On Oral Contraceptives Research Articles

Effect of hysteroscopy performed in the cycle preceding controlled ovarian hyperstimulation on the outcome of in vitro fertilization

Effect of hysteroscopy performed in the cycle preceding controlled ovarian hyperstimulation on the outcome of in vitro fertilization

Side effects and oral contraceptive discontinuation in rural Bangladesh

Using data from a survey on oral contraceptive (OC) compliance in rural Bangladesh, this study examines the role of side effects on OC discontinuation along with other potential predictors. A total of 1403 currently married women aged 15–49 years were interviewed; of these 43% discontinued OCs. Of the women who discontinued, 53% did so because of side effects, which was the main self-reported reason for OC discontinuation. Multivariate analysis revealed that after adjusting for duration of OC use, women who experienced side effects were 1.4 times more likely to discontinue OC use than their counterparts without such experience. Discontinued OC use was also associated with being Muslim, not being visited by field-workers, OC use as first method of contraception, lack of husband’s support, and was inversely associated with duration of OC use. Adequate counseling about OC use, emphasizing the possibility of side effects, and better management of them, coupled with improved client-provider interaction and husband’s supportive role could help in reducing OC discontinuation in rural Bangladesh.

Oral Contraceptives and Cancer

Most up-to-date information on oral contraceptives (OCs) and breast cancer risk comes from a collaborative re-analysis of individual data on 53297 cases and 100239 controls. It is now established that there is a moderately increased breast cancer risk among current OC users, which tends to level off in the few years after stopping use. With regard to cervical cancer, OC use has been found to be associated with increased risk in human papilloma virus-positive women. With reference to the well known protective effects of OCs against endometrial carcinogenesis, additional information has suggested a consistent protection across types of OCs used. Further data on ovarian cancer confirm that the protection of OCs is long lasting, and may well be observed 15 to 20 years after stopping use. Several studies have suggested an inverse relationship between use of OCs and risk of colorectal cancer, and in a meta-analysis of published data the pooled relative risk of colorectal cancer for DC ever-use was 0.82 (95% confidence interval 0.74 to 0.97). There was no association with duration of use. The increased risk for hepatocellular carcinoma in the absence of hepatitis B viruses is the only established evidence of a direct association between OC use and cancer risk, which led an International Agency for Research on Cancer Working Group to classify OCs as carcinogenic to humans in 1998.

Oral Contraceptives Can Cause Falsely Low Vitamin B12 Levels

Serum vitamin B₁₂ 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 B₁₂ levels, as reflected by normal urine methylmalonic acid and plasma homocysteine. After 1-month cessation of OCs, vitamin B₁₂ 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 B₁₂ blood levels of no clinical significance that can be associated with low TCI levels

International Headache Society (IHS) Task Force on oral contraceptives (OCs) and hormone replacement therapy (HRT) used in migraine sufferers.

International Headache Society (IHS) Task Force on oral contraceptives (OCs) and hormone replacement therapy (HRT) used in migraine sufferers.

Oral contraceptives and thrombosis, From risk estimates to health impact

The scientific debate on oral contraceptives (OCs) and thrombotic diseases continues unabated. The aim of this survey was to evaluate available scientific data on OCs and thrombotic diseases and to make tentative prescription recommendations of OCs to women with and without various thrombotic risk factors. In women 15-29 years old, venous thromboembolism is about twice as common as arterial complications. In women between 30 and 44 years, the number of arterial complications exceeds venous diseases by about 50%. The mortality from arterial diseases is 3.5 times higher than the number of deaths from venous diseases in women below 30 years, and 8.5 times higher in women 30-44 years old. A significant disability is more frequent in women suffering and surviving an arterial complication than in women with venous thromboembolism. Although many important scientific issues still have to be addressed, the available scientific data suggests a differential influence of OCs with second and third generation progestagens on the risk of venous and arterial diseases. OCs with second generation progestagens seem to confer a smaller increase in the risk of venous diseases and a higher increase in risk of arterial complications, compared with OCs containing third generation progestagens. The possible difference on the venous side seems to be smaller than primarily anticipated. Young women without any known risk factor for thrombotic diseases may use any low-dose OC. If OCs are prescribed to women with known risk factors for arterial thrombotic disease; e.g. smoking, diabetes, controlled hypertension, migraine without aura, family disposition of acute myocardial infarction (AMI) or thrombotic stroke, a low-dose pill with a third generation progestagen may have an advantage. If OCs are considered for women with risk factors for venous disease such as severe obesity, varicose veins, family history of VTE or with factor V Leiden mutation, a low-dose combined pill with a second generation progestagen may be preferable. In women above 30 years, OCs with third generation progestagens generally seem to confer less overall thrombotic morbidity, mortality and disability than OCs with second generation progestagens. These women should reconsider, however, the indication of combined OCs in the presence of significant risk factors of thrombotic diseases.

