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PubMed1983

Study on the presence of abnormal proteins in the serum of oral contraceptive users.

Beaumont reported that current and former oral contraceptive users and subjects with thromboembolic disease characteristically demonstrate elevated amounts of precipitated proteins, designated as "globulines anormalement precipitables (GAP)," following treatment of their sera with 25% saturated ammonium sulfate. In the present study, the reproducibility of Beaumont's methods and results was investigated in groups of women consisting of never users, current users, former users, and thrombosis subjects. The current users had the lowest serum GAP levels and no bimodal distribution. Values were higher for the never users and former users and highest in the thrombosis group. Race affected serum GAP values; mean values for blacks were significantly higher than for Caucasians. This study does not support Beaumont's earlier findings.

Adolescent↗

PubMed1988

Endometrial response to the use of a sequential oral contraceptive.

Belgium is 1 of the few countries where sequential oral contraceptives are still commercially available. The authors investigated the endometrial effect of Ortho-Novum SQ (14 tablets of 100 mcg mestranol and 7 tablets of 100 mcg mestranol + 2 mg norethisterone) in 222 biopsy specimens obtained from 184 asymptomatic Caucasian women (mean +or- s.d, age and parity, 34.6 +or- 6.7 and 2.0 +or- 1.0, respectively) who had used this sequential OC during an average of 52.5 months. Notwithstanding predominantly longterm use of Ortho-Novum SQ, 43% of the tissue samples had normal proliferative or luteal endometrium. The data suggest a positive correlation between the endometrial response and the duration of pill use. No premalignant or malignant changes were found. In 15 of 24 subjects for whom multiple biopsy specimens were available, the histological picture was static; 7 showed regression and only in 2 were the changes progressive, although never more severe than minor 'class 2' lesions. These results, which are at variance with those reported for users of other sequential brands (mainly Oracon), suggest that prolonged use of Ortho-Novum SQ does not enhance the risk of endometrial cancer in premenopausal women having no additional risk factors for the development of this type of neoplasia.

Anatomy↗

PubMed1989

The current status of oral contraceptive clinical development in Japan.

Since the oral contraceptive guideline was issued in April 1987, Japanese pharmaceutical firms have been asking physicians to perform clinical studies of the low-dose OCs. At present, eight products from six companies are under clinical development. Ethinyl estradiol (30-35 micrograms per tablet) as an estrogen component is common to all the test drugs. The progestin component in each OC is norethindrone, levonorgestrel, or desogestrel. Phase I clinical studies on small numbers of healthy volunteers showed that they could tolerate the test drugs without any serious complaints. The effects on endocrine systems, including the inhibition of ovulation, were also examined. Pharmacokinetic parameters of active ingredients were comparable to those of Western women, and no substantial difference seemed to exist between Japanese and Western women. As an example, the results of phase I studies of OJK-777 (Ortho-Novum 7/7/7) are mentioned. Phase III clinical studies, which are "open studies," are now under progress with more than 3,000 women. The major objectives are to examine (1) how well the drugs are tolerated, and the dropout rates; (2) the effects on cycle control, especially bleeding patterns; (3) effects on the cardiovascular system, including coagulation and lipid metabolism; (4) effects on hormone secretions. Although some women have been taking the test drugs for more than 12 cycles, overall statistics are not yet available, because the guideline requires long-term administration (for more than 24 cycles). However, some characteristic features observed thus far are discussed.

Adult↗

PubMed1988

The oral contraceptive user.

The use of oral contraceptives (OC) has been correlated to several diseases, primarily thromboembolic conditions. Whether these correlations represent a causal relationship or a mere statistical correlation based on other variables, depends on whether users of OC differ in other respects from women in fertile age not using OC. We interviewed 519 Danish women, 15-45 years old and selected at random, concerning present and past use of OC, age, occupation, years of schooling, marital status, income, smoking habits, urbanization, and their opinion on the postulated thrombotic risk among users of OC. The data were analysed by methods for multivariate contingency tables. Opinions on the thrombotic risk, age, smoking habits and, to a lesser degree, regarding income, were directly correlated to the oral contraceptive use. There was no direct interaction between the use of OC and the other variables. Users of OC were younger and smoked more than the non-users and were of the opinion that the use of OC implied only minor thrombotic risk, or none at all.

