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

BackgroundProgestin-only oral contraceptive pills (POPs) have fewer contraindications to use compared to combined pills. However, the overall prevalence of contraindications to POPs among reproductive-aged women has not been assessed.Study DesignWe collected information on contraindications to POPs in two studies: (1) the Self-Screening Study, a sample of 1267 reproductive-aged women in the general population in El Paso, TX, and (2) the Prospective Study of OC Users, a sample of current oral contraceptive (OC) users who obtained their pills in El Paso clinics (n=532) or over the counter (OTC) in Mexican pharmacies (n=514). In the Self-Screening Study, we also compared women's self-assessment of contraindications using a checklist to a clinician's evaluation.ResultsOnly 1.6% of women in the Self-Screening Study were identified as having at least one contraindication to POPs. The sensitivity of the checklist for identifying women with at least one contraindication was 75.0% [95% confidence interval (CI): 50.6%–90.4%], and the specificity was 99.4% (95% CI: 98.8%–99.7%). In total, 0.6% of women in the Prospective Study of OC Users reported having any contraindication to POPs. There were no significant differences between clinic and OTC users.ConclusionThe prevalence of contraindications to POPs was very low in these samples. POPs may be the best choice for the first OTC oral contraceptive in the United States.     

The progestin-only oral contraceptive —its place in postpartum contraception

The progestin-only oral contraceptive (POC) is not a widely-used method of contraception, possibly due to competition from other contemporary contraceptive methods or misunderstanding and prejudices among clients and/or service providers. Because of its underuse, the POC, as a contraceptive method, is under-studied.This article evaluates the general merits of the POC and its disadvantages relative to combined oral contraceptives (COCs) and other contraceptive methods, specifically during the postpartum period and particularly for breastfeeding women. We find that the POC appears to be a safe and acceptable contraceptive method for postpartum women who are fully or nearly fully breastfeeding at six months postpartum or when menstruation returns. The POC could be considered for use at any time by non-breastfeeding postpartum women. The need for empirical studies of the POC is also discussed.

---

Resumen El método anticonceptivo oral con productos que contienen sólo progesterona (POC) no se utiliza en gran medida, sin duda debido a la competencia de otros métodos modernos o a causa de malentendidos y prejuicios de parte de las clientas y/o de los proveedores de este servicio. Debido a su escaso uso, el POC ha sido poco estudiado.Este artículo evalúa los méritos generales del POC y sus inconvenientes en comparación con los anticonceptivos orales combinados (COC) y otros métodos anticonceptivos, específicamente durante el período de posparto y, en particular, en las mujeres que amamantan. Se ha determinado que el POC parece constituir un método anticonceptivo seguro y aceptable en el posparto para las mujeres que amamantan exclusivamente, o casi exclusivamente, seis meses después del parto o cuando se reanuda la menstruación. Se podría considerar el uso del POC en cualquier momento después del parto entre las mujeres que no amamantan. Este artículo examina asimismo la necesidad de realizar estudios empíricos relativos at POC.

---

Resumé La méthode de contraception par les produits ne contenant que de la progestine (POC) administrés par voie orale n'est pas largement utilisée, sans doute en raison de la concurrence que lui font d'autres méthodes modernes ou à cause de malentendus, voire de préjugés, de la part des clientes et/ou de ceux qui offrent ce service. Etant peu utilisé en tant que méthode contraceptive, le POC est aussi moins étudié.L'article présenté évalue les mérites généraux de ces produits et leurs inconvénients en les comparant à des contraceptifs oraux combinés (COC) et à d'autres méthodes de contraception, et cela spécifiquement durant la période du post-partum et plus particulièrement chez les femmes qui allaitent. On a constaté que les POC semblent constituer une méthode de contraception sûre et acceptable après le post-partum chez les femmes qui allaitent entièrement, ou presque, six mois après l'accouchement ou lorsque la menstruation reprend. On pourrait envisager l'utilisation des POC à n'importe quel moment après l'accouchement chez les femmes qui n'allaitent pas. L'article examine également la nécessité de conduire des études empiriques sur les POC.

     

The effects of a progestin-only oral contraceptive (levonorgestrel 0.03 mg) on breast-feeding

This study was a non-randomized clinical trial which compared the breast-feeding experience of 250 Argentine women taking levonorgestrel 0.03 mg daily (begun one week after delivery) with that of 250 women using non-hormonal contraceptives. Weight gain of unsupplemented infants, the most important of the several criteria used to assess breast-feeding performance, was similar for the two contraceptive groups. Levonorgestrel users began supplementary feeding of their infants significantly later than did non-hormonal users; levonorgestrel users were also somewhat less likely to discontinue breast-feeding during the study period. The two contraceptive groups were similar with regard to several other measures of breast-feeding performance: growth of all infants (regardless of supplementation), patterns of contraceptive discontinuation, mothers' subjective impressions of breast-milk sufficiency, and comparison of supplementation initiation with previous experience.     