EFFECTS OF THE MENSTRUAL CYCLE ON SERUM CORTISOL DURING MODERATE AND HIGH INTENSITY EXERCISE 1147

Twelve males, seven females on oral contraceptives (OC), and five hormonal contraceptive free females (NO-OC) cycled at both moderate (MOD, 60% VO2 peak) and high (HI, 80% VO2 peak) intensities. In MOD subjects rode for three 30 min bouts (25 min cycle, 5 min rest) and for one bout in HI. Males completed each test once while females completed each test twice, once during the follicular phase (FOL, 2-6 days post menses) and once during the luteal phase (LUT, 22-26 days post menses). Serial blood samples were collected and analyzed for serum cortisol levels (CORT) at rest, during exercise, and in recovery. Gender had no effect on CORT response to exercise in either MOD or HI. OC users had higher CORT at all time points in comparison to NO-OC in both MOD (p=0.016) and HI (p=0.002). At rest OC users had 50% higher CORT compared to NO-OC. Menstrual phase had no effect on CORT in NO-OC. However in OC, LUT CORT was consistently higher compared to FOL. This effect was more obvious in HI. Although these data are based on a small population, they suggest that OC use could have a significant effect on performance, especially during endurance exercise where metabolic regulation is more important. Further studies on the influence of OC use on metabolic responses during exercise are warranted.

Responsibility of health providers and the media in response to scientific information

During the last 2 years, there have been a number of reports on oral contraceptives (OCs) and their effects on breast cancer1 and vascular events2. The pill scare that followed the controversy of the third-generation combined OCs has produced immeasurable amounts of medical publications and public mass media coverage, all showing great disparity on the aspects that they have emphasized. It would seem that personal points of view, whether or not they are associated with other interests, and not directly related to the nature of the scientific information, could lead to opposed interpretations of the same facts and would lead the reader to perceive a different message. The consequences of over-reporting the adverse effects of oral contraceptives on the general population, such as pill discontinuation and a rise in abortion rates, deserve special consideration in regard to the responsibility of health professionals and the mass media in the diffusion of scientific information. The aim of this paper is to analyze the repercussions of the diffusion of scientific information about oral contraceptives on the general public and the responsibility of health professionals and the mass media, and to propose some considerations to be taken into account when giving scientific information on oral contraceptives.

Oral Contraceptives and Cancer

The following review considers epidemiological data published from 1990 onwards on oral contraceptives (OCs) and the risk of cancers of the breast, cervix uteri, endometrium, ovary, liver and skin. In several studies, breast cancer risk was seen to be elevated among women who were current users of an OC, or had recently stopped using an OC, whereas there was no residual risk 5 or more years after stopping OC use. No interaction was observed between type of OC, or with any recognised risk factor for breast cancer, or time-factor, except for some potential excess risk for women who started OC use at a young age. Most studies have confirmed that OCs moderately increase the risk of cervical cancer, particularly in human papilloma virus (HPV)-positive women, thus suggesting that OCs may act as a promoter for HPV-induced carcinogenesis. Recent epidemiological studies have confirmed that combined OCs provide substantial protection against endometrial and ovarian cancers, and results suggest that such protection is long-lasting, and may persist for 15 years or more after stopping OC use. Most case-control studies have shown a relationship between OC use and hepatocellular carcinoma. However, data from cohort studies or analysis of vital statistics indicate that the public health impact of such an association is modest, if not negligible. No association was observed between combined OC use and the incidence of skin melanoma, or any other common skin neoplasm. In terms of clinical and public health implications, the most relevant points regarding OC use are: (i) recent data confirm that OCs confer presistent protection against ovarian cancer; and (ii) any increased risk of breast cancer in OC users is moderate and is restricted to current/recent users. This is reassuring for younger women, whose baseline risk of this disease is extremely low.

