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PubMed2000

[Clinical and metabolic effects of oral contraceptives].

The oral contraception most employed, consists in a combination of estrogen and progestin, the main action in the prevention of ovulation through the inhibition of the secretion of luteinizing hormone (LH) and follicle stimulating hormone (FSH). The progestin in combination with estrogen produces an endometrium not receptive to the oocyte implantation and changes tubal, this affects capacitation and acrosomal reaction. Since 1960s up to date the reports made had been established that the OC had been developed adverse effects such as increase concentration of HDL, increase of apolipoprotein B-100, insulin resistance, increase in SHBG, atherogenicity, alteration in the coagulation factors and increase in the risk of venous thromboembolic disease. This work was elaborated with literature search on MEDLINE between 1985 to 1998, with the purpose to search the collateral effects of Oral Contraceptives evaluated by other authors.

Adipose Tissue↗
PubMed1998

Calcium and phosphorus in milk of Brazilian mothers using oral contraceptives.

OBJECTIVE: Oral contraceptives (OC) are the most efficient method of contraception and it is the most prescribed by doctors in developing countries. Therefore we studied the effects of combination pill and mini-pill on calcium and phosphorus in milk of breast-feeding mothers at different stages of lactation. METHODS: Fifty-four breast-feeding mothers made up three study groups: 33 mothers who had been advised by their doctors to use either combination pill (12), or mini-pill (21), as well as a control group of 21 mothers that used no hormonal contraceptives. All mothers completed a questionnaire and provided samples of milk before and after a measured period of observation. Mean duration of study was 76, 120, and 101 days, respectively for users of mini-pill, combination pill, and controls. Determination of calcium and phosphorus was done by inductively coupled plasma-atomic absorption spectrometry. RESULTS: Overall the decrease in milk concentrations of phosphorus (6%) and calcium (26.3%) during the study period was not influenced by OC treatment. Regression analyses which took into consideration length of treatment, socioeconomic status, number of children, duration of previous lactation, type of contraceptive, and age of mothers and repeated measurements (before and after OC) showed that milk calcium was significantly affected by stage of lactation (p=0.0013). CONCLUSION: The use of hormonal contraceptive such as the combination pill (levonorgestrel 0.15 mg+ethynilestradiol 0.03 mg) and mini-pill (norethindone 0.35 mg) does not seem to affect the secretion of calcium and phosphorus in milk of mothers.

Adolescent↗
PubMed2006

Risk of nonfatal venous thromboembolism with oral contraceptives containing norgestimate or desogestrel compared with oral contraceptives containing levonorgestrel.

CONTEXT: Previous studies have reported that users of the "third-generation" oral contraceptives (OCs) containing the progestins gestodene and desogestrel have about twice the risk for venous thromboembolism (VTE) compared to users of older OCs containing levonorgestrel. Estimates of the risk for VTE among users of norgestimate-containing OCs compared to other OCs, however, are lacking. OBJECTIVE: The purpose of this study is to obtain quantitative information on the risk of nonfatal VTE in women using OCs containing either norgestimate or desogestrel in comparison with women taking OCs containing levonorgestrel. DESIGN, SETTING AND PARTICIPANTS: Based on information from PharMetrics, a United States-based company that collects and records information on claims paid by managed care plans, we used a nested case-control study design to estimate relative risks of nonfatal VTE among 15- to 39-year-old current users of OCs containing norgestimate with 35 microg of ethinyl estradiol (EE), desogestrel with 30 microg of EE or levonorgestrel with 30 microg of EE, both monophasic and triphasic preparations, during the period January 2000 to March 2005. Cases were women with a well-documented VTE of uncertain origin that was diagnosed in current users of a study drug. Up to four controls were closely matched to each case by age and calendar time, and odds ratios (ORs) were calculated using conditional logistic regression comparing the risk of VTE among users of the three contraceptives. We also estimated and compared the incidence rates for all three OCs. RESULTS: Based on 281 newly diagnosed idiopathic cases of VTE and 1055 controls, we found that the adjusted ORs for nonfatal VTE comparing norgestimate- or desogestrel-containing OC users to users of levonorgestrel-containing OCs were 1.1 [95% confidence interval (CI), 0.8-1.6] and 1.7 (95% CI, 1.1-2.4), respectively. The incidence rates of VTE were 30.6 (95% CI, 25.5-36.5), 53.5 (95% CI, 42.9-66.0) and 27.1 (95% CI, 21.1-34.3) per 100,000 woman-years for users of norgestimate-, desogestrel- and levonorgestrel-containing OCs, respectively. The incidence rate ratios for norgestimate-containing OCs compared to levonorgestrel-containing OCs and desogestrel-containing OCs compared to levonorgestrel-containing OCs were 1.1 (95% CI, 0.8-1.5) and 2.0 (95% CI, 1.4-2.7), respectively. CONCLUSIONS: The risk of nonfatal VTE among users of desogestrel-containing OCs is significantly elevated compared to that of levonorgestrel-containing OCs. The risk of VTE in users of norgestimate-containing OCs was closely similar to that of users of levonorgestrel-containing OCs.