Adolescent↗

PubMed2004

The role of combined oral contraceptives in the management of acne and seborrhea.

Acne and seborrhea (or facial oiliness) are related androgenic skin disorders which affect a high proportion of women after menarche. They can have a negative effect on psychological well-being and social life. Androgens play an important role in the pathogenesis of acne through the stimulation of sebum secretion, increasing sebaceous gland size and possibly through follicular hyperkeratinization. Conversely, estrogens decrease sebum production by suppressing gonadotropin release and androgen production and increasing sex hormone binding globulin production. One of the treatment options for these conditions is hormonal therapy, especially for women who require contraception. The effect of combined oral contraceptives in androgenic skin disorders depends on their estrogen:progestogen balance and on the antiestrogenic activity of the progestogen component. Improved understanding of what women value about oral contraceptives suggests that the choice of product should be tailored as much as possible to the individual. Several combined oral contraceptives containing new-generation progestogens (e.g. desogestrel, gestodene) or progestational antiandrogens (e.g. cyproterone acetate, chlormadinone acetate) have demonstrated efficacy in the treatment of women with acne, although comparisons between trials are difficult because of differing endpoints. Seborrhea has been less well studied, but the few studies that are available show an improvement in women with this condition using combined oral contraceptives.

Acne Vulgaris↗

PubMed1999

Interactions between oral contraceptives and antifungals/antibacterials. Is contraceptive failure the result?

The effectiveness of oral contraceptives may be impaired by concomitant treatment with antimicrobials. This may occur because of reductions in plasma concentrations of ethinylestradiol by the induction of hepatic metabolism, as for rifampicin (rifampin) and possibly griseofulvin, or in a small percentage of women because of interference with enterohepatic recirculation. There are no scientific data to support the anecdotal evidence that the concomitant use of combined oral contraceptives and antimicrobials reduces contraceptive efficacy in the majority of women. It has been postulated that there is a subset of women in whom the enterohepatic recirculation of ethinylestradiol plays an important role. In these women the action of an antimicrobial may reduce the efficacy of oral contraceptives by interfering with this mechanism. Studies that have quantitatively examined these effects may have failed to include women from this subset because of the small numbers involved in the studies. On the other hand, there are no good prospective studies comparing contraceptive failure rates between compliant women who use combined oral contraceptives with and without antimicrobials. All women using combined oral contraceptives should be informed of the very low level of risk of interactions with antimicrobials (probably about 1%) and that it is not possible to identify who may be at risk. Women concerned about this low level of risk should be given information about the use of barrier methods or avoidance of intercourse during the first 7 days of concomitant antimicrobial therapy and for 7 subsequent days. Women who have had previous contraceptive failures or developed breakthrough bleeding during concomitant antimicrobial use should be strongly advised to follow these precautions, as they may be part of the subset of women at higher risk of contraceptive failure.

Animals↗

PubMed1990

Mechanism of action of oral contraceptives on carbohydrate metabolism at the cellular level.