Factors related to choosing oral contraception at age 15.

This report aims to identify factors which are related to use of oral contraceptives at an early age. A self-administered questionnaire was completed at schools in 1988 and 1992 in southern and western Finland (N = 1339). Sexually experienced girls (mean age 15.8 years) who had answered the question concerning their oral contraceptive use were included (N = 389). Logistic regression analysis was used to compare oral contraceptive users (N = 121) with the group of non-users. Total number of coital experiences was associated with oral contraceptive use: the odds ratio for those having at least 10 coital experiences was 6.30 compared with those with only one intercourse. The proportion was 73% among oral contraceptive users and 30% among non-users. Girls using oral contraceptives perceived more often (67%) that parents accept their sexual relationship (30% among non-users). Oral contraceptive users were less afraid of getting pregnant (9% compared with 31% among non-users) and felt more often that sex was very important in their life (31 and 13%, respectively). Other factors that entered the model were age at menarche, having a steady partner and frequency of disco visits. When a young girl asks for oral contraceptives, she is probably at true risk of pregnancy, and regular contraception should be considered both in view of effective prevention of pregnancies and sexually transmitted diseases.

Contraception:Oral contraceptives and breast cancer

Recent studies on oral contraceptives (OCs) suggest that the present rules for prescribing them are acceptable and that the benefits of OC use far outweigh the risks. Researchers seem to agree that women who use OCs before a first full-term pregnancy may have a slightly increased risk of breast cancer, but there is a more general view that it is impossible to establish an OC-breast cancer link and that OCs may even provide a beneficial effect for older women. Good clinical judgement should prevail when weighing risks versus benefits. There may even be benefits of OC and hormone replacement therapy in patients who have had breast and other gynecological cancers. Good medical practice calls for prevention of all diseases and maintenance of health, which is a state of physical, mental, and social well-being. It may, on the other hand, be beneficial to attempt to reduce longterm exposure to estrogens, but some of the benefits of OCs may be lost this way. Hopefully, in the near future, molecular genetics will identify the breast cancer gene, and women will be screened for risks of such longterm therapies.

Comparison of Recalled and Validated Oral Contraceptive Histories

From a case-control study of the relation between oral contraceptives and breast cancer carried out in East Germany during 1982-1986, the authors obtained information on oral contraceptive use through interviews of study subjects and from the records of prescribing gynecologists. The degree of agreement regarding information from these two sources was assessed for 234 breast cancer cases and 524 controls who had ever used oral contraceptives. Agreement between information obtained from medical records and that from interviews on total duration of use, number of episodes of use, and time since first and last use was reasonably good, and levels of agreement did not differ appreciably between cases and controls. Lower levels of agreement were observed for individual brand names and the duration of use of specific brands. Attempts should be made to obtain information on specific brands from medical records when investigating the effects of individual preparations.

Trends in oral contraceptive use in a Southern German population

In the surveys of the MONICA project Augsburg, conducted in 1984/85 (S1) and 1989/90 (S2), data on oral contraceptive (OC) use were gathered in two independent representative population-based samples of women aged 25–44 years (medication history over the previous seven days). OCs were categorized according to their oestrogen content (< 50mg, ≥50mg) and according to their progestogen component. The prevalence of OC use was unchanged between the two points in time (23.4% in S1 and 23.7% in S2). OCs with low oestrogen content were used in 49.0% of the OC users in S1 and in 76.6% in S2. The use of the progestogen component changed also: norethindrone (acetate), levonorgestrel, and lynestrenol were used less, desogestrel more often in S2. Gestoden and norgestimate were used by 15% of the OC users in S2. In conclusion, we can say that there was no change in the prevalence of OC use in the study population; however, a change in hormone content towards preparations with lower hormone content was observed.

