Long-term Oral Contraceptive Users Research Articles

Oral Contraceptive Use and Risks of Cancer in the NIH-AARP Diet and Health Study.

Although use of oral contraceptives (OCs) is common, their influence on carcinogenesis is not fully understood. We used Cox proportional hazards models to examine OC use (never/<1 year (referent), 1-4, 5-9, ≥10 years) and development of incident cancers across body sites within the same base population: women in the prospective National Institutes of Health-AARP Diet and Health Study (enrolled 1995-1996 and followed until 2011). Adjustment for confounding varied by outcome; all models accounted for age, race, body mass index, and smoking status, and included at least 100,000 women. Any OC use conferred a 3% reduction in the risk for any cancer (hazard ratio = 0.97, 95% confidence interval: 0.95, 0.99). Expected risk reductions that strengthened with duration of use were identified for ovarian and endometrial cancers and were suggested for kidney cancer (all P for trend < 0.05). Non-Hodgkin lymphoma risk (hazard ratio = 0.79, 95% confidence interval: 0.64, 0.97) was reduced with 10 or more years of OC use. There was a 37% reduced risk for bladder cancer and 46% increased risk for pancreatic cancer among long-term OC users who were 60 years of age or younger at baseline. OC use did not influence risks for most other cancers evaluated. Given the high prevalence of use and changing formulations, additional studies are warranted to fully understand the chemopreventive effects of these medications.

Modification of the Associations Between Duration of Oral Contraceptive Use and Ovarian, Endometrial, Breast, and Colorectal Cancers

Although oral contraceptive (OC) use is common, the influence of OC use on carcinogenesis is not fully understood. A recent Agency for Healthcare Research and Quality report identified a need to understand the consistency of OC use and cancer associations across subpopulations, including smokers and obese women. To determine whether associations between duration of OC use and risk of specific cancers were modified by lifestyle characteristics. The prospective NIH-AARP Diet and Health Study (enrolled 1995-1996, followed until 2011), with population-based recruitment of AARP members in 6 states and 2 metropolitan areas. All analyses included at least 100 000 women who reported OC use at enrollment. We identified 1241 ovarian, 2337 endometrial, 11 114 breast, and 3507 colorectal cancer cases during follow-up. Data analysis was performed between September 2016 and April 2017. Duration of OC use (never or <1 year [reference], 1-4, 5-9, or ≥10 years). Development of ovarian, endometrial, breast, and colorectal cancers. We examined effect modification by modifiable lifestyle characteristics: cigarette smoking, alcohol consumption, body mass index (BMI), and physical activity. We used Cox models adjusted for age, race, age at menarche, and the modifiers of interest. The analytic population was aged 50 to 71 years (median, 62 years) at enrollment and largely white (91%) and postmenopausal (96%). For ovarian cancer, OC use-associated risk reductions strengthened with duration of use (long-term OC use [≥10 years] HR, 0.60; 95% CI, 0.47-0.76; P < .001 for trend) and were similar across modifiable lifestyle factors. Risk reductions for endometrial cancer strengthened with duration of use (long-term OC use HR, 0.66; 95% CI, 0.56-0.78; P < .001 for trend); the most pronounced reductions were among long-term OC users who were smokers (HR, 0.47; 95% CI, 0.25-0.88), had obese BMIs (0.36; 95% CI, 0.25-0.52), and who exercised rarely (HR, 0.40; 95% CI, 0.29-0.56). Associations between OC use and breast and colorectal cancers were predominantly null. Long-term OC use is consistently associated with reduced ovarian cancer risk across lifestyle factors. We observed the greatest risk reductions for endometrial cancer among women at risk for chronic diseases (ie, smokers, obese BMI). Oral contraceptive use may be beneficial for chemoprevention for a range of women with differing baseline cancer risks.