Adolescent↗
PubMed1999

Update on oral contraceptive pills.

Oral contraceptive pills are widely used and are generally safe and effective for many women. The World Health Organization has developed a risk classification system to help physicians advise patients about the safety of oral contraceptive pills. The choice of pill formulation is influenced by clinical considerations. By choosing appropriately from the available pill formulations, family physicians can minimize negative side effects and maximize noncontraceptive benefits for their patients. Additional monitoring and follow-up are necessary in special populations, such as women over 35 years of age, smokers, perimenopausal women and adolescents. Third-generation progestins are additional options for achieving noncontraceptive benefits, but their use has raised new questions about thrombogenesis. The U.S. Food and Drug Administration has labeled emergency postcoital contraception for use following unprotected coitus. Oral contraceptive pills are associated with few clinically significant drug interactions, although consideration of interactions remains important.

Adolescent↗
PubMed1992

Update on oral contraceptive pills and postcoital contraception.

Modern oral contraceptive pills are safe for the majority of American women. The most important contraindications to oral contraceptive pill use are a history of thrombophlebitis or thromboembolism while on the pill or during pregnancy, smoking over 15 cigarettes daily if over 35 years of age, active liver disease, hypertension, diabetes, a lipid disorder, or breast cancer. A history of gestational diabetes is not an absolute contraindication to oral contraceptive pill use, but women with such a history must be encouraged to exercise and eat properly to reduce the high risk of developing overt diabetes. Couples should be encouraged to use condoms to reduce the risk of sexually transmitted diseases. Most antibiotics do not decrease the effectiveness of the pill. Nonuse of contraception among adolescents and older couples is the most common reason for failure. Postcoital contraceptive pills are available but are not completely effective. The use of modern contraceptives is almost always safer than nonuse.

Anti-Bacterial Agents↗
PubMed1995

Cutaneous melanoma in women. III. Reproductive factors and oral contraceptive use.

Oral contraceptive use and reproductive factors were investigated in a population-based case-control study of 452 women aged 25-59 years who were diagnosed with cutaneous malignant melanoma during the period 1981-1986 and 930 controls. Ever use of oral contraceptives was reported by 72 percent of melanoma patients and 79 percent of control subjects in this San Francisco Bay Area study, although duration of use was slightly longer for women with superficial spreading melanoma (5.5 years) than for controls (4.3 years). While some subgroups had elevated or reduced odds ratios, no consistent association was observed between cutaneous melanoma risk and oral contraceptive use when use was examined by duration, latency, age at diagnosis, age at first use, and time period of first use. Neither number of live births nor age at birth of the first child was associated with risk for cutaneous melanoma; nor was a history of miscarriage, induced abortion, or endometriosis. No association was observed with regularity of menstrual periods or with use of fertility drugs or hormones to regulate menstrual periods. Women who reported experiencing hyperpigmentation of facial skin during a prior pregnancy had a lowered risk for all cutaneous melanoma (odds ratio (OR) = 0.64, 95% confidence interval (CI) 0.44-0.93) and superficial spreading melanoma (OR = 0.54, 95% CI 0.36-0.83). This effect was more pronounced for light-complexioned women (for superficial spreading melanoma, OR = 0.37, 95% CI 0.20-0.70) than for women with a dark or medium complexion (for superficial spreading melanoma, OR = 0.84, 95% CI 0.48-1.5). Women who reported use of acne medication also had a reduced risk of superficial spreading melanoma (OR = 0.55, 95% CI 0.35-0.84). These results indicate an overall lack of effect of oral contraceptives on cutaneous melanoma risk in this population of women. The reduced melanoma risks associated with hyperpigmentation during a prior pregnancy and use of acne medication (or related hormonal indications for its use) should be studied further.