Postscript: starting oral contraceptives (25 May, page 41)

In our article on oral contraceptives (OCs) we state that ‘oral contraceptives increase the risk of breast cancer with long-term use but reduce the risk of endometrial and ovarian cancer’. Some commentators have questioned the breast cancer risk. The UK National Case-Control (UKNCC) study, which looked at oral contraceptive use in women with breast cancer diagnosed before age 36, found a trend for increased risk associated with duration of use.1 ‘The simplest and most plausible explanation’, say the authors of the study, ‘must be that there is a substantial causal relation between prolonged use and breast cancer in young women.’ The increased risk seems to be associated particularly with OC use before the first full-term pregnancy.2 Several studies found no excess risk in OC users aged 45 or over, few of whom had taken the pill before their first pregnancy.3–5 In the UKNCC study the relative risk of breast cancer was 1.43 after 4–8 years’ use and 1.74 after more than 8 years’ use. In broad terms this means that three women in 1000 who use oral contraceptives for 4 or more years might be expected to be under treatment for breast cancer by age 36, compared with two per 1000 non-users.

Noninvasive diagnosis of resistant ovary syndrome by ultrasonography

To compare transvaginal ultrasonographic features of the ovaries and endometrium of patients with premature ovarian failure to normally cycling women on oral contraceptives (OCs), menopausal women with an equivalent duration of amenorrhea to the premature ovarian failure group, and patients with Turner's syndrome. Transvaginal ultrasonography in groups of women with premature ovarian failure, OC, and menopause. All subjects were studied in an academic tertiary care center. Seventeen women with premature ovarian failure, 20 volunteers on OC, 20 with menopause, and 4 patients with Turner's syndrome were studied. None, except for OCs in the OC group only. Frequency of ovarian, ovarian follicle, and endometrial visualization and their respective measurement in the three groups. At least one ovary was visualized in 84% of the premature ovarian failure patients as compared with 95% of the OC and menopause groups and 25% of the Turner patients. Mean ovarian volume was smaller in the premature ovarian failure group as compared with the OC group but equal to that of the menopause group. In the premature ovarian failure group, 41% had follicles in their ovaries as compared with 95% in the OC group, 5% in the menopause group, and none in the Turner group. The number of follicles per ovary was significantly lower in the premature ovarian failure as compared with the OC group, whereas only one subject had a single follicle in the menopause group. Premature ovarian failure subjects with follicles had larger ovaries than those without follicles. Endometrial thickness was not different among the groups. Ultrasonography may serve to identify a substantial subset (approximately 40%) of premature ovarian failure patients with ovarian follicles and potential for fertility consistent with the diagnosis of resistant ovary syndrome.

Sex steroid hormones and breast cancer: is there a link with oral contraceptives and hormone replacement therapy?

To determine whether use of sex steroid hormones for contraception and hormone replacement therapy alters the risk of breast cancer, and whether the risk varies with their composition, duration of use, the period of a woman's life when the hormones are used, and after successful treatment for breast cancer. The results of important epidemiological reports, readily available from the English literature and published since 1981, were evaluated, using reports of basic scientific work as a background to the problem. An attempt was made to obtain most of the relevant reports. Twenty case-control and seven cohort studies were available on the oral contraceptive pill (OCP) and eleven case-control and five cohort studies on hormone replacement therapy (HRT). The relative risk estimates for breast cancer (and their 95% confidence intervals) determined by each report were tabulated according to the specific conditions of analysis, for example users under age 25, duration of use. Results by meta-analysis from previous studies were also used to determine risk. A significant positive association was present when the risk estimate exceeded 1.0 and the 95% confidence interval did not cross 1.0. Among OCP users, the vast majority of reports showed no significant risk of breast cancer--overall, longest duration of use, and use before first full-term pregnancy. However, a positive association between breast cancer and users under age 25 was found in three of eight reports. Similarly, the majority of reports showed no significant risk of breast cancer among HRT users, overall as well as in relation to duration of use and interval since first use. There was no increased risk with additional progestogen; it may be protective. An improved prognosis was found in users who developed breast cancer. On the limited data, use of hormones for postmenopausal symptoms did not appear to be harmful to women who had been successfully treated for breast cancer. The review revealed good evidence that use of sex steroid hormones had no significant effect on the risk of breast cancer, whether given for contraception or hormone replacement. There was some concern about increased risk with prolonged use of the OCP, especially in younger women. At present, use of these hormones is a matter of informed choice, with individual considerations of the risk-benefit ratio.