Abstract 3013: Duration of oral contraceptive use and the prevention of gynecologic cancers: Modification by modifiable factors

Abstract Background: Although oral contraceptive (OC) use is ubiquitous in the United States, the influence of OCs on the development of cancers is not fully understood. In 2013, an Agency for Healthcare Research and Quality Evidence Report identified several data gaps with regard to OC use and its associations with cancer, including a need to understand if associations are consistent across subpopulations of users, including smokers and obese women. Methods: To address this data gap, we used Cox proportional hazards models to examine duration of OC use (never/less than 1 year [reference], 1 to 4, 5 to 9, 10+ years) and subsequent development of incident ovarian or endometrial cancer among participants in the NIH-AARP Diet and Health Study. We further examined effect modification by a variety of modifiable risk factors, including body mass index (BMI), cigarette smoking, alcohol consumption, and physical activity, via interaction terms and a likelihood ratio test. Models were adjusted for age, race, age at menarche and the modifiers of interest. Results: For ovarian cancer (n=1,241 cases, 149,502 non-cases), a reduction in risk was conferred by OC use that linearly decreased with duration of use (hazard ratios [HR] ranging from 0.83 to 0.60 across categories of duration). We also identified linear, inverse associations between increasing duration of OC use and ovarian cancer risk across most potential modifiers. Some of the most pronounced reductions were observed among long-term OC users (10+ years) who were current smokers (HR compared to non-users of 0.44, 95% confidence interval [CI] 0.20, 0.97) or who engaged in moderate physical activity (0.44, CI 0.23, 0.85). For endometrial cancer (n=2,337 cases, n=112,132 non-cases), we observed pronounced reductions in risk associated with long-term OC use among women with obese BMIs (0.36, CI 0.25, 0.52) and those who exercised rarely (0.40, CI 0.29, 0.56) or moderately (0.50, CI 0.33, 0.75). However, long-term use was not associated with risk reductions among women with BMIs of less than 25 or among women who exercised at least three times per week. Conclusions: OC use is consistently associated with reduced risks of ovarian cancer across most strata of modifiable risk factors. For endometrial cancer risk, OC use seems to offer the greatest risk reduction among women in previously identified high-risk categories (i.e., overweight/obese BMI, physically inactive), findings which merit further discussion as these women may be more likely to have comorbid conditions that would contraindicate OC use (e.g., hypertension, diabetes). Citation Format: Kara A. Michels, Louise A. Brinton, Ruth M. Pfeiffer, Britton Trabert. Duration of oral contraceptive use and the prevention of gynecologic cancers: Modification by modifiable factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3013. doi:10.1158/1538-7445.AM2017-3013

Response of women using oral contraception to exercise in the heat.

To compare the response of long-term oral contraceptive users (WomenOC; n=8) to naturally menstruating women (WomenNM; n=8) at rest and during exercise in temperate (TEMP; 22°C) and hot (HEAT; 35°C) conditions. Participants performed a three-stage cycling trial in each condition at 90, 135, and 180% of lactate threshold 1 (total=52.5min). Heart rate (HR) and core temperature (T c) were recorded continuously, whereas blood pressure (BP), ratings of perceived exertion (RPE), blood lactate [La-], and skin blood flow (BFsk) were recorded every 7.5min. Baseline T c was higher in WomenOC (37.5±0.2, 37.6±0.3°C) than WomenNM (37.2±0.2, 37.0±0.4°C) before the TEMP (p=0.03) and HEAT (p<0.01) trials, respectively. This difference remained for 22.5min into both trials (p≤0.05), after which time no between-group differences were found (p>0.05). BFsk measured in WomenNM plateaued from 7.5min in the HEAT, whereas BFsk measured in WomenOC increased for 15.0min (p=0.02) before plateauing. There were no between-group differences in HR, BP, or blood [La-] before or throughout either trial (p>0.05). WomenOC had higher (p≤0.04) RPE values than WomenNM in the HEAT, reporting 8±1 and 6±2 at the end of Stage 3, respectively. WomenOC concluded both trials with a comparable T c to WomenNM, but had a prolonged BFsk response and elevated RPE in the HEAT. Changes to BFsk and RPE observed in women using OC may have implications for exercise tolerance in hot conditions.

Three-step method for menstrual and oral contraceptive cycle verification.