A comparative study of a progestin-only oral contraceptive versus non-hormonal methods in lactating women in Buenos Aires, Argentina

A non-randomized comparative clinical trial of the progestin-only oral contraceptive (POC), Ovrette (75 mcg norgestrel) (Wyeth), versus non-hormonal methods was conducted at two clinics in Buenos Aires, Argentina. The trial was designed to assess the breast-feeding patterns of women choosing progestin-only oral contraception and non-hormonal methods of contraception, and to study the relationship between lactation and the clinical performance of a POC. Five-hundred women were allocated to either the progestin-only pill group (n = 250) or to the non-hormonal group (n = 250) and were followed up monthly for six months after admission. Measurements in mean infant weight, mean infant length, and mean head circumference were similar throughout the follow-up period. Non-hormonal users reported significantly more self-perceived decreases in milk production at the 5th and 6th month follow-up intervals. Acceptance and continued use of the pill were excellent, with only one woman discontinuing because of a pregnancy which was attributed to user failure. The principal side effect reported by women in both groups was intermenstrual bleeding.     

Premature introduction of progestin-only contraceptive methods during lactation

Experts on contraceptive technology concur that progestin-only methods can be used safely during lactation. However, very few studies exist of the effects on lactation of the introduction of progestin-only methods prior to the sixth postpartum week. Since progesterone withdrawal is the likely stimulus that initiates lactogenesis, it appears necessary for natural progesterone levels to decline to baseline before a progestin-only contraceptive is initiated. There-fore, the use of such contraceptive methods should be delayed for at least 3 days after the birth. Non-hormonal methods remain the first choice category of contraceptive methods for breastfeeding women, since there is no possibility that they will interfere with lactation. Progestin-only methods comprise a viable and often desirable next choice category, although the timing of their commencement must be determined with care in order to support lactation.     

The science of sex research: Some methodological considerations

This paper represents a review of substantive theoretical, methodological, and statistical issues relevant to conducting research on human sexual behavior. Guidelines for maintaining rigor and precision in future investigations are also proposed. So as to be able to address issues that pervade all research on human sexual behavior, six topic areas are discussed: theory-related issues, issues involving research design, issues involving subject selection, measurement issues, data-analytic issues, and issues concerned with human-subject protection. The ultimate objective of this paper is to make suggestions aimed at improving the quality of research on human sexual behavior.Invited paper, Conference on Methodology in Sex Research, Washington, D.C., November 8–19, 1977. This investigation was supported in part by a Research Scientist Development Award (KO2-DA00017), Biomedical Research Support Grant from University of California, Los Angeles, and research grant DA1070 from the U.S. Public Health Service. The assistance of Bonnie Barron is gratefully acknowledged.     

Antibiotics and oral contraceptive failure - a case-crossover study

Background

Evidence on the association between antibiotic use and combined oral contraceptive (COC) failure is controversial. We examined the effect of concomitant antibiotic treatment on the risk of breakthrough pregnancy among COC users.

Study Designs

We performed a case-crossover study of 1330 COC failure cases among 17,721 women from the Slone Epidemiology Center Birth Defects Study (1997–2008) and among 25,941 women from the National Birth Defects Prevention Study (NBDPS, 1997–2005). Self-matched odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by comparing antibiotic use between the 4 weeks before conception (“case period”) and the 4–8 weeks before conception (“control period”) using conditional logistic regression. A case–time-control analysis was conducted using nonusers of COCs with unplanned pregnancies as controls.

Results

For the combined data, the self-matched OR was 1.08 (95% CI: 0.63–1.84) and the case–time-control OR was 1.12 (0.63–1.98) for antibiotics overall. The results did not appreciably differ when adjusted for characteristics that might vary between the case and control period. However, among COC failure cases from the NBDPS, allowing a 1-month gap between the case and control period resulted in a self-matched OR of 1.45 (0.85–2.50) and a case–time-control OR of 1.55 (0.86–2.79) for antibiotics overall.

Conclusions

We did not find an association between concomitant antibiotic use and the risk of breakthrough pregnancy among COC users. However, due to limited power and potential carryover effects, findings from this study cannot rule out an elevated risk of COC failure among antibiotic users.     

