seven women withdrew from the gestodene group and 8 women withdrew from the desogestrel group because of adverse reactions. The results of this study indicate that, although both OCs provided effective contraception, in comparison to the desogestrel-combination, the gestodene-containing OC is associated with better cycle control, less bleeding, and fewer subjective complaints.
Delmore, T; Kalagian, W F; Loewen, I R
Clients in birth control centers (St. Catharines, Niagara Falls, and Welland) in Ontario, Canada were profiled in 1989; factors affecting compliance with the use of oral contraceptives (OCs) were investigated. Compliance was assessed for those 16 years and after 3 months of OC use. A control group and 2 study groups were randomly formed. 1 group was told about a follow up telephone call if the 3-month checkup appointment was not kept and the other not told. Compliance was determined by keeping the follow-up appointment and taking the pill as directed. Self-administered questionnaires were obtained at the 1st appointment and the 2nd study group was interviewed at the 3-month appointment time. Of the 334 intake interviews, 28.4% were adolescents 16 years old. Information on birth control came most frequently from friends (78.7%; then high school classmates, 61.4% grade school classmates, 61.4%; and family, 38.0%). 94.3% had a boyfriend, primarily a steady one. 82.4% were sexually active before the Center visit. 21.3% had had sex when 15 years old. 9.2% of those sexually active had never used birth control. 85.2% of those using contraception had used a condom at least once, and 33.9% used withdrawal. In the preceding month, birth control was used 60% of the time. 46% of mothers and 25% of fathers were considered supportive of birth control. 228 16 years participated in the compliance study. The 2 study groups and the control group were not significantly different in their compliance. The only statistically significant predictor of compliance (from the intake interview) was the previous use of the condom. Those more likely to be compliant were the 10.9% sexually active who had never used a condom. Continuing with the family doctor, not sexually active, advice to stop, side effects concerns, and remembering to take the pill were the most common reasons for noncompliance. The implication for health and sex education is that emphasis needs to the placed on the risks taken
Raine-Bennett, Tina; Merchant, Maqdooda; Sinclair, Fiona; Lee, Justine W.; Goler, Nancy
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
Bond, A M; Heritage, I D; Briggs, M H
Reversed-phase high-performance liquid chromatography with UV detection is studied for the determination of both progestogenic and oestrogenic components of oral contraceptive formulations. The applicability of the assay is demonstrated for a number of different progestogen-oestrogen combinations in both conventional tablet and novel "paper" formulations. The results show that the method developed is a versatile technique for the routine assay of these pharmaceutical formulations.
Limberg, Jacqueline K.; Peltonen, Garrett L.; Johansson, Rebecca E.; Harrell, John W.; Kellawan, Jeremy M.; Eldridge, Marlowe W.; Sebranek, Joshua J.; Walker, Benjamin J.; Schrage, William G.
Background: β-adrenergic receptors play an important role in mitigating the pressor effects of sympathetic nervous system activity in young women. Based on recent data showing oral contraceptive use in women abolishes the relationship between muscle sympathetic nervous system activity and blood pressure, we hypothesized forearm blood flow responses to a β-adrenergic receptor agonist would be greater in young women currently using oral contraceptives (OC+, n = 13) when compared to those not using oral contraceptives (OC–, n = 10). Methods: Women (18–35 years) were studied during the early follicular phase of the menstrual cycle (days 1–5) or placebo phase of oral contraceptive use. Forearm blood flow (FBF, Doppler ultrasound) and mean arterial blood pressure (MAP, brachial arterial catheter) were measured at baseline and during graded brachial artery infusion of the β-adrenergic receptor agonist, Isoproterenol (ISO), as well as Acetylcholine (ACH, endothelium-dependent vasodilation) and Nitroprusside (NTP, endothelium-independent vasodilation). Forearm vascular conductance was calculated (FVC = FBF/MAP, ml/min/100 mmHg) and the rise in FVC from baseline during infusion quantified vasodilation (ΔFVC = FVCinfusion − FVCbaseline). Results: ISO increased FVC in both groups (p < 0.01) and ISO-mediated ΔFVC was greater in OC+ compared to OC– (Main effect of group, p = 0.02). Expressing data as FVC and FBF resulted in similar conclusions. FVC responses to both ACH and NTP were also greater in OC+ compared to OC–. Conclusions: These data are the first to demonstrate greater β-adrenergic receptor-mediated vasodilation in the forearm of women currently using oral contraceptives (placebo phase) when compared to those not using oral contraceptives (early follicular phase), and suggest oral contraceptive use influences neurovascular control. PMID:27375493
Janowitz, B; Kane, T T; Arruda, J M; Covington, D L; Morris, L
Oral contraceptives have many advantages, but sometimes also have side effects which can cause users to switch appropriately or inappropriately to less effective methods or abandon contraception. In Brazil, 2/3 of married women of childbearing age were using contraception in 1981, and 1/2 of these were using orals. Contraceptive behavior following reported side effects in users of oral contraceptives in Southern Brazil is examined in this study, in relation to diverse factors. Among 2904 currently-married women, aged 15-44, almost 75% reported that they had used the pill at some time, and of these, 45.6% were still doing so. Data on perceived side effects were gathered for all women. There was no independent medical evaluation of the effects, so the data did not necessarily represent actual prevalence of pill related problems. Women who reported problems with the pill were less likely to be current users (25%) than women who did not (65%). However, overall contraceptive prevalence was about the same in both groups (66.2% and 67.0% respectively), indicating that women who stop using oral contraceptives usually switch to another method. However, they are more likely to be using traditional methods than women in the general population, especially if they want more children. Termination of pill use varies little according to the type of problem reported. Women with problems who sought medical attention were more likely to stop using the pill, and 82.4% of women advised to stop by their physician did so, but the major factor affecting discontinuation was the reported experience of a problem. The most frequently reported problems were headaches (38.1%), nausea (34.1%), nervousness (27.9%), and vertigo (18.3%). Physician intervention should help to avoid women's abandoning oral contraceptives unnecessarily.
Radius, S M; Joffe, A; Gall, M J
Although they provide birth control and are easier to use, oral contraceptives (OCPs) are not the preferred approach to preventing sexually transmitted disease (STD). Do the knowledge, attitudes, and experiences of oral contraceptive users place them at greater risk for STDs than those who employ barrier methods? This study examined differences between sexually active female college students (ie, those who reported ever having had vaginal intercourse) who used OCPs and those who employed barrier methods of contraception at the time of their most recent intercourse. The authors analyzed HIV- and other STD-related knowledge, attitudes, and behaviors from three consecutive annual health surveys of young women about to begin their first year of college. Findings showed barrier and OCP users to be comparable in knowledge about the effectiveness of various contraceptive methods in protecting them against STDs, perceived personal susceptibility to HIV, and experiences with alcohol before sexual intercourse. Oral contraceptive users, compared with those in the group who used barrier methods, reported a greater number of recent partners (p less than .03) and greater perceived vulnerability to STDs (p less than .03). Student healthcare providers must develop creative educational strategies to encourage simultaneous use of both oral contraceptives and barrier methods to protect students against STDs and pregnancy.
Bancroft, J; Sartorius, N
The extent to which the high discontinuation rate for oral contraceptives is due to adverse effects of mood, well-being and sexuality is explored, taking into account early studies on high dose combined and sequential pills, recent studies on low-dose combined and triphasics, experimental design factors, effects of OCs on free androgen levels, psychosocial factors and reasons for choosing or stopping pills, effects on depressive illness, premenstrual syndrome, sexuality, and possible mechanisms for direct effects of steroids on mood and sexuality. Study design is complicated by selection of early or late oral contraceptive users, types of controls, and unknown confounding factors such as reason for choice of pills, effect of a reliable contraceptive on the sexual relationship, prior history of depression and premenstrual tension. Furthermore virtually all topics reviewed here resulted in inconsistent or contradictory findings, making a case for individual variation and subgroups of women with different responses regarding the end point being examined. Examples include whether progestogen alter female sexual desire or male attraction; and whether rising or falling free testosterone levels affect sexual response. Factors affecting experimental design include culture, language, life-cycle, type of relationship, personal qualities affecting contraceptive choice, manner of eliciting reports of side effects, steroid dose, whether ovulation was blocked, initial or established pill-use, possibility of missed pills, and type of controls. Current pill users seem to discontinue for depression and low libido less frequently than did users of higher dose pills, and severity scores of adverse effects are lower. Premenstrual and other cyclic events may be altered in timing, and premenstrual symptoms are relieved in most women, but worsened in some who take pills. It is likely that women with depressive and premenstrual complaints tend to discontinue pills, leaving the remaining
Koster, T; Small, R A; Rosendaal, F R; Helmerhorst, F M
A meta-analysis of controlled studies between 1966 and 1993 was conducted by means of a Medline computer search. A total of 588 articles were reviewed for controlled studies. 1 randomized trial, 6 follow-up studies, and 8 case-control studies were included. Summary thrombosis risk for oral contraceptive users, number needed to discontinue oral contraceptives to prevent one (recurrent) thrombosis, comparison of additional unwanted pregnancies, and postpartum thrombosis between alternative birth-control methods were the main outcome measures. The studies proved highly heterogeneous with regard to size and direction of the risk estimate. The summary relative risk of first thrombosis during oral contraceptive use was 2.9 (95% CI 0.5-17). The reported risks were higher in case control (RR 4.2) than in follow-up studies (RR 2.1). Various hypothetical assumptions were advanced wherein women would continue to take oral contraceptives after a first episode of thrombosis, or switch to use of an IUD, condom, or the progestogen-only pill. The cost-benefit ratio of advising against the use of oral contraceptives after a first thrombosis varied tremendously. The outcome with regard to pregnancies and thrombosis in 5 hypothetical cohorts of 100,000 post-thrombotic women monitored for 1 year indicated that under all but the highest assumption for recurrence risk, among typical couples the number of unexpected pregnancies as well as thrombotic episodes would be highest among condom users. IUDs would result in a reduction of at least 30% in the number of venous thrombotic episodes and accidental pregnancies. The lowest expected failures rates would lead to a decrease in thrombosis for both IUD and condom use. These findings indicate that there is a lack of necessary data for recurrence risk of venous thrombosis during continuing use of oral contraceptives, or after switching to other modes of contraception.
Some clinicians claim that the potential association between oral contraceptive (OC) use and HIV infection is cause for concern. A study of prostitutes conducted in Kenya showed OC use to be the single most common cofactor in sexually transmitted human immunodeficiency virus infection. A similar study conducted in the US was unable to confirm an association. In the Kenya study, 123 HIV seronegative prostitutes in Nairobi were followed for 54 months and assessed for seroconversion to HIV and occurrence of sexually transmitted diseases. 91% of the women who seroconverted were using OCs; 73% of the women who remained seronegative were using OCs. Demographic features, sexual behavior, number of daily sex partners, and parenteral exposure were not related to seroconversion. No significant associations were found between HIV infection and sexual activity and condom use. Independent associations were found between seroconversion and OC use, genital ulcer disease (GUD), and chlamydia trachomatis infections. It is possible that OCs increase the risk of acquiring chlamydia because cervical ectropion creates a greater exposure of columnar epithelium to infecting agents. The multicenter, cross-sectional, collaborative study of 638 prostitutes in 8 areas of the US found that HIV infection was totally unrelated to OC use. Prostitutes with no evidence of intravenous drug use were studied. 5% of the women were found to be infected with HIV. The most common variables associated with HIV infection were seromarkers for hepatitis B and syphilis and sex with "nonpaying partners." About 80% of the prostitutes reported using condoms regularly with clients; only 16% used condoms with their boyfriends or husbands. About 30% (194) of the prostitutes reported they had used OCs for at least 1 month out of the past 5 years. 9 of those women (4.6%) were positive for HIV. Of 444 prostitutes who had never used OC during the past 5 years, 21 or 4.73% were HIV positive.
Hahn, Kristen A.; Hatch, Elizabeth E.; Rothman, Kenneth J.; Mikkelsen, Ellen M.; Brogly, Susan B.; Sørensen, Henrik T.; Riis, Anders H.; Wise, Lauren A.
Purpose To examine the association between pregravid oral contraceptive (OC) use and spontaneous abortion (SAB). Methods In an Internet-based preconception cohort study of 4,862 Danish pregnancy planners, we used Cox proportional hazards models to estimate adjusted hazard ratios (HR) and 95% confidence intervals (CI) for the association between OC use and SAB. We controlled for maternal age, physical activity, parity, education, alcohol and caffeine consumption, body mass index, and smoking. Results Compared with women who discontinued OCs >1 year before conception, HRs were 0.95 (95% CI: 0.77, 1.17), 0.99 (95% CI: 0.82, 1.19), and 0.80 (95% CI: 0.60, 1.06) for women who discontinued OCs 7-12, 2-6, and 0-1 months before conception, respectively. Compared with <4 years of OC use, HRs for 4-7, 8-11, and ≥12 years of OC use were 1.05 (95% CI: 0.80, 1.37), 0.92 (95% CI: 0.71, 1.19), and 0.88 (95% CI: 0.65, 1.19), respectively. Dose of estrogen and generation of progestin were not materially associated with SAB risk. Conclusions We found no evidence that pregravid OC use is associated with an increase in SAB. Use within one month of conception was associated with a slightly lower risk of SAB, but this may be due to increased reproductive fitness in women who conceive quickly after discontinuation of OCs. PMID:26452607
Berenson, Abbey B.; Rahman, Mahbubur; Wilkinson, Gregg
Objective To estimate the effects of using depot medroxyprogesterone acetate (DMPA) or oral contraceptives (OC) containing 20 micrograms ethinyl estradiol and 0.15 mg desogestrel on serum lipid levels. Methods Serum lipids were measured at baseline and every 6 months thereafter for 3 years on 703 white, black, and Hispanic women using DMPA, OC, or nonhormonal (NH) birth control. DMPA discontinuers were followed for up to 2 additional years. Participants completed questionnaires containing demographic and behavioral measures every 6 months and underwent 24 hour dietary recalls annually. Mixed model regression analyses and general estimating equations procedures were used to estimate changes over time in lipids by method, along with their predictors. Results OC users experienced significantly greater increases in levels of triglycerides (TG), total cholesterol (TC), very low density lipoprotein cholesterol (VLDL-C), and high density lipoprotein cholesterol (HDL-C) than NH users (P<.001). However, no difference was noted in the LDL-C to HDL-C ratio between OC and NH users. Among DMPA users, HDL-C levels initially decreased for 6 months, but then returned to baseline. The LDL-C to HDL-C ratio rose during the first 6 months of DMPA use, but then dropped back to baseline over the next 24 months. After DMPA was discontinued, women who used OC increased their TG, TC, VLDL-C, and HDL-C levels significantly more than those who chose NH (P< .05). Conclusion Use of very low dose OC containing desogestrel can elevate lipid levels. DMPA users were at increased risk of developing an abnormally low HDL-C level as well as an abnormally high LDL level and an increase in the LDL to HDL cholesterol ratio, although these effects appeared to be temporary. PMID:19888036
Crona, N; Silfverstolpe, G
A review of the research data concerning cardiovascular disease induced by oral contraceptives (OC) relies on the findings of 3 US and British prospective studies involving 80,000 women. Pill users under 35 who were nonsmokers had 1/4 of the risk of dying as a result of this use than of pregnancy complications (in smokers, the risk is the same). Acute pathogenetical effects include blood coagulation homeostasis leading to thromboembolism and long-term disorders of lipid and carbohydrate metabolism. The estrogen component of OCs, ethinyl estradiol (EE), tends to increase Very Low Density Lipoprotein (VLDL) and High Density Lipoprotein (HDL) levels while decreasing Low Density Lipoprotein (LDL) levels. The gestagen component, a nortestosterone derivative, acts in the opposite way. The estrogen component also increases the level of triglycerides in the VLDL fraction and in serum. There seems to be an inverse ratio between VLDL and HDL levels (gestagen-dominant OCs lower the HDL cholesterol level). The thromboembolitic side effects of estrogen led to the introduction of low-dose pills in the 1970s (acute pancreatitis, a severe side effect, has been all but eliminated). The cardiovascular complications and cerebral insult induced by the gestagen component, a 19-nortestosterone derivative, have also resulted in decreased doses of gestagens in OCs. Non-alkylated estrogens ("natural" estrogens) have been favored recently because they do not increase VLDL levels, while still increasing HDL. A 17-alpha-hydroxprogesterone derivative as the gestagen component of pills has been used in recent years, since it is inert in lipid metabolism, unlike 19-nortestosterone. The effect of exogenous sexual steriods on prostaglandin synethis and on the balance of thromboxanes and prostacyclines will require futher study.
Beltz, Adriene M; Hampson, Elizabeth; Berenbaum, Sheri A
This article is part of a Special Issue "Estradiol and cognition". Estrogens have been seen to play a role in human cognitive abilities, but questions remain about the cognitive impact of ethinyl estradiol, which is contained in many oral contraceptives (OCs). Inconsistencies in past studies likely reflect small samples and heterogeneous groups of OC users. The aims of the present work were to examine OC effects on sex-typed spatial and verbal abilities by (a) comparing mental rotations and expressional fluency in normally-cycling (NC) women and men to OC users considered as a heterogeneous group and then to homogeneous groups of OC users created by classifying pills according to their active constituents, and (b) determining the relation between synthetic hormone doses in OCs and mental rotations and expressional fluency. Participants were 136 men, 93 NC women, and 148 OC users, including homogeneous monophasic (n = 55) and triphasic (n = 43) OC groups, aged 18 to 30 years. Significant effects of OC use were seen in homogeneous group comparisons but not when OC users were considered as a heterogeneous group. On mental rotations, men outperformed women, and monophasic OC users outperformed NC women. The latter difference may be attributable to estradiol, as ethinyl estradiol was inversely related to spatial ability among OC users and was lower in monophasic than in triphasic users. On expressional fluency, NC women and monophasic OC users outperformed men, and monophasic users outperformed triphasic users. Thus, results show the importance of ethinyl estradiol and of considering pill constituents when studying the cognitive effects of OCs.
Pharmacokinetics of gestodene and ethinylestradiol in 14 women during three months of treatment with a new tri-step combination oral contraceptive: serum protein binding of gestodene and influence of treatment on free and total testosterone levels in the serum.
Kuhnz, W; Baumann, A; Staks, T; Dibbelt, L; Knuppen, R; Jütting, G
The pharmacokinetics of gestodene (GEST) and ethinylestradiol (EE2) were determined in 14 healthy women (age 18 to 32 years) during a treatment period of three months with a new tri-step combination oral contraceptive (Milvane). Prior to this treatment period, the same women received a single administration of a coated tablet containing 0.1 mg GEST together with 0.03 mg EE2. There was a wash-out phase of one week between both treatments. Following single dose administration, a mean terminal half-life of 18 h was observed for GEST. The total clearance was 0.9 ml x min-1 x kg-1 and the volume of distribution was 84 l. During a treatment cycle, GEST levels in the serum accumulated by a factor of 8 as compared to single dose administration. Steady-state drug levels were reached during the second half of each cycle. As compared to single dose administration, the following changes were observed for GEST at the end of treatment cycles one and three: prolonged terminal half-life (20 to 22 h), reduced total (0.16 ml x min-1 x kg-1) and free clearance (ca. 27 ml x min-1 x kg-1), reduced volume of distribution (ca. 18 l). A concomitant EE2-induced increase in the SHBG concentrations by a factor of three as compared to pretreatment values was observed during a treatment cycle and appeared to be mainly responsible for the changes in the pharmacokinetics of GEST. Marked changes were also seen for the serum protein binding of GEST. After single dose administration, the free fraction of GEST was 1.3% and the fractions bound to SHBG and albumin were 69.4% and 29.3%, respectively. At the end of cycle one, the free fraction was only 0.6% and the fractions bound to SHBG and albumin were 81.4% and 18.0%, respectively. There was no difference in corresponding pharmacokinetic parameters and in the serum protein binding of GEST at the end of cycles one and three. On the last day of treatment cycles one and three, the AUC(0-4h) values of EE2 were 299.2 and 278.1 pg x ml-1 x h, respectively
Brill, K; Schnitker, J; Albring, M
Oral contraception has proved to be the most efficient reversible method of fertility control for over 25 years. During this period, various investigations and epidemiological studies have suggested that some risks may be involved, but, on the other hand, a number of non-contraceptive benefits have become obvious. The results of these investigations were taken into account when new formulations had to be developed, with an aim to improving hormonal fertility control with regard to its tolerance, cycle control, and impact on metabolism. Since then, the objective of research has been to contrive new hormonal contraceptives which ensure safety to the largest possible extent, from a medical point of view, for the sake of the patient, without affecting contraceptive effectiveness. The aim to reduce side-effects connected with the use of oral contraception, as well as to lower the risks possibly involved, has obviously been achieved by extensive research. Both by devising a new substance and reducing doses, the criteria of modern low-dose oral contraception have been met, as has become evident in the course of the clinical experience gathered with Femovan.
Shahnazi, Mahnaz; Bayatipayan, Somaye; Khalili, Azizeh Farshbaf; Kochaksaraei, Fatemeh Ranjbar; Jafarabadi, Mohammad Asghari; Banoi, Kamala Gaza; Nahaee, Jila
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
Elaut, Els; Buysse, Ann; De Sutter, Petra; Gerris, Jan; De Cuypere, Griet; T'Sjoen, Guy
Findings on women's sexuality across the menstrual cycle are inconsistent. One relatively consistent finding is a midcycle and premenstrual peak in sexual desire in freely cycling women. Results on the cycle-related effects on sexual behavior are less clear. Large proportions of reproductive-aged women use combined oral contraception (COC), but studies on potential cycle-related shifts in sexual desire and behavior are sparse. A prospective diary study assessed sexual desire, sexual behavior, and mood in 89 heterosexual couples. Women were using one of four contraceptive methods: (1) nonhormonal contraception, (2) low-dose COC containing 20 mcg ethinylestradiol and 75 mcg gestoden or desogestrel, (3) COC containing 35 mcg ethinylestradiol and 2 mg cyproteronacetate, and (4) COC containing 30 mcg ethinylestradiol and 3 mg drospirenone. No cycle effects of sexual desire were established in the COC group, but frequency of sexual intercourse declined in the last days of active pill taking. These results were similar in both female and male partners. Negative affect did not covary with sexual desire.
Kinghorn, G R; Waugh, M A
One thousand eight non-pregnant women aged 16-34 years, presenting for the first time at a clinic for sexually transmitted diseases (STD), were examined and screened for infection with Chlamydia trachomatis, Neisseria gonorrhoeae, Trichomonas vaginalis, and Candida species. The respective prevalence rates were 21.1%, 20.7%, 13.4%, and 27.8%. Isolation rates for C trachomatis, either occurring alone or in association with other genital infections, were significantly greater in women using oral contraceptive agents. This was not because oral contraceptive users were more promiscuous. The findings strengthen the case for providing a routine chlamydial culture service for women attending STD clinics. They also indicate that the likelihood of chlamydial infection in women taking oral contraceptives is increased.
Baker, D A; Salvatore, W; Milch, P O
Several reports indicate an association between oral contraceptives and increased infection rates. One mechanism that could explain this increased infection rate is a decrease in immune function. A study comparing T cell subsets showed no differences in numbers between oral contraceptive users and controls. In this study, natural killer cell activity was compared in women before and 3 and 6 months after oral contraceptive use. There was a statistically significant decrease in NK cell activity after three months. There was no further decrease by six months and the differences were no longer significant due to greater variability. No infections were reported during the study period. Thus, the observed reduction in NK activity was either physiologically insignificant or the previously reported increase in infections may be the result of non-immunological factors.
Rabe, T; Leppien, G; Fossman, W G; Hessing, C; Vladescú, E; Runnebaum, B
The objective of the study was to investigate histological changes in the endometrium in 20 volunteers treated with a low-dose, gestodene-containing triphasic oral contraceptive. Endometrial biopsy specimens were taken before, during a 6-month period of oral contraceptive use and in a post-treatment period. These specimens were evaluated using light microscopy, scanning and transmission electron microscopy. In addition, ultrasound examinations of the uterus, endometrial thickness and ovaries were performed. The low-dose, gestodene-containing triphasic oral contraceptive had no adverse effects on the endometrium (e.g. no proliferation, no polyps, no inflammatory processes), was well tolerated and showed a low side-effect profile. The inhibition of endometrial transformation was demonstrated both by endometrial morphology as well as by endometrial thickness, as measured by transvaginal ultrasound examination.
Pace, Lydia E; Dusetzina, Stacie B; Keating, Nancy L
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.
Venous thromboembolism is well known as one of the rare but serious adverse effects of combined oral contraceptives (COCs). The COCs with third and fourth generation progestogens were found to have higher risk of venous thrombosis than those with second generation progestogens. We present a case of pulmonary embolism in a 23-year-old nulligravid woman who was using COCs containing the third generation progestogen (desogestrel). At the time of presentation of the adverse effect, she had been using the COCs for 4 months. She had no additional risk factors for thrombosis such as smoking, surgery, tumor as well as genetic factors. This case demonstrates even young women in otherwise good health may be at risk of venous thromboembolism from low-dose formulations of COCs as an over-the-counter drug. We describe this case with a brief review of literatures. PMID:28344968
Chen, Sarah P.; Massaro-Giordano, Giacomina; Pistilli, Maxwell; Schreiber, Courtney A.; Bunya, Vatinee Y.
Purpose To examine the relationship between oral contraceptive pill (OCP) use, contact lens wear, and dry eye signs and symptoms in healthy young females. Methods Fifty-two women using OCPs and forty-five women not using any form of hormonal contraception were enrolled. Medical, menstrual, and contact lens histories were obtained and dry eye symptoms were assessed using the Ocular Surface Disease Index (OSDI) and Symptom Assessment iN Dry Eye (SANDE) questionnaires. Tear osmolarity testing was performed using the TearLab™ Osmolarity System. Results Mean age of all subjects was 26.0 ± 3.7 years. There were no significant differences in any of the measurements between the follicular and luteal phases. While SANDE scores were significantly higher in subjects with OCP and recent contact lens use (p<0.01), there were no significant differences in OSDI and tear osmolarity amongst the same subject groups. Subjects who reported both OCP and recent contact lens use had significantly higher OSDI and SANDE scores (p=0.015 and p<0.001, respectively). Conclusions There were no differences between the phases of the menstrual cycle. Tear osmolarity was not affected by OCP or contact lens use in young females. However, the combination of OCP use and contact lens wear may increase the severity of dry eye symptoms. PMID:23086364
Torkzahrani, Shahnaz; Heidari, Afrooz; Mostafavi-pour, Zohreh; Ahmadi, Majid
Objective Combined oral contraceptives (COCs) have some adverse effects on the serum lipid profile. Because hyperlipidemia is one of the risk factors in cardiovascular diseases, lipid abnormalities should be evaluated in women consuming COCs. Vitamins E and C are known to have beneficial effects on serum lipid profiles. Therefore, in this study, we evaluated the effects of vitamins E and C on serum lipids in women using COCs. Methods The study compared changes in lipid parameters with and without vitamin therapy in women consuming COCs compared to those of a control group (40 non-contraceptive users or NCU) for 4 weeks. Total cholesterol and triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) levels along with HDL/LDL ratios were measured for all participants. Results COC users experienced significantly higher increases in the levels of triglycerides and LDL than non-users (p<0.05). However, no significant differences were noted in the total cholesterol and HDL levels. In the treated COC group receiving vitamins E and C, the HDL level and the HDL/LDL ratio increased and the LDL and triglycerides levels decreased significantly compared with those of the other groups. Conclusion The results of our study indicate that supplementation with antioxidant vitamins E and C restores a normal lipid profile in COC users. PMID:24693493
The pill - combination; Oral contraceptives - combination; OCP - combination; Contraception - combination; BCP - combination ... Birth control pills help keep you from getting pregnant. When taken daily, they are one of the most ...
Roberts, S Craig; Little, Anthony C; Burriss, Robert P; Cobey, Kelly D; Klapilová, Kateřina; Havlíček, Jan; Jones, Benedict C; DeBruine, Lisa; Petrie, Marion
Hormonal fluctuation across the menstrual cycle explains temporal variation in women's judgment of the attractiveness of members of the opposite sex. Use of hormonal contraceptives could therefore influence both initial partner choice and, if contraceptive use subsequently changes, intrapair dynamics. Associations between hormonal contraceptive use and relationship satisfaction may thus be best understood by considering whether current use is congruent with use when relationships formed, rather than by considering current use alone. In the study reported here, we tested this congruency hypothesis in a survey of 365 couples. Controlling for potential confounds (including relationship duration, age, parenthood, and income), we found that congruency in current and previous hormonal contraceptive use, but not current use alone, predicted women's sexual satisfaction with their partners. Congruency was not associated with women's nonsexual satisfaction or with the satisfaction of their male partners. Our results provide empirical support for the congruency hypothesis and suggest that women's sexual satisfaction is influenced by changes in partner preference associated with change in hormonal contraceptive use.
Norell, S E; Boethius, G; Persson, I
In studies where women are interviewed about oral contraceptive (OC) use only after the emergence of disease (e.g., breast cancer), the experience of disease may enhance recall and reporting of OC use, resulting in overestimation of relative risks. This community-based study compared two sources of information on ever-use of OCs--structured interviews and pharmacy prescription records--in 427 women 20-34 years of age who were long-term residents of Sweden's Jamtland County where registration of prescriptions has been virtually complete since 1970. A life-events calendar and photographs of OCs in use since 1970 were used in the interviews to facilitate recall. 153 women reported current OC use; the pharmacy register failed to document a current prescription for 37 (24%). Only 4 (1.5%) of the 274 women who denied current OC use had an active prescription on file. Of the 37 women identified as never-users by interview, 2 (5%) had records of OC prescriptions (for under 2 years of use). Of the 36 women identified as never-users by pharmacy records, only 1 reported ever-use. Compared to the pharmacy registry, 13% reported a shorter and 28% a longer duration of OC use. Of women who reported OC use within 5 years of interview, 5-10 years earlier, and more than 10 years ago, 2.6% (8/312), 4.6% (14/307), and 12.8% (26/203), respectively, had no prescriptions on file for that time period. Discrepancies between the two data sources in time since first OC use were usually less than 2 years; the tendency was for women to overestimate rather than understate the actual duration of OC use. These findings suggest that interview data on OC use introduce minimal--if any--bias. Agreement between interviews and records in terms of the specific brands of OCs taken was less satisfactory. 19% of users of high-dose OCs, for example, did not recall the type of pill dispensed by the pharmacy. Thus, use of pharmacy records is recommended over interview data in studies where the specific OC
Kotsopoulos, Joanne; Lubinski, Jan; Moller, Pal; Lynch, Henry T; Singer, Christian F; Eng, Charis; Neuhausen, Susan L; Karlan, Beth; Kim-Sing, Charmaine; Huzarski, Tomasz; Gronwald, Jacek; McCuaig, Jeanna; Senter, Leigha; Tung, Nadine; Ghadirian, Parviz; Eisen, Andrea; Gilchrist, Dawna; Blum, Joanne L; Zakalik, Dana; Pal, Tuya; Sun, Ping; Narod, Steven A
It is not clear if early oral contraceptive use increases the risk of breast cancer among young women with a breast cancer susceptibility gene 1 (BRCA1) mutation. Given the benefit of oral contraceptives for the prevention of ovarian cancer, estimating age-specific risk ratios for oral contraceptive use and breast cancer is important. We conducted a case-control study of 2,492 matched pairs of women with a deleterious BRCA1 mutation. Breast cancer cases and unaffected controls were matched on year of birth and country of residence. Detailed information about oral contraceptive use was collected from a routinely administered questionnaire. Conditional logistic regression was used to estimate the odds ratios (OR) and 95 % confidence intervals (CI) for the association between oral contraceptive and breast cancer, by age at first use and by age at diagnosis. Among BRCA1 mutation carriers, oral contraceptive use was significantly associated with an increased risk of breast cancer for women who started the pill prior to age 20 (OR 1.45; 95 % CI 1.20-1.75; P = 0.0001) and possibly between ages 20 and 25 as well (OR 1.19; 95 % CI 0.99-1.42; P = 0.06). The effect was limited to breast cancers diagnosed before age 40 (OR 1.40; 95 % CI 1.14-1.70; P = 0.001); the risk of early-onset breast cancer increased by 11 % with each additional year of pill use when initiated prior to age 20 (OR 1.11; 95 % CI 1.03-1.20; P = 0.008). There was no observed increase for women diagnosed at or after the age of 40 (OR 0.97; 95 % CI 0.79-1.20; P = 0.81). Oral contraceptive use before age 25 increases the risk of early-onset breast cancer among women with a BRCA1 mutation and the risk increases with duration of use. Caution should be taken when advising women with a BRCA1 mutation to take an oral contraceptive prior to age 25.
