Oral contraceptive use and risk of diabetes among Chinese women

Oral contraceptive (OC) use has been associated with alterations in carbohydrate metabolism. We examined the effect of OC use on the risk of diabetes among Chinese women. A nested case-control study was conducted among 57,130 women screened for diabetes at enrollment for the Shanghai Women's Health Study, a population-based cohort study of Chinese women aged 40-70 years in Shanghai, China. Included in this study were 259 women newly diagnosed with diabetes and 2072 age-matched controls (8 controls per case), randomly selected from women who tested negative for urine glucose. Multivariate-adjusted odds ratios (OR) and 95% confidence intervals (CI) were used to measure the strength of the association between OC use and diabetes risk. Overall, OC use was not associated with the risk of diabetes. Stratified analysis by menopausal status revealed a dose-response relationship between the duration of OC use and the risk of diabetes among premenopausal women (p for trend = 0.02), with a 3.2-fold elevated risk observed among those who used OC longer than 1 year. Risk of diabetes diminished with increasing time since last OC use (p = 0.02). Use of intrauterine devices was associated with a reduced risk of diabetes in both pre- and postmenopausal women (OR = 0.67, CI: 0.48-0.93). These findings suggest that recent use (within 5 years) and continued use (>1 year) of OCs may increase the risk of diabetes among Chinese women. However, the attributable risk for diabetes among OC users in the general population, if confirmed by further studies, appears to be small.     

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

Background

Most of the millions of oral contraceptive (OC) users are under 30 years of age and in the critical period for bone mass accrual.

Study Design

This cross-sectional study of 606 women aged 14-30 years examined both OC duration and estrogen dose and their association with bone mineral density (BMD) at the hip, spine, and whole body (dual-energy X-ray absorptiometry).

Results

Of 389 OC users and 217 nonusers enrolled, 50% were adolescents (14-18 years). Of OC users, 38% used “low-dose” OCs [<30 mcg ethinyl estradiol (EE)]. In adolescents, mean BMD differed by neither OC duration nor EE dose. However, 19- to 30-year-old women's mean BMD was lower with longer OC use for spine and whole body (p=.004 and p=.02, respectively) and lowest for >12 months of low-dose OCs for the hip, spine and whole body (p=.02, .003 and .002, respectively).

Conclusions

Prolonged use of today's OCs, particularly <30 mcg EE, may adversely impact young adult women's bone density while using these agents.     

Oral contraceptives and risk of gestational trophoblastic disease

Clinical reports suggested that the use of oral contraceptives (OC) after a molar pregnancy may increase the risk of persistent throphoblastic disease. However, few epidemiologic studies have analyzed the effect of OC use on the risk of developing gestational trophoblastic disease (GTD). To give further information, we have analyzed data from a case-control study on risk factors for GTD. Cases were 268 women with a histologically confirmed diagnosis of complete or partial mole referred to the participating Trophoblastic Disease Centers. A total of 268 subjects were interviewed; 79 cases were classified as partial and 159 as complete mole. Controls were randomly selected women who gave birth to healthy infants at term on randomly selected days in the same network of hospitals in which cases had been identified. A total of 104 cases and 130 controls reported ever OC use, and the corresponding odds ratio (OR) was 1.5 (95% CI, 1.1–2.1). The risk of GTD increases with duration of OC use: the OR was 1.7 (95% CI 1.2–2.6) for ever-users reporting ≥12 months of use. No consistent pattern of risk was observed with time since last OC use. We have analyzed separately the association between OC use and risk of complete and partial moles: no statistically significant difference emerged, but the OR for partial moles was higher (OR 3.0, 95% CI 1.6–8.4) than for complete mole (OR 1.0, 95% CI 1.8). In conclusion, we observed a weak association between OC use and GTD; such a weak association could be explained by factors other than causality.     