Ectopic pregnancy with use of progestin-only injectables and contraceptive implants: a systematic review

BackgroundUse of contraception lowers a woman's risk of experiencing an ectopic pregnancy. In the case of method failure, however, progestin-only contraceptives may be more likely to result in ectopic pregnancies than some other methods such as combined hormonal and barrier contraceptives.ObjectiveTo describe ectopic pregnancy risk associated with use of implants and progestin-only injectable contraceptives through a systematic review of published studies.Data SourcesWe searched electronic databases for articles in any language published through May 2015 describing studies of progestin-only injectables and implants. We also searched bibliographies and review articles for additional studies.Study Selection and ExtractionStudies that reported any pregnancies were included in the review. Independent data extraction was performed by two authors based on predefined data fields, and where possible, we calculated the proportion of pregnancies that were ectopic and the ectopic pregnancy incidence rate per 1000 woman–years.ResultsFifty-three studies of implants and 28 studies of injectables were identified; 79% reported pregnancy location. The proportion of ectopic pregnancy ranged from 0 to 100% with an incidence of 0–2.9 per 1000 woman–years in studies of marketed levonorgestrel implants. Studies of etonogestrel implants and the injectables, depot-medroxyprogesterone acetate and norethisterone enanthate, reported few ectopic pregnancies.ConclusionProgestin-only contraceptive implants and injectables protect against ectopic pregnancy by being highly effective in preventing pregnancy overall; however, the absolute risk of ectopic pregnancy varies by type of progestin. Risk of ectopic pregnancy should not be a deterrent for use or provision of these methods.     

Weight change at 12 months in users of three progestin-only contraceptive methods

Background

Concerns about weight gain may influence contraceptive use. We compared the change in body weight over the first 12 months of use between women using the etonogestrel (ENG) implant, the levonorgestrel intrauterine system (LNG-IUS) or depot medroxyprogesterone acetate (DMPA) with women using the copper intrauterine device (IUD).

Study Design

This was a substudy of the Contraceptive CHOICE Project, a prospective cohort study of 9256 women provided no-cost contraception. Women who had been using the ENG implant, LNG-IUS, DMPA or copper IUD continuously for at least 11 months were eligible for participation. We obtained body weight at enrollment and at 12 months and compared the weight change for each progestin-only method to the copper IUD.

Results

We enrolled a total of 427 women: 130 ENG implant users, 130 LNG-IUS users, 67 DMPA users and 100 copper IUD users. The mean weight change (in kilograms) over 12 months was 2.1 for ENG implant users [standard deviation (SD)=6.7]; 1.0 for LNG-IUS users (SD=5.3); 2.2 for DMPA users (SD=4.9) and 0.2 for copper IUD users (SD=5.1). The range of weight change was broad across all contraceptive methods. In the unadjusted linear regression model, ENG implant and DMPA use were associated with weight gain compared to the copper IUD. However, in the adjusted model, no difference in weight gain with the ENG implant, LNG-IUS or DMPA was observed. Only Black race was associated with significant weight gain (1.3 kg, 95% confidence interval=0.2–2.4) when compared to other racial groups.

Conclusions

Weight change was variable among women using progestin-only contraceptives. Black race was a significant predictor of weight gain among contraceptive users.     

Inter-organ fluxes in a methodological perspective

Inter-organ fluxes remain a cornerstone as an investigating tool in metabolic research. Combination with isotopic labelling and microdialysis have now opened new possibilities of addressing a number of questions not previously accessible. However, the technique requires a high level of knowledge among investigators as well as among readers.     

Breast cancer risk and oral contraceptive use: results from a large case-control study.

The association between oral contraceptive use and breast cancer risk was examined using data from a case-control study of breast cancer in Long Island, New York. Cases were defined as female residents of Nassau and Suffolk Counties between the ages of 20 and 79, diagnosed with breast cancer between January 1, 1984 and December 31, 1986. Age- and county-matched controls were selected from driver's license files. Among all women under age 70 at diagnosis, there was no association between oral contraceptive use and breast cancer; there was, however, a positive association in the subgroup ages 20-49 (adjusted odds ratio = 1.68, 95% CI: 1.16-2.42). Risk increased with increasing duration of use, but did not differ between women who first used oral contraceptives before the first pregnancy and those who first used them later, or between women who first used oral contraceptives before age 25 and those who first used them at a later age. Risk also appeared to increase with number of years of use before the first pregnancy or before age 25, although numbers were small. History of benign breast disease did not influence risk. The association of breast cancer risk with oral contraceptive use appeared stronger in women from Suffolk County than Nassau County.     