Johnson, Bridget; Thorogood, Margaret
A questionnaire was circulated to a sample of general practitioners in Oxfordshire enquiring about the supervision of women taking oral contraceptives. A high standard of care was being offered and the doctors believed that there was a wide range of conditions that should influence the prescription of oral contraceptives. We conclude that while suitably trained paramedical staff could provide the same standard of care as the general practitioners, this could not be achieved through the use of a package insert listing possible contraindications. PMID:894634
Upton, G V
Figure 9 is an attempt to summate the influences of life-style on lipid parameters. Based on the work of Nikkila, it shows the source of the production of HDL and LDL, the factors that can affect these lipoprotein levels, and where in the cascade of lipoprotein metabolism these factors exert influence. The source of HDL production is the liver and the intestine. At this stage, diet, exercise, hormones, genetics, drugs, and certain disease states can affect HDL levels. Lecithin-cholesterol acyl transferase (LCAT) esterifies HDL-free cholesterol in plasma, and HDL3 is formed that in turn is transformed to HDL2. At the same time, VLDL from the gut and the liver will be converted, under the influence of LPL, to HDL2 and LDL. Thus HDL2 is being formed by the breakdown of VLDL and from the transformation of HDL3 to HDL2. Insulin, exercise, alcohol, fats, drugs, and diet affect lipoprotein lipase and consequently influence levels of LDL and HDL2 indirectly. Progestogens increase and estrogens decrease hepatic endothelial lipase, thus affecting the HDL2 concentration. It is at this point that combination OCs influence HDL2. The balance between estrogen and progestogen in a given contraceptive determines the extent and direction of HDL2 concentration. A separate pathway in the liver also catabolizes HDL2 and HDL3. LDL is generated partly from catabolism of VLDL and is partly secreted from the liver. The removal of LDL is mediated by receptors in both the liver and peripheral tissues. It is here that the Brown-Goldstein theory plays a major role. If LDL receptors are present in an insufficient number or are defective, then the C will accumulate and atherosclerosis may follow. Thus two key enzymes, LCAT and LPL, control the production of HDL2 and LDL, whereas a third enzyme, hepatic endothelial lipase, catabolizes HDL2.
Grimes, David A
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 (=2 pregnancies per 100 women per year) in typical use. Stated alternatively, the only class of contraceptives today with exclusively first-tier effectiveness is the one that can be started -- and then forgotten for years.
Deana, D G; Dean, P J
Ischemic colitis, a condition of middle-aged to elderly patients, occurs uncommonly in younger persons. In this study, we describe the clinical and pathological features of 18 young adults (mean age, 29 years; age range, 17-39 years) with spontaneous ischemic colitis, 17 of whom were women. All presented with abrupt onset of severe, cramping abdominal pain followed by hematochezia. Colonoscopic visualization of the mucosa showed segmental hyperemia, friability, and erosion affecting the distal transverse colon (three cases), splenic flexure (three cases), descending colon (five cases), and sigmoid (seven cases). Mucosal biopsy documented superficial ischemic necrosis in seven patients; 11 patients had full-thickness mucosal necrosis with regeneration. Colonic mucosa proximal and distal to the ischemic segment was endoscopically normal in all patients and histologically normal in the eight patients in whom biopsies were obtained. All patients recovered with supportive care. Median duration of illness was 2.1 days (range, 1-4 days). Ten women (59%) were using low-dose estrogenic oral contraceptive agents, compared with the 1988 national average of 18.5% oral contraceptive users among females aged 15 to 44 years. The calculated odds ratio yielded a greater than sixfold relative risk for the occurrence of ischemic colitis among oral contraceptive users. In addition, four women not currently on hormonal contraceptive therapy had a past history of oral contraceptive use; the three remaining women were taking estrogen as replacement therapy after oophorectomy. In one patient, documented reversible ischemic colitis recurred on resumption of oral contraceptive use; four women reported symptoms and signs of recurrent ischemia but did not seek further medical evaluation. Our data indicate that transient colonic ischemia represents a form of acute segmental colitis in young adults; before the 5th decade of life, spontaneous ischemic colitis is a disorder found almost
Spinillo, A; Gorini, G; Piazzi, G; Baltaro, F; Monaco, A; Zara, F
The prevalence of oral contraceptive use in association with chlamydial pelvic inflammatory disease (PID) and the presence of anti-chlamydial IgG and IgA in a population of 144 hospitalized and outpatient subjects with a standard diagnosis of PID was studied. The rates of chlamydial PID and IgA detection were 15.3% (22/144) and 13.9% (20/144), respectively. After stratification for age, number of pregnancies, and lifetime sexual partners, the rates of chlamydial PID (odds ratio = 0.30, 95% CI = 0.10 - 0.89) and IgA detection (odds ratio = 0.23, 95% CI = 0.07 - 0.73) were lower among previous or current oral contraceptive users than in women who had never used birth control methods. Analyses of linear trend indicated a negative association between increasing duration of exposure to hormonal contraception and anti-chlamydial IgG and IgA. This study confirms that among patients with chlamydial PID, the frequency of oral contraceptive use is lower than that in patients with PID of other etiology. Serologic studies suggest a possible relationship between hormonal contraception and changes in immune response or susceptibility to chlamydial infection.
Trussell, James; Portman, David
BACKGROUND Despite several drawbacks, the Pearl Index continues to be the most widely used statistical measure of contraceptive failure. However, Pearl indices reported in studies of newer hormonal contraceptives appear to be increasing. STUDY DESIGN We searched PubMed and MIS databases for prospective trials evaluating oral contraceptive (OC) efficacy to examine potential factors that could contribute to increasing Pearl indices. RESULTS Numerous potential factors were identified, including an increased rate of failures of newer OCs, deficiencies in methods of calculating contraceptive failure rates, differences in study design and changes in patient populations resulting in increased rates of contraceptive failures due to the inappropriate or inconsistent use of the method. CONCLUSIONS The two most likely important contributors to the increase in Pearl indices are more frequent pregnancy testing with more sensitive tests and less adherent study populations. Because study populations appear to be increasingly representative of the likely actual users once the product is marketed, we can expect to see even higher failure rates in ongoing and future studies. This result poses challenges for companies and regulatory agencies. PMID:23683581
The question of whether the formulation of the oral contraceptive (OC) pill makes any clinically significant difference is often raised because both physicians and patients are faced with the problem of selecting from a bewildering array of available pills. The answer involves examining the contribution of estrogen and progestin separately. The estrogen component of the combination birth control pill serves 3 important functions: it exerts negative feedback action on the secretion of gonadotropins; it provides stability to the endometrium, preventing irregular shedding and unwanted breakthrough bleeding; and it increases the potency of the progestational component in its inhibitory action on gonadotropin secretion and its antifertility effects on cervical mucus, endometrium, and possibly the Fallopian tube. The presence of estrogen may eliminate a need for higher progestin doses in OCs. This effect is mediated by estrogen induced increase in the concentration of intracellular progestin receptors. A minimal pharmacologic level of estrogen is needed to achieve effective contraception, and the new low dose pills are most likely at the limit of the ability to reduce dosage. Thrombosis is the most serious side effect of the OC; it plays a key role in the increased risk of death from a variety of circulatory problems such as myocardial infarction, pulmonary embolism, and stroke. A convincing argument can be made for a dose related response between the incidence of thrombosis and the estrogen content of the pill. Only the 19-nortestosterone family of progestins is approved for contraceptive use in the U.S. The progestin component exerts its principal contraceptive effect by suppressing luteinizing hormone (LH) secretion. In 1978 an early report from the Walnut Creek study suggested that HDL-cholesterol levels were positively associated with estrogen levels in OCs and negatively with progestin. The implication was that high dose progestins would be associated with a
Although it is estimated that the population growth rate will decline to a replacement level by 2050, it is also now predicted that the total world population will reach 8.9 billion in that year -- far higher than the 2004 estimate of 6.4 billion. More than 26 billion new couples will need contraceptives in the next half century. Although a steady increase in contraceptive use has been observed in both developed and developing countries, the contraceptive needs of a high percentage of couples have not yet been met and the number of unplanned pregnancies continues to increase. The actual use of contraception differs from region to region. Although no new method has been registered for many years, several new products have been marketed during the last 5. Among these are new implants, medicated intrauterine systems, contraceptive vaginal rings, transdermal patches and several new combined oral contraceptive formulations. New contraceptive methods have been developed to meet the objectives of expanding contraceptive choices for both women and men and answering an unmet need for contraceptives with a long-term action that meet the expectations of consumers. Simplicity, reversibility and effectiveness are the desired features of a male contraceptive, but no new male contraceptive method is yet available. New areas of basic research include studies on genes, proteins and enzymes involved in the reproductive system. The new methods will be targeted to specific interactions within the reproductive system at the level of ovaries and testes, as well as between spermatozoa and ova. This futuristic approach still keeps in mind the need for better access to existing contraceptive methods, as well as the discovery of new contraceptives that are simple to use, safe, reversible and inexpensive. In the future, contraceptives may be combined with other medicinal agents to provide dual protection against both pregnancy and other preventable conditions, such as sexually transmitted
O'Brien, Sarah H
Venous thromboembolism (VTE) is a rare but serious complication of combined hormonal contraception. While the absolute risk of VTE is low in adolescents, thrombotic events in contraception users younger than the age of 20 years account for 5 to 10% of total contraception-related VTE events in population studies, because of the high frequency of contraception use in adolescents. An increased risk of VTE exists not only with oral contraceptives, but also the contraceptive patch and vaginal ring. Most adolescents who experience contraception-related VTE have additional transient or inherited thrombotic risk factors at the time of VTE. Although the presence of inherited thrombophilia impacts the risk of contraception-related VTE, thrombophilia screening before contraception prescribing should be targeted only to high-risk populations. Pediatric institutions, caregivers, and young women need to be aware of the risk of VTE with estrogen-containing contraception, and maintain a high index of suspicion for this complication in women using these agents.
Batukan, Cem; Muderris, Iptisam Ipek; Ozcelik, Bulent; Ozturk, Ahmet
Combined oral contraceptives (COCs) are considered the first-line treatment for women with hirsutism. They diminish androgen release from the ovary and decrease plasma free testosterone levels by increasing sex hormone-binding globulin (SHBG) concentrations. COCs containing cyproterone acetate (CPA) and drospirenone (DRSP) have been proved effective for the treatment of acne and facial hirsutism. This study prospectively compared the clinical and biochemical efficacy of 3 mg DRSP/30 microg ethinyl estradiol (EE) and 2 mg CPA/35 microg EE combinations in a total of 91 patients with hirsutism. Individuals randomly received a cyclic combination of either DRSP/EE (n=48) or CPA/EE (n=43) for 12 months. Basal serum total testosterone, free testosterone, androstenedione, dehydroepiandrosterone sulfate and SHBG levels, as well as Ferriman-Gallwey scores, were determined before and after treatment. Both COCs achieved a similar effect on clinical hirsutism scores, in addition to serum androgen and SHBG levels, after completion of therapy. The percentage reductions in total hirsutism score (median % (min-max)) during therapy were 0.70 (0-0.58) vs. 0.57 (0.10-1.00) at 6 months (p = 0.028) and 0.80 (0-0.42) vs. 0.81 (0-0.75) at 12 months (p = 0.6) in the DRSP/EE and CPA/EE groups, respectively. In conclusion, the DRSP/EE combination is at least as effective as the CPA/EE combination in improving hirsutism scores.
Sagar, S; Stamatakis, J D; Thomas, D P; Kakkar, V V
Deep-vein thrombosis (D.V.T.) was detected by the fibrinogen-uptake test in six out of a total of thirty-one young women undergoing emergency abdominal surgery who gave a history of recent oral contraceptive intake. In contrast, no D.V.T. developed in nineteen similar patients who were not on oral contraceptives (P less than 0-01). Plasma-antithrombin-III activity was significantly lower preoperatively in patients taking oral contraceptives; postoperative D.V.T. subsequently developed in three out of five patients with preoperative antithrombin-III activity below 50%. In seventy-eight dental patients undergoing molar extraction, antithrombin-III activity was measured before, during, and after operation. Activity fell in all patients during operation, but the fall was significantly greater in women taking oral contraceptives (P less than 0-01). The intra-operative fall in antithrombin-III activity was prevented by a small preoperative dose of subcutaneous heparin.
Montón, F.; Rebollo, M.; Quintana, F.; Berciano, J.
Occlusion of the middle cerebral artery and thrombosis of the superior sagittal sinus are reported in a 30-year-old woman taking oral contraceptives (OC). The coexistence of arterial and venous cerebral pathology as a complication of OC use has only been previously reported in one case. The pathogenesis of this rare association is briefly discussed. Images Fig. 1 Fig. 2 PMID:6462985
Deuster, Patricia A; Powell-Dunford, Nicole; Crago, Mark S; Cuda, Amanda S
Menstrual cycle patterns and concerns and oral contraceptive use in the combat environment were examined in Caucasian, Asian, Hispanic, and African American women to guide the development of educational resources for women soldiers. An anonymous, questionnaire was completed by 455 U.S. Army women-Caucasian (CA: n = 141); Asian (AS: n = 67); Hispanic (HIS: n = 67); and African American (AA: n = 184) to compare menstrual patterns and concerns, dysmenorrhea, and oral contraceptive patterns. Total menstrual concerns were significantly lower among African Americans relative to Caucasians, Asians, or Hispanics; Asians and Hispanics reported the greatest concern. Overall, secondary amenorrhea was noted by 14.9% of women. Severe dysmenorrhea rates were significantly lower in African American (6.1%) compared to Caucasian (11.6%), Asian (20.9%) and Hispanic (19.7%) women. Asian women reported missing less work-only 9.3% with moderate to severe dysmenorrhea missed work compared to 25.1% of all other women. Only 9.2% of women with mild, compared to 25.8% with moderate to severe (OR = 3.44; p ≤ 0.0001) dysmenorrhea sought health care. Less than 50% of women took oral contraceptive, and less than half of those women took oral contraceptive continuously. African Americans seemed to experience menstruation as less bothersome than others, despite no difference in the proportion with menstrual irregularities, mean duration of menses, and/or mean time between cycles.
Rosenberg, L; Palmer, J R; Zauber, A G; Warshauer, M E; Lewis, J L; Strom, B L; Harlap, S; Shapiro, S
The relation of oral contraceptive use to the risk of ovarian cancer was assessed with data collected during 1977-1991 from patients under 65 years of age in hospitals in Boston, New York, Philadelphia, and Baltimore. We compared 441 women with recently diagnosed invasive epithelial ovarian cancer to 2,065 control women. Logistic regression was used to control risk factors for ovarian cancer. The multivariate relative risk estimate decreased with the increasing duration of oral contraceptive use (p < 0.05): the estimate was close to 1.0 for duration categories of less than 3 years; it was reduced for the categories of 3-4 years of use and greater, but it did not decline further as the duration of use increased. For > or = 3 years of use, the estimate was 0.6 (95% confidence interval 0.4-0.8). The inverse association of risk with > or = 3 years of use was consistently present across categories of age, parity, interview year, and geographic area. It was apparent for as long as 15-19 years after cessation. Many different specific oral contraceptive formulations appeared related to a decreased risk; however, data were sparse for the newer types, particularly phasic preparations, and the ability to assess specific preparations in the context of use of multiple preparations was limited. The present data confirm previous reports of an inverse association of ovarian cancer risk with oral contraceptive use of several years in duration. They also suggest that the association may persist for as long as two decades and that it is not confined to any particular type of oral contraceptive formulation.
Foroutan, Nazanin; Dabaghzadeh, Fatemeh
Background: 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. Objective: 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. Methods: 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. Results: 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). Conclusion: The quality of the pharmacists’ consultations regarding the over the counter use of oral contraceptive pills was not satisfactory and required improvement. PMID:28042350
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
Thompson, R. P. H.; Williams, Roger
The oral contraceptive chlormadinone acetate has been given for eight months to a woman who had developed jaundice during four pregnancies, and twice while taking a combined contraceptive pill. No side-effects or changes in liver function were observed. This is further evidence that progestogens used for contraception, and in particular those derived from hydroxyprogesterone, are less hepatotoxic than the oestrogenic components. PMID:4189931
The efficacy of a new estrogen-progestin contraceptive agent Ovidon was evaluated in 65 women. The women were taking the contraceptive for 47 cycles (each Ovidon pill contained 0.25 mg of D-norgestrel and 0.05 mg of ethinyl estradiol). Prior to the Ovidon treatment, 15 women did not use any contraceptive agents or devices, 5 used hormonal contraceptives, 2 used IUDs, 4 used mechanical devices, 20 practiced coitus interraptus, and 9 used a biological method. Ovidon administration provided a 100% contraceptive effect. Side effects of Ovidon included fatigue (15 women), headache (4), irritability (3), fullness of the breast (27), hemorrhage (12), vaginal discharge (6), and changes in libido (22). Ovidon administration did not induce amenorrhea. A 1-3 kg weight gain was observed in 5 women. Laboratory studies showed no changes in hemoglobin levels, leukocyte count, cholesterol, and alkaline phosphatase levels. These findings indicated the safety and contraceptive efficacy of Ovidon.
Grevers, Xin; Grundy, Anne; Poirier, Abbey E.; Khandwala, Farah; Feldman, Matthew; Friedenreich, Christine M.; Brenner, Darren R.
Background: Hormonal contraceptives and hormone replacement therapies are classified as carcinogenic to humans (group 1) by the International Agency for Research on Cancer. We sought to estimate the proportion and total number of cancers attributable to the use of oral contraceptives and hormone therapy in Alberta in 2012. Methods: Population attributable risks were used to estimate the proportion of attributable cases for each associated cancer site. Relative risk estimates were obtained from the most relevant and recent epidemiologic literature. Prevalences of the use of oral contraceptives and hormone therapy in Alberta were collected from Alberta's Tomorrow Project. Specific cancer incidence data were obtained from the Alberta Cancer Registry for the year 2012. Results: Overall, 6.3% of breast cancers (n = 135) diagnosed in Alberta in 2012 were estimated to be attributable to the use of oral contraceptives, and the exposure potentially prevented about 57.3% of endometrial cancers (n = 276) and 29.1% of ovarian cancers (n = 52). About 15.5% of breast cancers (n = 258) and 8.9% of ovarian cancers (n = 13) were estimated to be attributable to the use of hormone therapy, whereas 11.3% of endometrial cancers (n = 48) were possibly prevented by the exposure. Interpretation: Based on our estimates, oral contraceptive use resulted in a net protective effect among the cancer sites studied, thus reducing the cancer burden in Alberta in 2012. The use of hormone therapy was estimated to increase the cancer burden in the province, therefore the risk and benefit of hormone therapy should be carefully considered before use. PMID:28018891
Bolt, H M
Metabolism of contraceptive compounds may be influenced by various drugs. Of clinical importance is induction by barbiturates, by diphenylhydantoin, and especially by rifampicin, of enzymes that are responsible for degradation of estrogens. The major target is the hepatic microsomal estrogen-2-hydroxylase (cytochrome P450 3A4). Another type of interaction of drugs with disposition and effectiveness of estrogens is impairment of their enterohepatic circulation. This may be due to absorption of biliary estrogen conjugates (e.g., by cholestyramine) or to insufficient cleavage of the conjugate by intestinal bacteria, the latter being observed after administration of antibiotics (e.g., ampicillin, neomycin). PMID:7698081
Casey, Ellen; Reese, Maria; Okafor, Ezi; Chun, Danielle; Gagnon, Christine; Nigl, Franz; Dhaher, Yasin Y.
Background 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. Objective 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. Design This was a prospective cohort study. Setting The study took place at a biomechanics laboratory at a rehabilitation hospital. Participants 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). Main Outcome Measures H-reflex (Hmax/Mmax ratio), serum estradiol, and progesterone concentrations were measured at 3 time points during the menstrual and contraceptive pill cycle. Results 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. Conclusions Our results suggest that acute fluctuations of endogenous estradiol and progesterone do
Amate, P; Luton, D; Davitian, C
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
Charoenvisal, C; Thaipisuttikul, Y; Pinjaroen, S; Krisanapan, O; Benjawang, W; Koster, A; Doesburg, W
In Thailand, at the Prince of Sonkhla University in Sonkhla (Center A) and Rajvithi Hospital in Bangkok (Center B), researchers compared data on 32 women using a low-dose combined oral contraceptive (OC) containing 150 mcg desogestrel plus 30 mcg ethinyl estradiol (Marvelon) with data on 34 women using an OC containing 2000 mcg cyproterone acetate plus 50 mcg ethinyl estradiol (Diane) to examine their efficacy in acne treatment. All the women presented with acne and were between 16 and 30 years old. The study consisted of a baseline cycle and 6 successive treatment cycles. The mean objective acne score decreased with both OCs in Center A. This decrease was significant with Diane after 3 and 6 treatment cycles (p 0.05). At cycle 6, the mean objective score for Diane was much lower than that for Marvelon (p 0.05). At Center B, the mean objective score consistently and significantly decreased with Marvelon after 3 and 6 treatment cycles (p 0.05 and p 0.01, respectively) and with Diane after 6 treatment cycles (p 0.001). No significant between-group differences existed for Center B. The percentage of women with moderate/severe acne decreased significantly with Marvelon at Center B (p = 0.002) and with Diane in Centers A (p = 0.014) and B (p = 0.004). Both Diane and Marvelon significantly increased plasma levels of sex hormone binding globulin at 3 and 6 treatment cycles (p 0.01). They tended to reduce plasma levels of total and free testosterone. This decrease only reached significance with Marvelon, however (p 0.05). There were no significant associations between acne severity and biochemical variables. These findings suggest that both OCs cause significant improvement in acne in most Asian women who also may need a reliable contraceptive. There were no significant differences between the two OCs.
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…
Ellertson, C; Trussell, J; Stewart, F; Koenig, J; Raymond, E G; Shochet, T
Emergency contraceptives are methods that prevent pregnancy when used shortly after unprotected sex. Three different emergency contraceptive methods are safe, simple, and widely available in the United States. These are: (1) ordinary combined oral contraceptives containing ethinyl estradiol and levonorgestrel taken in a higher dose for a short period of time and started within a few days after unprotected intercourse; (2) levonorgestrel-only tablets used similarly; and (3) copper-bearing intrauterine devices inserted within approximately 1 week after unprotected intercourse. Emergency contraceptive use is best known for women who have been raped, but the methods are also appropriate for women who have experienced condom breaks, women who did not use any method because they were not planning on having sex, or women who had unprotected intercourse for any other reason. Unfortunately, few women know about emergency contraceptives, and few clinicians think to inform their patients routinely about the option. A nationwide toll-free hotline (1-888-NOT-2-LATE) and a website (http://not-2-late.com) can help women learn about these options. Sharing "family planning's best-kept secret" widely with women could prevent as many as a million unwanted pregnancies annually in the United States.
Petersen, J F; Bergholt, T; Nielsen, A K; Paidas, M J; Løkkegaard, E C L
Estimating the risk of venous thromboembolism (VTE) associated with combined hormonal contraceptives following early terminated pregnancies or birth, a Danish nationwide retrospective cohort observing a one-year follow-up was defined using three unique registries. All Danish women with confirmed pregnancies aged 15-49 during the period of 1995-2009 were included. The main outcomes were relative and absolute risks of first time venous thromboembolism in users as well as non-users of combined hormonal contraceptives. In 985,569 person-years, 598 venous thromboembolisms were recorded. After early terminated pregnancies and births, respectively, 113 and 485 events occurred in 212,552 and 773,017 person-years. After early terminated pregnancies, the crude VTE incidence ratios were similar, and the numbers needed to harm were equal between groups that did or did not use combined hormonal contraceptives throughout the follow-up year. After childbirth, individuals that used combined hormonal contraceptives were more likely than non-users to experience VTE depicted by crude incidence ratios; however, the difference was only significant after 14 weeks. This implied that the numbers needed to harm were lower for those that used compared to those that did not use combined oral contraceptives in the initial 14 weeks postpartum. In conclusion, the use of combined hormonal contraceptives after early terminated pregnancies was not detrimental, but during the puerperal period, they should be used with caution.
Robinson, Jennifer A; Burke, Anne E
Obesity is a major public health concern affecting an increasing proportion of reproductive-aged women. Avoiding unintended pregnancy is of major importance, given the increased risks associated with pregnancy, but obesity may affect the efficacy of hormonal contraceptives by altering how these drugs are absorbed, distributed, metabolized or eliminated. Limited data suggest that long-acting, reversible contraceptives maintain excellent efficacy in obese women. Some studies demonstrating altered pharmacokinetic parameters and increased failure rates with combined oral contraceptives, the contraceptive patch and emergency contraceptive pills suggest decreased efficacy of these methods. It is unclear whether bariatric surgery affects hormonal contraceptive efficacy. Obese women should be offered the full range of contraceptive options, with counseling that balances the risks and benefits of each method, including the risk of unintended pregnancy.
Menon, Sujatha; Riese, Richard; Wang, Ronnie; Alvey, Christine W.; Shi, Haihong; Petit, Wendy
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
Roberts, S. Craig; Gosling, L. Morris; Carter, Vaughan; Petrie, Marion
Previous studies in animals and humans show that genes in the major histocompatibility complex (MHC) influence individual odours and that females often prefer odour of MHC-dissimilar males, perhaps to increase offspring heterozygosity or reduce inbreeding. Women using oral hormonal contraceptives have been reported to have the opposite preference, raising the possibility that oral contraceptives alter female preference towards MHC similarity, with possible fertility costs. Here we test directly whether contraceptive pill use alters odour preferences using a longitudinal design in which women were tested before and after initiating pill use; a control group of non-users were tested with a comparable interval between test sessions. In contrast to some previous studies, there was no significant difference in ratings between odours of MHC-dissimilar and MHC-similar men among women during the follicular cycle phase. However, single women preferred odours of MHC-similar men, while women in relationships preferred odours of MHC-dissimilar men, a result consistent with studies in other species, suggesting that paired females may seek to improve offspring quality through extra-pair partnerships. Across tests, we found a significant preference shift towards MHC similarity associated with pill use, which was not evident in the control group. If odour plays a role in human mate choice, our results suggest that contraceptive pill use could disrupt disassortative mate preferences. PMID:18700206
Libbus, K; Arps, C A
This study looked at modal, salient beliefs regarding intention to use and use of oral contraceptives (OC) in a group of African American women aged 18-35 in a midwest urban community. Data were collected in face-to-face audio taped interviews using a format devised by Ajzen and Fishbein. Questions related to the identified behavior of deliberate action to avoid unwanted pregnancy by instituting the use of a contraceptive method. Twenty-five women consented to participate. Of these, 20 women (80%) reported using oral contraceptives as their primary birth control method. The study reports on women's perceptions of the advantages and disadvantages of OC acquisition and use and important social referents approving or disapproving of OC acquisition and use. Perceived barriers and facilitators to OC acquisition and use are also reported. Identification of individual and group attitudes regarding contraceptive behavior may be valuable in enhancing the provision of successful family planning services to women wishing to avoid delay of childbearing.
Díaz, Soledad; Hardy, Ellen; Alvarado, Gloria; Ezcurra, Enrique
This article presents the results of a study on the acceptability of emergency contraception (EC) in Brazil, Chile, and Mexico. Opinions of potential users and possible providers were obtained through discussion groups and those of authorities and policy-makers through semi-structured interviews. Most participants had a positive opinion of EC, based on the view that it can help reduce unplanned pregnancy, adolescent pregnancy, and unsafe abortion. Several interviewees felt that all women should be informed about EC, while others viewed it as a method for special situations such as rape and unprotected first sexual intercourse. Concern was expressed that its introduction might be associated with a decrease in condom use, increase in sexually transmitted diseases, and irresponsible or promiscuous sexual behavior among adolescents. The need for EC was clearly perceived by most participants, leading to the conclusion that health authorities have the responsibility of implementing programs for its introduction. Training of health care personnel should include the discussion of reproductive health problems that could be prevented by EC.
Budev, Marie M; Abu-Hajir, Majed; Deitcher, Steven R; Gomes, Marcelo P V
An 18-year-old woman without significant past medical and surgical history presents to discuss the safety and efficacy of oral contraceptives. She is sexually active and currently relying on condoms alone for birth control. Her cousin had a deep venous thrombosis (DVT) following a pregnancy. As part of the family screening, this patient was identified as a factor V Leiden heterozygote. The risks and benefits of initiating oral contraceptives are discussed.
Wreje, U; Kristiansson, P; Aberg, H; Byström, B; von Schoultz, B
Serum relaxin levels were analysed in 12 healthy women every other day during the menstrual cycle and during a second cycle on oral contraceptives. Relaxin levels in 7 women with posterior pelvic and lumbar pain were also measured. Relaxin was detected during both the follicular and luteal phases of the menstrual cycle in some of the healthy women. Serum levels were further increased during the use of oral contraceptives. Oestradiol levels in the untreated women correlated to the relaxin levels. Women with posterior pelvic and lumbar pain had higher relaxin levels than did healthy women, a finding that needs to be further explored. Our data indicate the existence of sources for relaxin production other than the corpus luteum in the non-pregnant woman. Endogenous and exogenous oestrogens may stimulate the production of relaxin.
Khomand, Payam; Hassanzadeh, Kambiz
Background: We report a case series of cerebral vein thrombosis (CVT) in women who used oral contraceptive pill (OCP) in the Muslims Ramadan and fasting month. Methods: This study was a retrospective case series of 9 patients with diagnosis of CVT, who admitted in the neurology ward of Tohid Hospital of Sanandaj, Iran, in July-August 2014-2015. Results: Patients had no history of thrombosis before. They were treated with oral contraceptive more than 1 month to be able to fast during Ramadan. They did not have other possible risk factors for CVT. A headache was the most common in 9/9 patients (100%) followed by vomiting and vertigo. Conclusion: We found that high rate of CVT in female population during Ramadan indicates that it needs be considered as a specific risk factor and should be considered by healthcare system. PMID:27326364
Contraceptive methods suitable for postpartum women include sterilization, intrauterine devices (IUDs), barrier methods, oral contraceptives, implants, injectables, breastfeeding, and natural family planning. Couples considering either male or female sterilization should receive counseling since this method is irreversible; however, it is very effective. IUDs are effective, reversible, and can be inserted as early as 10 minutes following placental delivery. Barrier methods are not as effective and include condoms, spermicides, diaphragm, and cervical caps. While condoms and spermicides can be employed whenever sexual activity resumes, diaphragms and cervical caps can be used 4-6 weeks postpartum. The progestin-only and the combined oral contraceptives are both very effective. There is disagreement among professionals regarding when nursing mothers should start taking oral contraceptives and implant and injectable contraceptives. Implants and injectable contraceptives have long acting effects. Breastfeeding is a natural form of contraception which can last up to 6 months; it also supplies nutritional and immunological benefits. Natural family planning requires providing women with information on fertility awareness.
Pregnancy, menstruation and hormonal contraceptives are no contraindications for necessary oral surgical procedures. If the pregnancy takes a normal course, surgical interventions with absolute indication are possible at any time. Surgical interventions with relative indication should be performed during the second trimester of pregnancy. The dental treatment of pregnant women should be terminated, as far as possible, by the 7th or 8th month of pregnancy. Metabolic imbalances, static loading and gingival changes deserve special attention.
Yasuda, M; Miller, J R
The hypothesis that female sex hormones in the first trimester of pregnancy are causally related to transposition of the great vessels (TGV) was tested by a retrospective study of 135 cases of TGV ascertained through the British Columbia Health Surveillance Registry. During 1962-1972 there was no increase in the annual incidence rates of TGV. Analysis of questionnaires completed on 58 cases revealed no definite association between inadvertent use of oral contraceptives or other sex hormones during early pregnancy and TGV.
Rimpelä, A. H.; Rimpelä, M. K.; Kosunen, E. A.