Oral contraceptives use and the risk of myocardial infarction: a meta-analysis

This meta-analysis of oral contraceptive use in relation to myocardial infarction is based on 19 case-control studies and 4 cohort studies that met pre-stated inclusion criteria. A comprehensive literature search was performed using the MEDLINE computerized database (for studies from January 1966 through October 2002). In addition, a manual search was performed for references cited in published original and reviewed articles. Current oral contraceptive (OC) users have an overall adjusted odds ratio (OR) of myocardial infarction (MI) of 2.48 [95% confidence interval (CI): 1.91-3.22] compared to never-users. The risk of MI for past OC users is not significantly different from that for never-users, overall OR = 1.15 (95% CI: 0.98-1.35; p = 0.096).     

Oral contraceptives and family history of breast cancer

Background

Questions remain regarding whether oral contraceptive (OC) use among women with a family history of breast cancer increases disease risk.

Study Design

We conducted a systematic review by searching MEDLINE and CENTRAL databases for evidence (in all languages) published in peer-reviewed journals from 1966 to July 2008 that provided estimates of breast cancer risk according to family history. Twelve articles were identified and the quality of each study was assessed using the United States Preventive Services Task Force grading system.

Results

Results from 10 studies and one pooled analysis of 54 studies suggest that the use of OCs does not significantly modify the risk of breast cancer among women with a familial history of breast cancer; however, evidence from four studies shows that some women may be at a greater risk, particularly women who took OCs prior to 1975.

Conclusions

Current evidence shows that women with a family history of breast cancer do not increase their disease risk by using OCs.     

Longitudinal changes in bone density in relation to oral contraceptive use

The primary aim of this 36-month prospective cohort study was to evaluate the association between use of oral contraceptives (OCs) and bone mineral density in reproductive-age women. The 36-month bone density (g/cm2) at the spine, hip and whole body and percent change from baseline (measured at 6-month intervals) were evaluated among 245 women 18-39 years of age; 89 were using OCs (median duration: 3.7 years at study entry) and 156 were not using any hormonal contraception. Before and after adjustment for covariates (baseline bone density, age, race, ever pregnant, exercise, body mass and calcium intake), women using OCs did not differ significantly from comparison women in percent change in bone density over 36 months or in absolute bone density at 36 months. All p-values for between-group differences were >0.55. In conclusion, within the limitations of this study, OCs did not appear to impact bone density over time in this cohort of reproductive-age women.     

Smoking and oral contraceptive continuation

Background

Smoking may be related to early discontinuation of oral contraceptives (OC).

Study design

This was a planned secondary analysis of a randomized clinical trial. Women aged less than 25 initiating OC at three inner-city publicly funded family planning clinics enrolled in the study. Subjects reported smoking status at enrollment; 3- and 6-month interviews assessed OC continuation.

Results

One hundred eighty-nine (12%) of 1598 participants were current smokers. Smokers were more often lost to follow-up than nonsmokers (P<.01). Among participants with a 6-month interview, only 26% of smokers and 46% of nonsmokers were continuing OC (P<.001). After adjustment for confounding factors, smokers were still somewhat less likely to be continuing OC (adjusted OR 0.6, 95% CI 0.4-1.0). This association was unrelated to number of cigarettes smoked per day.

Conclusions

These data suggest that young smokers may be more likely to discontinue OC within 6 months than nonsmokers. Smoking may be a marker for risk-taking behavior that extends to the premature discontinuation of OC.     

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.     

Oral contraceptive use and exercise-induced muscle damage and recovery

Endogenous estrogen appears to attenuate muscle damage in animals; however, similar evidence in humans is not as strong. This investigation tested the hypothesis that women taking oral contraceptives, thereby having higher exogenous estrogen levels, would be more susceptible to damage or have an attenuated recovery from exercise-induced muscle damage. Muscle damage in women taking combined estrogen and progesterone oral contraceptives (OC) were compared to noncontraceptive users (NOC) after 50 eccentric muscle contractions of the elbow flexors. Measures of maximal isometric strength (MIS), range of motion (ROM), arm circumference (CIR), soreness (SOR), and serum creatine kinase (CK) activity were taken pre- and for 5 days post-exercise. All measures following exercises were similar between groups with the exception of MIS. Force recovery began 2 days post-exercise in the NOC group, while in the OC group strength did not start to return to normal until 4 days post-exercise (p < 0.05). Women taking oral contraceptives had a delayed strength recovery after eccentric exercise.     