Although the available scientific data on the undesired metabolic effects of sex steroids have accumulated rapidly, most are of a descriptive nature, and only a few studies elucidate the impact at the cellular level and the possible interrelationship between different metabolic systems. This review summarizes the influence of different contraceptive steroid combinations on glucose metabolism and points to the possible mechanisms behind a disturbance of the euglycemic homeostasis with a concomitant change in lipid metabolism. Today the general concept is that the influence of combined sex steroid products on glucose metabolism is mainly caused by the progestogen components, although artificial estrogens may act synergistically. The diabetogenic effects of the progestogens make it important to consider the development during the last decade of the new more selective progestogens of the gonane type. From recent studies it seems, however, that intake of contraceptive combinations of ethinyl estradiol in combination with these types of gonanes, such as desogestrel and gestodene, may also be accompanied by increased insulin resistance, specifically, a hyperinsulinemic response to a glucose challenge despite unchanged glucose values compared with a baseline test. This is similar to observations made with combinations of ethinyl estradiol and other more traditional types of progestogens of the gonane and estrane type. It is conceivable that the diabetogenic effects of the progestogens are caused by a change in insulin receptor binding or a postreceptor defect in the cellular insulin action. The clinical implications of the diabetogenic effects of the sex steroids are hard to interpret, but more long-term exposure of arterial tissue to elevated concentrations of glucose and insulin results in inhibition of lipolysis and synthesis of cholesterol and triglycerides, which result in the development of lipid-filled lesions--fatty streaks--similar to those of early atherosclerosis.

Blood Glucose↗

PubMed1987

Coagulation effects of oral contraception.

In Europe and North America, estrogen/progestogen oral contraception has been associated with an increase in venous thromboembolism, myocardial infarction, and stroke. These hazards are found mainly in smokers and in women over the age of 35. Venous thromboembolism appears to correlate with the estrogen dosage, and the arterial complications with both the estrogen and progestogen components. Blood coagulation and vascular thrombosis are intimately related. Estrogen/progestogen oral contraception affects blood clotting by increasing plasma fibrinogen and the activity of coagulation factors, especially factors VII and X; antithrombin III, the inhibitor of coagulation, is usually decreased. Platelet activity is also enhanced with acceleration of aggregation. These changes create a state of hypercoagulability that, to a large extent, appears to be counterbalanced by increased fibrinolytic activity. Studies of the oral contraceptives in current use show that the coagulation effects depend on the dosage of estrogen and the type of progestogen used in combination. Current research is aimed at finding the estrogen/progestogen formulations that induce the least changes in the coagulation system and other physiologic processes. In this respect, the new low-dose formulations are a major step forward and should reduce the risk of vascular thrombotic complications.

Blood Coagulation↗

PubMed2002

Bone mineral density at various anatomic bone sites in women receiving combined oral contraceptives and depot-medroxyprogesterone acetate for contraception.

The association between users of combined oral contraceptives and depot-medroxyprogesterone acetate (DMPA) for contraception and bone mineral density (BMD) has been controversial because of variations among studies. Like other studies, this cross-sectional study compares BMD in users of combined oral contraceptives and DMPA with that in nonusers. Unlike previous studies, we defined long-term use as >2 years, and we measured more bone sites than previous studies including lumbar spines, femurs, and forearms. The study group consisted of 59 women aged 30 years to 34 years who had been using combined oral contraceptives for 57.36 +/- 27.02 months with a minimum period of 24 months, 34 women of the same age who had been using DMPA as contraceptive for 55.76 +/- 35.31 months, and 62 women of the same age who had not used any steroid hormonal contraceptives for more than 6 months. BMD was measured by dual energy photon absorptiometer at lumbar spine 2-4, neck of femur, Ward's triangle of femur, greater trochanter of femur, ultradistal radius, and distal ulnar, respectively. Age, body mass index, and lifestyles of both groups were matched with nonusers. Mean BMD at lumbar spine (L2-4) in the DMPA users was significantly lower than in the controls (1.031 +/- 0.090 vs. 1.096 +/- 0.116, p = 0.007). There were no significant differences in BMD values at bone sites other than lumbar spine between DMPA users and the controls. There were no significant differences in BMD values at all bone sites between combined oral contraceptives users and the controls. We conclude that combined oral contraceptives are not associated with changes in values of BMD, while DMPA is associated with decreased BMD only at lumbar spine. We comment that steroid hormonal contraceptives are safe to use for long-term contraception regarding bone mass effects.

Adult↗

PubMed1984

The Royal College of General Practitioners' Oral Contraception Study: some recent observations.

