Amenorrhea following use of combined oral contraceptives

Among a group of 249 women examined during 1969-1971 in Swedish hospitals because of amenorrhea after oral contraceptive therapy, 177 patients answered a follow-up questionnaire in April 1972. For purposes of study these latter patients were divided into Groups 1 (6-12 month amenorrhea, spontaneous recovery), 2 (12-39 month amenorrhea, spontaneous recovery), and 3 (ongoing amenorrhea in May 1972). The numbers of patients in Groups 1, 2, and 3 were 38, 67, and 72, respectively. For 122 of the patients, no explanation other than one relating to oral contraceptive therapy could be postulated for the amenorrhea. 63 patients (35.4%) had had menstrual irregularities before using oral contraceptives. However, it is impossible to foretell simply from past menstrual history whether a woman will develop amenorrhea after oral contraceptive therapy. No correlation was seen between therapy duration or age of patient and the duration of the subsequent amenorrheic period. In the women with amenorrhea lasting more than 12 months, low excretions of low polar estrogens and 17-ketogenic steroids were seen. Possible precise causes of amenorrhea relating to oral contraceptive therapy and treatment are discussed.     

Contraceptive therapy following therapeutic abortion: an analysis

Presented is a follow-up study of 823 women who were offered a contraceptive method after a therapeutic abortion. The 520 women who elected an oral contraceptive were started on the regimen the day of the abortion, and 93% were maintaining the therapy 6 weeks later. Postabortal bleeding ceased by Day 7 in 58% of the oral contraceptive users and in 59% of the control group. Virtually all bleeding had stopped by Day 28 (97%, 98%). 42% of the patients inserted with IUDs on the day of abortion had stopped bleeding by Day 7, and 85% had stopped by Day 28. About 80% of the oral contraceptors and 30% of the control group returned to menses within 28 days of the abortion. It is recommended that oral contraceptive therapy, if chosen, be initiated the day of the abortion.     

Effect of long-term oral contraceptive therapy before pregnancy on maternal and fetal zinc and copper status

Thirteen pregnant women who conceived within six months after terminating oral contraceptive agent therapy of at least three years' duration participated in this study. Nine pregnant women with no history of oral contraceptive agent use served as controls. At delivery, erythrocyte counts were reduced, and during the first trimester and at delivery mean corpuscular hemoglobin and volume values were increased and erythrocyte zinc values were reduced in the oral contraceptive agent group as compared with controls. These changes appeared to be subclinical in magnitude and oral contraceptive agents may have induced a macrocytic erythrocyte population. Because no changes in maternal plasma zinc and copper levels were observed and no hematologic, biochemical, or anthropometric differences were observed in neonates, long-term oral contraceptive agent usage appeared to have little or no effect on zinc and copper metabolism in a subsequent pregnancy.     

Endometriosis-associated ileo-cecal perforation in a woman on the pseudopregnancy regimen

Small intestinal obstruction and perforation associated with endometriosis is uncommon. We report a similar effect following treatment with the combined oral contraceptive. Caution should be exercised when prescribing the combined oral contraceptive in women with suggested small intestinal endometriosis. Disease flare-up after therapy may be associated with intestinal obstruction and perforation.     

Treatment of hirsutism with ethinyl estradiol-desogestrel contraceptive pills has beneficial effects on the lipid profile and improves insulin sensitivity

OBJECTIVE: To evaluate the effects on the lipid pattern and insulin sensitivity of hirsute women of an oral contraceptive pill containing 30 microg of ethinyl estradiol and 150 microg of desogestrel. DESIGN: Prospective clinical study. SETTING: Tertiary care institutional hospital. PATIENT(S): 16 hirsute women. INTERVENTION(S): Women were evaluated at baseline and after receiving six cycles of oral contraceptive therapy. MAIN OUTCOME MEASURE(S): Body mass index (BMI); hirsutism score (nine body areas); serum levels of total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B, lipoprotein(a), and serum adrenal and ovarian androgens; and fasting glucose and insulin concentrations. RESULT(S): The mean serum total, HDL, and LDL cholesterol levels increased after six cycles of oral contraceptive therapy. Levels of HDL cholesterol were < 50 mg/dL in 7 of the 16 patients at baseline; these levels normalized in 4 patients after treatment. Serum total and LDL cholesterol remained within the normal range in all patients before and after therapy. No significant changes were observed in serum triglyceride, apolipoprotein B and lipoprotein(a) concentrations. Fasting insulin levels and insulin resistance as analyzed by homeostasis model assessment were reduced significantly after therapy. No changes in BMI were observed. Administration of oral contraceptive pills signifiCantly reduced the hirsutism score and hyperandrogenemia. CONCLUSION(S): Oral contraceptive pills containing low-dose ethinyl estradiol and desogestrel are effective in controlling hyperandrogenism and hirsutism and ameliorate the abnormal metabolic profile of women with hirsutism.     