Abortion, Induced↗
PubMed1992

Noncontraceptive benefits of modern low-dose oral contraceptives.

Most oral contraceptive formulations in current use contain 50 micrograms or less of ethinyl estradiol and 1 mg or less of the various progestins: norethindrone (0.5-1 mg), norgestrel (0.3-0.5 mg), or levonorgestrel (0.05-0.25 mg) [1]. The new generation of progestins--norgestimate, desogestrel and gestodene--are derived from levonorgestrel, the biologically active enantiomer of norgestrel. These steroids have specific metabolic and pharmacologic activity that allow oral contraception at lower doses than previous progestins. Desogestrel and norgestimate are both prodrugs and must undergo hepatic and gastrointestinal metabolism to become biologically active compounds. Gestodene is immediately and completely bioavailable [2]. For the new formulations containing less than 50 micrograms of ethinyl estradiol, the incidence of complications has decreased. With most of the early medical problems identified, current research can now focus on other aspects of oral contraception such as compliance and OC use failure. Prominent noncontraceptive health benefits have been observed in OC users and represent new directions for future research. When the risk-benefit ratio of OC use is evaluated in healthy women today, it clearly favors the benefits. However, these will not be fully realized without an increase in method compliance.

Blood Coagulation↗
PubMed1998

Compliance and use behaviour, an issue in injectable as well as oral contraceptive use? A study of injectable and oral contraceptive use in Johannesburg.

This study examines the compliance, use behaviour and knowledge of method of women using injectable and oral contraceptives in two clinic sites in the Johannesburg area, South Africa. An interviewer administered questionnaire was used to collect information in the clients' home language. A total of 400 women were interviewed in the clinics. The mean age of clients was 26.2 years (range 13 to 43 years). Of the clients not wanting to get pregnant, 30.4 per cent of injectable users and 18.4 per cent of oral contraceptive (OC) users had stopped using their method temporarily before returning to the same method (called the nonuse segment) and had not used any other form of contraception during this time. Almost one third of injectable users (31.2 per cent) had been late for their next injection at least once. Although nearly all women using injectables had experienced some menstrual disturbances, over one third (38.5 per cent) had not been informed by the providers about the possibility of these changes. Many women gave the disruption of their menstrual cycle as the reason for the nonuse segment. The majority of OC users lacked information on how to use their method correctly. Nearly all women expressed an interest in obtaining more information on their current method and other available methods. This study shows that compliance is an issue in injectable as well as OC users.

Adolescent↗
PubMed1989

The pharmacologic and metabolic effects of oral contraceptives.