The Royal College of General Practitioners' Oral Contraception Study is a continuing cohort survey of the effects of oral contraceptives on the health of users. Neurotic depression is associated with the oestrogen content of combined oral contraceptives, but the risk is small in general, and there is no excess risk associated with oestrogen doses of 35 micrograms or less. It now appears likely that, in the long-term, oral contraceptives are not associated with any increased risk of gallbladder disease, although there is an acceleration of the disease in those women susceptible to it. The progestogen activity of combined oral contraceptives is associated with an increased risk of hypertension and arterial disease. Duration of use no longer seems to influence the occurrence of the latter. Cigarette smoking by oral contraceptive users is the predominant associated risk factor for the occurrence of arterial diseases. Non-smokers using low-progestogen-dose brands may safely use oral contraceptives, probably up to the age of 45 years. In the author's opinion, there is no convincing evidence that oral contraceptive use increases the risk of breast cancer. The evidence for an association with cervical cancer is firmer, but, if confirmed, is unlikely to affect more than one in 3000 users a year. Increased safety in the use of oral contraceptives in future is likely to be achieved through the use of tests which will allow the adjustment of dose to be made to each patient's particular requirements.

Adolescent↗

PubMed1978

Liver tumors and oral contraceptives.

A possible causal relationship between oral contraceptives and liver cell adenomas has been postulated in the recent literature. In this presentation three additional cases are reported to support the existence of such an association. The possible etiologic causes for this newly described condition and specific diagnostic procedures for its accurate diagnosis are presented.

Adenoma↗

PubMed1998

Effects of oral contraceptives on free fatty acid metabolism in women.

These studies examined whether women using oral contraceptives have abnormalities in free fatty acid (FFA) metabolism compared with women not using oral contraceptives. Plasma palmitate kinetics ([3H]palmitate) were measured at rest, following glucose ingestion, and during epinephrine infusion in 13 oral contraceptive users and 13 matched women not using oral contraceptives. Oral contraceptive users had significantly greater plasma triglyceride concentrations and glucose responses to oral glucose tolerance testing. No differences in basal (2.1 +/- 0.1 v 1.8 +/- 0.2 micromol x kg fat-free mass x FFM(-1) x min[-1]), glucose-suppressed (0.6 +/- 0.1 v 0.5 +/- 0.1 micromol x kg FFM(-1) x min[-1]), or epinephrine-stimulated (3.3 +/- 0.1 v 3.6 +/- 0.2 micromol x kg FFM(-1) x min[-1]) palmitate flux were detected between women using and not using oral contraceptives. The respiratory quotient (RQ) also was not different between groups. We conclude that the increase in plasma triglycerides and the mild glucose intolerance seen with oral contraceptive use is not associated with significant abnormalities of FFA metabolism.

Adult↗

PubMed1975

Oral contraceptives and human cervical mucus lipids.

Oral contraceptives containing estrogenic and progestational components caused a consistent increase in human cervical mucus lipids during the menstrual cycle. Cyclic variations in cervical mucus lipids occur during the normal cycle. Phospholipids, free cholesterol, and triglycerides in cervical mucus increase with the use or oral contraceptives.

Adult↗

PubMed1993

The effect of elevated ovarian hormones on periodontal health: oral contraceptives and pregnancy.

The most common oral manifestation of elevated levels of ovarian hormones, as seen in pregnancy or oral contraceptive usage, is an increase in gingival inflammation with an accompanying increase in gingival exudate. This gingivitis can be avoided or at least minimized by establishing low plaque levels at the beginning of pregnancy or the beginning of oral contraceptive therapy. It would appear that bacteria are not solely responsible for the gingivitis seen during these times, nor are the ovarian hormones solely responsible for the condition. Data from numerous studies suggest that the ovarian hormones alter the microenvironment of the oral bacteria so as to promote their growth and shifts in their populations. The present article reviews the current state of knowledge concerning the relationship of gingivitis to elevated levels of ovarian hormones, and describes the role that these hormones may play in the gingivitis associated with pregnancy or oral contraceptive usage.