Thrombotic complications due to oral contraceptives]

Cases reported here as well as the literary date tell attention to the vascular complications following contraceptive therapy. Shift of clotting-fibrinolysis system towards hypercoagulobolity is remarkable because of its role as a risk factor. If contraceptive therapy is accompanied by a condition or a disease altering clotting factors, vessel walls or circulation so that it presents an enhanced thrombosis capacity the risk may increase. In such cases indication of oral contraceptive therapy should be considered cautiously and the patients should be controlled with more intention.     

Cyproterone acetate versus a continuous monophasic oral contraceptive in the treatment of recurrent pelvic pain after conservative surgery for symptomatic endometriosis.

OBJECTIVE: To evaluate the efficacy and safety of cyproterone acetate versus an oral contraceptive in the treatment of endometriosis-associated recurrent pelvic pain. DESIGN: Randomized controlled trial. SETTING: Academic center. PATIENT(S): Ninety women with recurrent moderate or severe pelvic pain after conservative surgery for symptomatic endometriosis. INTERVENTION(S): Six months of continuous treatment with oral cyproterone acetate, 12.5 mg/d, or an oral contraceptive containing ethinyl estradiol, 0.02 mg, and desogestrel, 0.15 mg. MAIN OUTCOME MEASURE(S): Degree of satisfaction with therapy. RESULT(S): Six patients in the cyproterone acetate arm and nine in the oral contraceptive arm withdrew because of side effects (n = 9), treatment inefficacy (n = 4), or loss to follow-up (n = 2). At 6 months, dysmenorrhea, deep dyspareunia, and nonmenstrual pelvic pain scores were substantially reduced, and significant improvements were observed in health-related quality-of-life, psychiatric profile, and sexual satisfaction; no major between-group differences were seen. Subjective and metabolic side effects were limited. According to an intention-to-treat analysis, 33 of 45 (73%) of patients in the cyproterone acetate group and 30 of 45 (67%) in the oral contraceptive group were satisfied with the treatment received. CONCLUSIONS: Both cyproterone acetate and a continuous monophasic oral contraceptive were effective, safe, and inexpensive therapy for recurrent pain after conservative surgery for endometriosis.     

Influence of a new monophasic oral contraceptive on body metabolism

OBJECTIVES: Androgenic activity as adverse effects of oral contraception can influence on discontinuation of the therapy. New gestagens used in oral contraception do not reveal androgenic activity. The aim of the study is to assess the safety of the therapy with a new monophasic oral contraception on metabolism. MATERIAL AND METHODS: 99 healthy women aged mean 23.5 +/- 2.1 years were enrolled in the study. They received a monophasic contraceptive pill containing 30 micrograms ethinylestradiol and 2.0 mg dienogest during 13 cycles. Biochemical parameters in blood were measured before and after 6 and 12 cycles of therapy. RESULTS: The concentrations of liver enzymes, glucose and lipids did not differ significantly. CONCLUSIONS: The study suggests that a new monophasic oral contraceptive pill containing 30 micrograms ethinylestradiol and 2.0 mg dienogest is safe and good tolerated preparation.     