The oral contraceptive formulations in use today consist of three types. One type has a fixed dose of a combination of a synthetic estrogen and a synthetic progestin, the second has varying doses of each of these steroids, and the third consists of a fixed dose of a progestin without an estrogen. The estrogen in the older formulations contained mestranol, while all those developed since 1974 contain ethinyl estradiol. The estrogen is combined with varying dosages of nine different progestins to produce a wide variety of formulations. The major metabolic effects of the estrogen are an increase in hepatic production of globulins, some of which cause hypercoagulability, and an increase in blood pressure in certain users. By varying HDL-cholesterol, the estrogen has a beneficial effect upon lipids. Other estrogenic effects include fluid retention, depression, and breast tenderness. Most of the progestins have androgenic effects, being derived from 19-nortestosterone. These include peripheral insulin resistance, a lowering of HDL-cholesterol, nitrogen retention, and nervousness. Both the estrogen and progestins metabolic effects are dose-related and with the newer, low-dose formulations, the adverse metabolic and clinical effects are minimal. Thus the results of the epidemiologic studies performed 10 to 15 years ago, when women were using high-dose formulations, are not relevant to the oral contraceptive formulations in use today. Recent epidemiologic studies show that healthy, nonsmoking women using oral contraceptives do not have an increased risk of developing cardiovascular disease.

Adolescent↗
PubMed1993

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.

Adult↗
PubMed1997

Case-control study of oral contraceptives and risk of thromboembolic stroke: results from International Study on Oral Contraceptives and Health of Young Women.

OBJECTIVE: To determine the influence of oral contraceptives (particularly those containing modern progestins) on the risk for ischaemic stroke in women aged 16-44 years. DESIGN: Matched case-control study. SETTING: 16 Centres in the United Kingdom, Germany, France, Switzerland, and Austria. SUBJECTS: Cases were 220 women aged 16-44 who had an incident ischaemic stroke. Controls were 775 women (at least one hospital and one community control per case) unaffected by stroke who were matched with the corresponding case for 5 year age band and for hospital or community setting. Information on exposure and confounding variables were collected in a face to face interview. MAIN OUTCOME MEASURES: Odds ratios derived with stratified analysis and unconditional logistic regression to adjust for potential confounding. RESULTS: Adjusted odds ratios (95% confidence intervals) for ischaemic stroke (unmatched analysis) were 4.4 (2.0 to 9.9), 3.4 (2.1 to 5.5), and 3.9 (2.3 to 6.6) for current use of first, second, and third generation oral contraceptives, respectively. The risk ratio for third versus second generation was 1.1 (0.7 to 2.0) and was similar in the United Kingdom and other European countries. The risk estimates were lower if blood pressure was checked before prescription. CONCLUSION: Although there is a small relative risk of occlusive stroke for women of reproductive age who currently use oral contraceptives, the attributable risk is very small because the incidence in this age range is very low. There is no difference between the risk of oral contraceptives of the third and second generation; only first generation oral contraceptives seem to be associated with a higher risk. This small increase in risk may be further reduced by efforts to control cardiovascular risk factors, particularly high blood pressure.

Adolescent↗
PubMed1992

Medical aspects of oral contraceptive discontinuation.

Oral contraceptive (OC) compliance is adversely affected by three medical factors: side effects, poor cycle control, and patients' fears of serious diseases. Most physicians recognize these factors but fail to understand their true impact on continuation rates. In one study, half of current OC users who changed brands and half of former OC users cited unwanted side effects as their reason for discontinuation. Moreover, a substantial number of women discontinue OCs without consulting their physicians. Among the so-called nuisance side effects cited by patients, the most prominent are bleeding irregularities. In new patients just beginning OC therapy, bleeding irregularities such as breakthrough bleeding and amenorrhea can lead to a very high discontinuation rate; as many as 50% of new users discontinue OCs before the end of the first year because of such side effects. OC discontinuation rates among other patient populations vary. The problem has not been studied extensively, but existing data show the problem is a large one. One study involving 550 women of various ages and years of OC use confirmed that cycle control problems led many women to discontinue OC use--often resulting in an unplanned pregnancy. Six percent of the women in this study discontinued OC use because of poor cycle control, and 23% of this group experienced subsequent unwanted pregnancies. In contrast, clinical tolerance with the new progestins such as gestodene is good; in one study 86% of patients had normal bleeding patterns. The principal consequences of poor cycle control are loss of confidence in the OC and the physician, increased anxiety, disruption of sexual relations, additional physician calls and visits, pregnancy tests, discontinuation, and noncompliance. The perception that European women have regarding the pill is that it is a reliable method that does not interfere with sexual activities. However, doubts about the safety of OCs influence compliance with the method. While concerns regarding blood clots have diminished, the fear of cancer is still a concern for many women. The androgenic side effects of weight gain, acne,and breast tenderness are particularly troubling for adolescents, who are sensitive to changes in body image. In one recent study, 20% to 25% of women stopped taking OCs because of weight gain or acne, and another 25% stopped because of fear of cancer. The medical component of improving compliance is the physician's choice of OC. Formulations with low, effective doses of hormones and the fewest side effects should be selected. Cycle control and the side-effect profile are improved with the new progestins.(ABSTRACT TRUNCATED AT 400 WORDS)