OBJECTIVES--To study use of oral contraceptives among Finnish teenagers during 1981-91 and how abortions, childbirths, sexually transmitted diseases, and cardiovascular diseases changed during this period. DESIGN--Biannual cross sectional surveys with mailed questionnaires from 1981 onwards and analysis of national statistics. SETTING--Finland. SUBJECTS--A nationwide sample of 14, 16, and 18 year olds. Sample size varied from 1249 to 3887 and response rate from 85% to 94%. MAIN OUTCOME MEASURES--Proportion taking oral contraceptive, fertility and abortion rates, hospital discharge rates, rates of sexually transmitted diseases. RESULTS--The proportion of teenagers taking oral contraceptives increased steadily. In 1991 the percentages among 14, 16, and 18 year olds were 2%, 18%, and 41% compared with 0.2%, 7% and 22% in 1981. Most users had a steady partner (80% of 16 year olds and 85% of 18 year olds). By 1989 rates of abortion had fallen from 12/1000 to 9.3/1000 in 16 year olds and from 25/1000 to 19.2/1000 in 18 year olds; fertility rates had fallen from 4.5/1000 to 2.3/1000 and from 23.5/1000 to 15.3/1000 respectively. Rates in 14 year olds fell only slightly. Gonorrhoea infection fell and HIV infection remained rare. Rates of hospital discharge after thromboembolic venous disease rose slightly. CONCLUSIONS--The increased use of oral contraceptives is the most likely explanation for decreasing abortion and fertility rates among teenagers. Increased reliance on the condom because of the threat of AIDS may increase unwanted pregnancies. PMID:1467684
Bhatia, Shailaja S; Majka, Darcy S; Kittelson, John M; Parrish, Lezlie A; Ferucci, Elizabeth D; Deane, Kevin D; Arend, William P; Rewers, Marian; Holers, V Michael; Norris, Jill M
Objectives To examine whether oral contraceptive use is associated with the presence of serum rheumatoid factor in women of reproductive age without rheumatoid arthritis. Methods 304 women selected from parents of children who were at increased risk of developing type 1 diabetes were studied, because they were enriched with the human leucocyte antigen‐DR4 allele, a susceptibility marker for both type 1 diabetes and rheumatoid arthritis. Participants visited a clinic where blood was drawn for rheumatoid factor testing, and exposure data were collected via questionnaires. A medical history and joint examination were performed to rule out rheumatoid arthritis. Participants and examiners were unaware of the participants' rheumatoid factor status at the time of examination and questionnaire. Results Use of oral contraceptives at any time was inversely associated with rheumatoid factor positivity (adjusted odds ratio (OR) 0.2, 95% confidence interval (CI) 0.07 to 0.52) independent of age, education and smoking. Smoking ⩾20 pack‐years was also associated with rheumatoid factor positivity (adjusted OR 56.38, 95% CI 4.31 to 736.98) compared with never smoking. Smoking 1–19 pack‐years was not associated with a positive rheumatoid factor. Conclusions Our results suggest that oral contraceptive use, and possibly cigarette smoking, act early in the development of the immune dysregulation that occurs in rheumatoid arthritis. PMID:16868018
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.
Saif, M W; Volpe, B T; Dailey, M; Tsongalis, G J
Venous thromboembolism is a serious, potentially lethal health problem affecting one per 1,000 people annually. Major surgery, the use of oral contraceptives, complicated pregnancy, fractures, and immobilization increase the risk of thrombosis. In addition to these factors, thrombosis is associated with inherited deficiencies of antithrombin III, protein C, and protein S. Together these do not account for more than five to 10% of the cases. Hereditary activated protein C resistance has been recognized as a basis for a majority of cases of familial thrombosis. It accounted for more than a 10 times higher number than that of other known genetic defects. We describe a case of a young female who presented with a pulmonary embolism and was discovered to have activated protein C resistance. This patient had a heterozygous mutation for factor V Leiden and was taking oral contraceptives. This report underlines: 1) increased risk of venous thrombosis in oral contraceptive users who carry factor V Leiden mutation associated with functional resistance to the normal anticoagulation activities of protein C; 2) most episodes occurring in the young are minor, but pulmonary embolus can occur; 3) the importance of identifying other affected members of the family; and 4) the importance of anticoagulation prophylaxis at times of enhanced risk, particularly during pregnancy, postpartum, and major surgery.
Chabbert-Buffet, Nathalie; Gerris, Jan; Jamin, Christian; Lello, Stefano; Lete, Inaki; Lobo, Paloma; Nappi, Rossella E; Pintiaux, Axelle
The Pill has undergone many changes since its first appearance some 50 years ago. Key developments included the reduction of ethinylestradiol doses and the synthesis of new progestins in order to increase safety, compliance and efficiency. Low-dose combined oral contraceptives (COCs) are currently the preferred option for millions of women. Due to this widespread use, it has been argued that the safety of COCs should be even better, raising the threshold for excellence. Yet in spite of major improvements, there is still an associated risk of venous thromboembolism (VTE). The next step in COCs' evolution should take total estrogenicity and hepatic estro-androgenic balance into account. The focus on the estrogen component--which has not changed in 50 years--has yielded a new class of natural estrogen pills. Following the introduction of a first quadriphasic pill, a monophasic estradiol pill based on the concept of "natural balance" was subsequently made available. These recent achievements could represent a step forward in the evolution of COCs and pave the way for better safety.
Gardner, M J; Tornatore, K M; Jusko, W J; Kanarkowski, R
The independent as well as interactive effects of chronic (greater than 6 months) oral contraceptive (OC) use and cigarette smoking on single-dose (4 mg/kg) theophylline disposition were assessed in 49 young, healthy women. Significant elevations (40%) in theophylline plasma clearance were found in women who smoked. OC use resulted in decreases in clearance of a similar magnitude (28%). These factors do not appear to interact with respect to theophylline disposition. The combination of main effects tended to cancel one another (clearance of 49.1 ml h-1 kg-1 ideal body weight for OC non-user, non-smoker, vs 49.7 ml h-1 kg-1 for OC user-smoker). Single dose exposure to OC in non-users did not significantly alter theophylline pharmacokinetics for the group as a whole. However, in the subgroup of smoking subjects, significant decreases in clearance were evident (P less than 0.05). Analogous results were found for half-life. Volume of distribution was slightly diminished in smokers, but was unaffected in OC users. Areas under the serum concentration-time (AUC) profiles of norgestrel and ethinyloestradiol were examined in 27 women as indices of OC exposure. The smallest values of theophylline clearance were found in the subjects with largest AUC of both OC steroids. Appropriate statistical analyses of data which are influenced by multiple factors are discussed. Special concern is needed when the factor partitioning process yields subgroups of unequal sizes. PMID:6626419
Kaneshiro, Bliss; Edelman, Alison; Dash, Chandravanu; Pandhare, Jui; Soli, Faapisa M.; Jensen, Jeffrey T.
Objectives To describe the effect of combined oral contraceptives (COC) on Matrix Metalloproteinase (MMP) -2 and -9 activity and compare MMP activity in women taking aCOC with or without doxycycline. Study Design Subjects (n=20) underwent endometrial biopsies1) in the late luteal phase of a baseline cycle prior to initiating COCs, 2) on day 19 to 21 while taking COCs in a standard 28-day cycle (7-day hormone free interval), 3) on day 26 to 28 while taking active COCs continuously for a 28 day cycle. During the continuous COC cycle, they were randomized to receive daily sub-antimicrobial dose doxycycline 40 mg or placebo. Results Compared to baseline, COC treatment increased MMP-2 (p<0.001) and -9(p<0.001). MMP activity was lower in subjects taking a COC with doxycycline compared to those receiving placebo, although only significantly lower for MMP-2LF (p=0.002). Conclusions Unscheduled bleeding with COCs may be the result of increased endometrial MMPs. Sample size limitations prevent us from determining how doxycycline affects MMP activity in COC-users. PMID:26408375
Goldbaum, G.M.; Kendrick, J.S.; Hogelin, G.C.; Gentry, E.M.
Women who smoke and use oral contraceptives (OCs) are at increased risk for cardiovascular and cerebrovascular disease. To study the prevalence of smoking and OC use and of other behaviors affecting health, 28 states and the District of Columbia conducted telephone surveys during 1981 through 1983. More than 22,000 US adults were interviewed, of whom 5779 women aged 18 to 44 years were studied. Data were weighted to represent the US population. Overall, 7.4% of US women aged 18 to 44 years reported smoking and using OCs' 1.1% reported smoking 25 or more cigarettes per day while using OCs. Although women aged 18 to 24 years were most likely to smoke and use OCs, combined smoking and OC use contributed substantially to the number of excess cases of myocardial infarctions occurring among US women aged 35 to 44 years. However, regardless of OC use, smoking accounted for most of the excess cases. Therefore, health care providers need to intensity their efforts to reduce smoking among their patients.
Warren, Annabelle M; Gurvich, Caroline; Worsley, Roisin; Kulkarni, Jayashri
Combined oral contraceptives (OCs) are the most commonly prescribed medication in women of reproductive age, but despite widespread use, their effect on cognitive performance remains controversial. Given strong evidence for the neurological impact of reproductive hormones, a clear rationale for investigation exists. This systematic review sought to identify, collate and critically appraise studies assessing the impact of OCs on cognition in healthy premenopausal women. Ovid MEDLINE, PsychINFO and EMBASE were comprehensively searched using relevant keywords for original peer-reviewed observational studies or randomised trials published after 1960. Of 1289 references screened, 22 studies were eligible for inclusion. Assembled evidence supports a cognitive impact of OCs restricted to specific domains; however, the quality of evidence is poor. The most consistent finding is improved verbal memory with OC use. Evidence is also emerging that differing progestin androgenicity may lead diverse OC formulations to differentially impact certain cognitive domains, such as visuospatial ability. At present, evidence is inconclusive, contradictory and limited by methodological inconsistencies. There is scope for further research in this area to definitively determine the cognitive impact of OCs.
Naessén, S; Carlström, K; Byström, B; Pierre, Y; Hirschberg, A Lindén
High androgen levels in women with bulimia nervosa may promote bulimic behavior. The aim of the present study was to investigate the effects of an antiandrogenic oral contraceptive (OC) on appetite and eating behavior in women with bulimia nervosa compared to healthy controls. Twenty-one women with bulimia nervosa and 17 healthy controls matched for age and body mass index participated in the study. Basal and meal-related appetite and secretions of the satiety peptide cholecystokinin (CCK) and the appetite-stimulating peptide ghrelin were studied before and after 3 months of treatment with an antiandrogenic OC (30 microg ethinyl estradiol combined with 3 mg drospirenone). Bulimic behavior was evaluated in relation to changes in hormone levels. Before treatment, bulimic women had higher frequency of menstrual disturbances, acne and hirsutism and higher levels of testosterone but lower meal-related CCK secretion than controls. OC treatment reduced meal-related hunger and gastric distention in bulimics. CCK secretion in response to the meal was unchanged in bulimic women but decreased in the controls. Ghrelin secretion was comparable between groups and did not change in response to OC treatment. The treatment improved bulimic behavior in relation to a decline in testosterone levels in the entire group. Our results support the suggestion that androgens play a role in bulimic behavior. Treatment with an antiandrogenic OC may serve as a new strategy for treatment of bulimia nervosa and particularly in those patients with hyperandrogenic symptoms.
Thorneycroft, I H; Stanczyk, F Z; Bradshaw, K D; Ballagh, S A; Nichols, M; Weber, M E
Oral contraceptives (OC) suppress excess androgen production; however, different progestins in combination with low-dose estrogens produce divergent effects on sex hormone-binding globulin (SHBG) and testosterone that may influence clinical outcomes. This multicenter, open-label, randomized study compared biochemical androgen profiles and clinical outcomes associated with two OC containing the same amounts of ethinyl estradiol (EE, 20 micrograms) but different progestins, levonorgestrel (LNG, 100 micrograms), and norethindrone acetate (NETA, 1000 micrograms). Fifty-eight healthy women (18-28 years old) received three cycles of treatment with LNG/EE (n = 30) or NETA/EE (n = 28). The results showed that LNG reduced androgen levels in three compartments--adrenal, ovarian, and peripheral. NETA reduced only adrenal and peripheral androgens. Despite a 2.2-fold greater relative increase in SHBG with NETA than LNG, bioavailable testosterone (T) was reduced by the same amount with LNG and NETA. Both treatments improved acne and were well tolerated. Low-dose OC (EE, 20 micrograms) are effective in reducing circulating androgens and acne lesions without causing weight gain. Although LNG and NETA affected secondary markers differently, both OC formulations produced an equivalent decrease in bioavailable.
Kives, Sari; Hahn, Philip M; White, Emily; Stanczyk, Frank Z; Reid, Robert L
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.
Kabra, Aashish; Gelfond, Jonathan; Liss, Michael A
Androgens have been suspected to be involved in the initiation of renal cell carcinoma because of a two-fold increased risk in men compared with women. To investigate the role of self-reported finasteride or oral contraceptive use in the Prostate, Lung, Colorectal, and Ovarian (PCLO) to determine whether the androgen receptor reduces renal cancer development. We query the PCLO trial for predictor variables from the baseline questionnaire and follow-up questionnaires enquiring medication use, specifically the use of 5-α reductase inhibitors (dutasteride or finasteride) and oral contraceptive therapy. The primary outcome of this study was the incidence of renal cancer. Statistical analysis included Student's t-test for continuous variables, χ, or Fisher's exact tests for dichotomous or categorical variables, and multivariable analysis using Cox proportional hazards models. Eight percent (n=6117/73 694) of men in the PCLO trial reported the use of finasteride. 52 (10.6%) of the 492 men diagnosed with renal cancer had self-reported exposure to finasteride and this was not significant in univariable analysis (52/6169; 0.84% vs. 440/66 454; 0.67%, P=0.12) or multivariable main effects analysis (hazard ratio: 1.12; 95% confidence interval: 0.83-1.5; P=0.47). Approximately 54% of women (n=40 997/75 989) in the PCLO trial reported the use of oral contraceptives by questionnaire. 136 (52.1%) of the 261 women diagnosed with renal cancer had self-reported exposure to oral contraceptive therapy and this was not significant in univariable analysis (136/40 997; 0.33% vs. 125/34 992; 0.36%, P=0.36) or in multivariable main effects analysis (hazard ratio: 1.03; 95% confidence interval: 0.97-1.1; P=0.30). Self-reported use of finasteride or oral contraceptives is not associated with a reduced incidence of renal cancer.
Maia, Hugo; Haddad, Clarice; Casoy, Julio
Objective Menstrual symptoms such as dysmenorrhea usually occur during the hormone-free interval in oral contraceptive users. Progestin withdrawal activates NF-κB transcription factor, which upregulates both vascular endothelial growth factor (VEGF) and Cox-2 expression in the endometrium. The use of natural NF-κB inhibitors such as pycnogenol may block this response, improving dysmenorrhea. Patients and methods Twenty-four patients with severe dysmenorrhea were allocated to one of two treatment groups. In Group A (n=13), women were treated with an oral contraceptive containing 15 μg of ethinyl estradiol and 60 mg of gestodene (Adoless®) in a 24/4 regimen for three consecutive cycles. Women in Group B (n=11) used the same contraceptive regimen together with 100 mg of pycnogenol (Flebon®) continuously for 3 months. Pain scores were graded using a visual analog scale (VAS) before and during the hormone-free interval at the end of the third treatment cycle. Results Before treatment, VAS pain scores for dysmenorrhea were 8 and 9 in Groups A and B, respectively. However, by the end of the third treatment cycle, pain scores had decreased significantly (P<0.05) both in groups A and B. The final pain scores were 6 in Group A and 2 in Group B, a difference that was statistically significant (P<0.0001). In Group B, 27% of the patients became pain-free, while in Group A, none of the women reported complete disappearance of this symptom. The number of bleeding days was also lower in Group B. Discussion Pycnogenol effectively decreased pain scores and the number of bleeding days when administered concomitantly with a low-dose 24/4 oral contraceptive containing gestodene. PMID:25525393
Lin, Hsien-Chang; Lee, Hsiao-Yun
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.
Naz, Falaq; Jyoti, Smita; Rahul; Akhtar, Nishat; Siddique, Yasir Hasan
The continuous use of synthetic hormones as contraceptive pill or hormonal replacement therapy among women is increasing day by day. The widespread use of different formulations as oral contraceptives by women throughout their reproductive cycle has given rise to a serious concern for studying the effects of oral contraceptives on enzymatic profile and DNA damage in peripheral blood lymphocytes among users. The present study was carried out on women taking oral contraceptives. The study was based on the questionnaire having the information of reproductive history, fasting, age, health, nature of menstrual cycle, bleeding and other disease. The profile of the blood serum enzymes i.e. alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), lactate dehydrogenase (LDH), aminotransferases (SGOT and SGPT), serum proteins (albumin and globulin) and DNA damage in lymphocytes was studied among users and non-users. The results of the present study suggest that OCs not only effects enzymatic activity but also results in DNA damage that may vary with the duration of using oral contraceptives. A significant increase in LDH, GGT, SGPT, SGOT, globulin and decrease in ALP as well as albumin was found among users as compared to non-users. The observed DNA damage was more in users as compared to non-users. Hormonal contraceptives seem to exert DNA damage and also have significant effects on blood serum enzymes.
Results of the 1998 "Contraceptive Technology Update" Pill Survey indicate that oral contraceptives (OCs) remain the top birth control choice for US women. More than 70% of providers who responded to the survey reported that at least 50 women leave their offices each month with an OC prescription. When asked to cite their first OC choice, for a 21-year-old nonsmoking woman, Ortho Tri-Cyclen was selected by 43.6% of providers. This OC is considered an excellent choice for young women because of its ease of use, good cycle control, and beneficial effect on acne. The top choices for a 42-year-old nonsmoking woman were Loestrin (26.5%) and Alesse (21.1%), both of which have low estrogen doses. 25% of providers indicated they had prescribed OCs specifically to decrease the ovarian cancer risk in genetically predisposed women.
Lobert, M; Pigeyre, M; Gronier, H; Catteau-Jonard, S; Robin, G
The prevalence of obesity is increasing massively over several decades in industrialized countries. Obese women are sexually active but they use fewer contraceptive methods and are at high risk of unintended pregnancy. In addition, obesity is an important risk factor for venous thromboembolism events and arterial thrombosis (myocardial infarction and ischemic stroke). All of these data are to be considered in choosing a contraceptive method for obese women. Except depot medroxyprogesterone acetate injection, the progestin-only contraceptives (progestin only pills and etonogestrel subdermal implant) and the intra-uterine devices are the preferred contraceptive methods in obese women. The combined estrogen-progestin contraceptives (pill, patch and vaginal ring) may be proposed in very strict conditions (no other associated vascular risk factor). Obesity does not increase the risk of failure of most contraceptive methods. Bariatric surgery is a complex situation. It requires to program a possible pregnancy and contraception is needed for several months. Some bariatric surgical techniques such as by-pass can induce gastrointestinal malabsorption. In this situation, all oral contraceptives are not recommended because of a higher risk of failure.
MacGregor, E Anne
Most women have used at least 1 method of contraception during their reproductive years, with the majority favoring combined oral contraceptives. Women are often concerned about the safety of their method of choice and also ask about likely effects on their pre-existing headache or migraine and restrictions on using their headache medication. While there should be no restriction to the use of combined hormonal contraceptives by women with migraine without aura, the balance of risks vs benefits for women with aura are debatable. Migraine with aura, but not migraine without aura, is associated with a twofold increased risk of ischemic stroke, although the absolute risk is very low in healthy, nonsmoking women. Although ethinylestradiol has been associated with increased risk of ischemic stroke, the risk is dose-dependent. Low-dose pills currently used are considerably safer than pills containing higher doses of ethinylestradiol but they are not risk-free. This review examines the evidence available regarding the effect that different methods of contraception have on headache and migraine and identifies strategies available to minimize risk and to manage specific triggers such as estrogen "withdrawal" headache and migraine associated with combined hormonal contraceptives. The independent risks of ischemic stroke associated with migraine and with hormonal contraceptives are reviewed, and guidelines for use of contraception by women with migraine are discussed in light of the current evidence.
Amory, J K
Efforts are underway to develop additional forms of contraception for men. The most promising approach to male contraceptive development involves the administration of exogenous testosterone (T). When administered to a man, T functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary, thereby depriving the testes of the signals required for spermatogenesis. After 2-3 months of treatment, low levels of these gonadotropins lead to markedly decreased sperm counts and effective contraception in a majority of men. Hormonal contraception with exogenous T has proven to be free from serious adverse effects and is well tolerated by men. In addition, sperm counts uniformly normalize when the exogenous T is discontinued. Thus, male hormonal is safe, effective and reversible; however, spermatogenesis is not suppressed to zero in all men, meaning that some diminished potential for fertility persists. Because of this recent studies have combined T with progestogens and/or gonadotropin-releasing antagonists to further suppress pituitary gonadotropins and optimize contraceptive efficacy. Current combinations of T and progestogens completely suppress spermatogenesis without severe side effects in 80-90% of men, with significant suppression in the remainder of individuals. Recent trials with newer, long-acting forms of injectable T, which can be administered every 8 weeks, combined with progestogens, administered either orally or by long-acting implant, have yielded promising results and may soon result in the marketing of a safe, reversible and effective hormonal contraceptive for men.
Wright, K. P. Jr; Badia, P.; Czeisler, C. A. (Principal Investigator)
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.
Epplein, Meira; Reed, Susan D.; Voigt, Lynda F.; Newton, Katherine M.; Holt, Victoria L.; Weiss, Noel S.
Purpose Examine the relationship between recent use of oral contraceptives and hormone therapy and endometrial hyperplasia (EH) risk. Methods Cases comprised women diagnosed with complex EH (n=289) or atypical EH (n=173) between 1985-2003. One age-matched control was selected for each case; excluded were women with a prior hysterectomy or diagnosis of EH or endometrial cancer. Hormone use in the six months prior to the date of the case’s first symptoms was ascertained using a pharmacy database and medical records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated. Results Three (1.1%) cases had used oral contraceptives, compared to sixteen (6.0%) controls (OR = 0.2, 95% CI: 0.0–0.6). Fifty-one (16.8%) cases had taken estrogen-only hormone therapy, in contrast to two (0.7%) controls (OR = 37.6, 95% CI: 8.8–160.0). The risk of EH among estrogen plus progestin hormone users did not differ from that of non-users (OR = 0.7, 95% CI: 0.4–1.1). Conclusions This study suggests that previous findings of the association of estrogen-only hormone therapy with increased risk of EH and the lack of an association between estrogen plus progestin hormone therapy and EH risk are likely to apply to both complex EH and atypical EH. Further examination of the association between oral contraceptives and EH, with greater numbers of OC users, is warranted. PMID:19064186
Rosenberg, L; Palmer, J R; Rao, R S; Zauber, A G; Strom, B L; Warshauer, M E; Harlap, S; Shapiro, S
The relation of oral contraceptive use to the risk of breast cancer in white women aged 25-59 years was assessed with data collected during 1977-1992 in a case-control surveillance system in hospitals in Boston, New York, and Philadelphia. A total of 3,540 cases with breast cancer were compared with 4,488 controls with nonmalignant nongynecologic conditions unrelated to oral contraceptive use. Relative risk estimates were obtained by unconditional logistic regression with control for major risk factors. For at least 1 year of use relative to less than 1 year, the multivariate relative risk estimate was 1.7 (95% confidence interval (CI) 1.3-2.3) in women aged 25-34 years, 0.9 (95% CI 0.7-1.0) in women aged 35-44 years, and 1.2 (95% CI 1.0-1.4) in women aged 45-59 years (p < 0.01 for the difference across age). Among women aged 25-34 years, the relative risk estimates were greatest for use of long duration, but the trend was not statistically significant (p = 0.17); in addition, the duration of use was correlated with the recency of use, and it was not possible to distinguish their effects. Among women aged 35-44 years, the relative risk estimate decreased with increasing duration of use (p = 0.01). Among women aged 45-59 years, some relative risk estimates were increased, but there was no consistent pattern. The results add to the evidence of an association between oral contraceptive use and an increased risk of breast cancer at young ages.
Ribeiro-Alves, Mirna A; Trugo, Luiz C; Donangelo, Carmen M
Caffeine consumption increases the urinary excretion of calcium and other minerals. Factors that affect caffeine metabolism such as steroid hormones may modify this effect. The purpose of this study was to evaluate the influence of oral contraceptive (OC) use on the 4-h urinary excretion of calcium, phosphorus, magnesium, zinc, sodium, potassium and caffeine metabolites in response to a high caffeine dose given as coffee beverage. Adult women, 20-29 y, users (+OC, n = 15) and nonusers (-OC, n = 15) of oral contraceptives, with calcium intake approximately 500 mg/d, participated in two tests, caffeine load (5 mg/kg body weight) and no-caffeine control, in a randomized crossover design. The net increase (caffeine load corrected by no caffeine) in urinary excretion of most minerals was significantly higher in -OC than in +OC (P < 0.05), with the larger group difference for calcium (ninefold) followed by magnesium (twofold), zinc (onefold) and potassium (onefold). Net increases in urinary excretion of 1-methylurate and paraxanthine were about three- and fivefold higher, respectively, in -OC than in +OC (P < 0.05) whereas net increases in urinary excretion of 5-acetylamino-6-formylamino-3-methyluracil (AFMU) and 1,7-dimethylurate were over twofold higher in the +OC than in -OC (P < 0.05). Following the caffeine load, most urinary minerals showed negative correlation with urinary 1-methylurate in -OC (R = -0.78, P < 0.01), and with urinary AFMU and 1,7-dimethylurate in +OC (R = -0.84, P < 0.01). Oral contraceptives appear to limit the renal effect of caffeine on mineral excretion possibly by reducing paraxanthine excretion, the most active caffeine metabolite.
Veninga, K S
This article examines the effects of oral contraceptives (OCs) on the metabolism of vitamin B6, folacin, vitamin B12, and vitamin C and outlines educational strategies through which nurse-midwives can improve their clients' nutritional health. Evidence of vitamin B6 deficiency has been found among combination OC users in numerous studies. Derangement of tryptophan metabolism occurs within 1 month of initiation of OC use. OCs also may cause a deficiency of pyridoxal phosphate, a coenzyme needed for the tryptophan-nicotinic acid pathway. It is recommended that OC users take 1-1.5 mg/day of supplemental vitamin B6; new OC users should take 5 mg/day until plasma levels of 1.5-2 mg have been achieved. It has also been noted that OCs impair folacin metabolism, as evidenced by folacin deficiency in serum and an increase in urinary formiminoglutamic acid secretion. It is generally ageed that folacin, which plays a critical role in fetal development, can become deficient in late pregnancy and in women who become pregnant shortly after discontinuing longterm OC use. OCs further influence serum B12 concentrations and the possiblity of iron deficiency anemia. Among patients who are well nourished and nonsmokers, OC use does not appear to jeopardize vitamin C levels. An assessment of a patient's nutritional health should begin with a demographic evaluation focused on her age, parity, alcohol and nicotine consumption, and use of medications and vitamins. Next, a dietary evaluation should be made by having the patient record everything she eats during the following week. It should be remembered that adolescents, lactating women, those with repeated pregnancies closely spaced, and women who are chemically dependent have greater nutritional needs than normal. Nutritional counseling is particularly needed by OC users, who may be deficient in 1 or more of the essential vitamins. Nutritional counseling should be an ongoing part of any comprehensive patient-teaching program.
Kharbanda, Elyse Olshen; Parker, Emily D.; Sinaiko, Alan; Daley, Matthew F.; Margolis, Karen; Becker, Mary; Sherwood, Nancy E.; Magid, David; O’Connor, Patrick
Objectives To describe changes in systolic blood pressure (SBP), diastolic blood pressure (DBP) and body mass index (BMI) associated with initiation and continued use of combined oral contraceptives (COCs) in healthy adolescents. Study design This observational, matched cohort study was conducted in two large health systems. Utilizing claims and electronic medical records, we identified adolescents 14-17.9 years of age initiating medium-dose COCs (containing 30 or 35 micrograms of ethinyl estradiol or equivalent and a progestin) between 7/1/07-12/31/09 with a baseline and at least one follow-up BP and BMI. COC-users were matched 1:2 by age, race/ethnicity and site to controls (COC-non-users). All BPs and BMIs recorded during outpatient visits starting 1 month prior to COC initiation (index date for controls), through 12/31/2010 were collected. Mixed model linear regression with random intercepts and slopes were then used to estimate changes in SBP, DBP and BMI over time. Results The 510 adolescent COC-users and 912 controls did not differ significantly by age, race/ethnicity, insurance, baseline SBP, DBP or BMI. After adjusting for baseline values, over a median of 18 months follow-up, COC-users had an decrease in SBP of 0.07 mmHG/month, and controls had an increase of 0.02 mmHG/month (p=.65). Similarly, DBP decreased by 0.007 mmHG/month in COC-users versus 0.006 mmHG/month in controls (p=.99). BMI increased by 0.04 (kg/m2)/month in COC-users versus 0.025(kg/m2)/month in controls (p=.09). Conclusions These data should provide reassurance to patients and providers regarding the lack of significant associations between COC-use and BMI or BP changes in adolescents. PMID:25189822
Isacco, Laurie; Thivel, David; Pelle, Anne Meddahi; Zouhal, Hassane; Duclos, Martine; Duche, Pascale; Boisseau, Nathalie
Oral contraception (OC) and energy intake may play a role in fuel selection during exercise. The aim of this study was to investigate the effect of OCs (OC+ vs. OC-) in fed and fasting conditions on substrate oxidation and metabolic and hormonal responses in women during exercise. Substrate oxidation (respiratory exchange ratio and lipid and carbohydrates oxidation rates), metabolic (glycerol, free fatty acids (FFA), and glucose), and hormonal (insulin, adrenaline, and noradrenaline) responses were determined in 21 women: 10 regularly menstruating women (OC-) and 11 women using OCs (OC+: low-dose monophasic pill; ethinyl estradiol ≤ 30 µg) during 45 min at 65% of maximal oxygen consumption in fasting and postprandial states. At rest, OC+ presented higher low-density lipoprotein cholesterol, total cholesterol, and triglyceride plasma concentrations as compared with OC-. OC status had no influence on substrate oxidation and metabolic and hormonal responses during exercise. In the fasting state, whatever the OC status, women exhibited greater reliance on fat than in postprandial condition. This occurred in the presence of lower plasma insulin concentrations and higher plasma FFA and glycerol levels. The results indicated that the use of low-dose monophasic combined with OCs did not modify fuel selection and metabolic and hormonal responses during exercise in women. The fasting condition, compared with the fed condition, decreased carbohydrate oxidation during exercise, leading to a greater lipid mobilization and utilization whatever the OC status. Thus, in women, the realization of an exercise in either the fed or fasting conditions had a greater impact on substrate oxidation than OC status.
Montoya, Estrella R; Bos, Peter A
Millions of women worldwide use oral contraceptives ('the pill'; OCs), often starting at a pubertal age when their brains are in a crucial developmental stage. Research into the social-emotional effects of OCs is of utmost importance. In this review, we provide an overview of studies that have emerged over the past decade investigating how OCs, and their main ingredients estradiol (E) and progesterone (P), influence social-emotional behaviors and underlying brain functions. Based on this overview, we present a heuristic model that postulates that OCs modulate core social-emotional behaviors and brain systems. Research domains and challenges for the future, as well as implications, are discussed.
Mansvelt, B; Etienne, P Y; Bertrand, C; Henrion, J; Gerard, R
A 36-year-old woman presented with sudden abdominal pain and vomiting. Computed tomography showed a tumour of the right hepatic lobe with possible signs of acute haemorrhage. Her medical history revealed precocious puberty when she was a 5-year-old and the use of oral contraceptives for 18 years. Bisegmentectomy was performed and histological examination revealed hepatocellular carcinoma. The role of male and female sex hormones in the development of hepatic tumours has been well documented but, to our knowledge, association with precocious puberty has not yet been described.
Two oral postcoital contraceptive agents are currently available. The first is a 2 x 2 pill; the second is a 5 x 5. Both release a higher dose of hormones than conventional contraceptive pills. Success rates range between 96% and 99%. They must be taken within 72 hours of intercourse. Side effects include nausea and vomiting. Contraindications are the same as for the common oral contraceptives. The contraceptive mode of action can be any of the following: 1) by making the lining of the uterus unreceptive; 2) by slowing the movement of the egg in the fallopian tube; or 3) by affecting the release of the egg. Emergency contraceptive pills have no effect once implantation takes place. The IUD can be used as an emergency postcoital contraceptive method if placed within 10 days of coitus. They are usually placed within 5-7 days because of laws regarding when birth control becomes abortion. One failure has been reported in Great Britain (December, 1993). Side effects are the same as with regular use. RU486/PG may be used in the future as an emergency contraceptive agent. Research is in progress on success rates and side effects. This agent could potentially be used at any time. Currently, emergency contraception can only be obtained by prescription. Limited hours and interrogating staff are obstacles in such emergencies. British women's groups are asking that emergency oral contraceptive pills be made available over the counter with advice from the pharmacist.