The association between oral contraceptive use, bone mineral density and fractures in women aged 50-80 years

Background

The associations between oral contraceptive (OC) use, bone mineral density (BMD) and the risk of fractures remain controversial.

Study Design

A cross-sectional study of 491 women aged 50–80 years was performed. We assessed OC use and fractures by questionnaire, and BMD and vertebral deformity by dual-energy x-ray absorptiometry.

Results

Ever use of OC was associated with significantly higher BMD at the total body (6%, p<.001) and spine (4%; p=.05) (but not hip) after adjustment for confounders. There was also a significant association between duration of OC use and total body and spine BMD. Use of OCs for 5–10 years was associated with reduced vertebral deformity (adjusted odds ratio 0.46, 95% confidence interval 0.22–0.94).

Conclusions

Oral contraceptive use and duration were associated with higher total body and spine BMD and a consistent reduction in vertebral deformities, although most associations did not reach significance.     

Antimullerian hormone and obesity: insights in oral contraceptive users

Background

The study was conducted to examine the impact of oral contraceptives (OCs) on serum antimullerian hormone (AMH) levels by obesity status in reproductive-age women.

Study Design

Ovulatory women, ages 18-35 years, of normal (<25 kg/m²; n=10) and obese (>30 kg/m²; n=10) body mass index (BMI) received a low-dose OC (20 mcg ethinyl estradiol/100 mcg levonorgestrel) for two cycles. Serum samples obtained at several time points during active pill use and hormone-free intervals were analyzed for AMH, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol and inhibin B.

Results

AMH levels did not differ by OC cycle day in either BMI group. On average, AMH levels were 34% lower in the obese group (2.9±2.1 vs. 4.4±1.8 ng/mL, p<.05). Modeling to determine differences in AMH throughout the cycle based on obesity status demonstrated significantly lower levels (p<.05), whereas serum AMH, FSH, LH, estradiol and inhibin B levels revealed no correlations when all time points were included.

Conclusions

In reproductive-age women, serum AMH levels do not appear to fluctuate during OC use, but AMH levels are significantly lower in obese women. Lower levels do not appear to be due to differences in gonadotropin levels or ovarian activity.     

Depot-medroxyprogesterone acetate injection (Depo-Provera): a highly effective contraceptive option with proven long-term safety

Depot-medroxyprogesterone acetate (Depo-Provera(R)) is a highly effective, nondaily hormonal contraceptive option that has been available in the United States for a decade, and worldwide for 40 years. Benefits and risks of hormonal therapy are often under scrutiny; however, long-term clinical experience has established the safety of this long-acting contraceptive. This article reviews the contraceptive efficacy, potential noncontraceptive health benefits and long-term safety of with regard to risk of cardiovascular events, breast and gynecologic malignancy and osteopenia. Comparisons with other hormonal contraceptives are made as clinically appropriate. Common patient management issues, including effects on menstrual cycle, body weight and mood, are also addressed. Finally, this review provides recommendations for appropriate patient selection.     

Gender and risk assessment in contraceptive technologies

This paper concerns a comparison of risk assessment practices of contraceptives for women and men. Our analysis shows how the evaluation of health risks of contraceptives does not simply reflect the specific effects of chemical compounds in the human body. Rather, we show how side‐effects were rated differently according to the risk model that was adopted. Our analysis shows an important new aspect of risk assessment: lay perspectives of men are taken more seriously by experts and policymakers than those of women. In the case of male contraceptives, men’s wellbeing when using contraceptives was a central issue from the very beginning. Men’s emotional wellbeing and sexuality has been put on the international research agenda by the reproductive scientists themselves, and the need for long‐term data about male contraceptives has been emphasised by the pharmaceutical industry. In the case of female contraceptives, the concern for the long‐term effects of contraceptives was put forward by women’s health movements, and research into women’s mental health and libido when using hormonal contraceptives was initiated only at the instigation of women’s health advocates. We therefore conclude that the incorporation of lay interests in the experts’ methods of risk assessment shows a clear gender pattern. Whereas the perspectives of male contraceptive users have been emphasised and negotiated by authoritative spokespersons within the medical establishment, the incorporation of the interests and needs of female contraceptives users depended on women’s health advocates.     