Contraceptives, Oral, Combined↗
PubMed2000

100 mg acetylsalicylic acid acutely decreases red cell aggregation in women taking oral contraceptives.

Since oral contraceptives (OC) are known to impair blood fluidity and to increase the risk of venous and arterial thrombosis, while acetylsalicylic acid (ASA) decreases the thrombotic risk and modifies some rheologic parameters, we compared the hemorheologic effects of ASA on blood rheology between women treated by OC and women who never received this medication. 25 women under OC were compared to 25 matched women who had never used OC. Blood viscosity (MT90 viscometer) and RBC aggregation (Myrenne aggregometer and AFFIBIO erythroaggregometer) were measured before and 1 hr after women received per os 100 mg ASA, after an overnight fast. The only significant difference between women under OC and controls was an increased RBC aggregation ('M' index +28%, p < 0.04; Affibio aggregation time -21%, p < 0.03). On the whole sample of 50 women as well as in the subgroup of women under OC, ASA decreased RBC partial disaggregation threshold (-1.7%, p < 0.01). These results confirm that RBC aggregation is increased under OC and suggest that 100 mg ASA acutely induces a partial reversal of this RBC hyperaggregation.

Adult↗
PubMed1987

Metabolic effects of oral contraceptives.

Combination oral contraceptives (OCs) are probably not an independent risk factor for cardiovascular disease but through their metabolic actions, may partly amplify the effects of known risk factors for cardiovascular disease. This review of the literature and our own data indicate that use of high-dose, progestogen-dominant OCs induces a potentially atherogenic lipoprotein profile (high low-density lipoprotein-cholesterol:high-density lipoprotein-cholesterol ratio), mostly attributable to the antiestrogenic action of the progestogen content of these OCs. In contrast, lower-dose combination OCs with reduced amounts of progestogens and slight estrogen dominance, either monophasic or multiphasic, produce strikingly fewer adverse effects on lipoproteins. Moreover, use of low-dose, as opposed to high-dose, OCs results in almost unchanged glucose tolerance, marginally increased or unchanged insulin and glucagon responses to glucose, and probably unchanged levels and activity of peripheral insulin receptors. Further in-depth studies of low-dose OC formulations are mandatory to ascertain reduced metabolic risk of these OCs.

Cardiovascular Diseases↗
PubMed1999

An open label, randomized study to evaluate the effects of seven monophasic oral contraceptive regimens on hemostatic variables. Outline of the protocol. Oral Contraceptive and Hemostasis Study Group.

Complementary to the epidemiological knowledge on the association between oral contraceptive use and the occurrence of venous thromboembolism, a study was designed to obtain more conclusive data regarding the effect of estrogen dose and progestogen type of oral contraceptives on risk markers for the occurrence of venous thromboembolism. The protocol for this multicenter, randomized, open label, parallel group, comparative study is outlined in the present article. A total of 730 healthy, nonsmoking, mulliparous women were treated for six cycles with one of the seven monophasic oral contraceptives tested in this study. The effects of progestogen type (desogestrel, gestodene, levonorgestrel, and norgestimate) and the effects of ethinyl estradiol dose (50, 30, and 20 micrograms) on various hemostatic variables was assessed, including the key components of the anticoagulant and fibrinolytic system, as well as the coagulation system. The primary outcome variables in the study were prothrombin fragment 1 + 2 and D-dimer.

Blood Coagulation↗