Ruedl, Gerhard; Ploner, Patrick; Linortner, Ingrid; Schranz, Alois; Fink, Christian; Sommersacher, Renate; Pocecco, Elena; Nachbauer, Werner; Burtscher, Martin
Oral contraceptive use and menstrual cycle phase are suggested to influence the risk of anterior cruciate ligament (ACL) injuries in female athletes. However, only few data are available for recreational sports. Therefore, female recreational skiers with a non-contact ACL injury and age-matched controls completed a self-reported questionnaire relating to menstrual history, oral contraceptive use and previous knee injuries. Menstrual history data were used to group subjects into either preovulatory or postovulatory phases of menstrual cycle. Our findings suggest that oral contraceptive use did not show any protective effect against ACL injuries nor did self-reported previous knee injuries show any association with ACL injury rate in recreational alpine skiing. Analysis of menstrual history data revealed that recreational skiers in the preovulatory phase were significantly more likely to sustain an ACL injury than were skiers in the postovulatory phase.
Ghosh, P K; Ghosh, R
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.
Pelletier, J; Cabanot, C; Lévrier, O; Thuillier, J N; Chérif, A A
Two seventeen year-old women, developed acute onset left choreic movements following two months and two weeks use of oral contraceptives. Left hemiparesia appeared a few days later, while involuntary movements discontinued. Cranial CT scan and MRI showed bilateral ischemic lesion in the frontal region for the first case and isolated lesion in the right centrum ovale for the second. Angiography showed nearly complete obstruction of the terminal portion of the internal carotid artery with an outline Moya-Moya network. After discontinuing oral contraceptives, there has been no relapse of neurologic dysfunction for more than three years for the first case and twelve months for the second one. The role of perfusion insufficiency in limb-shaking carotid transient ischemic attack is discussed and the possible relations between oral contraceptives, chorea and angiographic features resembling Moya-Moya disease are evaluated.
If complications occur within a pregnancy planned and brought to term, they often can be dealt with and accepted. They are even more traumatic when they occur in an unwanted pregnancy that could have been prevented through contraception. Teenagers, because of their physical and psychological immaturity and also because of their social environment, seem to suffer with undue frequency from the complications of induced abortion. Its result, for the teenager, is a handicapped future in comparison to other women. Hence, access to contraception is important for all women, and especially for teenagers, in order to avoid such prejudicial situations. It is important, then, to prescribe oral contraception for its efficacy and its short- and long-term innocuousness. Because of her immaturity, the pregnant teenager is at risk: of spontaneous abortion, pre-eclampsia, anemia, hemorrhage, and prematurity. She is also at risk because of the social difficulties she will be facing. This is particularly true in families from developing countries. From birth, the child is also at risk: of low birth weight for the term, mortality in the first year of life, and all risks linked to abandonment, or education by a third party. In a proportion of 13 to 30% in western countries and in a proportion of 3% in East Asia or in Northwest Africa (Maghreb), induced abortions are a reflection of the following: early sexual activity without contraception even if fertility is still low in very young teenagers, absence of social protection or social independence, refusal of forced marriage, and presence or absence of liberal legislation.(ABSTRACT TRUNCATED AT 250 WORDS)
Wright, K. P. Jr; Myers, B. L.; Plenzler, S. C.; Drake, C. L.; Badia, P.; Czeisler, C. A. (Principal Investigator)
Caffeine and bright light effects on nighttime melatonin and temperature levels in women were tested during the luteal phase of the menstrual cycle (n=30) or the pseudo luteal phase for oral contraceptive users (n=32). Participants were randomly assigned to receive either bright (5000 lux) or dim room light (<88 lux) between 20:00 and 08:00 h under a modified constant routine protocol. Half the subjects in each lighting condition were administered either caffeine (100 mg) or placebo in a double-blind manner at 20:00, 23:00, 02:00 and 05:00 h. Results showed that the combination of bright light and caffeine enhanced nighttime temperature levels to a greater extent than did either caffeine or bright light alone. Both of the latter groups had higher temperature levels relative to the dim light placebo condition and the two groups did not differ. Temperature levels in the bright light caffeine condition were maintained at near peak circadian levels the entire night in the luteal and pseudo luteal phase. Melatonin levels were reduced throughout the duration of bright light exposure for all women. Caffeine reduced the onset of melatonin levels for women in the luteal phase, but it had little effect on melatonin levels for oral contraceptive users. The results for women in the luteal phase of the menstrual cycle are consistent with our previous findings in men. The results also suggest that oral contraceptives may alter the effects of caffeine on nighttime melatonin levels.
Khalili, Hamed; Neovius, Martin; Ekbom, Anders; Ludvigsson, Jonas F.; Askling, Johan; Chan, Andrew T; Olen, Ola
BACKGROUND Oral contraceptive (OC) use has been consistently linked to increased risk of inflammatory bowel disease (IBD). Nonetheless, a specific role of OC on the natural history of ulcerative colitis (UC) is unknown. METHODS We identified 6,104 incident female UC cases aged 16–51 years at diagnosis from the Swedish National Patient Register starting in January of 2003. Information on current OC use was obtained from the Prescribed Drug Register starting in July of 2005. We followed cases through December of 2014 for primary outcome defined as first UC-related surgery, and the secondary outcomes defined by recipient of the first prescription of oral steroids or anti-TNF use. We used Cox proportional hazard modeling with time-varying covariates to estimate multivariable-adjusted hazard ratio (aHR) and 95% confidence interval (CI). RESULTS Over 31,421 person-years of follow up, we observed 162 cases of UC-related surgery. Compared to non-users, current and past use of OC were not significantly associated with risk of UC-related surgery (aHR = 0.79, 95% CI, 0.52–1.18, and 0.74, 95% CI 0.46–1.18, respectively). The association did not appear to be modified by type of OC use (progestin-only vs. combination of progestin and estrogen), longer duration of use or higher number of dispensed prescriptions (All Ptrend > 0.28). Similarly, longer use or higher cumulative number of OC prescriptions were not associated with increased risk of receiving a steroid prescription (Ptrend = 0.68 and 0.63, respectively). In exploratory analyses restricted to Stockholm county, current OC use was not associated with increased risk of receiving anti-TNF therapy (aHR = 0.83, 95% CI, 0.59 – 1.18). CONCLUSIONS In a large nationwide registry of UC patients, we found no association between OC use and UC progression. Our data offer reassurance regarding the safety of OC assessed by its effect on risk of surgery and steroid or anti-TNF use in women with established UC. PMID:27725646
Treffers, P E
In the Netherlands many women stop breastfeeding in the first few months postpartum. In 1997, only 16.9% of all 3-month-old babies received full breastfeeding. One of the causes may be insufficient support by the medical profession. A second factor is that often combined oral contraceptives are prescribed to breastfeeding women. As it has been shown that estrogens in these contraceptives inhibit lactation, this is probably one of the reasons why breastfeeding frequently fails in this country. WHO advises not to use estrogens during lactation. According to recent research the lactational amenorrhoea method of contraception (LAM) is highly effective during the first 4 months postpartum. In the 5th and 6th month the effectiveness is strongly dependent on the accuracy by which the conditions are met. The medical profession should pay more attention to the support of breastfeeding and contraception in relation to each other.
Sueta, Daisuke; Akahoshi, Rika; Okamura, Yoshinori; Kojima, Sunao; Ikemoto, Tomokazu; Yamamoto, Eiichiro; Izumiya, Yasuhiro; Tsujita, Kenichi; Kaikita, Koichi; Katabuchi, Hidetaka; Hokimoto, Seiji
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.
Sueta, Daisuke; Akahoshi, Rika; Okamura, Yoshinori; Kojima, Sunao; Ikemoto, Tomokazu; Yamamoto, Eiichiro; Izumiya, Yasuhiro; Tsujita, Kenichi; Kaikita, Koichi; Katabuchi, Hidetaka; Hokimoto, Seiji
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. PMID:28202862
Rogers, S M; Back, D J; Stevenson, P J; Grimmer, S F; Orme, M L
The effect of a single dose of paracetamol (1 g) on plasma concentrations of the oral contraceptive steroids ethinyloestradiol (EE2) and levonorgestrel (LNG) has been studied in six healthy female volunteers. The area under the plasma concentration-time curve (AUC0-24) of EE2 was significantly increased following paracetamol administration by 22% (control 2221 +/- 291; following paracetamol, 2702 +/- 452 pg ml-1 h; mean +/- s.d.; P less than or equal to 0.05). The greatest effect was evident in the time period 0-3 h. There was a significant decrease in the AUC of EE2-sulphate after paracetamol (7736 +/- 3791 pg ml-1 h) compared with control (13161 +/- 4535 pg ml-1 h; P less than or equal to 0.05). Plasma concentrations of LNG were unaltered by concurrent paracetamol administration. We conclude that the administration of a single 1 g dose of paracetamol causes an increase in plasma concentrations of EE2 as a result of a reduction in the sulphation of the steroid. This interaction may be of clinical significance in women on oral contraceptive steroids who regularly take paracetamol. PMID:3111513
Carranza-Lira, S; Bueno Fontal, J P
The association between oral contraceptives and the modification of corporal weight and body fat distribution is controversial. The characteristics of the menstrual cycle, lipids and glucose levels were also analyzed. Thirty women who received ethinylestradiol 0.035 mg and norethindrone 0.400 mg for one year were studied. The following variables were analyzed every 3 months: weight, body mass index (BMI), hip perimeter, waist perimeter, waist-hip ratio (WHR), duration of menstrual cycle, quantity of uterine bleeding, as well as blood levels of cholesterol, triglycerides and glucose. Waist and hip perimeters increased during the third evaluation; as well as the BMI starting from the second evaluation. The triglycerides levels rose from the first evaluation. No modifications were found in the WHR, glucose and cholesterol levels and the duration of the menstrual cycle, but the quantity of uterine bleeding decreased from the third month. The oral contraceptive significantly increased BMI and triglycerides level, but no changes were detected in body fat distribution, cholesterol and glucose levels. Uterine bleeding decreased from the first evaluation.
Grodstein, Francine; Stampfer, Meir J.; Willett, Walter C.; Hu, Frank B.; Manson, JoAnn E.
Objectives. To review the contribution of the Nurses’ Health Study (NHS) to our understanding of the complex relationship between exogenous hormones and health outcomes in women. Methods. We performed a narrative review of the publications of the NHS and NHS II from 1976 to 2016. Results. Oral contraceptive and postmenopausal hormone use were studied in relation to major health outcomes, including cardiovascular disease and cancer. Current or recent oral contraceptive use is associated with a higher risk of cardiovascular disease (mainly among smokers), melanoma, and breast cancer, and a lower risk of colorectal and ovarian cancer. Although hormone therapy is not indicated primarily for chronic disease prevention, findings from the NHS and a recent analysis of the Women’s Health Initiative indicate that younger women who are closer to menopause onset have a more favorable risk–benefit profile than do older women from use of hormone therapy for relief of vasomotor symptoms. Conclusions. With updated information on hormone use, lifestyle factors, and other variables, the NHS and NHS II continue to contribute to our understanding of the complex relationship between exogenous hormones and health outcomes in women. PMID:27459451
Sandoval, Darleen A.; Matt, Kathleen S.
To test whether the oral contraceptive pill cycle affects endocrine and metabolic responses to hypoxic (fraction of inspired oxygen = 13%, P(IO2): 95 mmHg; H) versus normoxic (P(IO2):153 mmHg; N) exercise, we examined eight women (28 +/- 1.2 yr) during the third (PILL) and placebo (PLA) weeks of their monthly oral contraceptive pill cycle. Cardiopulmonary, metabolic, and neuroendocrine measurements were taken before, during, and after three 5-min consecutive workloads at 30%, 45%, and 60% of normoxic V(O2peak) in H and N trials. Heart rate response to exercise was greater in H versus N, but was not different between PILL and PLA. Lactate levels were significantly greater during exercise, and both lactate and glucose levels were significantly greater for 30 min after exercise in H versus N (p < 0.0001). When expressed relative to baseline, lactate levels were lower in PILL versus PLA, but glucose was greater in PILL versus PLA (p < 0.001). Cortisol levels were also significantly greater in PILL versus PLA (p < 0.001). Norepinephrine levels were significantly increased during exercise (p < 0.0001) and in H versus N (p < 0.0001). However, epinephrine levels were not different over time or with trial. Thus, the presence of circulating estradiol and progesterone during the PILL phase reduces glucose and lactate responses to hypoxic exercise.
Suárez, Víctor J; Zavala, Renzo; Ureta, Juan Manuel; Hijar, Gisely; Lucero, Jorge; Pachas, Paul
There is wide controversy about the mechanism of action of the levonorgestrel used for emergency oral contraception, and many organizations, both scientific as well as from the civil society, show their discrepancy with its use, due to its possible action as an abortion- inducer. In order to evaluate the scientific evidence available on the mechanisms of action of the levonorgestrel used for emergency oral contraception (EOC), a systematic revision was performed in the Medline and Cochrane library databases. We found 444 articles. After reviewing the abstracts, we selected 22 articles, whose complete texts were evaluated. We found that the main mechanism of action of the levonorgestrel, given at the doses recommended for EOC, is the inhibition or retardation of the ovulation, it doesn't affect the spermatozoa in their migration or egg-penetration capacities. No morphological or molecular alterations in the endometrium that could interfere with the implantation of the fertilized egg have been demonstrated. There is no actual scientific evidence available supporting that the use of levonorgestrel for EOC is abortive.
Schenker, J G; Rabenou, V
Humans have tried to control fertility for centuries. Primitive, preliterate societies practiced infanticide and abortion. When primitive women understood the advantages of conception control, they tried, when possible, to use contraception. In the 4th century B.C., Plato and Aristotle advocated a one-child family. Greek medical literature reported a hollow tube inserted through the cervix into the uterus and a potion as contraceptives. Islamic physicians had much knowledge about conception control. The attitudes toward contraception. In the 5th century B.C., Saint Augustine condemned contraception, even among married couples. The condom emerged in the early modern period. Yet, they were usually worn to protect against disease, e.g., bilharzia in Egypt and syphilis in Europe. The cervical cap and the diaphragm are examples of occlusive pessaries. By 1880, contraceptives and spermicides were advertised. In 1928, the IUD joined the existing contraceptives. Today we have combined oral contraceptives. Judaic law requires husbands to fulfill their wives sexual needs, separate from their duty to procreate. It also calls men, not women, to procreate and forbids men from masturbating, thus Judaic law does not forbid women from practicing contraception. The Roman Catholic church forbids contraceptive use because it is a sin against nature. Some Protestant denominations have allowed contraceptive use. Islamic law states that children are gifts from Allah. Some Moslems believe that they must have many children, but Allah and the Prophet state that children have rights to education and future security. These rights allow couples to prevent pregnancy. Neither Hinduism nor Buddhism prohibit contraceptive use. Differences in husband-wife communication, sex roles, access to contraceptives, and traditional family values will have more of an effect on contraceptive use and fertility than theological barriers or the social class of religious groups.
Del Pup, Lino; Berretta, Massimiliano; Di Francia, Raffaele; Cavaliere, Carla; Di Napoli, Marilena; Facchini, Gaetano; Fiorica, Francesco; Mileto, Mario; Schindler, Adolf E
Combined hormonal contraceptives (CHCs) contain estrogen and progestin, which can stimulate estrogen-sensitive and/or progesterone-sensitive breast cancer growth. Until recently, ethinylestradiol had been almost the only estrogen used for decades, and its dose has been greatly reduced over time. The first generations of birth control pills contained approximately five times more estrogen and four times more progestin than the latest contraceptives. Newer CHCs also contain steroids that more closely mimic the physiological estradiol (E2) and progesterone effects. The newer CHC formulations are thus expected to have less influence on the breast, although it is very difficult to demonstrate any difference among the recent available preparations in human studies. Recently, nomegestrol acetate (NOMAC), a neutral, nonandrogenic, progesterone-like profile progestin, has become available in combination with the 'natural' estrogen, E2. According to the literature, NOMAC/E2 is expected to have either a lesser stimulating effect or a neutral effect on estrogen-sensitive breast cancers. We performed an analysis of the available studies and a bibliographical review. The endocrine and metabolic effects of NOMAC/E2 formulation might lead to a lesser breast tissue stimulation. The data reported, confirmed through clinical studies, should be considered when choosing a hormonal contraceptive, especially when breast stimulation is a concern.
Balkus, Jennifer E.; Brown, Elizabeth R.; Hillier, Sharon L.; Coletti, Anne; Ramjee, Gita; Mgodi, Nyaradzo; Makanani, Bonus; Reid, Cheri; Martinson, Francis; Soto-Torres, Lydia; Karim, Salim S. Abdool; Chirenje, Zvavahera M.
Objective To assess the effect of oral and injectable contraceptive use compared to non-hormonal contraceptive use on HIV acquisition among Southern African women enrolled in a microbicide trial. Study Design Prospective cohort study using data from women enrolled in HIV Prevention Trials Network (HPTN) protocol 035. At each quarterly visit, participants were interviewed about self-reported contraceptive use and sexual behaviors and underwent HIV testing. Cox proportional hazards regression was used to assess the effect of injectable and oral hormonal contraceptive use on HIV acquisition. Results The analysis included 2,830 participants, of whom 106 became HIV infected (4.07 per 100 person-years.) At baseline, 1,546 (51%) participants reported using injectable contraceptives and 595 (21%) reported using oral contraceptives. HIV incidence among injectable, oral and non-hormonal contraceptive method users was: 4.72, 2.68 and 3.83 per 100 person-years, respectively. Injectable contraceptive use was associated with a non-statistically significant increased risk of HIV acquisition (adjusted hazard ratio [aHR] = 1.17; 95% confidence interval [CI] 0.70, 1.96), while oral contraceptive use was associated with a non-statistically significant decreased risk of HIV acquisition (aHR=0.76; 95% CI 0.37,1.55). Conclusion In this secondary analysis of randomized trial data, a marginal, but non-statistically significant, increase in HIV risk among women using injectable hormonal contraceptives was observed. No increased HIV risk was observed among women using oral contraceptives. Our findings support the World Health Organization’s recommendation that women at high risk for acquiring HIV, including those using progestogen-only injectable contraception, should be strongly advised to always use condoms and other HIV prevention measures. PMID:26519646
Baratloo, Alireza; Safari, Saeed; Rouhipour, Alaleh; Hashemi, Behrooz; Rahmati, Farhad; Motamedi, Maryam; Forouzanfar, Mohammadmehdi; Haroutunian, Pauline
Introduction: Oral contraceptives (OCs) are considered as one of the most common risk factor of venous thromboembolism (VTE) in childbearing age. Some of the recent researches indicate that the odds of VTE may be even higher with newer generations of OCs. The present meta-analysis was designed to evaluate the effect of different generation of OCs on the occurrence of VTE. Methods: Two researchers independently ran a thorough search in Pubmed, ISI Web of Science, EMBASE, CINAHL and Scopus databases regarding study keywords including thromboembolic event, thromboembolism, embolism, thromboembolic, thrombotic and thrombosis, combined with oral contraceptive. The outcomes were the incidence of diagnosed thromboembolism, such as deep vein thrombosis, pulmonary embolism and cerebral venous thrombosis. Based on the heterogeneity of the studies, random effect model was used and pooled odds ratio was reported. Results: Three cohort and 17 case-control studies with 13,265,228 subjects were entered into meta-analysis. Analysis showed that the odds of VTE in women taking OCs are more than three-fold (OR=3.13; 95% CI: 2.61-3.65). The risk of VTE in women taking first-, second- and third-generation OCs are 3.5 fold (OR=3.48; 95% CI: 2.01-4.94), 3 fold (OR=3.08; 95% CI: 2.43-3.74) and 4.3 fold (OR=4.35; CI: 3.69‒5.01), respectively. Conclusion: It seems that the risk of VTE is not same between different generations of OCs, so that third-generation has highest risk. Taking second and third-generation OCs increases the risk of VTE up to 3 and 4.3 fold, respectively. The researchers of the present study suggest that more trials be designed in relation to the effect of newer generations of OCs in different communities. PMID:26495334
Dieben, T O; op ten Berg, M T; Coelingh Bennink, H J
In a multicentre study 882 women were treated during a total of 12,850 cycles with a new combiphasic contraceptive: CTR 24. The study period was 18 cycles. The combiphasic preparation CTR 24 contains 25 micrograms desogestrel (CAS 54024-22-5) plus 40 micrograms ethinylestradiol (CAS 57-63-6) daily for the first 7 days followed by the combination of 125 micrograms desogestrel and 30 micrograms ethinyl-estradiol daily for the subsequent 15 days. The bleeding patterns were analysed over pill cycles and a comparison was made between starters and switchers. The cycle control of the combination was very good. The side effect profile was favourable.
Romero, Iris L; Gordon, Ilyssa O; Jagadeeswaran, Sujatha; Mui, Keeley L; Lee, Woo Seok; Dinulescu, Daniela M; Krausz, Thomas N; Kim, Helen H; Gilliam, Melissa L; Lengyel, Ernst
Although epidemiologic evidence for the ability of combined oral contraception (OC) to reduce the risk of ovarian cancer (OvCa) is convincing, the biological mechanisms underlying this effect are largely unknown. We conducted the present study to determine if OC also influences ovarian carcinogenesis in a genetic mouse model and, if so, to investigate the mechanism underlying the protective effect. LSL-K-ras(G12D/+)Pten(loxP/loxP) mice were treated with ethinyl estradiol plus norethindrone, contraceptive hormones commonly used in combined OC, or norethindrone alone, or a gonadotropin-releasing hormone agonist. The combined OC had a 29% reduction in mean total tumor weight compared with placebo (epithelial tumor weight, -80%). Norethindrone alone reduced mean total tumor weight by 42% (epithelial tumor weight, -46%), and the gonadotropin-releasing hormone agonist increased mean total tumor weight by 71% (epithelial tumor weight, +150%). Large variations in tumor size affected the P values for these changes, which were not statistically significant. Nonetheless, the OC reductions are consistent with the epidemiologic data indicating a protective effect of OC. Matrix metalloproteinase-2 activity was decreased in association with OC, indicating that OC may affect ovarian carcinogenesis by decreasing proteolytic activity, an important early event in the pathogenesis of OvCa. In contrast, OC increased invasion in a K-ras/Pten OvCa cell line established from the mouse tumors, suggesting that OC hormones, particularly estrogen, may have a detrimental effect after the disease process is under way. Our study results support further investigation of OC effects and mechanisms for OvCa prevention.
Tsilidis, K K; Allen, N E; Key, T J; Bakken, K; Lund, E; Berrino, F; Fournier, A; Olsen, A; Tjønneland, A; Overvad, K; Boutron-Ruault, M-C; Clavel-Chapelon, F; Byrnes, G; Chajes, V; Rinaldi, S; Chang-Claude, J; Kaaks, R; Bergmann, M; Boeing, H; Koumantaki, Y; Stasinopoulou, G; Trichopoulou, A; Palli, D; Tagliabue, G; Panico, S; Tumino, R; Vineis, P; Bueno-de-Mesquita, H B; van Duijnhoven, F J B; van Gils, C H; Peeters, P H M; Rodríguez, L; González, C A; Sánchez, M-J; Chirlaque, M-D; Barricarte, A; Dorronsoro, M; Borgquist, S; Manjer, J; van Guelpen, B; Hallmans, G; Rodwell, S A; Khaw, K-T; Norat, T; Romaguera, D; Riboli, E
Background: Oral contraceptive use and reproductive factors may initiate long-term changes to the hormonal milieu and thereby, possibly influence colorectal cancer risk. Methods: We examined the association of hormonal and reproductive factors with risk of colorectal cancer among 337 802 women in the European Prospective Investigation into Cancer and Nutrition, of whom 1878 developed colorectal cancer. Results: After stratification for center and age, and adjustment for body mass index, smoking, diabetes mellitus, physical activity and alcohol consumption, ever use of oral contraceptives was marginally inversely associated with colorectal cancer risk (hazard ratio (HR), 0.92; 95% confidence interval (CI), 0.83–1.02), although this association was stronger among post-menopausal women (HR, 0.84; 95% CI: 0.74–0.95). Duration of oral contraceptive use and reproductive factors, including age at menarche, age at menopause, type of menopause, ever having an abortion, parity, age at first full-term pregnancy and breastfeeding, were not associated with colorectal cancer risk. Conclusion: Our findings provide limited support for a potential inverse association between oral contraceptives and colorectal cancer risk. PMID:21045829
Levrier, M; Degrelle, H; Bestaux, Y; Bourry-Moreno, M; Brun, J P; Sailly, F
The authors conducted a comparative study of the effect of two oral contraceptives Varnoline and Diane in the treatment of androgenic manifestations: acne and hirsutism. The two products tested seem to have a similar efficacy on this type of clinical manifestations.
The alterations in lipid metabolism that occur with the use of oral contraceptives (OCs) have aroused considerable concern that OCs might increase the risk of premature atherosclerosis. However, most studies examining the role of OCs in atherogenesis were performed using earlier-generation preparations employing larger doses of sex hormones than present formulation. Therefore, we undertook a comparative and standardized determination of the effects on lipid metabolism of six modern, low-dose OCs. This open, randomized, comparative study included patients recruited at 21 study centers throughout Europe. Four hundred sixty-six women, aged 18-38 years, participated. They were randomly assigned to the following OC formulations:(1) norgestimate 250 micrograms + ethinyl estradiol (EE) 35 micrograms (Cilest); (2) norgestimate 180/215/250 micrograms + EE 35 micrograms (Tricilest); (3) desogestrel 150 micrograms + EE 20 micrograms = (Marvelon); (4) desogestrel 150 micrograms + EE 30 micrograms (Mercilon); (5) gestodene 75 micrograms + EE 30 micrograms (Femovan); and (6) gestodene 50/70/100 micrograms + EE 30/40/30 micrograms (Trifemovan). There were three parallel studies with six parallel patient groups. Fasting blood samples were drawn at baseline (between days 24 and 28) and on days 18-22 of cycle 6, and cycle 12. Sample were analyzed for total cholesterol,high-density lipoprotein (HDL) cholesterol, HDL2 cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein (apo)A1, and apoB at one central laboratory. Two hundred eighty-two women completed all 12 cycles and were included in the final evaluation. As expected, triglyceride and total cholesterol concentrations increased in all study groups but to lesser levels with the formulations containing gestodene. All OCs, except the monophasic gestodene preparation, slightly but significantly increased HDL. The HDL2 subfraction did ot change significantly except in the group using the monophasic
Farmer, R D; Lawrenson, R A; Thompson, C R; Kennedy, J G; Hambleton, I R
Four studies published since December 1995 have reported an increased risk of venous thromboembolism (VTE) in women using oral contraceptives (OCs) containing the third-generation progestogens gestodene and desogestrel compared to users of OCs containing second-generation progestogens. The results of these studies could have been compromised, however, by bias and confounding. To reassess this association with a more rigorous study design, computerized medical records from 143 general practices in the UK of about 540,000 women born from 1941 to 1981 were reviewed and 83 cases of deep-vein thrombosis, venous thrombosis not otherwise specified, and pulmonary embolus (all treated with an anticoagulant) were identified. Two women were using a progestogen-only OC. Of the 83 VTE cases associated with combined OC use, 43 were diagnosed as deep-vein thrombosis, 35 as pulmonary thrombosis, and 5 as venous thrombosis not otherwise specified. The crude rate of VTE per 10,000 woman-years was 4.10 in current users of any OC, 3.10 in users of second-generation OCs, and 4.96 in users of third-generation OCs. After exact age matching of cases and controls, the odds ratio of VTE in users of third-generation compared to second-generation OCs was 1.68 (95%, confidence interval, 1.04-2.75). Logistic regression revealed no significant difference in VTE risk between users of the 2 groups of OCs. Using all second-generation OCs as the reference, the VTE risk was higher for third-generation OCs containing desogestrel and 20 grams of ethinyl estradiol than for those containing desogestrel or gestodene and 30 grams of ethinyl estradiol--an implausible finding presumed to reflect preferential prescribing of the former OCs to older women. The previously reported increased VTE risk associated with third-generation OCs likely reflects residual confounding by age. Exact age-matching is recommended for all future studies to ensure that controls are representative of the population from which cases
Peyman, Nooshin; Oakley, Deborah
Background Oral contraceptive pills effectiveness is lower in actual use than in clinical trials. The views of a group of married Iranian women were sought as a step toward improving the enhanced use of contraceptive pills. Methods Two focus groups of current pill users (n=13) and two focus groups of women not currently taking the pills (n=14) were held. Leaders trained facilitators; themes were identified from line-by-line analysis of transcripts. Results The majority of the participants were primary school graduates with a mean age of 34 years. Knowledge about mechanisms of action was low; some women wanted more information. Both users and non-users recognized positive and negative characteristics of contraceptive pills. For non-users, physical and emotional side-effects were the most important; and anecdotal information from their social network was more important. They tended to trust more traditional methods. For users, their own experience and more reality-based understanding of side-effects mitigated concerns about side-effects. They also felt that health clinic staff had a negative attitude toward the pills. A stronger expression of self-efficacy seemed to be associated with more positive attitudes toward oral contraceptive pills. Conclusion Although Iran has had a government-funded family planning program since 1990, and pills are the single most popular modern contraceptive method, women who take OCPs can provide important information that could increase effective health education about their use. PMID:23926515
Ahn, H K; Choi, J S; Han, J Y; Kim, M H; Chung, J H; Ryu, H M; Kim, M Y; Yang, J H; Koong, M K; Nava-Ocampo, A A; Koren, G
To evaluate whether periconceptional exposure to oral contraceptives (OCs) increased adverse pregnancy outcomes, 136 pregnant women taking OCs within the periconceptional period were identified at the Korean Motherisk Program. Of them, 120 pregnant women accepted to participate in their study and were followed up until completion of the pregnancy. A control group of 240 age- and gravidity-matched pregnant women exposed to non-teratogen drugs for at least 1 month before pregnancy was also included. The median gestational age at delivery was 39.1 (27.0-41.0) weeks in the exposed group and 39.3 (27.4-42.0) weeks in the control group (P = 0.19). In the exposed group, 7.1% of babies were born with low birth weight versus 2.6% in the control group (P = 0.068). The number of preterm deliveries or babies born large for gestational age did not differ between the two groups. In the exposed group, the rate of birth defects was 3.2% (n = 3/99) versus 3.6% (n = 7/193) in the control group (P = 1.0). There were 15 women who took high doses of progesterone (emergency contraception) and no adverse fetal outcomes were observed. In conclusion, periconceptional exposure to OCs does not appear to increase the risk for adverse pregnancy outcomes.
Lemay, A; Langley, R G
There is compelling evidence that oral contraceptives (OCs) are effective in the management of mild-moderate acne vulgaris, as well as cumulative evidence that elevated levels of androgens in acne patients, relative to appropriate controls, are an underlying pathophysiological factor in acne. All low dose OCs reduce serum free testosterone (T) to a similar extent, which is contrary to the traditional concept that a patient who has acne should not use an OC containing a progestin with androgenic properties. The efficacy of various OCs to improve acne has been reported in transverse, cohort and comparative studies, and more recently in multicenter, randomized, placebo-controlled trials. Recently, an ultra-low dose OC (Alesse, Wyeth) was shown to effectively reduce non-inflammatory and inflammatory lesions in mild-to-moderate acne, while having a profile of side-effects similar to that of a placebo. Besides its contraceptive efficacy, an ultra-low dose OC represents an attractive alternative as a single or associated medication in the management of acne.