Safety and efficacy of fluoxetine in patients who receive oral contraceptive therapy

OBJECTIVE: Because many women who receive pharmacologic therapy with antidepressants are also prescribed oral contraceptives, it is important to assess the risk of clinically significant drug interactions. We reviewed the United States fluoxetine clinical trial database, specifically analyzing women ages 18 to 45 years, for differences in safety, antidepressant efficacy, and unplanned pregnancies that were associated with oral contraceptive use. STUDY DESIGN: Data from 17 double-blind, placebo-controlled clinical trials in 1698 women were analyzed retrospectively. A subgroup of women with oral contraceptive use was compared with a subgroup of women with no oral contraceptive use. Differences in treatment-emergent adverse events, unplanned pregnancies, and 17-item Hamilton Depression Scale (HAMD-17) scores were analyzed. RESULTS: The only treatment-emergent adverse events that showed a statistically significantly different odds ratio for oral contraceptive use versus no oral contraceptive use were headache, asthenia, and pain. There was not a statistically significant interaction in the incidence of unintended pregnancies (P =.111) or in the changes from baseline in HAMDD-17 scores. CONCLUSION: There is no clinical evidence that concomitant use of oral contraceptives and fluoxetine affects the safety or efficacy of either agent.     

The Relationship of Oral Contraception to Depressive Symptoms

Summary : A double-blind cross-over trial involving 45 patients was carried out to determine the relationship between oral contraception and pharmacologically-induced depressive symptoms. Oral contraception produced pharmacological symptoms in 15% of women from a selected group, of whom half had previously experienced adverse side-effects from the contraceptive pill. This depression occurred in 2 forms. Three women had endogenous depression which increased on oral contraception, becoming worse during the second month of therapy. A fourth woman had reactive depression due to associated nausea and vomiting which improved during the second month of therapy. "Scapegoat" depressive symptoms were at least as common as pharmacological effects when taking oral contraception. About half the number of women with a history of depressive ill-nessness experienced an increase in depression on oral contraception. Oestrogen-progesterone balance was not important in the development of depressive side-effects; the latter bore no relationship to the cytohormonal status of the patient, either before treatment or during oral contraceptive therapy.     

Pregnancy in premature ovarian failure after therapy with oral contraceptives despite resistance to previous human menopausal gonadotropin therapy

We report the case of a 35-year-old woman with premature ovarian failure that was documented at 29 years of age, who wanted to conceive. Although she failed to respond to high doses of menotropin therapy, she ovulated and conceived after she took an oral contraceptive. The oral contraceptive was used to reduce the elevated level of gonadotropins in an effort to restore receptors to the luteinizing hormone and follicle-stimulating hormone, which theoretically may have been down-regulated.     

Erythema multiforme limited to the oral mucosa in a teenager on oral contraceptive therapy

BACKGROUND: Erythema multiforme has been linked to numerous drugs and infectious agents. A link to oral contraceptive use has been reported in the past in the adult population but thus far has not been reported in children or adolescents. CASE: We report the case of an 18-yr-old female who developed oral erosions consistent with erythema multiforme two and a half weeks after initiating therapy with an oral contraceptive agent. A thorough examination for other inciting factors was negative, and the lesions slowly resolved over the course of 3 weeks. CONCLUSIONS: This case illustrates that erythema multiforme should be considered in the differential diagnosis of adolescents with oral erosions who have been prescribed oral contraceptives.     

Pregnancy after treatment with the insulin-sensitizing agent troglitazone in an obese woman with the hyperandrogenic, insulin-resistant acanthosis nigricans syndrome

OBJECTIVE: To report a case of unassisted pregnancy after 5 months of troglitazone treatment in a severely hyperandrogenic, insulin-resistant woman with acanthosis nigricans (HAIR-AN) previously managed with depot leuprolide acetate (LA) plus oral contraceptive and dexamethasone therapy. DESIGN: Case report. SETTING: Private infertility clinic. PATIENT(S): A 28-year-old African-American woman with excessive obesity (body mass index = 42 kg/m2) and HAIR-AN syndrome. INTERVENTION(S): Androgen suppression with depot LA plus oral contraceptive and dexamethasone therapy, troglitazone treatment resulting in normalization of fasting insulin and testosterone, spontaneous menses, and an unassisted pregnancy. MAIN OUTCOME MEASURE(S): Luteinizing hormone and testosterone concentrations, fasting insulin and glucose levels, insulin-glucose ratios, hCG levels, and ultrasound examinations. RESULT(S): Spontaneous menses followed by an intrauterine pregnancy after 5 months of treatment with troglitazone, an insulin-sensitizing agent, in a woman with severe HAIR-AN syndrome whose hyperandrogenism previously could be normalized only with depot LA plus oral contraceptive therapy and dexamethasone. CONCLUSION(S): Troglitazone treatment resulted in attenuation of both hyperinsulinemia and hyperandrogenism in an obese woman with HAIR-AN and resulted in resumption of menses and a spontaneous pregnancy.     