Oral contraceptive use and the risk of myocardial infarction

The relation of oral contraceptive use to the risk of myocardial infarction was assessed in a hospital-based case-control study of women aged 25-64 years conducted from 1985 to 1988 in New England; 910 women with first myocardial infarctions were compared with 1,760 control women. Oral contraceptive use, after discontinuation, was not associated with an increased risk of myocardial infarction, whether use had ceased in the distant past or more recently. The overall relative risk estimate for women who had used oral contraceptives in the past for at least 5 years compared with nonusers was 1.1 (95% confidence interval 0.8-1.5) after allowance for confounding factors. Past use was not associated with risk in any age group, in subgroups of women with predisposing factors, or in women at low risk because of the absence of predisposing factors. The results suggest that long-term oral contraceptive use, after discontinuation, does not influence the risk of myocardial infarction. There were few current users and the results for current use were inconclusive: for premenopausal women who had used oral contraceptives in the previous month relative to those who had not, the age-adjusted relative risk estimate was 1.1 (95% confidence interval 0.4-3.1).     

Official warnings on thromboembolism risk with oral contraceptives fail to inform users adequately

Following the 1995 "pill scare" relating to the risk of venous thrombosis from taking second- or third-generation oral contraceptives, the Committee on Safety of Medicines (CSM) withdrew their earlier recommended restrictions on the use of third-generation pills and published recommended wording to be used in patient information leaflets. However, the effectiveness of this wording has not been tested. An empirical study (with 186 pill users, past users, and non-users) was conducted to assess understanding, based on this wording, of the absolute and relative risk of thrombosis in pill users and in pregnancy. The results showed that less than 12% of women in the (higher education) group fully understood the absolute levels of risk from taking the pill and from being pregnant. Relative risk was also poorly understood, with less than 40% of participants showing full understanding, and 20% showing no understanding. We recommend that the CSM revisit the wording currently provided to millions of women in the UK.     

Oral contraceptive use and risk of invasive cervical cancer

A case-control study of 759 invasive cervical cancer patients and 1430 controls in Panama, Costa Rica, Colombia and Mexico enabled an evaluation of risk in relation to oral contraceptive use. Overall use was associated with a 21% nonsignificant elevation in risk, with some further increases in risk for more extensive durations of use. Although risks were similar for recent and non-recent users (RRs = 1.3 versus 1.2), recent long-term users were at highest risk (RR for 5+ years use = 1.7, 95% Cl 1.1-2.6). Relationships were similar for women with and without a recent Pap smear, arguing against detection bias. There was little evidence that other risk factors, including smoking and detection of human papillomaviruses (HPV), altered the effects of oral contraceptives. The risk associated with oral contraceptives was significantly increased for adenocarcinomas (RR = 2.2), whereas for squamous cell tumours the effect was minimal (RR = 1.1). These results provide some support for an adverse effect of oral contraceptives on cervical cancer risk, although possibly limited only to a subpopulation of cases.     

Further results on the risk of nonfatal venous thromboembolism in users of the contraceptive transdermal patch compared to users of oral contraceptives containing norgestimate and 35 microg of ethinyl estradiol