Fluctuating endogenous and exogenous ovarian hormones may influence exercise parameters; yet control and verification of ovarian hormone status is rarely reported and limits current exercise science and sports medicine research. The purpose of this study was to determine the effectiveness of an individualised three-step method in identifying the mid-luteal or high hormone phase in endogenous and exogenous hormone cycles in recreationally-active women and determine hormone and demographic characteristics associated with unsuccessful classification. Cross-sectional study design. Fifty-four recreationally-active women who were either long-term oral contraceptive users (n=28) or experiencing regular natural menstrual cycles (n=26) completed step-wise menstrual mapping, urinary ovulation prediction testing and venous blood sampling for serum/plasma hormone analysis on two days, 6-12days after positive ovulation prediction to verify ovarian hormone concentrations. Mid-luteal phase was successfully verified in 100% of oral contraceptive users, and 70% of naturally-menstruating women. Thirty percent of participants were classified as luteal phase deficient; when excluded, the success of the method was 89%. Lower age, body fat and longer menstrual cycles were significantly associated with luteal phase deficiency. A step-wise method including menstrual cycle mapping, urinary ovulation prediction and serum/plasma hormone measurement was effective at verifying ovarian hormone status. Additional consideration of age, body fat and cycle length enhanced identification of luteal phase deficiency in physically-active women. These findings enable the development of stricter exclusion criteria for female participants in research studies and minimise the influence of ovarian hormone variations within sports and exercise science and medicine research.

Risk of cancer with combined oral contraceptive use among Iranian women.

Oral contraceptive use is the most common type of contraception. More than 300 million women worldwide take oral contraceptives every day. However, there is a concern about the relationship with the incidence of cancer. This analytical retrospective study aimed to investigate the relationship between the incidence of cervical and breast cancers and oral contraceptive use in 128 Iranian patients with cervical cancer, 235 with breast cancer and equal numbers of controls. Data were collected through interviews with an organized set of questions. Details were also extracted from patient files. Data were analyzed using Student's t-test, chi-square and Fisher's exact tests, and Pearson's correlation analysis. The result revealed correlations between both cervical and breast cancers and history of contraceptive pills use. While cervical cancer significantly correlated with duration of use of pills, breast cancer had significant correlations with the type of oral contraceptive and age at first use. No significant relationships were found between the two types of cancer and age at discontinuation of oral contraceptives, patterns of use, and intervals from the last use. The use of oral contraceptives may triple the incidence of cervical cancer and doubles the incidence of breast cancer. Therefore, performing Pap smears every six months and breast cancer screening are warranted for long-term oral contraceptive users.

Impact of oral contraceptive use and menstrual phases on patellar tendon morphology, biochemical composition, and biomechanical properties in female athletes

Sex differences exist with regards to ligament and tendon injuries. Lower collagen synthesis has been observed in exercising women vs. men, and in users of oral contraceptives (OC) vs. nonusers, but it is unknown if OC will influence tendon biomechanics of women undergoing regular training. Thirty female athletes (handball players, 18-30 yr) were recruited: 15 long-term users of OC (7.0 ± 0.6 yr) and 15 nonusers (>5 yr). Synchronized values of patellar tendon elongation (obtained by ultrasonography) and tendon force were sampled during ramped isometric knee extensor maximum voluntary contraction to estimate mechanical tendon properties. Furthermore, tendon cross-sectional area and length were measured from MRI images, and tendon biopsies were obtained for analysis of tendon fibril characteristics and collagen cross-linking. Overall, no difference in tendon biomechanical properties, tendon fibril characteristics, or collagen cross-linking was observed between the OC users and nonusers, or between the different phases of the menstrual cycle. In athletes, tendon cross-sectional area in the preferred jumping leg tended to be larger than that in the contralateral leg (P = 0.09), and a greater absolute (P = 0.01) and normalized tendon stiffness (P = 0.02), as well as a lower strain (P = 0.04), were observed in the jumping leg compared with the contralateral leg. The results indicate that long-term OC use or menstrual phases does not influence structure or mechanical properties of the patellar tendon in female team handball athletes.

Pre-gravid oral contraceptive use and time to pregnancy: a Danish prospective cohort study