Tsilidis, K K; Allen, N E; Key, T J; Dossus, L; Lukanova, A; Bakken, K; Lund, E; Fournier, A; Overvad, K; Hansen, L; Tjønneland, A; Fedirko, V; Rinaldi, S; Romieu, I; Clavel-Chapelon, F; Engel, P; Kaaks, R; Schütze, M; Steffen, A; Bamia, C; Trichopoulou, A; Zylis, D; Masala, G; Pala, V; Galasso, R; Tumino, R; Sacerdote, C; Bueno-de-Mesquita, H B; van Duijnhoven, F J B; Braem, M G M; Onland-Moret, N C; Gram, I T; Rodríguez, L; Travier, N; Sánchez, M-J; Huerta, J M; Ardanaz, E; Larrañaga, N; Jirström, K; Manjer, J; Idahl, A; Ohlson, N; Khaw, K-T; Wareham, N; Mouw, T; Norat, T; Riboli, E
Background: It is well established that parity and use of oral contraceptives reduce the risk of ovarian cancer, but the associations with other reproductive variables are less clear. Methods: We examined the associations of oral contraceptive use and reproductive factors with ovarian cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 327 396 eligible women, 878 developed ovarian cancer over an average of 9 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard models stratified by centre and age, and adjusted for smoking status, body mass index, unilateral ovariectomy, simple hysterectomy, menopausal hormone therapy, and mutually adjusted for age at menarche, age at menopause, number of full-term pregnancies and duration of oral contraceptive use. Results: Women who used oral contraceptives for 10 or more years had a significant 45% (HR, 0.55; 95% CI, 0.41–0.75) lower risk compared with users of 1 year or less (P-trend, <0.01). Compared with nulliparous women, parous women had a 29% (HR, 0.71; 95% CI, 0.59–0.87) lower risk, with an 8% reduction in risk for each additional pregnancy. A high age at menopause was associated with a higher risk of ovarian cancer (>52 vs ⩽45 years: HR, 1.46; 95% CI, 1.06–1.99; P-trend, 0.02). Age at menarche, age at first full-term pregnancy, incomplete pregnancies and breastfeeding were not associated with risk. Conclusion: This study shows a strong protective association of oral contraceptives and parity with ovarian cancer risk, a higher risk with a late age at menopause, and no association with other reproductive factors. PMID:21915124
Bombas, Teresa; Costa, Ana Rosa; Palma, Fátima; Vicente, Lisa; Sá, José Luís; Nogueira, Ana Maria; Andrade, Sofia
ABSTRACT Objectives To evaluate knowledge, attitude and practices of Portuguese gynaecologists regarding combined hormonal contraceptives. Methods A cross-sectional survey was conducted among 303 gynaecologists. Results Ninety percent of the gynaecologists considered that deciding on contraceptive methods is a process wherein the woman has her say. Efficacy, safety and the woman's preference were the major factors influencing gynaecologists, while efficacy, tolerability and ease of use were the major factors perceived by the specialists to influence the women's choice. Gynaecologists believed that only 2% of women taking the pill were 100% compliant compared to 48% of those using the patch and 75% of those using the ring. The lower risk of omission was the strong point for the latter methods. Side effects were the main reason to change to another method. Vaginal manipulation was the most difficult topic to discuss. Conclusions Most gynaecologists decided with the woman on the contraceptive method. The main reasons for the gynaecologist's recommendation of a given contraceptive method and the women's choice were different. Counselling implies an open discussion and topics related to sexuality were considered difficult to discuss. Improving communication skills and understanding women's requirements are critical for contraceptive counselling.
Lund, E; Jacobsen, B K
The relationship between oral contraceptive (OC) use, dietary habits and alcohol consumption in young women was studied in Tromsø, Norway. A total of 5,800 women aged 20-39 years answered a questionnaire in 1986/1987. Women with long-term duration of OC use reported more frequent intake of meat for dinner, preferred low-fat milk and drank less coffee. For other food items such as intake of fats, fish, fruit and vegetables, no differences were found. Strong associations were found for alcohol consumption, with increasing frequency of use among long-term users of OCs. These results are discussed in relation to the possible association between OC use and breast cancer in young women.
Liu, Ze-hua; Ogejo, Jactone Arogo; Pruden, Amy; Knowlton, Katharine F
Synthetic oral contraceptives (SOCs) are a group of compounds with progestagenic and/or androgenic activities, with some also possessing estrogenic activities. Recent research has documented that some of these emerging contaminants have adverse effects on aquatic organisms at very low concentrations. To facilitate the evaluation of their latent risks, published works on their occurrence and fate in the environment are reviewed. Androgenic/progestagenic relative potencies or relative binding affinity of these SOCs as well as their physicochemical properties and toxicity are summarized. Appropriate analytical methods are outlined for various environmental sample types, including methods of sample preparation and limit of detection/quantification (LOD/LOQ). Finally results on their occurrence and fate in wastewater treatment plants (WWTPs) and other environments are critically examined.
Kinghorn, G R; Waugh, M A
1080 nonpregnant women ages 16-34 years, presenting for the 1st time at a clinic for sexually transmitted diseases (STD), were examined and screened for infection with Chlamydia trachomatis, Neisseria gonorrheae, Trichomonas vaginalis, and Candida species. The respective prevalence rates were 21.1%, 20.7%, 13.4%, and 27.8%. Isolation rates for Chlamydia trachomatis, either occurring alone or in association with other genital infections, were significantly greater in women using oral contraceptives (OCs). This was not because OC users were more promiscuous. The findings strengthen the case for providing a routine chlamydial culture service for women attending STD clinics. They also indicate that the likelihood of chlamydial infection in women taking OCs is greater. (author's)
Davis, A; Wysocki, S
Myths and misperceptions continue to influence women's opinions about oral contraceptives (OC), despite the immense body of evidence regarding OC safety and efficacy. Patient opinions about OC failure rates and health risks are often far from proven fact, and the health benefits of OC are too often unrecognized. Because successful OC use requires an informed patient, effective communication between clinicians and their patients is needed to correct misinformation, relieve unnecessary fears, and increase OC use. A variety of interactive counseling skills and attitudes can improve the process of patient counseling; they are especially crucial for adolescents, who may be reluctant or unable to easily articulate their concerns. Counseling messages can be geared specifically to the interests and concerns of particular age groups: adolescents, young adults, and perimenopausal women. With thoughtful planning and involvement of all members of the healthcare team, clinicians can create time and opportunities for the provision of consistent, appropriate counseling to all candidates for OC use.
Wise, Amber; O'Brien, Kacie; Woodruff, Tracey
Recent observed feminization of aquatic animals has raised concerns about estrogenic compounds in water supplies and the potential for these chemicals to reach drinking water. Public perception frequently attributes this feminization to oral contraceptives (OCs) in wastewater and raises concerns that exposure to OCs in drinking water may contribute to the recent rise in human reproductive problems. This paper reviews the literature regarding various sources of estrogens, in surface, source and drinking water, with an emphasis on the active molecule that comes from OCs. It includes discussion of the various agricultural, industrial, and municipal sources and outlines the contributions of estrogenic chemicals to the estrogenicity of waterways and estimates that the risk of exposure to synthetic estrogens in drinking water on human health is negligible. This paper also provides recommendations for strategies to better understand all the potential sources of estrogenic compounds in the environment and possibilities to reduce the levels of estrogenic chemicals in the water supply.
Among the reasons why male hormonal contraception has lagged behind female methods are the necessity of preserving virility, the fact that spermatogenesis is a continuous process, the need to control secondary effects and toxicity, and the requirement that modes of administration be acceptable to both partners. Among currently available reversible mehtods, withdrawal is undoubtedly the most ancient. It is still widespread but cannot be recommended because of its limited effectiveness. The condom is used by about 10% of couples worldwide as a principal or temporary method, but its inter-ference with sensation has limited its acceptance. Condoms are nevertheless highly effective when used with a spermicide. Various androgens are currently under investigation. High doses of testosterone can induce azoospermia without affecting libido but their side effects may be serious. The use of combinations of steroids permits doses to be reduced and offers promise for the future. The combination of oral medroxyprogesterone acetate and percutaneous testosterone is one of the better approaches; the combination is effective and nontoxic but has the disadvantage of percutaneous administration. Gossypol, a pigment extracted from the cotton plant, has been used as a contraceptive in China with a reported efficacy of 99.89%, recovery of fertility within 3 months, and no effect on future fertility. However, its toxicity appears to be significant in the animal and its reversibility is uncertain. A search is on for analogs which would preserve the contraceptive effects while eliminating toxic effects. Several gonadotropin releasing hormone (GnRH) analogs under investigation for their interference with spermatogenesis have given promising results. Several chemicals tested for contraceptive effects have had unacceptably high toxicity. Chinese investigators have reported good results with various physical methods of interfering with sperm production, but their reversibility and innocuity
The development of steroid-based oral contraceptives had revolutionized the availability of contraceptive choice for women. In order to expand the contraceptive options for couples by developing an acceptable, safe and effective male contraceptive, scientists have been experimenting with various steroidal/non-steroidal regimens to suppress testicular sperm production. The non-availability of a long-acting androgen was a limiting factor in the development of a male contraceptive regimen since all currently tested anti-spermatogenic agents also concurrently decrease circulating testosterone levels. A combination regimen of long-acting progestogen and androgen would have advantage over an androgen-alone modality since the dose of androgen required would be much smaller in the combination regimen, thereby decreasing the adverse effects of high steroid load. The progestogen in the combination regimen would act as the primary anti-spermatogenic agent. Currently, a number of combination regimens using progestogen or GnRH analogues combined with androgen are undergoing trials. The side effects of long-term use of androgens and progestogens have also undergone evaluation in primate models and the results of these studies need to be kept in view, while considering steroidal regimens for contraceptive use in men. Efforts are also being made to popularize non-scalpel vasectomy and to develop condoms of greater acceptability. The development of contraceptive vaccines for men, using sperm surface epitopes not expressed in female reproductive tract as source, still requires considerable research efforts.
Zittermann, A; Rühl, J; Berthold, H K; Sudhop, T; van der Ven, H; Reinsberg, J; Stehle, P
This study investigated the effect of ethinylestradiol(EE2)-containing oral contraceptives on mineral and bone metabolism and on serum soluble-interleukin-6-receptor (sIL-6R) during the menstrual cycle. Twelve women, aged 24.3 +/- 2.9 years, were examined. Blood and 24-hour and fasting urine samples were obtained during one menstrual cycle between cycle day 3-5 (t(1)), cycle day 10-12 (t(2)), cycle day 24-26 (t(3)), and again on day 3-5 of the next cycle (t(4)). EE2 intake was 0 mg at t(1), 30 mg at t(2), 30 mg at t(3) and 0 mg at t(4). Fasting renal phosphorus and calcium excretions were slightly reduced at t(2) and t(3) compared with t(1) and t(4) (P < 0.05-0.001). Moreover, renal excretion of the bone resorption marker C-Teleopeptide was at t(3) reduced by 26% compared with t(1)(P < 0.01) and by 13% compared with t(4)(P > 0.05). Fasting sIL-6R levels were 16.5% lower at t(2) and 12% lower at t(3) than at t(4) (P < 0.01 and P < 0.05). sIL-6R was correlated with total deoxypyridinoline excretion (r = +0.35; P < 0.05) and with fasting renal excretions of calcium (r = +0.36; P < 0.05) and phosphorus (r = +0.29; P < 0.05). In summary, our data suggest that in young women, cyclic monthly oral contraceptive intake is associated with small, but significant variations in bone resorption processes and in serum sIL-6R levels. Results are a further indication that monthly fluctuations of bone resorption in young women are mediated by sex hormones and that osteoclastic activity is stimulated by cytokines in vivo.
Borland, Julie; Chen, Shuguang; Wajima, Toshihiro; Peppercorn, Amanda F.; Piscitelli, Stephen C.
Background: Dolutegravir (DTG; Tivicay; ViiV Healthcare, Research Triangle Park, NC) is an HIV-1-unboosted integrase inhibitor with no cytochrome P450 or uridine 5′diphosphate-glucuronosyltransferase inhibition or induction. As DTG is administered to HIV-1–infected women receiving oral contraceptives, assessing the potential for drug interactions was warranted. Objective: To determine the impact of DTG on the pharmacokinetics (PK) and pharmacodynamics (PD) of a common oral contraceptive, norgestimate/ethinyl estradiol (NGM/EE; Ortho-Cyclen; Ortho-McNeil-Janssen Pharmaceuticals, Inc, Raritan, NJ). Methods: This randomized, 2-period, double-blind, placebo-controlled study was conducted within 1 menstrual cycle at 1 clinical center in the United States; 16 women were enrolled. Participants received NGM 0.25 mg/EE 0.035 mg throughout the study. During days 1 to 10, they were randomized to receive twice-daily DTG 50 mg or matching placebo with food and switched to the other treatment during days 12 to 21. Results: Ratios of area under the concentration-time curve from time 0 until end of the dosage interval (AUC0-τ), maximum plasma concentration, and concentration at the end of the dosage interval of norelgestromin with DTG treatment to the same PK parameters with placebo treatment were 0.975, 0.890, and 0.932, respectively; for EE, ratios were 1.03, 0.99, and 1.02, respectively. No significant differences in luteinizing hormone, follicle-stimulating hormone, and progesterone were detected on days 1, 10, 11, 21, and 22. DTG steady-state AUC0-τ was similar to historical data. No severe or grade 3/4 adverse events occurred. Conclusions: DTG had no effect on NGM/EE PK or PD. NGM/EE can be administered with DTG without dose adjustment. PMID:25862012
Sena, Armando; Couderc, Rémy; Vasconcelos, Joana C; Ferret-Sena, Véronique; Pedrosa, Rui
Experimental and clinical data suggest a role of sex steroids in the pathogenesis of multiple sclerosis (MS). Scant information is available about the potential effect of oral contraceptive (OC) use on the prognosis of the disease. We aimed to evaluate this. The study population consisted of 132 women with relapsing-remitting MS before receiving disease modifying treatment and a mean disease duration 6.2 (SD 5.1) years. Three groups of patients were distinguished according to their OC behavior:  never-users, patients who never used OC  past-users, patients who stopped OC use before disease onset, and  after-users, those who used these drugs after disease onset. Multiple linear and logistic regression models were used to analyze the association between oral contraceptive use and annualized relapse rates, disability accumulation and severity of the disease. After-user patients had lower Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Severity Score (MSSS) values than never users (p<0.001 and p=0.002, respectively) and past users (p=0.010 and p=0.002, respectively). These patients were also more likely to have a benign disease course (MSSS<2.5) than never and past users together (OR: 4.52, 95%CI: 2.13-9.56, p<0.001). This effect remained significant after adjustment for confounders, including smoking and childbirths (OR: 2.97, 95%CI: 1.24, 6.54, p=0.011 and for MSSS β: -1.04; 95% C.I. -1.78, -0.30, p=0.006). These results suggest that OC use in women with relapsing-remitting MS is possible associated with a milder disabling disease course.
Sitruk-Ware, Regine; Nath, Anita; Mishell, Daniel R
Steady progress in contraception research has been achieved over the past 50 years. Hormonal and nonhormonal modern contraceptives have improved women's lives by reducing different health conditions that contributed to considerable morbidity. However, the contraceptives available today are not suitable to all users, and the need to expand contraceptive choices still exists. Novel products such as new implants, contraceptive vaginal rings, transdermal patches and newer combinations of oral contraceptives have recently been introduced in family planning programs, and hormonal contraception is widely used for spacing and limiting births. Concerns over the adverse effects of hormonal contraceptives have led to research and development of new combinations with improved metabolic profile. Recent developments include use of natural compounds such as estradiol and estradiol valerate with the hope to decrease thrombotic risk, in combination with newer progestins derived from the progesterone structure or from spirolactone, in order to avoid the androgenic effects. Progesterone antagonists and progesterone receptor modulators are highly effective in blocking ovulation and preventing follicular rupture and are undergoing investigations in the form of oral pills and in semi-long-acting delivery systems. Future developments also include the combination of a contraceptive with an antiretroviral agent for dual contraception and protection against sexually transmitted diseases, to be used before intercourse or on demand, as well as for continuous use in dual-protection rings. Although clinical trials of male contraception have reflected promising results, limited involvement of industry in that area of research has decreased the likelihood of having a male method available in the current decade. Development of nonhormonal methods is still at an early stage of research, with the identification of specific targets within the reproductive system in ovaries and testes, as well as
Bassuk, Shari S.; Manson, JoAnn E.
Purpose To summarize the relative risks (RR) and attributable risks (AR) of major health outcomes associated with use of combined oral contraceptives (OCs) and menopausal hormone therapy (HT). Methods For OCs, measures of association are from meta-analyses of observational studies. For HT, these measures are from the Women’s Health Initiative (WHI), a large randomized trial of HT for chronic disease prevention in postmenopausal women aged 50-79. Results Current OC use increases risks of venous thromboembolism and ischemic stroke. However, women of reproductive age are at low baseline risk, so the AR are small. OC use also increases risk of breast and liver cancer and reduces risk of ovarian, endometrial, and colorectal cancer; the net effect is a modest reduction in total cancer. The WHI results show that HT does not prevent coronary events or overall chronic disease in postmenopausal women as a whole. Subgroup analyses suggest that timing of HT initiation influences the relation between such therapy and coronary risk, as well as its overall risk-benefit balance, with more favorable effects (on a relative scale) in younger or recently menopausal women than in older women or those further past the menopausal transition. However, even if the RR do not vary by these characteristics, the low absolute baseline risks of younger or recently menopausal women translate into low ARs in this group. Conclusion OC and HT can safely be used for contraception and treatment of vasomotor symptoms, respectively, by healthy women at low baseline risk for CVD and breast cancer. PMID:25534509
Taneepanichskul, Surasak; Dusitsin, Nikorn
Women in their forties are still potentially fertile, and pregnancy in this age group is attended with increased maternal mortality, spontaneous abortion, fetal anomalies and perinatal mortality. Contraception for women in this age group has special risks and benefits; both should be balanced to choose between the different options available. Recent epidemiological and clinical pharmacology studies have indicated the safety of extending the use of combined oral contraceptives (COCs) beyond the age of 35 years and up to menopause. Women who have reasons for avoiding COCs can use progestogen-only contraceptives like pills, depot injectables and implants. Implant combines high efficacy and long-term effect. Both copper-releasing and levonorgestrel-releasing intrauterine contraceptive device (LNG-IUD) combine the advantages of high efficacy and long-term effect. The reduced fecundity above the age of forty can allow extending the use beyond the accepted term, and up to one or two years beyond the menopause without the need for replacement. The levonorgestrel IUD has the advantage of reducing the amount of menstrual bleeding. The condom has the added benefit of protection against sexual transmitted diseases (STDs). Male or female sterilization is an excellent contraceptive option, provided that this approach is culturally acceptable and available at reasonable cost and low risk.
Farmer, R D; Lawrenson, R A; Todd, J C; Williams, T J; MacRae, K
The results of three independent studies of venous thromboembolic disease (VTE) and oral contraceptives are reviewed together with two further cohort/case-control studies which we conducted using the MediPlus and General Practice Research Database (GPRD) databases. These latter studies jointly involved 395 cases and uniquely examined the association between VTE and individual combined oral contraceptive (COC) formulations. The two studies yielded very similar results. Crude incidence rates for idiopathic VTE of 4.6 and 3.8 were found per 10,000 exposed woman-years (EWY), in the MediPlus and GPRD studies respectively. Incidence rates increased markedly with age, and in both databases the rates amongst users of levonorgestrel products were lower than those amongst users of desogestrel and gestodene products. A case fatality rate of 3% and a mortality rate of 10 per million EWY were estimated. Odds ratios (OR) were calculated for confounding variables and different COC formulations. Both database studies indicated an excess of current smokers and women with high body mass indices amongst cases. There were significantly more cases with asthma in the GPRD study and cases who had been using their COC for less than a year. No statistically significant differences between COC formulations were found in the analyses where controls were matched to cases by practice and year of birth in both the MediPlus and GPRD studies. In the GPRD study we also ran a study where controls were matched by practice and within 5 year age bands. In this study the OR were consistently higher for the newer or 'third generation' products than when controls were matched by year of birth. However only the acne formulation/OC containing cyproterone acetate and 35 microg ethinyloestradiol yielded a significant OR of 2.3. It may be concluded that improvements in prescribing are paramount as the results strongly indicate that overweight women and those who smoke are at a greater risk of VTE. Further
Van Look, P F; von Hertzen, H
The term 'emergency contraception', as employed in this paper, refers to methods that are used as emergency procedures to prevent pregnancy following unprotected intercourse. Alternative, less appropriate, terms are postcoital and 'morning-after' contraception. References to postcoital preparations can be found as far back as 1500 BC in Egyptian papyri, but it was not until fairly recently that contraceptive research has been able to at least partially fulfill that need. The development of hormonal methods of emergency contraception goes back to the 1960s when the first human trials of postcoitally administered high-dose oestrogens were undertaken. Combined oestrogen- progestogen combination therapy (the so-called Yuzpe regimen) was introduced in the early 1970s, while the postcoital insertion of an intrauterine contraceptive device (IUD) for emergency contraception was first reported in 1976. Other compounds that have been tested more recently include levonorgestrel, the antiprogestogen mifepristone, and danazol. Although there is some debate about the magnitude of the protective effect, few people question the important role that emergency contraception can play in preventing unwanted pregnancy and hence maternal mortality and morbidity resulting from unsafe abortion. Given that the most often used methods of emergency contraception, namely the Yuzpe regimen and postcoital insertion of an IUD, rely on technology that has been available for some 30 years, family planning programmes that claim to be concerned with improving women's reproductive health, cannot really be excused if they do not provide emergency contraception as part of their routine services.
Maguire, Karla; Westhoff, Carolyn
In the 50 years since the advent of combined oral contraceptives the amount of estrogen in oral contraceptives dropped from over 100 mcg to less than 30 mcg. Many noncontraceptive health benefits have emerged that decrease mortality and improve quality of life. Some of the immediate benefits include improvement of menorrhagia and dysmenorrhea, reduction in premenstrual dysphoric disorder symptoms, and decreased acne. As an effective birth control method oral contraceptives also decrease pregnancy-related deaths by preventing pregnancy. After the reproductive years, previous use of oral contraceptives continues to be beneficial, reducing the risk of death from ovarian and endometrial cancer. All these benefits have held up over time whereas cardiovascular risks have lessened because of the decrease in oral contraceptive pill dosage. Decreased ovarian cyst formation is an example of benefit with higher-dose oral contraceptive formulations that no longer holds true with low-dose pills.
Grimes, David A; Raymond, Elizabeth G
Emergency contraception is used to prevent pregnancy after a coital act not adequately protected by a regular method of contraception. In contrast to early medical abortion, emergency contraception prevents a pregnancy from starting and does not disrupt an established pregnancy. The most commonly used approaches consist of two oral doses of contraceptive steroids. The levonorgestrel-only regimen (levonorgestrel, 0.75 mg, repeated in 12 hours) appears to be more effective and better tolerated than the Yuzpe regimen (ethinyl estradiol, 100 microg, and levonorgestrel, 0.5 mg, repeated in 12 hours). In the largest randomized, controlled trial to date, levonorgestrel prevented about 85% of pregnancies that would have occurred without its use. Hormonal emergency contraception has no known medical contraindications, although it is not indicated for suspected or confirmed pregnancy. However, if hormonal emergency contraception is inadvertently taken in early pregnancy, neither the woman nor the fetus will be harmed. Nausea and vomiting associated with the Yuzpe regimen can be reduced by prophylactic use of meclizine. A strong medical and legal case exists for making hormonal emergency contraception available over the counter, as has happened in countries other than the United States. Easier access to and wider use of emergency contraception could dramatically lower the high rates of unintended pregnancy and induced abortion in the United States.
Background Poor adherence to the oral contraceptive pill (OCP) is reported as one of the main causes of unintended pregnancy in women that rely on this form of contraception. This study aims to estimate the associations between a range of well-established modifiable psychological factors and adherence to OCP. Method A cross-sectional survey of 130 female University students currently using OCP (Mean age: 20.46 SD: 3.01, range 17–36) was conducted. An OCP specific Medication Adherence Report Scale was used to assess non-adherence. Psychological predictor measures included necessity and concern beliefs about OCP, intentions, perceived behavioural control (pbc), anticipated regret and action and coping planning. Multiple linear regression was used to analyse the data. Results Fifty-two per cent of participants reported missing their OCP once or more per month and 14% twice or more per month. In bivariate analysis intentions (r = −0.25), perceived behavioural control (r= −0.66), anticipated regret (r=0.20), concerns about OCP (r =0.31), and action (r= −0.25) and coping (r= −0.28) planning were all significantly associated with adherence to OCP in the predicted direction. In a multivariate model almost half (48%) of the variation in OCP adherence could be explained. The strongest and only statistically significant predictors in this model were perceived behavioural control (β=−0.62, p<0.01) and coping planning (β =−0.23, p=0.03). A significant interaction between intentions and anticipated regret was also observed. Conclusion The present data point to a number of key modifiable psychological determinants of OCP use. Future work will establish whether changing these variables results in better adherence to the OCP. PMID:23031437
Hatch, Elizabeth E; Hahn, Kristen A; Mikkelsen, Ellen M; Riis, Anders H; Sorensen, Henrik Toft; Rothman, Kenneth J; Wise, Lauren A
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 to 12 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.
Hatch, EE; Hahn, KA; Mikkelsen, EM; Riis, AH; Sorensen, HT; Rothman, KJ; Wise, LA
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
Kurtul, Bengi Ece; Inal, Besime; Ozer, Pinar Altiaylik; Kabatas, Emrah Utku
Objectives: Hormonal changes during oral contraceptive pill (OCP) use may affect central corneal thickness (CCT) values. We aimed to evaluate the impact of OCP use on CCT values in healthy young women. Materials and Methods: Fifty women subjects who use OCP for contraception (Group 1) and forty control subjects (Group 2) who do not use OCP were included in this prospective study. None of the patients had any history of systemic or ocular diseases. The CCT values measured by ultrasonic pachymeter (Nidek US-4000 Echoscan, Japan) and the intraocular pressure (IOP) values were measured by noncontact tonometer (Reichert 7 CR Corneal Response Technology, USA) at the time of admission to our clinic. The demographic findings and body mass index (BMI) scores of participants were also recorded. Results: The mean ages were 32.8 ± 5.6 for OCP + patients (Group 1) and 31.3 ± 6.9 for OCP-patients (Group 2) (P = 0.28). The mean CCT values were significantly higher in Group 1 when compared to that of the Group 2 (540.9 ± 30.4 μm and 519.6 ± 35.6 μm, respectively) (P = 0.003). The mean IOP value was 14.3 ± 2.5 mmHg in Group 1 and 14.4 ± 2.7 mmHg in Group 2 (P = 0.96). The mean BMI scores were 24.4 ± 5.8 kg/m2 in Group 1 and 24.6 ± 3.5 kg/m2 in Group 2 (P = 0.83). Conclusion: Our findings revealed that CCT values were significantly higher in patients with OCP use. Ophthalmologists should be aware of potential elevated CCT levels in these patients. PMID:28066104
Doody, K; Bain, J
Twenty-three men who participated in a 15-month clinical trial to assess the potential effectiveness of using a combination of varying doses of medroxyprogesterone acetate (MPA) and methyltestosterone (MT) as a male contraceptive agent, completed a "sexual problem checklist" every two weeks. The study was divided into three phases: pre-treatment (3 months), treatment (6 months), post-treatment (6 months). The questionnaire evaluated changes in various aspects of sexual behaviour and sexual perception and explored whether the treatment influenced any of the parameters considered. The results indicated a small, but significant, decrease in subjective assessment of sexual drive. This was not, however, accompanied by a change in sexual behaviour, in that subjects experienced the same number of erections, ejaculations and frequency of intercourse. It is concluded that the combination of MPA and MT in the doses used may produce a slight decrease in subjective assessment of sexual drive, but no change in actual sexual behaviour.
Ferrari, S; Piacenti, I; Napolitano, A; Cagnacci, A
Introduction of new compounds containing natural estrogens represented a major development in the field of hormonal contraception. Micronized estradiol (E2) and its estere valerate (EV), is more easily metabolized by the liver than ethynylestradiol (EE). This causes minimal metabolic impact, but the weak estrogenic activity needs not be antagonized by androgenic progestin and requires progestin capable to stabilize the endometrium. Dienogest (DNG), an antiandrogenic progestin with a short half-life, is associated with estradiol valerate (EV) in a quadriphasic fashion. In comparison to EE/levonorgestrel (LNG), EV/DNG is more neutral on metabolism and coagulation. Furthermore, it does not seem to negatively affect the cardiovascular system and breast. Cycle control is optimal with a higher prevalence of amenorrhea and reduction of menstrual flow. For this reason EV/DNG can be tehrapeutic for heavy menstrual bleedings. Nomegestrol acetate (NOMAc), an anti-andogen progestin with a long half-life is combined in monophasic regimen with micronized E2. E2/NOMAc is more neutral than EE/LNG on metabolism and more neutral than EE/DRSP on coagulation. NOMAc reduces peripheral tissue estrogen formation, and this may be beneficial for the breast. The two formulations exert a high contraceptive efficacy similar to the ones containing EE, but with less estrogen-related side-effects. The additional benefits due to DNG and NOMAc need to be further explored.
McGregor, L.; Toor, B.; McGregor, J.L.; Renaud, S.; Clemetson, K.J.
The aggregation to ADP and the binding of /sup 125/I-fibrinogen to platelets from rats treated with oral contraceptives or normal platelets treated in vitro with lanosterol were compared to their respective controls. Both types of platelets showed a significant increase in ADP-induced aggregation and in binding of fibrinogen, indicating that the effect of oral contraceptives could be partly due to increased levels of lanosterol in platelet membrane.
Merki-Feld, G S
Perimenopausal women are still potentially fertile and pregnancy is attended with increased maternal and perinatal mortality. Several contraceptive methods can be used therapeutic for the treatment of climacteric symptoms like menstrual irregularities, flushes and vaginal dryness. Low-dose oral contraceptives (OC) prevent climacteric symptoms and additionally protect from perimenopausal bone loss. However, the individual cardiovascular risk increases with age and is even higher in perimenopausal women using OCs. Therefore for women with cardiovascular risk factors sterilization, barrier methods, progestin-only methods and intrauterine devices (IUD) are the better choice. Prolonged and heavy menses can be treated with the levonorgestrel-releasing IUD or injectable progestogens. If estrogen replacement is necessary, a low-dose treatment with natural estrogens can be combined with barrier methods, the levonorgestrel-releasing IUD and injectable progestogens. The variety of contraceptive options available to perimenopausal women allows individual counseling and thus may enhance compliance.
Grenader, Tal; Peretz, Tamar; Lifchitz, Meyer; Shavit, Linda
Approximately 10% of the cases of breast cancer and invasive ovarian cancer are hereditary, occurring predominantly in women with germ-line mutations in the BRCA1 or BRCA2 gene. In deciding whether women with germ-line mutations in the BRCA1 gene should use oral contraceptives a possible increase in the risk of breast cancer needs to be weighed against the convenience of this means of birth control and its potential to reduce the risk of ovarian cancer. In women with BRCA2 mutations, oral contraceptive use has not been associated with an increased risk of breast cancer and does have the potential to reduce the risk of ovarian cancer. Prophylactic surgical options and intensified surveillance should, of course, be discussed with these patients.
Sherk, Vanessa D; Howard, Clint D; Bemben, Michael G; Bemben, Debra A
In premenopausal women, low bone density may reflect attainment of a lower peak bone mass which can increase risk of osteoporosis after menopause. The purpose of this study was to examine the relationship between total body, lumbar spine, and proximal femur bone mineral density (BMD) and body composition and oral contraceptive (OC) use in 18-30 year old women. Sixty-five healthy women, split into groups of oral contraceptive users (OC, n = 36) and non oral contraceptive users (Non-OC, n = 29), completed Baecke physical activity, calcium intake, and menstrual history questionnaires. Total body, AP lumbar spine, and dual proximal femur scans were performed using Dual Energy X-Ray Absorptiometry (DXA). Body composition measures were obtained from the total body scan analysis. No significant differences were found for BMD in OC users and non-users. Bone free lean body mass (BFLBM) and weight were positively correlated to all BMD sites, and fat mass was related to total body and L1-L4 spine BMD (p < 0.05). Stepwise regression analyses determined that weight was a significant predictor for all BMD sites (p < 0.05). When separating the two components of body weight, BFLBM was a significant predictor for all BMD sites, and fat mass only predicted total body BMD. In conclusion, this study indicates that weight and BFLBM are significant contributors to BMD in young healthy premenopausal women, and OC use did not influence the relationship between BMD and BFLBM.
Hamerlynck, J V
Some form of postcoital contraception for protection against unwanted pregnancy is indispensable today especially in cases of rape, failed mechanical contraception, or 1st sexual contact without contraception. A tabletform of postcoital contraceptive would be acceptable if 100% certainty is assured and it doesn't involve adverse effects. Postcoitally administered high-dose estrogens proved effective in Macaca mulatta. Diethylstilbestrol in variable dosages with or without ethinylestradiol was used in various studies and with variable results. Pregnancy rates depended on time of coitus in cycle, contraceptive dosage, and time of administration after coitus (within 72 hours). Conjugated estrogens and various progestagens or combinations of both have been tried with variable success. Another form of postcoital contraception is IUD insertion within 7 days following unprotected coitus. Advantages of this method are the time factors and absence of adverse effects of hormonal contraceptives. Postcoital hormonal contraceptives cause changes in the endometrium which prevent blastocyst implantation. They alter tubal function affecting zygote movement towards the uterus. They have an antiovulatory effect and may be luteolytic. Estrogens have more severe side effects than progestagens. Nausea, vomiting, mastodynia, fluid retention, and vaginal bleeding can result from estrogens. Progestagens can cause irregular bleeding. Combination of both can cause menstrual irregularity. Postcoital hormonal contraceptives are contraindicated in heart and liver diseases, thrombosis, and pregnancy (teratogenic and carcinogenic effects on offspring). Pregnancy despite postcoital contraception results in extrauterine pregnancy in 10% of patients. The most important reservations in evaluating publications on this subject are: 1) lack of control group; 2) estimation of pregnancy probability is not reliable because of study population used; 3) patient fertility cannot be ascertained; and 4
Shirai, Hiroyuki; Yashima, Jun; Tojimbara, Tamotsu; Honda, Kazuho
Thrombotic microangiopathy (TMA) after kidney transplantation has various aetiologies, including acute antibody-mediated rejection, bacterial or viral infection and immunosuppressive drugs, particularly calcineurin inhibitors. We present the case of a 28-year-old woman who developed TMA 30 months after the transplantation of an ABO-incompatible kidney from a living unrelated donor. The patient developed a sudden onset of allograft renal dysfunction and became uremic. She was transferred to our institution from a community hospital with strongly suspected acute allograft rejection. Intensive treatments for both T- and B-cell mediated acute rejection, including steroid pulse therapy, double-filtration plasmapheresis, antithymocyte globulin (1.5 mg/kg × 14 days) and rituximab (100 mg), were initiated during haemodialysis. However, her renal allograft function did not improve. Histopathological analysis 8 days after the treatment indicated TMA, despite the absence of apparent acute T-cell- or acute antibody-mediated rejection. There were no symptoms of infectious diseases, such as intestinal haemorrhagic colitis or viral infection. We concluded that the use of oral contraceptives, which had been initiated 3 weeks before TMA onset for the treatment of irregular vaginal bleeding, was the aetiologic agent.