CONTEXT: In 2006, we published a study that indicated that the new transdermal contraceptive patch containing ethinyl estradiol (EE) and the progestin norelgestromin did not increase the risk for venous thromboembolism (VTE) compared to oral contraceptive containing norgestimate and 35 microg of EE. OBJECTIVE: This report updates information on the risk of nonfatal VTE in women using the contraceptive patch in comparison to women using oral contraceptives containing norgestimate (either monophasic or triphasic) and 35 microg of EE (norgestimate-35) using an additional 17 months of data. DESIGN, SETTING AND PARTICIPANTS: Nested case-control design based on information from PharMetrics, a US-based company that collects and organizes information on claims paid by managed care plans. The study was nested among all women, aged 15 to 44 years, who started either the contraceptive patch or norgestimate-35 after April 1, 2002. Cases were women with current use of one of these two study drugs and a documented diagnosis of VTE in the absence of identifiable clinical risk factors (idiopathic VTE) who were not in the earlier study. Up to four controls were matched to each case by age and calendar time. MAIN OUTCOME MEASURES: Odds ratios (ORs) comparing the risk of nonfatal VTE in new users of the two contraceptives. RESULTS: We identified 56 new cases of newly diagnosed, idiopathic VTE in the updated study population. The OR comparing the contraceptive patch to norgestimate-35 was 1.1 (95% CI 0.6-2.1). CONCLUSIONS: After evaluating an additional 17 months of data, the results indicate that the risk of nonfatal VTE for the contraceptive patch is closely similar to the risk for oral contraceptives containing 35 mug of EE and norgestimate.     

High BMI and the risk of lower extremity fractures in fertile-aged women: A nationwide register-based study in Finland

ObjectivesBoth high and low body mass index (BMI) is known to be associated with increased risk for osteoporotic fractures in the postmenopausal population. However, the association between BMI and risk for fracture in the fertile-aged (15–49 years) population is not well studied. We aim to examine how increased BMI affects the risk for fracture leading to hospitalization after delivery in fertile-aged women.Material and methodsIn this nationwide registry-based study, data on all women aged 15–49 years with fractures leading to hospitalization were retrieved from the Care Register for Health Care for the years 2004–2018. The data were linked with data from the National Birth Register, where the BMI status is collected for each pregnancy. Cox regression was used to examine the effect of increased BMI on the risk for fracture within five years after delivery. Risks were analyzed separately for upper extremity, spine and pelvis, and lower extremity fractures. The results were interpreted with hazard ratios (HR), adjusted hazard ratios (aHR), and 95% confidence intervals (CI).ResultsA total of 529 992 pregnant women with 3276 fractures leading to hospitalization within 5-year follow-up were included in this study. Of these, a total of 548 fractures required surgical treatment. Patients with BMI of 30 kg/m² or more had a higher rate of fractures in the lower extremity (≥50%). In lower extremity fractures, risk for fracture increased with increasing BMI. The risk fracture was highest in the group with BMI of 35–40 kg/m² (overall lower extremity aHR 2.43 95% CI 1.92–3.06; knee aHR 2.04, 95% CI 1.45–2.87; ankle aHR 3.01, 95% CI 2.16–4.20).ConclusionsHigher BMI was associated to the increased risk for lower extremity fractures, especially ankle fractures, within five years of delivery. Information gained from this study is important in the clinical setting, as patients can be informed of the negative effect of obesity on the post-delivery risk for fractures.     

Measured and reported weight change for women using a vaginal contraceptive ring vs. a low-dose oral contraceptive

BACKGROUND: Women often stop hormonal contraception because of perceived weight change. We conducted a randomized trial comparing the contraceptive vaginal ring to a low-dose oral contraceptive (OC). We examined the difference between women's reported and measured baseline weights and looked at factors affecting perceived weight change. METHODS: We randomized 201 participants to either the vaginal ring or an OC for three cycles. We weighed participants upon enrollment (n=194) and at exit (n=167), using the same instrument for all measurements. Participants also provided self-reported height and their reactions to perceived weight changes. RESULTS: Baseline weight and body mass index were similar for both groups (mean weight=145.9 lb). Measured weight was, on average, 4.4 lb more than reported weight; this difference was greater in overweight and obese participants. Participants gained an average of 2.8 lb over 3 months; this gain did not differ between groups or by baseline weight. Subjects who reported a "bad change" in weight at exit (n=34) gained an average of 4.4 lb, whereas those who reported "no change" (n=112) gained 2.2 lb and those who reported a "good change" (n=14) gained 3.3 lb. CONCLUSION: Participants underreported their weight, and this difference was greater for heavier women. There was little weight change for the women in our study. Participants' opinions about weight change were not correlated with measured weight changes.