Herpes gestationis

A case of clinically typical herpes gestationis is presented. The diagnosis was confirmed by light microscopy and immunofluorescence studies. The symptoms subsided at delivery, but recurred during subsequent oral contraceptive medication. The newborn infant was affected temporarily. The treatment, the fetal risk and the implications of the diagnosis on future pregnancies and contraceptive therapy are discussed.     

Oral contraceptives and focal nodular hyperplasia of the liver

Summary A variety of benign liver tumors associated with the use of oral contraceptives has been described. However, there is controversy regarding the possible relation of focal nodular hyperplasia of the liver to oral contraceptive therapy. Over a ten-year period at the Soroka Medical Center, two young women were found to have hepatic tumors diagnosed as focal nodular hyperplasia. In both cases the hepatic nodules were an incidental finding at laparotomy and were thought to be metastatic tumors. The clinical and pathological findings in both cases are reported. The features of focal nodular hyperplasia and its possible relation to oral contraceptive use is discussed.     

Health benefits of oral contraceptives

A sizeable literature corroborates the multiple health benefits of oral contraceptive use. The first estrogen/progestin combination pills were marketed to treat a variety of menstrual disorders. Although currently used oral contraceptives no longer carry FDA-approved labeling for these indications, they remain important therapeutic options for a variety of gynecologic conditions. Well-established gynecologic benefits include a reduction in dysmenorrhea and menorrhagia, iron-deficiency anemia, ectopic pregnancy, and PID. Although older, higher-dose pills reduced the incidence of ovarian cysts, low-dose pills suppress follicular activity less consistently. Nevertheless, cycle-related symptoms, including functional cysts, dysmenorrhea, chronic pelvic pain, and ovulation pain (mittelschmerz), generally improve. Women with polycystic ovary syndrome note improvement in bleeding patterns and a reduction in acne and hirsutism. Symptoms from endometriosis also improve with oral contraceptive therapy. Current data suggest that oral contraceptive therapy increases bone density and that past use decreases fracture risk. Oral contraceptives also improve acne, a major health concern of young women. Oral contraceptives provide lasting reduction in the risk of two serious gynecologic malignancies--ovarian and endometrial cancer. The data with respect to ovarian cancer are compelling enough to recommend the use of oral contraceptives to women at high risk by virtue of family history, positive carrier status of the BRCA mutations, or nulliparity, even if contraception is not required. Health care providers must counsel women regarding these benefits to counteract deeply held public attitudes and misconceptions regarding oral contraceptive use. Messages should focus on topics of interest to particular groups of women. The fact that oral contraceptives increase bone mineral density and reduce ovarian cancer is of great interest to women in their forties and helps influence use and compliance in this group. In contrast, the beneficial effects of oral contraceptives on acne resonates with younger women. Getting the good news out about the benefits of oral contraceptives will enable more women to take advantage of their positive health effects.     

The contraceptive and hormonal requirements of the premenopausal woman: the years from forty to fifty

There is a growing awareness that many women over 40 require both contraceptive protection and hormonal replacement for the symptoms of the climacteric. These women are still menstruating and the risk of pregnancy remains, overshadowed by the increased life-threatening risk due to childbirth in this age group. The risk of mortality due to the use of oral contraceptives is little increased for the nonsmoking woman in the over 40 years compared with the years under 40. In contrast, women over 40 who smoke are best advised not to use hormonal contraceptives. It is evident from all the existing data that combination therapy is strongly advised if any replacement therapy is to be given a woman. There is considerable evidence suggesting that estrogen alone may be insufficient therapy and progestogen should be added to prevent endometrial hyperplasia, decrease the risk of breast cancer and prevent bone loss. In the premenopausal woman, such therapy should also provide contraception. Many physicians allow women 35 to 45 who do not smoke to continue on an oral contraceptive if there is no contraindication. However, a minimum-dose product has yet to be found close to the ideal of fulfilling both the contraceptive and therapeutic needs of women traversing a physiologically very hazardous period.     