Sedlak, Tara; Shufelt, Chrisandra; Iribarren, Carlos; Lyon, Liisa L; Merz, C. Noel Bairey
Background A prolonged corrected QT (QTc) interval is a marker for an increased risk of sudden cardiac death. We evaluated the relationship between oral contraceptive (OC) use, type of OC, and QTc interval. Methods We identified 410,782 ECGs performed at Northern California Kaiser Permanente on female patients between 15–53 years from January, 1995 to June, 2008. QT was corrected for heart rate using log-linear regression. OC generation (first, second and third) was classified by increasing progestin androgenic potency, while the fourth generation was classified as anti-androgenic. Results Among 410,782 women, 8.4% were on OC. In multivariate analysis after correction for comorbidities, there was an independent shortening effect of OCs overall (slope = −0.5ms; SE = 0.12, p<0.0002). Users of first and second generation progestins had a significantly shorter QTc than non-users (p<0.0001), while users of fourth generation had a significantly longer QTc than non-users (slope = 3.6ms, SE = 0.35, p<0.0001). Conclusion Overall, OC use has a shortening effect on the QTc. Shorter QTc is seen with first and second generation OC while fourth generation OC use has a lengthening effect on the QTc. Careful examination of adverse event rates in fourth generation OC users is needed. PMID:23879279
Huber, Larissa R. Brunner; Broel, Elizabeth C.; Mitchelides, Ashley N.; Dmochowski, Jacek; Dulin, Michael; Scholes, Delia
BACKGROUND The purpose of this study was to determine if retrospective recall of oral contraceptive (OC) adherence provides data that are similar to data collected via daily diaries over the same time period. Factors associated with inconsistent agreement between prospective and retrospective measurements of adherence also were explored. STUDY DESIGN A total of 185 women participated in a longitudinal, prospective cohort of OC users and 113 of these women provided complete information on OC adherence during follow-ups. Concordance beyond chance was assessed using weighted kappa statistics and logistic regression was used to identify factors associated with inconsistent reporting of adherence. RESULTS There was substantial agreement between prospective and retrospective adherence information (weighted kappa=0.64; 95% CI: 0.52, 0.77). Participants with a high school education or less and those who had problems with feeling sad while using OCs had increased odds of inconsistent reporting of adherence (OR=4.38, 95% CI: 1.41, 13.61 and OR=3.52, 95% CI: 1.25, 9.94; respectively). CONCLUSION While prospective data collection via diaries may improve accuracy, the added expense and burden on study participants may not be necessary. However, the use of retrospective recall may not be appropriate for all study populations. PMID:23582236
Merz, Christian Josef; Tabbert, Katharina; Schweckendiek, Jan; Klucken, Tim; Vaitl, Dieter; Stark, Rudolf; Wolf, Oliver Tobias
An important feature of the human defense system comprises fear learning, which stress hormones can crucially modulate. However, stress hormones might influence men and women differently, in part because of interactions with sex hormones. In women, distinct stages of the menstrual cycle or the intake of oral contraceptives (OC) affect sex hormone levels. In this study, we used a differential fear conditioning paradigm with electrical stimulation as unconditioned stimulus (UCS) following one neutral stimulus (conditioned stimulus, CS+), but not another (CS-).To investigate implicit fear learning, participants were distracted from detecting the contingencies between CS and UCS. To address interaction effects of sex and stress hormones, 32 men, 30 women in the early follicular phase of the menstrual cycle (FO), 30 women in the luteal phase (LU), and 30 OC women received either 30 mg cortisol or a placebo. In the contrast CS+ minus CS-, an interaction between cortisol administration and sex hormone status emerged in the anterior parahippocampal gyrus and the hippocampus. Cortisol reduced fear learning in men, FO, and LU women, but enhanced it in OC women. Additionally, cortisol attenuated differential amygdala activation in the entire group. These results demonstrate that OC usage substantially modifies cortisol effects on emotional learning in women, particularly in memory-related medial temporal lobe regions. Further, a high dose of cortisol reduces amygdala differentiation pointing to a lowered learning ability of the defense system under high cortisol concentrations, irrespective of current sex hormone availability.
Genzel, Lisa; Bäurle, Anna; Potyka, Alina; Wehrle, Renate; Adamczyk, Marek; Friess, Elisabeth; Steiger, Axel; Dresler, Martin
Many young females take exogenous hormones as oral contraceptive (OC), a condition rarely controlled for in studies on sleep and memory consolidation even though sex hormones influence consolidation. This study investigated the effects of OCs on sleep-related consolidation of a motor and declarative task, utilizing a daytime nap protocol. Fifteen healthy, young females taking OCs came to the sleep lab for three different conditions: nap with previous learning, wake with previous learning and nap without learning. They underwent each condition twice, once during the "pill-active" weeks and once during the "pill-free" week, resulting in 6 visits. In all conditions, participants showed a significant off-line consolidation effect, independent of pill week or nap/wake condition. There were no significant differences in sleep stage duration, spindle activity or spectral EEG frequency bands between naps with or without the learning condition. The present data showed a significant off-line enhancement in memory irrespective of potential beneficial effects of a nap. In comparison to previous studies, this may suggest that the use of OCs may enhance off-line memory consolidation in motor and verbal tasks per se. These results stress the importance to control for the use of OCs in studies focusing on memory performance.
Fox, Michelle C; Creinin, Mitchell D; Murthy, Amitasrigowri S; Harwood, Bryna; Reid, Lynn M
Women who ingest their oral contraceptive pill (OCP) as part of a daily routine are more likely use their OCPs correctly. This trial examines the feasibility of an electronic-mail (e-mail) reminder system to improve OCP compliance. An e-mail reminder was sent to 50 new OCP users daily for 3 months. Subjects sent an e-mail reply to confirm receipt. OCP compliance was recorded on diaries. Four subjects were discontinued for not checking their e-mail. Active participants missed a median of 18% of the e-mail reminders (range: 0-65%). A follow-up visit was scheduled after completion of three OCP cycles. Of the 40 subjects returning completed diaries, 50% missed no active pills at all and 20% missed at least one in each cycle. Most found the daily e-mail somewhat (65%) or very helpful (19%) for OCP compliance. Of those continuing OCPs, 64% wanted to continue receiving e-mail reminders at the completion of the study. Because inconsistent OCP use is a significant cause of unplanned conception, the use of e-mail to improve OCP compliance has the potential to decrease unintended pregnancies.
In response to unpublished data revealing a doubling of venous thromboembolism risk with oral contraceptives (OCs) containing desogestrel or gestodene compared with levonorgestrel, the UK Committee on Safety of Medicines advised physicians that women taking these third-generation OCs should be switched to another formulation. There are indications, however, that the studies on which this recommendation was based were flawed by prescriber bias and confounding. In addition, laboratory measures of thrombosis and fibrinolysis do not indicate a shift toward a thrombotic state associated with the newer progestogens. Moreover, desogestrel and gestodene OCs have been associated with a reduced risk of arterial disease when compared to levonorgestrel-containing OCs. Since the mortality associated with acute myocardial infarction is almost 50%, compared with 1-2% for venous thromboembolism, this information should be considered when counseling OC users about their risk of cardiovascular disease. Although the European Union Committee on Proprietary Medicinal Products has taken the position that all OCs are contraindicated in women with current or past cardiovascular disease, unlike the UK Committee, it has not made any specific recommendations about the suitability or non-suitability of the third-generation OCs.
The influence of oral contraceptive (OC) use in young women on the risk of development of venous thromboembolism, myocardial infarction, and thrombotic stroke was assessed through an analysis of nationwide register data from Denmark for 1980-93 and for 1994-95 from three ongoing case-control studies. All three diseases increased rapidly with increasing age; the arterial diseases increased almost exponentially, while the venous diseases increased more linearly. Venous thromboembolism was almost twice as prevalent as arterial complications in women 15-29 years old, while the number of arterial complications exceeded that of venous diseases by about 50% in women 30-44 years of age. Mortality from arterial diseases was 3.5 times higher than that from venous diseases among women under 30 years of age and 8.5 times higher than that from venous diseases in women 30-44 years old. The proportion of women with a significant disability was about 30% among those with an arterial complication; this proportion was 5% among women with venous thromboembolism. Users of OCs with second-generation progestogens had a 30% greater increased risk of thrombotic diseases, a 260% greater increased risk of thrombotic mortality, and a 220% greater increased risk of thrombotic disability than users of OCs with third-generation progestogens.
Birtch, Rebecca L; Baerwald, Angela R; Olatunbosun, Olufemi A; Pierson, Roger A
Background Computer-assisted analyses were used to examine ultrasound image attributes of human dominant ovarian follicles that developed during natural and oral contraceptive (OC) cycles. We hypothesized that image attributes of natural cycle follicles would quantitatively differ from those in OC cycles and that OC cycle follicles would possess image attributes indicative of atresia. Methods Dominant ovarian follicles of 18 clinically normal women were compared using transvaginal ultrasonography for the 7 days before ovulation during a natural cycle (n = 9) or the 7 days before peak estradiol in women using OC (n = 11). Follicles were analyzed using region and line techniques designed to compare the image attributes numerical pixel value (NPV), pixel heterogeneity (PH) and area under the curve (AUC). Results NPV was higher in OC cycle follicles with region analysis and tended to be higher with line analysis (p = 0.005 and p = 0.06, respectively). No differences were observed in two other image attributes (AUC and PH), measured with either technique, between natural and OC cycle follicles. Conclusion The increased NPV value of OC cycle follicles and lack of differences in PH and AUC values between natural cycle and OC cycle follicles did not support the hypothesis that OC cycle follicles would show ultrasonographically detectable signs of atresia. Image attributes observed in OC cycle follicles were not clearly indicative of atresia nor were they large enough to preclude preovulatory physiologic status in OC cycle follicles. PMID:15829004
This review covers 10 articles published during 1981-96 to determine which subgroups within the population of smokers and oral contraceptive (OC) users are at especially elevated risk for thromboembolic events. It was found that the thrombogenic effects of smoking are mediated by two pathways: 1) increased biosynthesis of thromboxane, which promotes platelet aggregation; 2) degenerative changes in the vascular endothelium leading to the formation of atheromas and necrotic plaque, which in turn results in formation of thrombi. There was evidence showing that cardiovascular disease associated with OC use is due to thrombosis rather than atherosclerosis. The effects of smoking, resulting in an increase in arterial wall stiffness and changes in the patterns of arterial blood flow, would lead to formation of thrombi. However, there was an inconsistency in the data presented; studies revealed that smoking alone constitutes greater cardiovascular risk. Cigarette smoking and OC use can act synergistically to favor the formation of thrombi and increase the risk of thromboembolic events. Heavy smoking, a longer history of smoking, and inhaling smoke in association with OC use increases the risk of thrombosis.
Despite the safety and effectiveness of low oestrogen-dose oral contraceptives (OC) and postmenopausal hormone replacement there is poor continuity of use of these agents by women. Patterns of use and the reasons affecting different frequencies of use in different countries are presented. Continuity and discontinuation rates are difficult to assess accurately but it is believed that the main reasons why women discontinue use of these agents are concerns about their perceived health risks and the presence of, or fear of, adverse clinical effects, particularly unscheduled uterine bleeding and weight gain. More information is needed about OC continuation rates in order to improve the acceptability of these safe, effective agents. Most women discontinue use of postmenopausal hormonal replacement within 2 years of initiating the therapy. Reasons include disappearance of symptoms of oestrogen deficiency, lack of awareness of health benefits of oestrogen, presence of side-effects (such as breast tenderness and weight gain), presence of uterine bleeding and increasing age. Suggestions to increase continuation of OC include extensive individual pretreatment counselling with a different emphasis in different age groups, education at the time of follow-up visits and telephone calls, and extensive use of educational aids such as brochures, pamphlets and audio tapes, and improvement of pharmaceutical packaging information. In conclusion there is an urgent need to assess the value of these strategies by long-term large controlled studies.
van Voorst Vader, P C; Lier, J G; Posma, A L; Schröder, F P; Schirm, J; Kauer, F M
We determined the prevalence of genital Chlamydia trachomatis infection in women who visited a clinic for sexually transmitted diseases (STD) and the influence of the number of partners and the use of oral contraceptives (OC), with special attention to the recognition of pelvic inflammatory disease (PID) and to the results of therapy. Of 217 women, with a mean age of 26 years (range 14-56), who visited the STD clinic of the University Hospital of Groningen from July 1985 until November 1987, anamnestic data were collected as well as the results of swabs from cervix and urethra taken for culture and direct immunofluorescence test of C. trachomatis and for gonococcal culture. The influence of the number of partners (1 versus greater than 1) and OC on the prevalence of C. trachomatis infection was evaluated by logistic regression analysis. PID was excluded in coöperation with the department of gynaecology. C. trachomatis-infected women were treated by doxycycline orally (day 1 2 x 100 mg, day 2-7 1 x 100 mg) according to the dosage scheme advised by the Dutch Health Council in 1986. A control culture was taken 2-3 weeks after treatment. C. trachomatis was detected in 72/217 (33%) women by culture and (or) direct IF test and in 22/41 (54%) women with gonorrhoea. In connection with the number of partners in the year preceding the examination, the following prevalences were found: 18/74 (24%) (1 partner), 43/108 (40%) (2-5 partners) and 10/27 (greater than 5 partners).(ABSTRACT TRUNCATED AT 250 WORDS)
Little, Anthony C; Burriss, Robert P; Petrie, Marion; Jones, Benedict C; Roberts, S Craig
Millions of women use hormonal contraception and it has been suggested that such use may alter mate preferences. To examine the impact of oral contraceptive (pill) use on preferences, we tested for within-subject changes in preferences for masculine faces in women initiating pill use. Between two sessions, initiation of pill use significantly decreased women's preferences for male facial masculinity but did not influence preferences for same-sex faces. To test whether altered preference during pill use influences actual partner choice, we examined facial characteristics in 170 age-matched male partners of women who reported having either been using or not using the pill when the partnership was formed. Both facial measurements and perceptual judgements demonstrated that partners of women who used the pill during mate choice have less masculine faces than partners of women who did not use hormonal contraception at this time. Our data (A) provide the first experimental evidence that initiation of pill use in women causes changes in facial preferences and (B) documents downstream effects of these changes on real-life partner selection. Given that hormonal contraceptive use is widespread, effects of pill use on the processes of partner formation have important implications for relationship stability and may have other biologically relevant consequences.
Rivera, R; Yacobson, I; Grimes, D
Modern hormonal contraceptives and intrauterine contraceptive devices have multiple biologic effects. Some of them may be the primary mechanism of contraceptive action, whereas others are secondary. For combined oral contraceptives and progestin-only methods, the main mechanisms are ovulation inhibition and changes in the cervical mucus that inhibit sperm penetration. The hormonal methods, particularly the low-dose progestin-only products and emergency contraceptive pills, have effects on the endometrium that, theoretically, could affect implantation. However, no scientific evidence indicates that prevention of implantation actually results from the use of these methods. Once pregnancy begins, none of these methods has an abortifacient action. The precise mechanism of intrauterine contraceptive devices is unclear. Current evidence indicates they exert their primary effect before fertilization, reducing the opportunity of sperm to fertilize an ovum.
Guzelmeric, K; Seker, N; Unal, O; Turan, C
Using an ultrasensitive assay, prostate-specific antigen (PSA) has been detected in female serum and has been proposed as a potential marker of androgen excess in hirsute women. Measurement of PSA levels in serum may play a role in monitoring hirsutism during antiandrogen therapy. We investigated the role of PSA as a marker of androgen activity in hirsute patients taking spironolactone together with oral contraceptive pills containing ethinyl estradiol and gestodene. Twenty-eight hirsute patients were included in the study. Clinical and biochemical variables including serum levels of PSA (using an ultrasensitive chemiluminscent immunoassay), dehydroepiandrosterone sulfate, total testosterone, free testosterone and 17-hydroxyprogesterone concentrations were recorded at baseline and after six cycles of treatment. Fifteen healthy women were included in the study as controls. Serum PSA levels in hirsute women were clearly higher than in the control group (0.023 +/- 0.004 vs. 0.006 +/- 0.003 ng/ml, p < 0.001) and correlated with baseline serum free testosterone concentrations (r = 0.518, p = 0.005). After 6 months, serum PSA concentrations as compared with baseline values did not change significantly in patients who were given spironolactone plus contraceptive pills (p = 0.4) despite a marked decrease in total testosterone, free testosterone, 17-hydroxyprogesterone, dehydroepiandrosterone sulfate and hirsutism score (p < 0.05). Thus, serum PSA levels in hirsute women were higher than in non-hirsute healthy controls. A 6-month course of treatment with spironolactone combined with contraceptive pills containing ethinylestradiol and gestodene did not reduce high serum PSA levels in these subjects. In conclusion, the serum PSA level is not a convenient biochemical marker with the available assays for the management of hirsute women treated with the combination of spironolactone and oral contraceptives.
Bassol, S; Alvarado, A; Celis, C; Cravioto, M C; Peralta, O; Montaño, R; Novelli, J; Albornoz, H; Kesseru, E; Soares, A; Petracco, A; Isaia, B; Mendes, J; Bahamondes, L; de Melo, N R; Reyes-Marquez, R; Albrecht, G
The objective of this study was to compare cycle control, efficacy and tolerance of an oral contraceptive containing 20 microg ethinylestradiol and 150 microg desogestrel with a preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. This study involved 342 women and 4104 cycles use in Argentina, Brazil, Chile, and Mexico. Contraceptive efficacy was good with both formulations. Two pregnancies occurred in the desogestrel group but were not due to method failure. With respect to cycle control, the incidence of intermenstrual bleeding was higher during the first 3 cycles in the desogestrel group; it was significant (p <0.01) during the first 3 days of the cycle for a normal or heavy bleeding only in the Mexican group. Amenorrhea was not reported for any group, but the incidence of dysmenorrhea was significantly higher (p <0.01) in the Brazilian desogestrel group (13.8%) and was significantly lower (p <0.01) in the Mexican gestodene group (8.5%). Adverse events were similar in all the countries with headache, breast tension, and nausea, the most frequently reported symptoms. The range of mean increase in body weight varied from 0.2 kg in the Argentine group to 2.6 kg in the Chilean group (95% confidence limit, +/- 2.51) in the gestodene group, and 0.2 kg in the Argentine group to 2.5 kg in Brazilian group (95% confidence limit, +/- 2.36) in the desogestrel group. Fifteen women discontinued because of headache, but there were no significant differences between the groups regarding discontinuation for this and other medical or non-medical reasons. Both oral contraceptive preparations are reliable and well tolerated, and both have favorable effects on control cycle.
Amory, John K
Efforts are underway to develop new methods of contraception for men. The most promising approach to male contraceptive development is hormonal and involves the administration of testosterone. When testosterone is administered to a man, it functions as a contraceptive by suppressing the secretion of luteinizing hormone and follicle-stimulating hormone from the pituitary gland, thereby depriving the testes of the signals required for spermatogenesis. After two to three months of treatment, low levels of gonadotropins lead to markedly decreased sperm counts and effective contraception in a majority of men. In many clinical trials, male hormonal contraception has proven to be free from serious adverse effects and is well-tolerated by men. In addition, sperm parameters uniformly normalize when treatment is discontinued. The main drawback to this approach is the observation that spermatogenesis is not suppressed to zero in all men, meaning that some potential for fertility persists. Because of this, recent studies have combined testosterone with progestogens and/or gonadotropin-releasing antagonists to synergistically suppress pituitary gonadotropins and improve suppression of spermatogenesis. Current combinations of testosterone and progestogens severely suppress spermatogenesis without severe side effects in 80-90% of men, with significant suppression in the remainder of individuals. Recent trials with newer, long-acting forms of injectable testosterone, such as testosterone undecanoate, which can be administered every 8-10 weeks, combined with progestogens, administered either orally or by long-acting implant, have yielded promising results and may soon result in the marketing of a safe, reversible and effective hormonal contraceptive for men.
Fisher, William A.; Boroditsky, Richard; Bridges, Martha L.
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…
The annual risk of venous thrombosis has been estimated at 5 to 10 cases per 100 000 women aged 15 to 44 years who are not using hormonal contraception.The risk increases with age for all women. Combined oral oestrogen-progestin contraceptives increase the risk of venous and arterial thrombosis. The risk of venous thrombosis varies, depending on which oestrogen-progestin combination is used. It is about 20 cases per 100,000 woman-years with contraceptives combining norethisterone or levonorgestrel with ethinylestradiol at doses below 50 microgram.The risk is twice as high with third-generation oral contraceptives. In addition to the oral route, hormonal contraception is available as a a transdermal patch or a vaginal ring. What is the risk of thrombosis associated with these non-oral forms? A cohort study showed that the risk of venous thrombosis was approximately 8-fold higher among women using a transdermal patch and 7-fold higher in those using a vaginal ring compared to women not using contraception. Another study on arterial thrombosis demonstrated a statistically significant increase in the risk of stroke among vaginal ring users, but not in the risk of myocardial infarction. In practice, overall, these data show that the use of contraceptive transdermal patch or the contraceptive vaginal ring increases the risk of venous thrombosis.The excess risk of arterial thrombosis is unknown.When hormonal contraception is requested, it is better to recommend a combination containing levonorgestrel and less than 50 microgram of ethinylestradiol per tablet, which carries a lower risk of venous or arterial thrombosis.
Background Both oral contraceptive pills (OCPs) and estradiol (E2) valerate have been used to schedule gonadotropin-releasing hormone (GnRH) antagonist in vitro fertilization (IVF) cycles and, consequently, laboratory activities. However, there are no studies comparing treatment outcomes directly between these two pretreatment methods. This randomized controlled trial was aimed at finding differences in ongoing pregnancy rates between GnRH antagonist IVF cycles scheduled with OCPs or E2 valerate. Methods Between January and May 2012, one hundred consecutive patients (nonobese, regularly cycling women 18–38 years with normal day 3 hormone levels and <3 previous IVF/ICSI attempts) undergoing IVF with the GnRH antagonist protocol were randomized to either the OCP or E2 pretreatment arms, with no restrictions such as blocking or stratification. Authors involved in data collection and analysis were blinded to group assignment. Fifty patients received OCP (30 μg ethinyl E2/150 μg levonorgestrel) for 12–16 days from day 1 or 2, and stimulation was started 5 days after stopping OCP. Similarly, 50 patients received 4 mg/day oral E2 valerate from day 20 for 5–12 days, until the day before starting stimulation. Results Pretreatment with OCP (mean±SD, 14.5±1.7 days) was significantly longer than with E2 (7.8±1.9 days). Stimulation and embryological characteristics were similar. Ongoing pregnancy rates (46.0% vs. 44.0%; risk difference, –2.0% [95% CI –21.2% to 17.3%]), as well as implantation (43.5% vs. 47.4%), clinical pregnancy (50.0% vs. 48.0%), clinical miscarriage (7.1% vs. 7.7%), and live birth (42.0% vs. 40.0%) rates were comparable between groups. Conclusions This is the first study to directly compare these two methods of cycle scheduling in GnRH antagonist cycles. Our results fail to show statistically significant differences in ongoing pregnancy rates between pretreatment with OCP and E2 for IVF with the GnRH antagonist protocol. Although the
Newcomb, P A; Longnecker, M P; Storer, B E; Mittendorf, R; Baron, J; Clapp, R W; Trentham-Dietz, A; Willett, W C
We examined the association between recent oral contraceptive (OC) use and the risk of breast cancer in data from a large population-based case-control study in the United States. Cases (n = 6,751) were women less than 75 years old who had breast cancer identified from statewide tumor registries in Wisconsin, Massachusetts, Maine, and New Hampshire. Controls (n = 9,311) were selected randomly from lists of licensed drivers (if aged under 65 years) and from lists of Medicare beneficiaries (if aged 65 through 74 years). Information on OC use, reproductive experiences, and family and medical history was obtained by telephone interview. After adjustment for parity, age at first delivery, and other risk factors, women who had ever used OCs were at similar risk of breast cancer as never-users (relative risk [RR] = 1.1, 95 percent confidence interval [CI] = 1.0-1.2). Total duration of use also was not related to risk. There was a suggestion that more recent use was associated with an increased risk of breast cancer; use less than two years ago was associated with an RR of 1.3 (CI = 0.9-1.9). However, only among women aged 35 to 45 years at diagnosis was the increase in risk among recent users statistically significantly elevated (RR = 2.0, CI = 1.1-3.9). Use prior to the first pregnancy or among nulliparous women was not associated with increased risk. Among recent users of OCs, the risk associated with use was greatest among non-obese women, e.g., among women with body mass index (kg/m2) less than 20.4, RR = 1.7, CI = 1.1-2.8. While these results suggest that, in general, breast cancer risk is not increased substantially among women who have used OCs, they also are consistent with a slight increased risk among subgroups of recent users.
Elomaa, K; Rolland, R; Brosens, I; Moorrees, M; Deprest, J; Tuominen, J; Lähteenmäki, P
The hypothesis that omission of the first three pills of the oral contraceptive (OC) cycle leads to ovulation by extending further the pill-free period was investigated in 107 healthy women 18-35 years of age recruited from family planning programs in Finland, the Netherlands, and Belgium. Study participants were randomly allocated to one of the following treatment groups: 1) monophasic gestodene--75 mcg of gestodene and 30 mcg of ethinyl estradiol; 2) triphasic gestodene--6 days of 50 mcg gestodene and 30 mcg ethinyl estradiol, 5 days of 70 mcg gestodene and 40 mcg ethinyl estradiol, and 10 days of 100 mcg gestodene and 30 mcg ethinyl estradiol; or 3) monophasic desogestrel--150 mcg desogestrel and 20 mcg ethinyl estradiol. Noncompliance with OC taking was simulated by extending the pill-free period from 7 to 10 days. During or after the extended pill-free interval, follicular growth exceeding 18 mm occurred in 24% of women in the monophasic gestodene group, 24% in the triphasic gestodene group, and 40% in the monophasic desogestrel group. Follicle-stimulating hormone reached a maximum serum concentration in most women during the first 7 pill-free days, indicating complete pituitary recovery. No normal ovulation was observed after either a 7- or 10-day pill-free period as evaluated by ultrasonography of follicles and serum progesterone assays. Since normal ovulation did not occur when pill omissions were limited to 3 days, OC users who forget to take these three tablets can be safely advised to start the pill cycle on day 11.
Rechichi, Claire; Dawson, Brian
The purpose of this study was to examine whether swimming performance was affected by acute hormonal fluctuation within a monophasic oral contraceptive (OC) cycle. Six competitive swimmers and water polo players completed a 200-m time trial at 3 time points of a single OC cycle: during the consumption phase (CONS), early (WITH1), and late in the withdrawal phase (WITH2). Split times and stroke rate were recorded during the time trial, and heart rate, blood lactate, glucose, and pH were measured after each performance test. Resting endogenous serum estradiol and progesterone concentrations were also assessed. No significant differences were observed between phases for body composition, 200-m swim time, mean stroke rate, peak heart rate, or blood glucose (p > 0.05). The mean peak blood lactate was significantly lower during WITH2 (9.9 ± 3.0 mmol·L(-1)) compared with that of CONS (12.5 ± 3.0 mmol·L(-1)) and mean pH higher during WITH2 (7.183 ± 0.111) compared with that of CONS (7.144 ± 0.092). Serum estradiol levels were significantly greater during WITH2 compared with that during WITH1 and CONS, but there was no difference in serum progesterone levels. These results demonstrate that for monophasic OC users, cycle phase does not impact the 200-m swimming performance. There was a reduction in blood lactate and an increase in pH during the withdrawal phase, possibly because of an increase in fluid retention, plasma volume, and cellular alkalosis. Therefore, female 200-m swimmers taking a monophasic OC need not be concerned by the phase of their cycle with regard to competition and optimizing performance. However, coaches and scientists should exercise caution when interpreting blood lactate results obtained from swimming tests and consider controlling for cycle phase for athletes taking an OC.
Liu, Huan; Wang, Xing-Chun; Hu, Guang-Hui; Huang, Tian-Bao; Xu, Yun-Fei
Previous studies have investigated the relationship between oral contraceptives (OCs) use and kidney cancer risk. However, they yielded inconsistent results. To our knowledge, a comprehensive assessment of the association between OC and kidney cancer risk has not been reported. Hence, we conducted a meta-analysis to quantify the association. We identified all relevant studies up to July 2014 through a literature search of using PubMed and EMBASE, and by reviewing the references from the retrieved articles. Fixed-effect and random-effect models were used to estimate summary relative risks (SRRs) and the corresponding 95% confidence intervals (CIs). A total of 12 studies were eligible and included in this meta-analysis, involving 4,206 kidney cancer cases and 638,677 participants. The SRR of kidney cancer for ever versus never OC use was 0.89 (95% CI: 0.82-0.98). The protection became stronger when compared the longest duration of OC use with never use (RR = 0.80; 95% CI: 0.68-0.94). In dose-response analysis, we found that the kidney cancer risk decreased by 2% for per 1 year increment in OC use (RR = 0.98; 95% CI: 0.96-0.99). No apparent heterogeneity was observed across studies included in this analysis. Egger’s and Begg’s test also indicated no publication bias. The present study suggested that OC may reduce the risk of kidney cancer, especially for long-term users. More well-conducted and large-scale prospective studies are warranted to confirm the effects of OC use on kidney cancer. PMID:25550903
Okwusidi, J I; Alabi, K I; Olatunji, L A; Oyesola, T O
Administration of oral contraceptive (OC) has been associated with body fluid retention and in high doses over a long period, promotes hypertension. This present investigation tests the hypothesis that the dietary calcium supplementation increases salt and water excretion in OC (norgestre/ethinylestradiol) treated 32 female albino rats randomly distributed into four (1-4) groups of 8 rats each: Control, OC-treated, OC-treated+ Calcium diet fed and Calcium diet fed only respectively. OC was administered to the appropriate groups by gavage. Experimental diet contained 2.5% calcium supplement. Plasma and urinary [Na+] [K+] were evaluated after 8 weeks of experimentation by flame photometry and plasma [Ca2+] by colorimetric method. OC-treatment induced a significant fall in urinary [Na+]. Water excretion was significantly reduced in these animals (control, 3.1±0.56 Vs OC-treated rats, 1.47±0.16). OC-treated rats had significantly higher plasma [K+] compared to control rats. Calcium supplementation induced increases in plasma [Na+], [K+] and augmented urinary Na+ excretion (OC-treated + Ca2+ diet Vs OC-treated only). Compared with the control rats, high Ca2+ diet fed rats exhibited significant increases in plasma [Na+] and [K+] accompanied by significant decreases in urinary H20 excretion. These results strongly suggest that high dietary Ca2+ supplementation increases salt and water excretion in OC-treated rats and potentially moderates fluid retention and blood pressure in these animals, and may be of clinical significance in OC-induced abnormal fluid retention and perhaps OC-induced hypertension.