MALIGNANT HYPERTENSION AND ANTIPHOSPHOLIPID ANTIBODIES AS PRESENTING FEATURES OF SLE IN A YOUNG WOMAN USING ORAL CONTRACEPTIVES

A 24-year-old woman developed malignant hypertension while on oral contraceptives (OCs). She was found to have incomplete systemic lupus erythematosus (SLE) with DNA antibodies and high levels of antiphospholipid antibodies (APLA). She later developed SLE and has had three miscarriages and a cerebellar infarction.

Lipid and lipoprotein changes during the seven days off oral contraception in women using two triphasic preparations

This study was designed to determine whether mean values for lipids and lipoproteins changed during the 21 days on oral contraceptive (OC) preparations and during the seven days off the pills. The design allowed for comparison of the effects of Triphasil ∗ and Ortho 777 ∗ and for examining the consistency over two pill cycles. The mean values for total cholesterol, HDL-cholesterol, LDL-cholesterol and HDL3-subfraction were consistently lower on Day 20 when compared to Day 2 ( p < 0.05) for the two cycles and higher on Day 2 of Cycle II when compared to Day 20 of Cycle I. This fall-rise-fall pattern was consistent for cholesterol in 17 out of 28 of the women studied and these women were heavier ( p < 0.05), had a greater mean Quetelet Index ( p < 0.05) and had been using OCs for a shorter mean period of time ( p < 0.05). Consistently higher apolipoprotein A1 mean values were found on Day 20 of both cycles for Triphasil ∗ users compared to Ortho 777 ∗ users ( p < 0.02). This paper discusses the importance of these findings in relation to study design when measuring for differences between OC preparations and changes over time.

Oral contraceptives and venous thromboembolism: findings in a large prospective study.

This article reports recent data from the Oxford-Family Planning Association study on oral contraceptives (OCs) and venous thromboembolism. 105 of the over 17000 women in the study suffered a 1st attack of venous thromboembolism uanassociated with pregnancy or the puerperium during the study period. This group was subdivided into 34 women who developed disease within 3 months after a surgical procedure and 71 women suffering thromboembolism unassociated with surgery. The incidence of postoperative thromboembolism in women who used OCs in the month before surgery was almost twice as high as that in nonusers but the difference was not significant. The group of women who became ill independently of surgery was divided into 3 diagnostic categories: certain or probable deep vein thrombosis pulmonary embolism or both; possible deep vein thrombosis pulmonary embolism or both; and superficial venous thrombosis only. There was a strong association between current OC use and certain or probable venous thromboembolism (relative risk 7.2) a weaker association with possible thromboembolism (relative risk 3.1) and little or no association with superficial venous thrombosis (relative risk 1.4). There was no significant association between risk and duration of OC use. The crude incidence of certain or probable thromboembolism/1000 woman-years was 0.62 in women using OCs containing 50 mcg or more of estrogen and 0.39 in those using preparations containing less than 50 mcg of estrogen. These findings are consistent with those obtained in other major studies in this area.

Oral Contraceptives and Breast Cancer

In 1976, information on oral contraceptive (OC) use as well as numerous risk factors for breast cancer was provided by 121,964 married female registered nurses aged 30 to 55 years. Ninety-two percent of women in the cohort completed follow-up questionnaires, and vital records were systematically searched to ascertain deaths among nonrespondents. After four years of follow-up, 592 incident cases of breast cancer were identified. Compared with never users, the age-adjusted relative risk (RR) of breast cancer, regardless of menopausal status, among all women who had ever used OCs was 1.0. Among premenopausal women compared with those who had never used OCs, the RR of breast cancer was 1.5 for current use of OCs in 1976 and 1.0 for past use. Among postmenopausal women, the RR for past use of OCs was 1.0. These estimates were essentially unaltered after controlling for other known risk factors for breast cancer in multiple logistic regression analysis. Furthermore, there was no modification of these effects by family history of breast cancer, age at first use, timing of the first birth, or other breast cancer risk factors. Data on past use of OCs provide substantial reassuring evidence that there is no large excess risk of breast cancer within a few years of cessation of pill use. The observed moderate elevation of breast cancer risk with current use was of borderline statistical significance. However, the observation was based on 29 cases and may reflect the effect of sampling variability, as most other studies have not observed a relationship between current use of OCs and breast cancer in women of this age.