Is there an association between oral contraceptive (OC) use (age at the start of use, duration of use, ethinylestradiol dose and generation) and time to pregnancy (TTP)? Although OC use was associated with a transient delay in the return of fertility, we found no evidence that long-term OC use deleteriously affects fecundability. Studies using retrospective data on TTP have reported a short-term delay in the return of fertility after OC use. However, little is known about the long-term OC use and TTP. Data were derived from 'Snart Gravid.dk', a prospective cohort study that enrolled participants from 1 June 2007 to 31 May 2010. The final study population consisted of 3727 women. Eligible women were Danish pregnancy planners, aged 18-40 years, who completed a baseline questionnaire and bimonthly follow-up questionnaires until conception or for 12 months, whichever came first. Cohort retention was 80%. We used proportional probability regression models to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), with adjustment for potential confounders. Compared with barrier methods, the use of OCs as the last contraception method before attempting to conceive was associated with a short-term delay in return of fertility (FR = 0.87, 95% CI: 0.79-0.96). Longer term OC use was associated with higher fecundability: compared with OC use for less than 2 years; FRs were 0.98 (95% CI: 0.83-1.15) for 2-3 years, 1.16 (95% CI: 0.98-1.37) for 4-5 years, 1.10 (95% CI: 0.93-1.29) for 6-7 years, 1.17 (95% CI: 0.99-1.38) for 8-9 years, 1.23 (95% CI: 1.04-1.46) for 10-11 years and 1.28 (95% CI: 1.07-1.53) for ≥12 years of OC use. Because this was a non-experimental study, where study volunteers provided information about their history of contraceptive use at baseline and were followed prospectively to assess their waiting times to pregnancy, there was some potential for error in the reporting of OC use and TTP. Nevertheless, participants reported data on OC use before the occurrence of pregnancy, thereby reducing the potential for systematic bias. Women who have used OCs for many years should be reassured as there was no evidence that long-term OC use has a deleterious affects on fecundability. Both short- and long-term OC users are likely to experience a transient delay in conception compared with those discontinuing barrier methods. This study was supported by the National Institute of Child Health and Human Development (R21050264) and the Danish Medical Research Council (271-07-0338). The authors declare that there are no conflicts of interest.

Risk factors for inflammatory bowel disease in the general population

The aetiology of inflammatory bowel disease remains largely unknown. We performed a comprehensive assessment of potential risk factors associated with the occurrence of inflammatory bowel disease. We identified a cohort of patients 20-84 years old between 1995 and 1997 registered in the General Practitioner Research Database in the UK. A total of 444 incident cases of IBD were ascertained and validated with the general practitioner. We performed a nested case-control analysis using all cases and a random sample of 10 000 frequency-matched controls. Incidence rates for ulcerative colitis, Crohn's disease, and indeterminate colitis were 11, 8, and 2 cases per 100 000 person-years, respectively. Among women, we found that long-term users of oral contraceptives were at increased risk of developing UC (OR: 2.35; 95% CI: 0.89-6.22) and CD (OR: 3.15; 95% CI: 1.24-7.99). Similarly, long-term users of HRT had an increased risk of CD (OR: 2.60; 95% CI: 1.04-6.49) but not UC. Current smokers experienced a reduced risk of UC along with an increased risk of CD. Prior appendectomy was associated with a decreased the risk of UC (OR: 0.37; 95% CI: 0.14-1.00). Our results support the hypothesis of an increased risk of inflammatory bowel disease associated with oral contraceptives use and suggest a similar effect of hormone replacement therapy on CD. We also confirmed the effects of smoking and appendectomy on inflammatory bowel disease.

Effects of oral contraceptives on total serum proteins, albumin, globulins and cholesterol levels in Ibadan, Nigeria.

Total serum protein, albumin, globulin, albumin/globulin ratio and cholesterol levels were determined in 25 subjects on oral contraceptives and 25 controls. The mean serum total protein, globulin and cholesterol levels were significantly increased in oral contraceptive and their control counterparts. The albumin/globulin ratio in subjects on oral contraceptives users is significantly decreased compared with controls. In view of the findings of this study, it is suggested that the biochemical profile of long-term oral contraceptive users be assessed periodically.

Effect of oral contraceptives on risk of cervical cancer in women with human papillomavirus infection: the IARC multicentric case-control study

Use of oral contraceptives could increase risk of cervical cancer; however the effect of human papillomavirus (HPV), the main cause of cervical cancer, is not usually taken into account. We aimed to assess how use of oral contraceptives affected risk of cervical cancer in women who tested positive for HPV DNA. We pooled data from eight case-control studies of patients with histologically confirmed invasive cervical carcinoma (ICC) and from two studies of patients with carcinoma in situ (ISC). Information about use of oral contraceptives was obtained from personal interviews. Effects were estimated as odds ratios, with logistic-regression models adjusted for possible confounders. 1465 of 1561 (94%) patients with ICC, 211 of 292 (72%) with ISC, and 255 of 1916 (13%) controls were positive for HPV DNA. Compared with never-users, patients who had used oral contraceptives for fewer than 5 years did not have increased risk of cervical cancer (odds ratio 0.73; 95% CI 0.52-1.03). The odds ratio for use of oral contraceptives was 2.82 (95% CI 1.46-5.42) for 5-9 years, and 4.03 (2.09-8.02) for use for 10 years or longer, and these risks did not vary by time since first or last use. Long-term use of oral contraceptives could be a cofactor that increases risk of cervical carcinoma by up to four-fold in women who are positive for cervical HPV DNA. In the absence of worldwide information about HPV status, extra effort should be made to include long-term users of oral contraceptives in cervical screening programmes.