Trivers, Katrina F; Gammon, Marilie D; Abrahamson, Page E; Lund, Mary Jo; Flagg, Elaine W; Moorman, Patricia G; Kaufman, Jay S; Cai, Jianwen; Porter, Peggy L; Brinton, Louise A; Eley, J William; Coates, Ralph J
Recent oral contraceptive (OC) use is associated with modestly higher breast cancer incidence among younger women, but its impact on survival is unclear. This study examined the relationship between OC use before breast cancer diagnosis and survival. A population-based sample of 1,264 women aged 20 to 54 years with a first primary invasive breast cancer during 1990 to 1992 were followed up for 8 to 10 years. OC and covariate data were obtained by interviews conducted shortly after diagnosis and from medial records. All-cause mortality was ascertained through the National Death Index (n = 292 deaths). Age- and income-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression methods. All-cause mortality was not associated with ever use of OCs or duration of use. Compared with nonusers, mortality estimates were elevated among women who were using OCs at diagnosis or stopped use in the previous year (HR, 1.57; 95% CI, 0.95-2.61). The HR for use of high-dose estrogen pills within 5 years before diagnosis was double that of nonusers (HR, 2.39; 95% CI, 1.29-4.41) or, if the most recent pill included the progestin levonorgestrel, compared with nonusers (HR, 2.01; 95% CI, 1.03-3.91). Because subgroup estimates were based on small numbers of OC users, these results should be cautiously interpreted. Overall, most aspects of OC use did not seem to influence survival, although there is limited evidence that OC use just before diagnosis, particularly use of some pill types, may negatively impact survival in breast cancer patients aged 20 to 54 years.
Dumeaux, Vanessa; Alsaker, Elin; Lund, Eiliv
The aim of our study was to examine the risk of breast cancer according to specific types of estrogens and progestagens in oral contraceptives (OCs) based on the prospective Norwegian Women and Cancer study (NOWAC). Between 1991-97 women aged 30-70 years were drawn at random from the central person register and mailed an invitation and a questionnaire. Women (102,443) were enrolled with follow-up information collected throughout 1999 by linkage with national registries of cancer, mortality and emigration based on the unique national identification number. Among the 96,362 women included in the present analysis 851 invasive breast cancer were diagnosed. The adjusted risk of breast cancer increased with 25% for ever use of OCs and the risk increased with increasing duration of use (test for trend: p = 0.007). No association between time since last use and breast cancer risk was found after stratification on duration of use. Positive trend was still found for total duration of use among women who used OCs more than 5 years ago. Second generation of OCs had an increased risk with increasing duration of use. Classifying progestagens according to chemical groups, the relative risk increased significantly with increasing cumulative dose of levonorgestrel progestagen. It was difficult to conclude for the other groups due to lack of power. In a multivariate analysis the cumulative dose for all progestagen groups were non-significant, although we observed a significant increased risk with increasing milligram-months of estrogen exposure (p = 0.002). In conclusion, the increased risk of breast cancer related with OC formulations could be due mostly to estrogen component.
Teixeira, André L; Ramos, Plínio S; Vianna, Lauro C; Ricardo, Djalma R
Previous studies have shown that resting heart rate variability (HRV) is modified by different phases of the menstrual cycle in nonusers of oral contraceptive pills (OCP); however, the effect of OCP on autonomic control of the heart remains unclear. The purpose of this study was to investigate HRV during the low hormone (LH-not taking OCP) and during the high hormone (HH-active OCP use) phases of the menstrual cycle in young women. Seventeen healthy women (19-31 years) taking OCP for at least 6 consecutive months were enrolled in this study. Plasma estradiol and progesterone were verified at each visit. HRV was assessed by using one-lead electrocardiography in time and frequency domains, in which participants rested in the supine position for a 20-min period with a breathing rate of 15 cycles/min. In addition, resting heart rate, and systolic and diastolic blood pressure were obtained. Both plasma estradiol (LH: 19.8 ± 4.2 pg/mL vs. HH: 12.4 ± 1.5 pg/mL; p > .05) and progesterone (LH: 0.247 ± 0.58 ng/mL vs. HH: 0.371 ± 0.08 ng/mL; p > .05) (mean ± SE) levels were similar in both phases. No significant difference was obtained for any component of HRV, heart rate, or blood pressure between the LH and HH phases (p > .05). These results provide preliminary evidence that use of OCP does not affect HRV during the menstrual cycle in healthy women.
Timms, Barry G.; Howdeshell, Kembra L.; Barton, Lesley; Bradley, Sarahann; Richter, Catherine A.; vom Saal, Frederick S.
Exposure of human fetuses to man-made estrogenic chemicals can occur through several sources. For example, fetal exposure to ethinylestradiol occurs because each year ≈3% of women taking oral contraceptives become pregnant. Exposure to the estrogenic chemical bisphenol A occurs through food and beverages because of significant leaching from polycarbonate plastic products and the lining of cans. We fed pregnant CD-1 mice ethinylestradiol (0.1 μg/kg per day) and bisphenol A (10 μg/kg per day), which are doses below the range of exposure by pregnant women. In male mouse fetuses, both ethinylestradiol and bisphenol A produced an increase in the number and size of dorsolateral prostate ducts and an overall increase in prostate duct volume. Histochemical staining of sections with antibodies to proliferating cell nuclear antigen and mouse keratin 5 indicated that these increases were due to a marked increase in proliferation of basal epithelial cells located in the primary ducts. The urethra was malformed in the colliculus region and was significantly constricted where it enters the bladder, which could contribute to urine flow disorders. These effects were identical to those caused by a similar dose (0.1 μg/kg per day) of the estrogenic drug diethylstilbestrol (DES), a known human developmental teratogen and carcinogen. In contrast, a 2,000-fold higher DES dose completely inhibited dorsolateral prostate duct formation, revealing opposite effects of high and low doses of estrogen. Acceleration in the rate of proliferation of prostate epithelium during fetal life by small amounts of estrogenic chemicals could permanently disrupt cellular control systems and predispose the prostate to disease in adulthood. PMID:15867144
A comparison of cycle control, efficacy, and side effects among healthy Thai women between two low-dose oral contraceptives containing 20 microg ethinylestradio1/75 microg gestodene (Meliane) and 30 microg ethinylestradio1/75 microg gestodene (Gynera).
Taneepanichskul, S; Kriengsinyot, R; Jaisamrarn, U
The purpose of this study was to compare cycle control, efficacy and side effects of an oral contraceptive containing 20 microg ethinylestradiol and 75 microg gestodene, with a reference preparation containing 30 microg ethinylestradiol combined with 75 microg gestodene. From the study, it was demonstrated that the two regimens had no difference in cycle control, efficacy, and side effects. The occurrence of spotting and breakthrough bleeding was low and was not different between these two preparations. The most common adverse events in both treatment groups were nausea, vomiting, dizziness, and chloasma. There were no statistically significant change in body weight and blood pressure in both groups at the end of study. It is concluded that both preparations are good cycle control, reliable and low side effects oral contraceptives.
Dutton, Caryn; Foldvary-Schaefer, Nancy
Contraceptive counseling is a critical component of the management of the female patient with epilepsy because of the increased risk of pregnancy associated with epilepsy and the multitude of interactions between antiepileptic drugs (AEDs) and hormonal contraception. Steroid hormones and many of the AEDs are substrates for the cytochrome P450 enzyme system, in particular, the 3A4 isoenzyme. As a result, concomitant use of hormonal contraceptives and AEDs may pose a risk for unexpected pregnancy, seizures, and drug-related adverse effects. The risk of combined oral contraceptive (COC) failure is slightly increased in the presence of cytochrome P450 3A4 enzyme-inducing AEDs. Several AEDs induce the production of sex hormone binding globulin (SHBG) to which the progestins are tightly bound, resulting in lower concentrations of free progestin that may also lead to COC failure. There is no increase in the risk of COC failure in women taking nonenzyme-inducing AEDs. Oral contraceptives significantly increase the metabolism of lamotrigine, posing a risk of seizures when hormonal agents are initiated and/or toxicity during pill-free weeks. There is no evidence that COCs increase seizures in women with epilepsy. While higher dose COCs are one contraceptive option for women on enzyme-inducing AEDs, a variety of other options are available. Injectable contraception (depot medroxyprogesterone acetate) appears effective with AED use, but the potential for bone mineral density loss is a concern. Intrauterine devices (IUDs) and barrier methods do not rely on hormonal components for contraceptive efficacy, and are therefore appropriate to recommend for use in women using enzyme-inducing medications. This chapter reviews the evidence regarding the pharmacokinetic interaction between AEDs and oral contraceptive hormones, the known or potential interactions with alternative contraceptive methods, and provides practical advice for management of contraceptive needs in reproductive
Blanco-Molina, Angeles; Monreal, Manuel
Hormonal contraceptives are a popular method of contraception, but their use has been associated with an increased risk for venous thromboembolism. In order to reduce such risk, these compounds have been changed in their dosage, chemical composition and route of administration. The absolute risk of death from pulmonary embolism in contraceptive users has been estimated to be 10.5 (95% CI: 6.2-16.6) per million woman-years. The safest option is an oral contraceptive containing levonorgestrel combined with a low dose of estrogen. Identifying women at increased risk for venous thromboembolism is difficult, and greater use of thromboprophylaxis during immobility or minor surgery should be warranted. Several authors have called for all women to be screened for thrombophilia before prescription of hormonal contraceptives, but its cost-effectiveness remains uncertain.
Women rarely depend on progestational contraception. In France, physicians are unsure of its indications. Progestational contraception presents advantages for certain indications where a particular condition exists and, more particularly, for women aged 40 and over. Women who can use it are those who have contraindications to estrogen use. These contraindications include uterine fibroids, endometrial hyperplasia, endometriosis, and fibro-cystic disease of the breast. It does produces side effects but those affecting metabolism seem to be almost negligible, like those of the third generation progestins. These side effects are metrorrhagias, amenorrhea, weight gain, and atherogenic metabolic changes. Yet, the nor-pregnane derivatives (which do effectively suppress ovulation) do not adversely affect glucose and lipid parameters. Progestational contraception probably cannot assure absolute safety as can combined oral contraceptives. It is not yet clear whether women who have been treated for breast cancer should use progestational contraception.
A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 20 micrograms ethinylestradiol/150 micrograms desogestrel, with respect to efficacy, cycle control and tolerance.
Endrikat, J; Jaques, M A; Mayerhofer, M; Pelissier, C; Müller, U; Düsterberg, B
The aim of this study was to compare contraceptive reliability, cycle control and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol and 75 micrograms gestodene, with a reference preparation containing the same dose of estrogen combined with 150 micrograms desogestrel. This article presents interim data from centers in France and Austria, involving a total of 479 women and 4,991 cycles. Contraceptive reliability was good with both preparations. Two pregnancies occurred in the gestodene group, but neither were due to method failure. In the desogestrel group there were also two pregnancies, of which one was due to method failure. With respect to cycle control, there is a trend towards a lower incidence of intermenstrual bleeding in the gestodene group. The incidence of spotting (scanty bleeding) during the important first three cycles was 3.5% lower in the gestodene group, and over the first six cycles, it was 7.6% lower. Amenorrhea was similar in both groups, but the incidence of dysmenorrhea was significantly lower in the gestodene group (p=0.001). Adverse events were similar in both groups, with headache, breast tension and nausea the most frequently reported symptoms. Body weight remained relatively constant during treatment in both groups, and no hypertension was reported for any woman during the course of the study. In each treatment group, 19 women discontinued because of adverse events. It is concluded that both preparation are reliable and well tolerated oral contraceptives are reliable and well tolerated oral contraceptives; however, there is a more favourable effect on dysmenorrhea by the gestodene formulation.
Petto, Jefferson; Vasques, Leila Monique Reis; Pinheiro, Renata Leão; Giesta, Beatriz de Almeida; dos Santos, Alan Carlos Nery; Gomes Neto, Mansueto; Ladeia, Ana Marice Teixeira
Background: Postprandial Lipemia (PPL) is a physiological process that reflects the ability of the body to metabolize lipids. Even though the influence of oral contraceptives (OC) on PPL is not known, it is a known fact that their use increases fasting lipid values. Objective: To compare the PPL between women who are on OC and those who are not. Methods: A prospective analytical study which assessed eutrophic women, aged between 18 and 28 years old, who were irregularly active and with fasting triglycerides ≤150 mg/dL. They were divided into two groups: oral contraceptive group (COG) and non-oral contraceptive group (NCOG). Volunteers were submitted to the PPL test, in which blood samples were collected in time 0 (12-hour fasting) and after the intake of lipids in times 180 and 240 minutes. In order to compare the triglyceride deltas, which reflect PPL, the two-tailed Mann-Whitney test was used for independent samples between fasting collections and 180 minutes (∆1) and between fasting and 240 minutes (∆2). Results: Forty women were assessed and equally divided between groups. In the fasting lipid profile, it was observed that HDL did not present significant differences and that triglycerides in COG were twice as high in comparison to NCOG. Medians of ∆1 and ∆2 presented significant differences in both comparisons (p ≤0.05). Conclusion: The results point out that women who are irregularly active and use OC present more PPL in relation to those who do not use OC, which suggests that in this population, its chronic use increases the risk of heart conditions. PMID:25317941
Soroush, Ali; Farshchian, Negin; Komasi, Saeid; Izadi, Neda; Amirifard, Nasrin; Shahmohammadi, Afshar
Background Cancer is one of the main public health issues in the world. Breast cancer is one of the most common types of cancer among women. It is also the second cause of mortality in women. The association between the use of oral contraceptive pills and breast cancer is controversial and a main issue in public health. Some findings have shown that taking these pills does not have a significant effect in increasing the risk of breast cancer, while others have confirmed the carcinogenic effect of these products. These contradictory findings necessitated this meta-analysis, through of all correlated studies in Iran. Methods All published studies were considered from June 2000 until June 2015, using reliable Latin databases like PubMed, Google Scholar, Google search, Scopus, and Science Direct, and Persian database like SID, Irandoc, IranMedex, and Magiran. Finally, 26 papers were selected: 24 studies were case control while two were population based studies. A total of 26 papers with 46,260 participants were assessed since 2001. Results Overall estimate of OR for the effect of oral contraceptive pills on breast cancer is 1.521 (CI = 1.25–1.85), which shows that the intervention group had more chance (52%) compared to the control group (P = 0.001). Using these pills increased the risk of breast cancer up to 1.52 times. Conclusions Because of directly increasing levels of estrogen and the role of estrogen in gaining weight indirectly, oral contraceptive pills can stimulate the occurrence of breast cancer. More studies should be conducted for controlling the period of pill use. PMID:28053965
Meade, T W; Greenberg, G; Thompson, S G
Progestogens probably have metabolic effects that may contribute to the increased risk of cardiovascular reactions associated with combined oestrogen-progestogen oral contraceptives. This possibility was investigated by a study of nearly 2000 reports to the Committee on Safety of Medicines from 1964 to 1977. The reports concerned preparations in which norethisterone acetate in doses of 1.0, 2.5, 3.0, or 4.0 mg was combined with 50 microgram of ethinyloestradiol and those in which levonorgestrel in doses of 150 or 250 microgram was combined with 30 microgram of ethinyloestradiol. Observed and expected numbers of reports were compared, using retail pharmacy purchase figures as a measure of the use of different preparations. There was a significant positive association between the dose of norethisterone acetate and deaths from stroke and ischaemic heart disease (IHD); this association was also found for all cases of these two conditions, fatal plus non-fatal. There were no associations of dose of norethisterone acetate with hypertension or venous thrombosis. The higher dose of levonorgestrel was associated with a possible excess of deaths, non-venous plus venous, and an excess of strokes. There was no association between dose of levonorgestrel and hypertension or venous thrombosis. The reports were also used to assess the relative safety of 30-microgram and 50-microgram oestrogen preparations. Those with 30 microgram of oestrogen were associated with significantly fewer reports of death and IHD (both fatal, and fatal plus non-fatal) than those with 50 microgram of oestrogen. In view of the large-scale move towards preparations with progressively lower oestrogen doses, there are no grounds for major changes in oral contraceptive practice. Within the range of preparations currently in use, however, there is a case for minimising the dose of progestogen to reduce the chances of thromboembolism.
Cibula, D; Hill, M; Fanta, M; Sindelka, G; Zivny, J
Polycystic ovarian syndrome (PCOS) is an obvious indication for long-term treatment. Combined oral contraceptives (COC) remain the first choice for the treatment of hyperandrogenism in most patients. However, differences in endocrine and metabolic parameters between obese and lean patients have been postulated. This is the first study evaluating the effect of COC treatment in obese versus non-obese PCOS patients. In total, 28 lean [body mass index (BMI) <25 kg/m(2))] and 15 obese (BMI >30 kg/m(2)) women patients were enrolled in the study. The concentrations of androgens, sex hormone-binding globulin (SHBG) and lipids were measured before and after 6 months of treatment with COC containing low-androgenic progestins. Clinical androgenic symptoms were monitored. There was a lower concentration of SHBG in obese patients, but there were no differences in androgen concentrations between both groups before the study. Highly significant changes in concentrations of testosterone (P < 0.001), androstenedione (P < 0.0001), SHBG (P < 0.001) and LH (P = 0.01) were demonstrated in lean patients, with only less significant changes in SHBG (P < 0.01) and testosterone (P < 0.05) in obese patients during the study. Clinical androgenic symptoms improved significantly (P = 0.05) only in the group of lean women. No reduction in low-density lipoprotein-cholesterol/high-density lipoprotein-cholesterol ratio was observed in either group. In conclusion, the positive effect of COC treatment on androgen production, serum androgen binding capacity, and clinical androgenic symptoms was negatively influenced by an increased BMI.
Lourenço, Benito; Kozu, Katia T; Leal, Gabriela N; Silva, Marco F; Fernandes, Elisabeth G C; França, Camila M P; Souza, Fernando H C; Silva, Clovis A
Contraception is an important issue and should be a matter of concern in every medical visit of adolescent and young patients with chronic rheumatic diseases. This narrative review discusses contraception methods in adolescents with juvenile systemic lupus erythematosus (JSLE), antiphospholipid syndrome (APS), juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). Barrier methods are safe and their use should be encouraged for all adolescents with chronic rheumatic diseases. Combined oral contraceptives (COC) are strictly prohibited for JSLE and APS patients with positive antiphospholipid antibodies. Reversible long-acting contraception can be encouraged and offered routinely to the JSLE adolescent patient and other rheumatic diseases. Progestin-only pills are safe in the majority of rheumatic diseases, although the main concern related to its use by adolescents is poor adherence due to menstrual irregularity. Depot medroxyprogesterone acetate injections every three months is a highly effective contraception strategy, although its long-term use is associated with decreased bone mineral density. COC or other combined hormonal contraceptive may be options for JIA and JDM patients. Oral levonorgestrel should be considered as an emergency contraception method for all adolescents with chronic rheumatic diseases, including patients with contraindication to COC.
Lourenço, Benito; Kozu, Katia T; Leal, Gabriela N; Silva, Marco F; Fernandes, Elisabeth G C; França, Camila M P; Souza, Fernando H C; Silva, Clovis A
Contraception is an important issue and should be a matter of concern in every medical visit of adolescent and young patients with chronic rheumatic diseases. This narrative review discusses contraception methods in adolescents with juvenile systemic lupus erythematosus (JSLE), antiphospholipid syndrome (APS), juvenile idiopathic arthritis (JIA) and juvenile dermatomyositis (JDM). Barrier methods are safe and their use should be encouraged for all adolescents with chronic rheumatic diseases. Combined oral contraceptives (COC) are strictly prohibited for JSLE and APS patients with positive antiphospholipid antibodies. Reversible long-acting contraception can be encouraged and offered routinely to the JSLE adolescent patient and other rheumatic diseases. Progestin-only pills are safe in the majority of rheumatic diseases, although the main concern related to its use by adolescents is poor adherence due to menstrual irregularity. Depot medroxyprogesterone acetate injections every three months is a highly effective contraception strategy, although its long-term use is associated with decreased bone mineral density. COC or other combined hormonal contraceptive may be options for JIA and JDM patients. Oral levonorgestrel should be considered as an emergency contraception method for all adolescents with chronic rheumatic diseases, including patients with contraindication to COC.
Polak, Karina; Pityński, Kazimierz; Banaś, Tomasz; Bubel, Magdalena; Kałwa, Maria; Jamroga, Joanna; Knysak, Magdalena; Kusior, Magdalena; Truszkiewicz, Katarzyna; Oleksy, Piotr
In December 2014 the authors carried out a research among Jagiellonian University Collegium Medicum medical students in a form of a questionnaire which consisted of two parts: personal information and multiple choice test concerning student's knowledge on OCPs. It showed that the level of medical education, defined as the year of study, increases student's knowledge about oral hormonal contraceptive pills. New program of study introduced from academic year 2012/2013 gives students wider knowledge on OCPs at earlier stage of education. Factors as female sex, usage of OCPs by student or his partner, positive attitude towards recommending OCPs to future patients show positive correlation with student's knowledge.
Nanda, Kavita; Stuart, Gretchen S.; Robinson, Jennifer; Gray, Andrew L.; Tepper, Naomi K.; Gaffield, Mary E.
Objective: To summarize published evidence on drug interactions between hormonal contraceptives and antiretrovirals. Design: Systematic review of the published literature. Methods: We searched PubMed, POPLINE, and EMBASE for peer-reviewed publications of studies (in any language) from inception to 21 September 2015. We included studies of women using hormonal contraceptives and antiretrovirals concurrently. Outcomes of interest were effectiveness of either therapy, toxicity, or pharmacokinetics. We used standard abstraction forms to summarize and assess strengths and weaknesses. Results: Fifty reports from 46 studies were included. Most antiretrovirals whether used for therapy or prevention, have limited interactions with hormonal contraceptive methods, with the exception of efavirenz. Although depot medroxyprogesterone acetate is not affected, limited data on implants and combined oral contraceptive pills suggest that efavirenz-containing combination antiretroviral therapy may compromise contraceptive effectiveness of these methods. However, implants remain very effective despite such drug interactions. Antiretroviral plasma concentrations and effectiveness are generally not affected by hormonal contraceptives. Conclusion: Women taking antiretrovirals, for treatment or prevention, should not be denied access to the full range of hormonal contraceptive options, but should be counseled on the expected rates of unplanned pregnancy associated with all contraceptive methods, in order to make their own informed choices. PMID:28060009
Ruusuvaara, L; Johansson, E D
Safe, effective and affordable contraceptives have been available for a few decades, yet, in many countries, the struggle for reproductive rights continues. Children, still, are forced to give birth to children in many nations. In most industrialized countries, where contraceptive counselling and abortions have been options, fertility rates have reached all time lows. Effective contraception improves health and well-being as well and may be used for conditions other than birth control. Young girls often initially take oral contraceptives primarily to reduce menstrual pain and blood loss; they also welcome a contraceptive that eliminates menstrual bleeding. Women using oral contraceptives and Norplant experience about 50% reduction in menstrual blood; 90% reduction in blood loss is achieved with the levonorgestrel intrauterine system (Mirena). Teenagers and their parents are often misinformed about the side-effects of oral contraceptives and birth control in general, which may adversely affect compliance. Adequate, user-friendly and supportive information about contraception is necessary to ensure proper use of the pill and other birth control methods. In addition, emergency contraceptives should be easily accessible. The mortality and morbidity of young women would be dramatically reduced by the global use of medical abortion as well. Only a combined effort by policy makers, educators, parents and health-care providers can enhance the reproductive (and future!) health of both young females and males.
Damario, Mark A
The identification of patients at high risk for excessive responses to ovarian stimulation for in vitro fertilization and embryo transfer is essential in the tailoring of safe and effective treatment strategies. Known factors associated with increased sensitivity to gonadotropins include polycystic ovary syndrome, young age, prior ovarian hyperstimulation syndrome (OHSS), high baseline antral follicle count, and high baseline ovarian volume. Although several treatment strategies have been proposed for these patients, this report describes the experience using the dual suppression with gonadotropin step-down protocol. This protocol uses oral contraceptive pretreatment in combination with a long gonadotropin-releasing hormone agonist followed by a programmed step-down in gonadotropin dosing. Hormonal characteristics of dual suppression include an improved luteinizing hormone-to-follicle-stimulating hormone ratio and lower serum androgens, particularly dehydroepiandrosterone sulfate. Clinical characteristics of the protocol include a lower cancellation rate and favorable clinical and ongoing pregnancy rates per initiated cycle while mitigating the risk of OHSS.
Prata, Ndola; Weidert, Karen; Fraser, Ashley; Gessessew, Amanuel
Background In Sub-Saharan Africa, policy changes have begun to pave the way for community distribution of injectable contraceptives but sustaining such efforts remains challenging. Combining social marketing with community-based distribution provides an opportunity to recover some program costs and compensate workers with proceeds from contraceptive sales. This paper proposes a model for increasing access to injectable contraceptives in rural settings by using community-based distributers as social marketing agents and incorporating financing systems to improve sustainability. Methods This intervention was implemented in three districts of the Central Zone of Tigray, Ethiopia and program data has been collected from November 2011 through October 2012. A total of 137 Community Based Reproductive Health Agents (CBRHAs) were trained to provide injectable contraceptives and were provided with a loan of 25 injectable contraceptives from a drug revolving fund, created with project funds. The price of a single dose credited to a CBRHA was 3 birr ($0.17) and they provide injections to women for 5 birr ($0.29), determined with willingness-to-pay data. Social marketing was used to create awareness and generate demand. Both quantitative and qualitative methods were used to examine important feasibility aspects of the intervention. Results Forty-four percent of CBRHAs were providing family planning methods at the time of the training and 96% believed providing injectable contraceptives would improve their services. By October 2012, 137 CBRHAs had successfully completed training and provided 2541 injections. Of total injections, 47% were provided to new users of injectable contraceptives. Approximately 31% of injections were given for free to the poorest women, including adolescents. Conclusions Insights gained from the first year of implementation of the model provide a framework for further expansion in Tigray, Ethiopia. Our experience highlights how program planners can
Wang, Christina; Swerdloff, Ronald S
Currently approved male-directed contraceptive methods include condoms and vas occlusion. Vas occlusion is very effective but is intended to be non-reversible. Condoms have a relatively high failure rate, at least partially due to compliance problems and are not accepted by many couples. The only other male-oriented methods in clinical trials utilize the administration of testosterone alone or its combination with another gonadotropin-suppressing agent such as a progestin or a gonadotropin-releasing hormone antagonist. Studies published in the 1990s demonstrated that a testosterone-containing hormonal contraceptive method suppressed spermatogenesis to azoospermia in most men and severe oligozoospermia in the remaining. The contraceptive efficacy after treatment with testosterone alone was comparable to that of female hormonal methods. Having proven that reversible male contraception is a reality, present trials are attempting to identify the best androgen delivery system and the most effective androgen plus progestin preparation. It is likely that the first marketed male hormonal contraceptive method will be a long-acting (injectable or implant) combination of an androgen plus a progestin. Research is continuing to identify other target areas for male contraceptive development, including agents with post-testicular and epididymal sites of action.
Lidegaard, Øjvind; Edström, Birgitte; Kreiner, Svend
The objective of this study was to assess the influence of oral contraceptives (OCs) on the risk of venous thromboembolism (VTE) in young women. A 5-year case-control study including all Danish hospitals was conducted. All women 15-44 years old, suffering a first ever deep venous thrombosis or a first pulmonary embolism (PE) during the period January 1, 1994, to December 30, 1998, were included. Controls were selected annually, 600 per year in 1994-1995 and 1200 per year 1996-1998. Response rates for cases and controls were 87.2% and 89.7%, respectively. After exclusion of nonvalid diagnoses, pregnant women, and women with previous thrombotic disease, 987 cases and 4054 controls were available for analysis. A multivariate, matched analysis was performed. Controls were matched to cases within 1-year age bands. Adjustment was made for confounding influence (if any) from the following variables: age, year, body mass index, length of OC use, family history of VTE, cerebral thrombosis or myocardial infarction, coagulopathies, diabetes, years of schooling, and previous birth. The risk of VTE among current users of OCs was primarily influenced by duration of use, with significantly decreasing odds ratios (OR) over time: <1 year, 7.0 (5.1-9.6); 1-5 years, 3.6 (2.7-4.8); and >5 years, 3.1 (2.5-3.8), all compared with nonusers of OCs. After adjustment for confounders, current use of OCs with second- (levonorgestrel or norgestimate) and third- (desogestrel or gestodene) generation progestins when compared with nonuse resulted in ORs for VTE of 2.9 (2.2-3.8) and 4.0 (3.2-4.9), respectively. After adjusting for progestin types and length of use, the risk decreased significantly with decreasing estrogen dose. With 30-40 microg as reference, 20 and 50 microg products implied ORs of 0.6 (0.4-0.9) and 1.6 (0.9-2.8), respectively (p(trend) = 0.02). After correction for duration of use and differences in estrogen dose, the third/second-generation risk ratio was 1.3 (1.0-1.8; p <0
Edelman, Alison B; Carlson, Nichole E; Cherala, Ganesh; Munar, Myrna Y.; Stouffer, Richard L; Cameron, Judy L; Stanczyk, Frank Z.; Jensen, Jeffrey T
Objective This study was conducted to determine whether increased body mass index (BMI) affects oral contraceptive (OC) pharmacokinetics and suppression of hypothalamic-pituitary-ovarian (HPO) axis activity. Study design Ovulatory reproductive-age women of normal (< 25 kg/m2; n = 10) and obese (> 30 kg/m2; n = 10) BMI received OCs for two cycles (prospective cohort). Subjects were admitted for two 48-h inpatient stays at the beginning and end of the hormone-free interval. Ethinyl estradiol (EE) and levonorgestrel (LNG) levels were evaluated during both inpatient stays. Gonadotropin pulsatility (FSH and LH) was measured during the second inpatient stay. Estradiol (E2) and progesterone (P) were measured daily during inpatient stays and twice per week in Cycle 2. Results BMI was greater in the obese, compared to the normal BMI group [37.3 kg/m2 (SD 6.0) versus 21.9 kg/m2 (SD 1.6); p < 0.05]. The LNG half-life was significantly longer in the obese group (52.1 ± 29.4 h versus 25.6 ± 9.3 h, p < 0.05) which correlated with a lower maximum LNG concentration on Cycle 2, Day 1 [1.9 ng/mL (SD 0.5) versus 2.5 ng/mL (SD 0.7)] and a longer time to reach steady-state (10 versus 5 days), in obese women. There were no significant differences in volume of distribution between groups. LH pulse parameters did not differ statistically between groups but trended towards greater HPO activity in the obese group. Additionally, more obese (6/10 versus 3/10 normal BMI, p > 0.05) women exhibited E2 levels consistent with development of a dominant follicle, and P levels consistent with ovulation (2/10 versus 1/10) during Cycle 2. Conclusions Compared to women of normal BMI, obese women exhibit differences in OC pharmacokinetics that are associated with greater HPO activity. PMID:19631786
Honoré, L H
Thirty-one adolescent females, aged 14 to 20 years, underwent cholecystectomy for pathologically documented cholesterol gallstones. A retrospective study, using the Mantel-Haenzel method of statistical analysis, showed a strong association between cholesterol cholelithiasis and obesity and parity. The patients with gallstones had a higher rate of oral contraceptive use, which just failed to attain statistical significance. These findings indicate that adolescent cholelithiasis is largely preventable. Dietary obesity can be controlled by balanced diets and physical exercise. Early pregnancy should be discourgaed, espeically if there is a strong family history of cholelithiasis and if weight control is unsuccessful. Oral contraceptives should be used cautiously in the presence of other predisposing factors.
Zhang, Chao; Li, Haiyan; Xiong, Xin; Zhai, Suodi; Wei, Yudong; Zhang, Shuang; Zhang, Yuanyuan; Xu, Lin; Liu, Li
We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet(®)) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax), extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration-time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations.