Contraceptives, Oral, Hormonal↗

PubMed1994

Are low-dose oral contraceptives safer and better?

It is widely believed that the use of low-dose oral contraceptives decreases thrombotic risks, compared with higher-dose oral contraceptives. Two recent epidemiologic studies infer a lower risk with 30 to 35 mcg than with 50 mcg estrogen oral contraceptives. However, as with prior studies from which similar conclusions were drawn, these studies have major flaws, the worst being that all 50 mcg oral contraceptives are lumped together, whereas 50 mcg mestranol oral contraceptives are actually bioequivalent to 35 mcg ethinyl estradiol oral contraceptives, thus confounding all such studies. Moreover, while rare thrombotic events have received inordinate attention, the major protective effect against endometrial and ovarian cancer that has been shown in older studies among users of oral contraceptives containing > or = 50 mcg ethinyl estradiol or > or = 80 mcg mestranol are almost totally ignored. The theoretical benefits of using lower-dose oral contraceptives have not been demonstrated, whereas the protection against these types of reproductive cancer have been shown repeatedly with high-dose oral contraceptives but not, to date, with lower-dose oral contraceptives. Such protection may be diminished by lowering the oral contraceptive dosage. Should every woman of reproductive age use high-dose oral contraceptives for 2 years? Are we throwing out the baby with the bath water?

Contraceptives, Oral↗

PubMed1977

Fetal loss, twinning and birth weight after oral-contraceptive use.

To evaluate the effect of oral-contraceptive use on subsequent offspring, I reviewed information on the pregnancies of 19,887 women who indicated, in response to a mail questionnaire, that they had used oral contraceptives. The rates of spontaneous abortion and stillbirth were smaller for former users than for nonusers--a finding consistent with previous studies. Twinning was more frequent among births of infants conceived soon after cessation of oral contraceptives, the rate being approximately twice the expected value for women who had used oral contraceptives for more than six months (P = 0.1). The sex distribution of the twins indicated that the increase was mainly in dizygous twins (P = 0.02), in accordance with predictions about increased twinning after cessation of oral contraceptive use. No relation was evident between oral contraceptive use and birth weight.

Abortion, Spontaneous↗

PubMed1982

Normalization of testosterone levels using a low estrogen-containing oral contraceptive in women with polycystic ovary syndrome.

Oral contraceptives reduce the elevated androgen levels in polycystic ovary disease. However, treatment with oral contraceptives is associated with undesirable side effects because of their high estrogen content. This study was undertaken to examine the effects of low estrogen-containing oral contraceptive (Loestrin:norethindrone acetate 1.5 mg and ethinyl estradiol 30 micrograms) on 25 women with polycystic ovary disease of ovarian origin. Loestrin treatment normalized the elevated luteinizing hormone and total and unbound testosterone levels and increased testosterone binding globulin levels. In a time-course study, unbound testosterone declined within a week of initiating treatment and by 12 to 16 weeks was completely normal. Reduction in hair growth and improvement in complexion were noted by about 12 to 16 weeks. Side effects of treatment were minimal.

Contraceptives, Oral↗

PubMed1965

THE EMOTIONAL RESPONSES OF MARRIED WOMEN RECEIVING ORAL CONTRACEPTIVES.

One hundred women taking oral contraceptives were questioned concerning their opinions about personal and sociological effects of this method of conception control. Fifty-three per cent reported improved coital satisfaction while 4% noted the opposite effect. Libido was increased in 22% and decreased in 13%. One woman in five believed that an increase in premarital and extramarital sexual activity would take place in the general population as a result of tablet-induced infertility. The problem of population control is discussed. It is paradoxical that the incidence of unplanned pregnancies continues to increase despite the availability of completely reliable conception control. This reflects present inability to communicate contraceptive knowledge to the appropriate people.

Adult↗