Benign cholestatic jaundice of pregnancy and benign cholestatic jaundice from oral contraceptives

A discussion of benign cholestatic jaundice of pregnancy and from oral contraceptives is presented. It has been established that recurrent cholestatic jaundice of pregnancy is caused by interference with liver secretory processes such that conjugated bilirubin accumulates in the blood stream. The condition maybe caused by a possible inherited metabolic effect resulting in an increased secretion of estrogen and progesterone. Women with a history of cholestatic jaundice of pregnancy may experience generalized pruritus or cholestatic jaundice if they are on an oral contraceptive regimen. Pruritus may be a symptomatic sign of the onset of cholestatic jaundice and in women using oral contraceptives, the condition indicates the possible development of choletic jaundice during pregnancy. Cholestatic jaundice will usually disappear 1 to 8 weeks after parturition or the cessation of oral contraceptive therapy.     

Does the pill cause post-pill amenorrhoea?

An attempt is made in this paper to analyze the available epidemiological, pharmacological, endocrinological, and clinical data concerning the relationship of amenorrhoea to previous treatment with the oral contraceptive. Amenorrhoea is defined as an interval without vaginal bleeding which has lasted for 180 days (6 months) or more since the last menstrual period. Post-pill amenorrhoea is defined as amenorrhoea occurring immediately following the withdrawal bleed that comes after discontinuation of an oestrogen and progestogen containing oral contraceptive. Although available information on epidemiological grounds is limited, it does not appear likely that previous use of the oral contraceptive is associated with more cases of amenorrhoea than occur in the general population. It is clear that if the pill does cause amenorrhoea the effect is idosyncratic and not related to the specific formulation, dose or duration of therapy. 1 hypothesis to account for these data has been the contraceptive therapy may "bring out" a preexisting tendency, i.e. that post-pill amenorrhoea is likely to occur in a subject with an hypothalamic-pituitary-ovarian axis whose normal function is in some way specially vulnerable to impairment by exogenous sex steroids. Yet, post-pill amenorrhoea does not occur exclusively in women with previously irregular cycles. Also, the clinical and endocrinological information that exists provides no support for an aetiological role for the pill. Moreover, the risks of accepting a causal association are very great. 1st such an explanation may delay diagnosis and treatment of important and often remediable conditions. 2nd, it may deny a woman subsequent contraceptive protection with this highly effective and convenient preparation.     

Effects of third-generation oral contraceptives on high-sensitivity C-reactive protein and homocysteine in young women

OBJECTIVE: To evaluate the effect of third-generation oral contraceptives on high-sensitivity C-reactive protein (CRP), homocysteine, and lipids levels in a population of young, fertile, nonobese women. METHODS: Blood markers were evaluated in 277 healthy white women (mean age 23 years and mean body-mass index 21 kg/m(2)). Seventy-seven oral contraceptive users were compared with 200 non-oral contraceptive users. Progressive cutoffs of high-sensitivity CRP and homocysteine levels were examined. RESULTS: Levels of high-sensitivity CRP posing a high risk of cardiovascular disease (3.0 to less than 10.0 mg/L) were found in 27.3% of oral contraceptive users and in 8.5% of non-oral contraceptive users (odds ratio 4.04; 95% confidence interval [CI] 1.99-8.18). Levels of high-sensitivity CRP at intermediate risk (1.0 to less than 3.0 mg/L) were found in 32.5% of oral contraceptive users and in 11.0% of non-oral contraceptive users (odds ratio 3.89; 95% CI 2.03-7.46). Notably, non-oral contraceptive users were 8.65 (95% CI 4.39-17.1) times as likely to demonstrate a protective level of high-sensitivity CRP (less than 0.5 mg/L) compared with oral contraceptive users. Oral contraceptive use increased serum triglycerides (P<.001) and total cholesterol P=.001); however, high-density lipoprotein, not low-density lipoprotein, contributed to this increase. A decreased ratio of low-density lipoprotein to high-density lipoprotein cholesterol was observed in oral contraceptive users compared with nonusers (P=.016). Oral contraceptive use did not affect homocysteine levels. CONCLUSION: Third-generation oral contraceptive use increases low-grade inflammatory status measured by high-sensitivity CRP concentrations. Alteration of inflammatory status in oral contraceptive users could affect the risk of venous thromboembolism, cardiovascular disease, and other oral contraceptive-associated adverse conditions in young women.