Zhang, Chao; Li, Haiyan; Xiong, Xin; Zhai, Suodi; Wei, Yudong; Zhang, Shuang; Zhang, Yuanyuan; Xu, Lin; Liu, Li
We investigated the pharmacokinetics and safety profiles of a newly developed combined ethinylestradiol (EE)/gestodene (GSD) transdermal contraceptive patch after a single-dose administration and compared with the market available tablet formulation in healthy adult subjects. An open-label, two-period comparative study was conducted in 12 healthy women volunteers. A single dose of the study combined EE/GE transdermal contraceptive patch and oral tablet (Milunet®) were administered. Blood samples at different time points after dose were collected, and concentrations were analyzed. A reliable, highly sensitive and accurate high-performance liquid chromatography coupled with tandem mass spectrometry (HPLC/MS/MS) assay method was developed in this study to determine the plasma concentrations of EE and GSD. Compared to the tablet, the study patch had a significantly decreased maximum plasma concentration (Cmax), extended time to reach the Cmax and half-life, as well as increased clearance and apparent volume of distribution. The half-lives of EE and GSD of the patch were 3.3 and 2.2 times, respectively, than the half-life of the tablet. The areas under the plasma concentration–time curve (AUCs) of EE and GSD of the patch were 8.0 and 16.2 times, respectively, than the AUC of the tablet. No severe adverse event was observed during the whole study, and the general safety was acceptable. In conclusion, compared to the oral tablet Milunet, the study contraceptive patch was well tolerated and showed potent drug exposure, significant extended half-life and stable drug concentrations. PMID:28331292
Jick, H; Jick, S S; Gurewich, V; Myers, M W; Vasilakis, C
Concern about the risks of cardiovascular illness in women using combined oral contraceptives (OC) containing the progestagens desogestrel and gestodene prompted two studies of data from the UK General Practice Research Database. We compared the risks of certain cardiovascular illnesses in otherwise healthy women exposed to one of three OCs containing < 35 micrograms oestrogen plus levonorgestrel, desogestrel, or gestodene. In the first study, based on some 470 general practices, there were 15 cases of unexpected idiopathic cardiovascular death among 303,470 women who were current users of one of the study OCs. The estimated incidence rates were 8/184,536 (4.3 per 100,000) woman-years at risk for users of combined OCs containing levonorgestrel, 2/135,567 (1.5 per 100,000) for desogestrel users, and 5/105,201 (4.8 per 100,000) for gestodene users. The relative risk (RR) estimates were 0.4 (95% CI 0.1-2.1) and 1.4 (CI 0.5-4.5) for desogestrel and gestodene, respectively, compared with levonorgestrel. In the second study, derived from some 370 general practices, there were 80 cases of nonfatal venous thromboembolism (VTE) in a cohort of 238,130 otherwise healthy women. The incidence rates of VTE per 100,000 woman-years at risk were 16.1 for levonorgestrel users, 29.3 for desogestrel, and 28.1 for gestodene. The adjusted RR estimates from the cohort analysis were 1.9 (1.1-3.2) and 1.8 (1.0-3.2) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. In a nested case-control analysis the adjusted matched RR estimates were 2.2 (1.1-4.4) and 2.1 (1.0-4.4) for desogestrel and gestodene users, respectively, compared with users of levonorgestrel. The excess risk for nonfatal VTE associated with the new generation of combined OCs containing low-dose oestrogen and the progestagens desogestrel or gestodene compared with levonorgestrel is estimated to be 16 per 100,000 woman-years.
Thomas, Sanjeev V.
Contraception is an important choice that offers autonomy to women with regard to prevention of unintended pregnancies. There is wide variation in the contraceptive practices between continents, countries, and societies. The medical eligibility for contraception for sexually active women with epilepsy (WWE) is determined by the type of anti-epileptic drugs (AEDs) that they use. Enzyme inducing AEDs such as phenobarbitone, phenytoin, carbamazepine, and oxcarbazepine increase the metabolism of orally administered estrogen (and progesterone to a lesser extent). Estrogen can increase the metabolism of certain AEDs, such as lamotrigine, leading to cyclical variation in its blood level with resultant adverse effect profile or seizure dyscontrol. AEDs and sex hormones can increase the risk of osteoporosis and fracture in WWE. The potential interactions between AEDs and hormonal contraception need to be discussed with all women in reproductive age-group. The alternate options of oral contraception such as intrauterine copper device, intrauterine levonorgestrel release system, and supplementary protection with barriers need to be presented to them. World Health Organization has recommended to avoid combination contraceptive pills containing estrogen and progesteron in women who desire contraception and in breastfeeding mothers. Care providers need to consider the option of non-enzyme-inducing AEDs while initiating long-term treatment in adolescent and young WWE. PMID:26425002
Casper, Robert F
For decades, combined estrogen-progestin oral contraceptive pills (OCPs) have been the first-line treatment for menstrual and pelvic pain associated with endometriosis without any clinical evidence of efficacy. Initial relief provided by OCPs is likely a result of improvement in primary dysmenorrhea. Biologic data and limited clinical evidence support a potential adverse effect of long-term use of OCPs on the progression of endometriosis. In contrast, there is randomized, controlled trial data to support the use of oral progestin-only treatment for pelvic pain associated with endometriosis and for suppressing the anatomic extent of endometriotic lesions. Both norethindrone acetate and dienogest have regulatory approval for treating endometriosis and may be better than OCPs as a first-line therapy.
Wogelius, Pia; Horváth-Puhó, Erzsébet; Pedersen, Lars; Nørgaard, Mette; Czeizel, Andrew E; Sørensen, Henrik Toft
The aim of this population-based case-control study was to examine the risk of isolated hypospadias in boys born to mothers who have used oral contraceptives in early pregnancy. The study was based on data from the Hungarian Case-Control Surveillance of Congenital Abnormalities from 1980 to 1996, and included 3,038 boys with hypospadias (cases), 24,799 boys without congenital abnormalities (CA-free controls), and 11,881 boys with abnormalities other than hypospadias. We used unconditional logistic regression to adjust for birth order, maternal age, maternal employment status, maternal diabetes, and pre-eclampsia. When comparing cases with CA-free controls the OR for maternal use of OC was 1.21 (95% CI: 0.67-2.17). When comparing cases with boys with other abnormalities, the OR for maternal use of OC was 0.83 (95% CI: 0.46-1.50). Our data showed that self-reported maternal use of oral contraceptives during pregnancy was not associated with an increased risk of hypospadias in the offspring.
Crook, D; Godsland, I F; Worthington, M; Felton, C V; Proudler, A J; Stevenson, J C
A comparative study of low-dose oral contraceptives (OCs) containing either desogestrel or gestodene failed to detect any major differences in metabolic risk markers for coronary heart disease. Included in the investigation were 70 women who used an OC composed of 30 mcg of ethinyl estradiol and 150 mcg of desogestrel, 43 women who took an OC containing 30 mcg of ethinyl estradiol and 75 mcg of gestodene, and 54 controls who did not use hormonal contraception. The study subjects, 18-35 years of age, were recruited from family planning clinics and general practices in England. Concentrations of serum total cholesterol, high-density lipoproteins (HDL), and apolipoproteins were higher in both groups of OC users than in controls, primarily because of increases in the protective HDL subfraction 3. Low-density lipoprotein cholesterol concentrations were unaffected, but serum triglyceride concentrations were elevated in OC users. Fasting plasma glucose, insulin, and C-peptide concentrations were similar in all three groups. The only significant differences between the two OCs were in HDL subfraction 2 concentrations (higher with desogestrel) and the late oral glucose tolerance test plasma insulin response (higher with gestodene). Further research and development, perhaps involving modification of the estrogen component, are needed to avoid the increased triglyceride concentrations and insulin responses associated with these low-dose formulations.
Paraíso Torras, B; Maldonado Del Valle, M D; López Muñoz, A; Cañete Palomo, M L
There are currently 6 million immigrants living in Spain. Half of them are women, the majority of whom are of childbearing age. These women, who suffer high rates of induced abortion, form a special group who require a special approach to their reproductive health. In order to study the use of contraceptive methods in this population, a review was made of 1100 clinical histories from our Sexual Health and Reproduction Clinic. Latin American women were the most prevalent group who came to seek information about contraception, followed by Eastern Europeans and Moroccans. Fewer Asian and Sub-Saharan women sought these services. The contraceptives most frequently used were the intrauterine device (used mostly by Latin American and Eastern European women), and combined oral contraception, most used by Moroccan women. It is important to advise the immigrant women about contraceptive methods, taking into account their preferences, in order to improve adherence to the method.
contraceptives is gratefully acknowledged as are the efforts of Ms. Edith A. Crohn and SPJ Linda S. Gowenlock in collecting most of the data. References...thermal responses during exercise. Ins Pandolf KB, Sawka MN, Gonzalez RR (Eds) Human performance physiology and environmental medicine at terrestrial
Brown, Susan G; Morrison, Lynn A; Larkspur, Louona M; Marsh, Ariel L; Nicolaisen, Nicola
Overall well-being, sleep and exercise patterns were investigated in women between the ages of 18 and 36 years with natural hormone profiles (n = 12), and women using oral contraceptives (n = 12) or Depo-Provera (n = 12) from January 18, 2005 to December 7, 2005. Daily questionnaires on the above variables were obtained across 3 menstrual cycles (108 cycles). Women using hormonal contraception reported more overall negative well-being than women with natural hormone profiles (p = .038). Positive well-being at mid-cycle was positively correlated with increased sleep by the natural hormone (p < .05) and oral contraception groups (p < .05) but not by the Depo-Provera group. Women with natural hormone profiles walked more when they reported decreased well-being. Our findings indicate that the use of Depo-Provera interferes with the natural relations between sleep, cycle phase and well-being.
Enea, C; Boisseau, N; Ottavy, M; Mulliez, J; Millet, C; Ingrand, I; Diaz, V; Dugué, B
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.
A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20 micrograms ethinylestradiol/75 micrograms gestodene and 30 micrograms ethinylestradiol/75 micrograms gestodene, with respect to efficacy, cycle control, and tolerance.
Endrikat, J; Müller, U; Düsterberg, B
The aim of this study was to compare contraceptive reliability, cycle control, and tolerance of an oral contraceptive containing 20 micrograms ethinylestradiol (EE2) and 75 micrograms gestodene (GSD), with a reference preparation containing a similar dose of gestodene but in combination with 30 micrograms ethinylestradiol. A higher incidence of intermenstrual bleeding was apparent under the 20 micrograms EE2 oral contraceptive. For the 20 micrograms EE2 preparation, 47.4% of all women reported spotting at least once over a period of 12 treatment cycles, whereas this figure was 35.5% for the 30 micrograms EE2 pill (p < 0.05). However, the incidence was within a range that corresponds to that of other OCs. The cumulative breakthrough bleeding rates (at least once during the one year of treatment) of 14.5% (20 micrograms EE2) and 11.8% (30 micrograms EE2) of women were not significantly different. In relation to all cycles, the intermenstrual bleeding rates were remarkably lower, indicating that the majority of the volunteers experienced such events only in few cycles under treatment: the spotting rate was 11.5% (20 micrograms EE2) and 7.2% (30 micrograms EE2) of all cycles, and the breakthrough bleeding rate was 2.6% and 1.6% of all cycles, respectively. Three pregnancies were recorded during the study (one in the 20 micrograms EE2 + 75 micrograms GSD group, two in the 30 micrograms EE2 + 75 micrograms GSD group). All three could be explained either by intake irregularities or by circumstances impairing the contraceptive effect. The influence of both treatments on the blood pressure and body weight proved to be extremely slight. Adverse events in both groups were rare and differences in the frequency of adverse events were not apparent. The discontinuation rate due to adverse events, including intermenstrual bleeding, was low (9.8% for 20 micrograms EE2 + 75 micrograms GSD, and 7.2% for 30 micrograms EE2 + 75 micrograms GSD) and was in the lower range known for other
Caruso, Salvatore; Agnello, Carmela; Intelisano, Giorgia; Farina, Marco; Di Mari, Lucia; Cianci, Antonio
The objective of this prospective study was to assess the effects of a low-dose oral contraceptive (OC) containing 15 microg ethinylestradiol and 60 microg gestodene on sexuality. Forty-eight healthy volunteers (age range, 18-35 years), having regular menstrual cycles with ovulation, participated in the study. Sexual behavior was assessed using the self-administered Personal Experience Questionnaire, at baseline, and at 3, 6 and 9 months of pill use. Women reported decreased sexual desire (p < 0.005) and sexual activity (p < 0.05) at the 9th month of pill use, and diminished sexual arousal at the 3rd month of pill intake (p < 0.05), with respect to baseline. The frequency of orgasm did not change during OC use (p = NS). Moreover, sexual enjoyment was worse at the 3rd, 6th and 9th month with respect to baseline (p < 0.001). The low dose of ethinylestradiol could cause decreased vaginal lubrication, and diminished sexual arousal could be due to hypoandrogenism. Women may expect increased sexual performance when they take the pill, as compared to before starting contraception. Consequently, they could have an unexpected effect with pill use, though sexuality may remain the same.
Turcio, Karina Helga Leal; Garcia, Alício Rosalino; Zuim, Paulo Renato Junqueira; Moreno, Amália; Goiato, Marcelo Coelho; Guiotti, Aimée Maria; dos Santos, Daniela Micheline
Objective: The aim of this study was to evaluate the influence of oral contraceptive use on the silent period (SP) of anterior temporal and masseter muscles during the menstrual cycle. Materials and Methods: Totally, 28 women on reproductive age were selected including 15 nonusers of any hormone and 13 contraceptive users. All patients were dentate without muscular temporomandibular disorders. Electromyography (SP test) of the anterior temporal and masseter muscles was conducted every week during three consecutive menstrual cycles at 1st day of menstruation (P1), 7th day (P2), 14th day (P3) and 21st day (P4). Results: The SP values in the anterior temporal and masseter muscles were measured at both sides. The SP values of the right side (13.49 ms) at P2 were significantly different compared to the left side (12.28 ms). However, there was no significant difference on the interactions among the three factors. Conclusion: It can be concluded that the SP values in healthy women in reproductive age may not be influenced by the menstrual cycle with similar results for both muscles. PMID:26038645
Contraceptive sponge Overview By Mayo Clinic Staff The contraceptive sponge is a type of birth control (contraceptive) that prevents ... shaped, and made of polyurethane foam. The contraceptive sponge contains spermicide, which blocks or kills sperm. Before ...
Smith, M; Barwin, B N
The alleged adverse effects of oral contraceptives and intrauterine devices have led to increased consumer and physician demand for vaginal contraceptive devices. The efficacy and the advantages and disadvantages of vaginal sponges, cervical caps and diaphragms are discussed and compared in this article.
Gluck, J A; Shek, E
A specific and sensitive analytical method is described for the simultaneous determination of ethinylestradiol and norethisterone in a capsule formulation. These steroids, commonly used in oral contraceptives, were extracted from the capsules with acetonitrile and tetrahydrofuran. The steroids were then quantitated with a high performance liquid chromatograph using a ODS reversed-phase column and a ternary solvent system of water, acetonitrile, and tetrahydrofuran as the mobile phase. Several solvent systems for the mobile phase were examined using various C18 columns. The k' values for several steroids are reported, together with column performance parameters. It was found that columns from different manufacturers had significantly different behaviors with respect to separation parameters for these steroids.
Alexander, N J
This article looks at the improvements that may occur in contraceptives in the near future. While no product currently under study would be ideal (highly effective, safe, readily reversible, free of side effects, coitally independent, counteract the spread of sexually transmitted diseases, and inexpensive), several would come closer than those available today. For men, the condom is the only currently available contraception, and a thinner version has recently been introduced in response to the criticism that condoms reduce sexual pleasure. Methods under study for men include manipulating hormones to halt sperm production by the intramuscular injection of an androgen in combination with a progestin or by blocking the activity of gonadotropin-releasing hormone. In the future, long-acting reversible agents should be available to directly halt sperm production or maturation. In men and women, vaccines should become available that would use antibodies to disrupt reproduction. Additional hormonal options in women should include hormone-releasing vaginal rings, a simplified contraceptive implant delivery system, a hormone-releasing IUD, and a monthly pill. Vaginal chemicals could be used to impede some of the necessary changes that sperm undergo after ejaculation. Spermicides will also be available with the ability to prevent STDs. The order of appearance of these new contraceptives will probably be nonlatex condoms, vaginal rings, and new implants, followed by disease-reducing spermicides, hormone-releasing IUDs, new emergency contraceptives, a three-month injectable for men, biodegradable implants for women, and immunocontraceptives (if they receive the backing of the industry).
Wiegratz, I; Jung-Hoffmann, C; Gross, W; Kuhl, H
The effect of a triphasic oral contraceptive containing ethinyl estradiol and gestodene (EE/GSD) on various lipid and lipoprotein parameters was compared with that of a monophasic formulation containing 35 micrograms ethinyl estradiol and 250 micrograms norgestimate (EE/NGM). Blood samples were collected from 46 women on days 2, 11, and 21 of the preceding control cycle and of the third, sixth, and twelfth treatment cycles. There was no significant difference between formulations with regard to the influence on any measured parameter. As compared with controls, a significant increase was observed in the plasma levels of total triglycerides (24-78%), total phospholipids (7-20%), very low density lipoprotein (VLDL) triglycerides (61-76%), VLDL-phospholipids (14-60%), low density lipoprotein (LDL) triglycerides (8-35%), LDL-phospholipids (28-30%), high density lipoprotein (HDL) cholesterol (8-16%), HDL 3-cholesterol (11-20%), HDL-triglycerides (17-66%), HDL-phospholipids, HDL 3-phospholipids (7-11%), apolipoprotein (apo) A-I (5-20%) and apo A-II (10-40%) during treatment with both formulations. In contrast, the LDL-cholesterol levels were significantly decreased. These changes in lipid metabolism appear to reflect a predominance of the effect of the estrogen component. The results indicate that both low dose oral contraceptives containing different progestins and different amounts of EE do not exert a deleterious effect on lipoprotein metabolism, as high HDL-cholesterol and low LDL-cholesterol levels are known as low risk factors of cardiovascular disease. In contrast to endogenous hypertriglyceridemia, an EE-induced rise in triglyceride levels does not appear to increase cardiovascular risk if LDL is not increased.
Peck, Susan A
Although short-acting reversible hormonal contraceptives, such as oral contraceptives and the contraceptive patch and vaginal ring, remain the most commonly used contraceptive methods in the United States, they are also associated with the highest failure rates. Long-acting reversible contraception (LARC) methods, such as intrauterine devices and contraceptive implants, offer high continuation rates and very low failure rates, and are safe for use in most women. The provision of LARC methods to adolescent, young adult and nulliparous women is a relatively new concept that offers an innovative option for these populations.
German, P; Moorehead, L; Pang, Phillip; Vimal, M; Mathias, A
This study evaluated the potential for a drug-drug interaction between HCV direct-acting antivirals sofosbuvir or ledipasvir and oral hormonal contraceptive (OC) norgestimate/ethinyl estradiol (norgestimate 0.18/0.215/0.25 mg with ethinyl estradiol 25 μg). This was a 112-day, open-label, fixed-sequence pharmacokinetic (PK) study in healthy female subjects that included a lead-in cycle (OC only; N = 21), cycle 1 (OC only; N = 15), cycle 2 (OC + sofosbuvir; N = 15), and cycle 3 (OC + ledipasvir; N = 15). Administration of sofosbuvir with OC did not alter PK of norelgestromin (primary norgestimate metabolite) or ethinyl estradiol. Small increases in norgestrel (secondary norgestimate metabolite) AUC(tau) (19%) and C(tau) (23%) with sofosbuvir were noted. Ledipasvir did not impact PK of norelgestromin or norgestrel but modestly increased ethinyl estradiol C(max) (40%). Sofosbuvir, GS- 331007 (predominant circulating metabolite of SOF), and ledipasvir PK were similar to historical data. Pharmacodynamic markers luteinizing hormone, follicle-stimulating hormone, and progesterone values were generally comparable in all cycles. No loss in contraceptive efficacy is expected upon administration of sofosbuvir or ledipasvir/sofosbuvir with oral contraceptives containing norgestimate and ethinyl estradiol. The use of sofosbuvir or ledipasvir/sofosbuvir FDC with oral contraceptives is permitted.
Pieh Holder, Kelly Lynne
Postpartum contraception is important to lengthening birth intervals and improving the health of women and children. For breastfeeding women the choice and timing of contraception may influence breastfeeding and infant growth patterns. Nonhormonal methods of contraception are the preferred choice for breastfeeding women. Progestin-only methods comprise a viable next option. Combined hormonal methods of contraception containing estrogen and progestin may be considered as a third option for birth control in breastfeeding women. The objective of this chapter is to review the current literature and recommendations for the use of hormonal and nonhormonal methods of contraception while breastfeeding.
To avoid unintended pregnancy, women in the UK need to consistently use reliable contraception for over 30 years. The long-acting reversible contraceptive methods compromise the progestogen-only implant, the progestogen-only injectable contraceptive, the copper-bearing intra-uterine device and the levonorgestrel-releasing intra-uterine system. These methods of contraception are highly reliable in pregnancy prevention, and are amongst the medically safest methods for users. Despite this, these long-acting methods are used by less than 10% of the UK population. National guidance has advised that increasing uptake of these long-acting methods will reduce the unplanned pregnancy rate. In addition, these methods are more cost effective than the oral contraceptive even at 1 year of use. Obstetricians and gynaecologists frequently come into contact with women requiring contraceptive advice, and should have a sound knowledge of the long-acting methods.
Barber, H R
A less-publicized aspect of the famed Louisiana abortion bill would have outlawed the use of IUDs and oral contraceptives (OCs), a provision that ignores the difference between contraceptives and abortifacients. The bill, which was vetoed by Governor Buddy Roemer, stirred widespread controversy in its effort to sharply restrict abortion. Many of those involved in the discussion -- including the State Attorney General's office -- have contended that IUDs and OCs induce abortions by destroying fertilized eggs. But such statements disregard scientific studies that indicate that both contraceptive methods work by preventing fertilization. Research has shown that IUDs, especially copper-IUDs, restrict the transport of sperm, thereby preventing fertilization. One study revealed the presence of sperm in the fallopian tubes of non-IUD users 15-30 minutes after insemination, but found no sperm in the tubes of IUD users. Inhibiting ovulation, OCs work through a combination of estrogen and progestin. OCs prevent fertility by activating various mechanisms: they suppress the release of certain hormones, and cause a thickening of the cervical mucus which impairs sperm motility. Although neither IUDs nor OCs can be considered abortifacients, a small but vocal minority has succeeded in obscuring this fact. And it is the role of science to resolve the controversy by making the facts clear.
Dorjgochoo, Tsogzolmaa; Shu, Xiao-Ou; Li, Hong-Lan; Qian, Han-Zhu; Yang, Gong; Cai, Hui; Gao, Yu-Tang; Zheng, Wei
The association of contraceptive methods, including oral contraceptives (OC), intrauterine devices (IUD) and tubal sterilization (TS), with overall and site-specific cancer were prospectively investigated in a cohort of 66,661 Chinese women in Shanghai, 76.7% of whom used contraception. During a median follow-up time of 7.5 years, 2,250 women were diagnosed with cancer. Ever-use of any contraceptive method was not associated with overall cancer risk [adjusted hazard ratio (HR(adj)) = 1.02, 95% CI, 0.92-1.12]. Use of any contraceptive method was associated with increased risk of rectal cancer (HR(adj) = 1.68, 95% CI, 1.08-2.62) and reduced risk of thyroid cancer (HR(adj) = 0.63, 95% CI, 0.38-1.04). Risk of gallbladder cancer increased with ever use of OC (HR(adj) = 2.38, 95% CI, 1.26-4.49). IUD use was associated with a possible reduced risk of thyroid cancer (HR(adj) = 0.64, 95% CI, 0.38-1.07). Longer duration of IUD use decreased risk for breast, thyroid and lung cancers. Ever having a TS was associated with increased uterine body cancer (HR(adj) = 2.50, 95% CI, 1.47-4.25) and decreased risk of stomach cancer (HR(adj) = 0.59, 95% CI, 0.39-0.91). We did not find any contraceptive method to be related to the risk of ovarian cancer but the analyses were based on few events. Although chance findings are a likely explanation for some of the associations found in our study, these findings suggest that various contraceptive methods or reproductive patterns may play a role in the etiology of cancer.
Contraception can be perceived by a woman either as a subjugation to socioeconomic imperatives or as a means of escaping the fate of repeated pregnancies or abortions. Whether contraception liberates or constrains depends on the individual attitude. In France, decision of whether to have a child is influenced by the couple's perception of cultural norms such as the ideal 4-member family proposed by advertisers, the organization of collective life, and the design of consumer goods such as 4-seat automobiles. The 2-child norm is rapidly becoming internalized, but may be influenced by such societal factors as declining employment opportunities for women which prompt them to reassume the career of motherhood. Among sources of resistence to contraception are those stemming from the physician who may be reluctant to prescribe potent drugs with obvious societal implications to a healthy woman. The patient seeking cure of an ailment and the patient seeking OCs have completely different psychological encounters with the physician in the position of furnishing supplies rather than of diagnosing and explaining treatment. The resulting loss of power may frustrate some physicians. The woman may however return power to the physician by demanding reassurances about the medical aspects of pill use. Concern about the possibility of thromboses or other side effects also serves to return the OC consultation to the realm of a more traditional medical practice. The attitude of the physician can reinforce resistence of the woman to contraception or provide a scientific rationalization for it. Taking the pill daily, a regular reminder to the woman that she is suppressing her maternal potential, is a cause of stress and perhaps of forgetfulness for some women. OCs, because of their efficacy, may not be seen merely as the means of suspending the procreative function for a given time, but as suppressing and negating it permanently. Women who for various reasons are disturbed by the loss of
Riphagen, F E; von Schoultz, B
In 1987, a survey of contraceptive use, knowledge and attitudes was conducted in Sweden by the International Health Foundation (IHF) as part of a multi-country study that has so far involved six other countries in Europe. The women involved, who were aged 15-44, completed a standard questionnaire. The overall percentage use of contraceptive methods, especially the reliable ones, was found to be high (95%). Oral contraception was the most frequently used method, followed by barrier methods and the intrauterine device (IUD). Contraceptive methods were chosen or abandoned mainly because of health reasons and better reliability. Knowledge of fertility proved to be generally good. Medical methods such as oral contraceptives and IUDs were associated with health hazards. In the case of the pill, fears of cardiovascular risks, thrombosis and cancer were widespread, while infection risk and menorrhagia were the most frequently quoted perceived disadvantages of the IUD. Indeed, these two methods suffer from a very negative image among Swedish users.
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
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
Fuchs, N; Düsterberg, B; Weber-Diehl, F; Mühe, B
To obtain an overview of the effect of monophasic gestodene on blood pressure and to determine the frequency of "OC elevated BP/hypertension," the results of blood pressure monitoring from four clinical studies of contraceptive efficacy and safety have been retrospectively analyzed. A total of 1930 women took part in the studies, which recorded BP for up to 24 cycles. Analysis of results revealed that 97 women (5.0%) showed an increase in blood pressure from previously normal to elevated values while taking monophasic gestodene, with only 26 (1.35%) fulfilling the criteria of "OC elevated BP/hypertension." Only four women dropped out of the trials due to hypertensive blood pressure values, while 67 women (3.5%) experienced a normalization of previously elevated blood pressure measurements. In conclusion, this analysis has confirmed that gestodene has a negligible effect on blood pressure, with increased BP a relatively rare event.
Starks, G C
During the past 20 years, contraceptive steroids have undergone significant changes as the result of an increased understanding of their metabolic, pharmacologic, and hormonal activities. During this time, prospective and retrospective epidemiologic studies have elucidated several noncontraceptive health benefits of oral contraceptive steroids, including their therapeutic effects for endometriosis, dysmenorrhea, polycystic ovarian disease, and benign breast disease. From this review it appears that the benefits of oral contraceptive steroids in young, healthy, nonsmoking women far outweigh their more publicized, infrequent risks.
Shahnazi, Mahnaz; Farshbaf-Khalili, Azizeh; Pourzeinali-Beilankouh, Samira; Sadrimehr, Farnaz
Background Combined oral contraceptives (COCs) have not been shown to have major effects on lipid and carbohydrate metabolism in normal-weight women. However, we have limited information about the effects on women at high risk for cardiovascular disease and diabetes due to being overweight and obese. Objectives To evaluate the effects of second and third generation contraceptive pills on lipid and carbohydrate metabolism in overweight and obese women. Patients and Methods This triple-blind controlled trial was performed on 137 healthy women aged 18 - 40 years with a body mass index of 25-34.9 (kg/m2) who were referred to health centers in Tabriz, Iran from 2014 to 2015. The women were randomly divided into groups who were to take 30 mcg ethinyl estradiol/150 mcg levonorgestrel (EE/LGN) (n = 69) or 30 mcg ethinyl estradiol/150 mcg desogestrel (EE/DSG) (n = 68) with an allocation ratio of 1: 1 for three cycles. As primary outcomes, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and fasting plasma glucose (FPG) were assessed; total cholesterol (TC), triglycerides (TG), and 2-hour plasma glucose in the 75-g oral glucose tolerance test (2-hour 75-g OGTT) were assessed as secondary outcomes. Results The differences in lipid and carbohydrate parameters were not significant between the two groups, except for HDL-C (Adjusted MD (CI95%) = 7.00 (2.98 to 11.02)). HDL-C decreased with EE/LGN (P = 0.016) and increased with EE/DSG (P = 0.004). LDL-C and TC increased in both groups, whereas TG increased only with EE/DSG (P < 0.05). Compared with the baseline, FPG levels did not differ significantly in both groups, but EE/DSG increased 2-hour 75-g OGTT (P = 0.010). Conclusions We observed no significant differences between the two groups in lipid and carbohydrate metabolism, except for HDL-C. Considering the importance of overweight and obese women’s health, studies with longer follow-up periods are recommended in this respect. PMID
Mechanical methods of contraception tend nowadays to be considered as unsafe and the "modern" contraceptives are more popular. The advantage of the intrauterine device is that once it has been placed, one can forget about it. However it is necessary for the woman to undergo checkups and have the device replaced regularly. IUD's are not always very well tolerated psychologically. Women are influenced by information, the fear of the risks, the opinion of their friends and families and the media, and they end up getting tired of this method of contraception. Oral contraceptives are 100% safe but only provided one does not forget to take it: it imposes a daily routine which disturbs many women after a certain time. They then tend to relate all their problems to the pill. Women are aware of the risks contained in oral contraceptives, and they refuse to run these risks by themselves. Whichever method of contraception one chooses, it liberates the woman from the fear of unwanted pregnancy. A good contraception should do this, plus separate the idea of procreation from the sexual intercourse. This seems to be going well for a few years, but after a while a weariness appears. The answer may be to find a contraception suitable to both partners, so that they could make their own decision.
Capilli, Gianfranco; Patané, Anella Antonietta
We present the case of a 28-year-old woman who was admitted to our cardiology unit for acute coronary syndrome. Her history was notable for cardiovascular disease familiarity, active smoking, and oral contraceptive use. On further analysis, she was noted to have thrombophilic polymorphisms involving the plasminogen activator inhibitor (PAI), angiotensin-converting enzyme (ACE), and methylenetetrahydrofolate reductase (MTHFR) genes. We discuss the implications that these cofactors may have had in the genesis of the disease. PMID:25587456
Brouquet, J; Chameaud, J; Vire, O; Fabre, P; Catanzano, G; Baudet, J H
Following a recent case, the authors review the literature of hepatic nodular hyperplasia. The incidence of this condition increases regularly with the consumption of oestrogens. They attempt to define the methods of detection for patients at highest risk. Without exaggerating the incidence of this complication of oral contraceptives, the authors believe that it will become increasingly more common than the vascular complications which, although frequently discussed, are relatively rare.
Prilepskaia, V N
Effective contraceptives contribute to the regulation of births, protect the health of women, reduce maternal and perinatal mortality and gynecological diseases, and prevent abortion-related complications. Complications after abortion average 30%, and among primigravidas the rate reaches 45%. Abortion can result in sterility and in the inability to carry out the pregnancy. Oral contraceptives (OCs) are used by 150 million globally. In new preparations ethinyl estradiol (EE) and levonorgestrel (LNG) are the most common components. In the 2-phase and 3-phase preparations Sequilar, Anteovin, and lipid profile safe Triquilar the gestagen component was reduced 40%. Continuin and Famulen are minipills, and Postinor is a postcoital contraceptive. Absolute contraindications of OCs include thromboembolytic diseases, severe cardiovascular system diseases, liver disorders, cirrhosis, cerebral vascular diseases, grave diabetes, jaundice, and malignant tumors of the mammae and sexual organs. Rigevidon, Triquilar, and Trisiston have high steroid content with minimal side effects. The protective effect of OCs are: 2-3 times lower risk of inflammation of the small pelvis, lower risk of malignant and benign ovarian tumors that lasts even after discontinuation, uterine cancer prevention (antiproliferation effect on the endometrium and inhibition of mitotic activity of the myometrium), and reduced risk of benign breast neoplasms. The finding that estrogen-induced risk of breast cancer increases with longterm contraceptive use in young nulliparas has not been persuasively proven. The optimal duration of uninterrupted OC use is 1-1.5 years. Monophasic estrogen-gestagen preparations include Bisecurin, Non-Ovlon, Ovidon, Rigevidon, Minisiston, and Demulen with low dosages of EE, LNG, norethisterone acetate, and diacetate ethonodiol. Norplant is a subdermal silastic capsule with effectiveness for up to 5 years.
f AQ FREQUENTLY ASKED QUESTIONS FAQ114 CONTRACEPTION Emergency Contraception • What is emergency contraception (EC)? • How does EC work? • What are the different types of EC? • What is the most ...
Morning-after pill; Postcoital contraception; Birth control - emergency; Plan B; Family planning - emergency contraception ... Emergency contraception most likely prevents pregnancy in the same way as regular birth control pills: By preventing or delaying ...