Use of oral contraceptive pills and vulvar vestibulitis: a case-control study

Vulvar vestibulitis is characterized by superficial pain during intercourse. Exploratory studies have suggested that oral contraceptives (OCs) could be associated with occurrence of vulvar vestibulitis. This 1995-1998 case-control study in Québec, Canada, sought to reassess this association. Included were 138 women with vulvar vestibulitis whose symptoms had appeared in the previous 2 years and 309 age-matched controls who were consulting their physicians for reasons other than gynecologic problems or contraception. Cases and controls were interviewed to obtain a detailed history of OC use and information on potential confounding factors. Relative risks were estimated by using logistic regression. The authors found that 4 percent of cases had never used OCs compared with 17 percent of controls. The relative risk of vulvar vestibulitis was 6.6 (95 percent confidence interval: 2.5, 17.4) for ever users compared with never users. When OCs were first used before age 16 years, the relative risk of vulvar vestibulitis reached 9.3 (95 percent confidence interval: 3.2, 27.2) and increased with duration of OC use up to 2-4 years. The relative risk was higher when the pill used was of high progestogenic, high androgenic, and low estrogenic potency. The possibility that OC use may contribute to the occurrence of vulvar vestibulitis needs to be evaluated carefully.     

Use of placebo controls in an oral contraceptive trial: methodological issues and adverse event incidence

Two multicenter, double-blind, placebo-controlled studies were conducted to evaluate the effectiveness of triphasic norgestimate/ethinyl estradiol (Ortho Tri-Cyclen) for the treatment of acne vulgaris. To our knowledge, these studies were the first double-blind, placebo-controlled trials to evaluate the efficacy of an oral contraceptive (OC) in the treatment of acne; in fact, they are probably the first placebo-controlled trials ever completed using modern OC. This article examines the conduct and feasibility of these studies including discussions on study planning enrollment, maintenance of the blind, continuation rates, and pregnancy prevention. Subjects were between the ages of 15 and 49 years, with moderate acne vulgaris, no contraindications to oral contraceptive use, and were willing to use a nonsteroidal method of birth control during the 6 months of the trial. More than 500 participants were enrolled in 1 year. Discontinuation rates between groups were similar. To explore the reasons for the similar and low discontinuation rates, OC-related side effects were evaluated in comparison to placebo. This analysis revealed that the OC exhibited a side effect profile that was similar, in many cases, to that of placebo. Although pregnancies occurred in the placebo arm, the incidence was consistent with expected failure rates for users of nonsteroidal methods in the general population.     

Estrogen-free oral hormonal contraception: benefits of the progestin-only pill

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.     

A study of interaction of a low-dose combination oral contraceptive with anti-tubercular drug

Low-dose combination contraceptive (containing norethisterone acetate 1 mg and ethinyl estradiol 30 μg) was administered to women receiving concurrent therapy with either Rifampicin or “triple” antitubercular treatment consisting of paraaminosalicylic acid (PAS), isonicotinic acid hydrazide (INH) and streptomycin. Plasma levels of norethisterone (NET) and ethinyl estradiol (EE), PAS and INH were measured and the area under curve (AUC) was calculated for NET and EE. Rifampicin treatment (9 women) caused a statistically significant reduction of the plasma NET levels as well as the AUC of NET. In this group of women, though a trend for reduction in EE levels was observed in individual subjects, it was not statistically significant. Out of 7 regularly menstruating women on Rifampicin therapy, 2 showed a premenstrual rise of plasma progesterone (P) levels (> 4 ng/ml) suggesting an ovulatory cycle and 3 experienced menstrual irregularities. In contrast, plasma levels of NET and EE as well as their AUCs were not altered in 8 women receiving “triple” antitubercular therapy. Only one women out of 8, had menstrual irregularity and all women had P levels in the anovulatory range. Furthermore, oral contraceptive treatment did not alter the plasma levels of PAS and INH.     

Clinical evaluation of a new combined oral contraceptive

This paper presents the results of a clinical study of 176 women using a combined oral contraceptive — Chlormadinone acetate 3 mg plus Mestranol 100 mcg (Aconcen) — for a total of 2,525 cycles (lunar months). The evaluation included extensive examinations and laboratory testing, as well as examinations of thirteen children born to mothers who had used Aconcen previously. The study compound was found to be an acceptable and effective antifertility agent. No evidence was found of harmful effects from its use.     

A andomized contraceptive trial comparing a daily progestogen with a combined oral contraceptive steroid

This study was designed as a double-blind trial of .25 mg ethynodiol diacetate versus the combined, established preparation, Ovulen 21 (1 mg ethynodiol diacetate and .1 mg mestranol). Blanks were added to the sets of Ovulen 21 capsules so that there was no obvious difference in appearance of the medications. 43 young women enrolled in each group. There were more dropouts in the experimental group so that the average number of months of study was 9.2 for the control group and only 6.7 for the experimental group. The experimental group reported more intercyclic bleeding and more irregularity of cycles than the Ovulen 21 control group (p.001 in each case). Cramping was reported 3 times more frequently by the experimental group, (p.05). There was 1 unusually prolonged case of amenorrhea (7 months) in a patient taking ethynodiol diacetate. This patient responded to discontinuation of the tablet and had a menstrual cycle within 36 days. There were no unintended pregnancies.