Oral contraceptives and cervical cancer--further findings from the Oxford Family Planning Association contraceptive study.

In 1983, we reported results from the Oxford Family Planning Association contraceptive study regarding the association between oral contraceptives (OCs) and cervical neoplasia, after a 10 year follow-up of a cohort of 17,000 women. Further findings from this study are reported here after an additional 12 years of follow-up. A nested case--control design was used in which cases were all women diagnosed under 45 years of age with invasive carcinoma (n = 33), carcinoma in situ (n = 121) or dysplasia (n = 159). Controls were randomly selected from among cohort members and matched to cases on exact year of birth and clinic attended at recruitment to study. Conditional logistic regression analysis was used to determine odds ratios (ORs) and 95% confidence intervals (CIs) associated with various aspects of OC use relative to never users adjusted for social class, smoking, age at first birth and ever use of diaphragm or condom. Ever users of OCs had a slightly elevated OR for all types of cervical neoplasia combined (OR = 1.40, 95% CI 1.00-1.96). Odds ratios were highest for invasive carcinoma (OR = 4.44, 95% CI 1.04-31.6), intermediate for carcinoma in situ (OR = 1.73, 95% CI 1.00-3.00) and lowest for dysplasia (OR = 1.07, 95% CI 0.69-1.66). The elevated risk associated with OC use appeared to be largely confined to current or recent (last use in the past 2 years) long-term users of OCs. Among current or recent users, ORs for all types of cervical neoplasia combined were 3.34 (95% CI 1.96-5.67) for 49-72 months of use, 1.69 (95% CI 0.97-2.95) for 73-96 months and 2.04 (95% CI 1.34-3.11) for 97 or more months. These results suggest a possible effect of OC use on later stages of cervical carcinogenesis, although residual confounding due to sexual factors or human papillomavirus (HPV) infection cannot be ruled out.

Reproductive factors and the risk of renal cell cancer among women.

In etiologic studies of renal cell carcinoma the role of reproductive variables and the use of exogenous hormones have not been well examined. In a population-based case-control study including 165 female cases and 227 controls, we assessed the risk of renal cell cancer associated with reproductive factors and use of oral contraceptives and menopausal hormones. Odds ratios were computed using logistic regression analyses. Risk was positively associated with number of births and inversely associated with age at first birth, with the largest increases in risk (more than 2-fold) among women with 5 or more births after age 25. After adjustment for age, smoking status, body mass index and age at first birth, women with 5 or more births had a 2-fold risk (OR = 2.2, 95% CI = 1.2-4.0) relative to those with 1 or 2 births. Age at first birth, however, was no longer a risk factor when the number of births was adjusted for. The association with parity was considerably stronger among women with a history of hypertension or above-median body mass index than among those without these conditions. In addition, risk was reduced among long-term oral contraceptive users but elevated among women who had had a hysterectomy or used menopausal hormones. Our findings suggest that reproductive factors, particularly the number of births, may play an etiologic role in renal cell cancer among women and deserve further study.

The response of the pituitary-ovarian axis to pulsatile administration of gonadotropin-releasing hormone in long-term oral contraceptive users

OBJECTIVE: Our purpose was to differentiate between pituitary and hypothalamic feedback effects of oral contraceptives. STUDY DESIGN: Twenty micrograms of gonadotropin-releasing hormone was administered intravenously at 90-minute intervals for 4 days to 14 long-term users of a combined oral contraceptive (30 μg of ethinyl estradiol and 150 μg of levonorgestrel), starting at different moments in the pill cycle. On the fourth day of administration the pulsatile release of luteinizing hormone was determined by blood sampling every 10 minutes for 6 hours. The sensitivity of the pituitary was determined before, during, and after treatment with gonadotropin-releasing hormone by a 100 μg gonadotropin-releasing hormone challenge test. On each sampling day serum estradiol, progesterone, and prolactin levels were measured, and ovarian ultrasonography was performed. RESULTS: After 4 days of pulsatile gonadotropin-releasing hormone administration every exogenous gonadotropin-releasing hormone bolus was followed by an endogenous luteinizing hormone pulse of high amplitude (median 3.30 U/L). Both serum luteinizing hormone and follicle-stimulating hormone levels increased significantly (p < 0.001). The increase in follicle-stimulating hormone levels was accompanied by an increase in serum estradiol (p < 0.01). The luteinizing hormone response to a 100 mg bolus of gonadotropin-releasing hormone decreased during gonadotropin-releasing hormone treatment (p < 0.01), whereas the follicle-stimulating hormone response did not change. CONCLUSION: Pituitary sensitivity is not impaired during oral contraceptive use, suggesting that oral contraceptives exert their negative feedback effects predominantly at the hypothalamic level. (AM J OBSTET GYNECOL 1994;170:462-8.)

Beeinflußt die vorangegangene Einnahme oraler Kontrazeptiva das Überleben beim Mammakarzinom?*

The influence of a positive history of oral contraceptive (OC) use on survival of breast cancer was studied in 471 patients. 297 (63%) of them were ever users of OCs and 202 (43%) were long-term users (> or = 49 months). The median follow-up amounted to 56 (6-96) months. Except for a significantly higher frequency of poorly differentiated tumours in OC users (p = 0.01) there was no difference in the distribution of histopathological features between OC users and non-users. Nevertheless, compared to non-users OC user showed a significantly increased 5-year-survival (p = 0.017). This effect was strongly correlated with duration of use (p = 0.004) and time since last use (p = 0.02). The influence of OC use achieved significance after a duration of use of four or more years or in case of OC use at the time of diagnosis. The positive effect persisted in multivariate analyses and was mainly attributed to long-term OC users with tumours of a generally expected poor prognosis.

The response of the pituitary-ovarian axis to pulsatile administration of gonadotropin-releasing hormone in long-term oral contraceptive users

OBJECTIVE: Our purpose was to differentiate between pituitary and hypothalamic feedback effects of oral contraceptives. STUDY DESIGN: Twenty micrograms of gonadotropin-releasing hormone was administered intravenously at 90-minute intervals for 4 days to 14 long-term users of a combined oral contraceptive (30 μg of ethinyl estradiol and 150 μg of levonorgestrel), starting at different moments in the pill cycle. On the fourth day of administration the pulsatile release of luteinizing hormone was determined by blood sampling every 10 minutes for 6 hours. The sensitivity of the pituitary was determined before, during, and after treatment with gonadotropin-releasing hormone by a 100 μg gonadotropin-releasing hormone challenge test. On each sampling day serum estradiol, progesterone, and prolactin levels were measured, and ovarian ultrasonography was performed. RESULTS: After 4 days of pulsatile gonadotropin-releasing hormone administration every exogenous gonadotropin-releasing hormone bolus was followed by an endogenous luteinizing hormone pulse of high amplitude (median 3.30 U/L). Both serum luteinizing hormone and follicle-stimulating hormone levels increased significantly (p < 0.001). The increase in follicle-stimulating hormone levels was accompanied by an increase in serum estradiol (p < 0.01). The luteinizing hormone response to a 100 mg bolus of gonadotropin-releasing hormone decreased during gonadotropin-releasing hormone treatment (p < 0.01), whereas the follicle-stimulating hormone response did not change. CONCLUSION: Pituitary sensitivity is not impaired during oral contraceptive use, suggesting that oral contraceptives exert their negative feedback effects predominantly at the hypothalamic level. (AM J OBSTET GYNECOL 1994;170:462-8.)

Pulsatile luteinizing hormone patterns in long term oral contraceptive users.

Oral contraceptives (OC) inhibit folliculogenesis by a central suppressive action on the release of gonadotropins. To characterize the nature of these central effects, we studied 40 long term OC users on 3 different OCs: two monophasic preparations with 30 micrograms ethinyl estradiol and 150 micrograms l-norgestrel (group 1; n = 15), 150 micrograms desogestrel (group 2; n = 10), and a triphasic formulation containing 30-40 micrograms ethinyl estradiol and 50, 75, and 125 micrograms l-norgestrel (group 3; n = 15). Blood sampling at 10-min intervals during 6-h periods was performed at different moments in the pill cycle. Thirteen healthy volunteers with regular ovulatory cycles served as normal controls. FSH and LH were measured by a sensitive immunoradiometric assay. Pulsatile LH release was observed in all OC users. Mean serum LH and FSH levels, number of LH pulses per 6 h, and the amplitude of LH pulses on day 1 of the pill cycle did not differ from early follicular phase control values. FSH levels were rapidly suppressed from day 2 onward in all three groups, whereas LH levels progressively declined in groups 1 and 2 from day 8 onward. In group 3, however, LH levels were only significantly suppressed after day 13. The number of LH pulses per 6 h decreased in all groups starting on day 2, whereas the amplitude of LH pulses increased. A substantial percentage of LH pulses observed in OC users after day 1 were of low amplitude (< 0.75 IU/L). From these results, we conclude that 1) pulsatile release of LH is maintained during OC use; 2) FSH levels are suppressed equally early and equally effective by all OCs studied; 3) during OC use, the number of LH pulses per 6 h is reduced; 4) modulation of LH pulse amplitudes, and subsequently of serum LH levels, is mainly mediated by a dose- and time-dependent effect of the gestagenic component of the OC; and 5) after the 7-day pill-free interval, a normal early follicular phase pulse pattern is found, even in long term OC users, suggesting that in this period, most of the steroidogenic feedback effects wear off.

Do oral contraceptive agents affect the risk of breast cancer? A meta-analysis of the case-control reports.

We designed a study to assess the association of oral contraceptive use and the development of breast cancer for women in the following groups: (1) ever oral contraceptive users, (2) long-term oral contraceptive users, and (3) oral contraceptive users before a first full-term pregnancy. A MEDLINE search of studies published in English from 1966 to 1990 was conducted using the following key words: "oral contraceptive and breast carcinoma." Eligible studies included all published case-control reports of nonduplicated data on a population (hospital or community-based). The following data were extracted from each report: country, age of subjects, number of cases and controls, whether it was a hospital or community-based study, and results. Two evaluators using a quality-assessment instrument independently and blindly reviewed the methods and data analysis section from each eligible study. In the category of "ever oral contraceptive users," an estimate of the pooled relative risk with 95 percent confidence intervals (CIs) was calculated. In the categories of "duration of oral contraceptive use" and "duration of oral contraceptive use before a first full-term pregnancy," Spearman's rank correlation coefficient (rs) was calculated. For the categories of "ever oral contraceptive users" and "long-term oral contraceptive users," no association between the use of oral contraceptives and the development of breast cancer could be detected (pooled relative risk "ever oral contraceptive users" = 1.07, 95 percent CI 0.78 to 1.36, rs "duration of use" -0.153, P = 0.189). For the category of "oral contraceptive use before a first full-term pregnancy," a significant correlation was found (rs = +0.497, P = 0.011). Many reports failed to demonstrate adequate protection against the biases most relevant to case-control methods (namely, recall bias, interviewer bias, surveillance bias, and nonresponse bias) and therefore received low-quality scores. This meta-analysis suggests a possible increased risk for breast cancer in women who use oral contraceptives before a first full-term pregnancy. The data, however, are confounded by studies that are generally of low quality. Further studies addressing the risk for breast cancer in oral contraceptive users need to be designed with methods that limit the biases inherent in case-control studies.

Oral contraceptives and breast cancer: Review of the epidemiologic literature

Oral contraceptives have caused little or no overall increase in risk of breast cancer in women in developed countries, even in long-term users or after more than two decades since initial exposure. Limited evidence suggests a possible small increase in risk in users of oral contraceptives in developing countries, and further studies of breast cancer and oral contraceptives in low risk populations are warranted. Oral contraceptives may enhance risk of breast cancer in young women with a history of benign breast disease, and this possibility should also be investigated further. Multiple investigations have fairly consistently shown risk of breast cancer in women under age 45 years to be increased slightly in long-term users of oral contraceptives. Further studies should be conducted to elucidate the mechanism of this apparent phenomenon.

Endocervical neoplasia in long-term users of oral contraceptives: Clinical and pathologic observations : Valente PT; Hanjani P Department of Pathology, Temple University Health Sciences Center, Philadelphia, PA 19140, USA Obstet. Gynecol.; 67/5 (695–704) 1986

Endocervical neoplasia in long-term users of oral contraceptives: Clinical and pathologic observations : Valente PT; Hanjani P Department of Pathology, Temple University Health Sciences Center, Philadelphia, PA 19140, USA Obstet. Gynecol.; 67/5 (695–704) 1986