Oral contraception for women in their 40s.
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Adult↗
Biomedical subjects
D R Mishell
Publications and source records attributed to D R Mishell.
Comparison of TestPack and Ovustick for predicting ovulation.
A study was designed to compare two methods of predicting the time of ovulation by detection of the urinary luteinizing hormone (LH) surge with two immunoassay kits designed for home use. A newly developed kit, TestPack, was compared with an existing kit, Ovustick. A group of 20 women with regular cycles were studied for one menstrual cycle. Ovulation was established with a serum LH surge and disappearance of the dominant follicle using transvaginal sonography followed by a rise in the serum progesterone level. In the 20 subjects, presumptive evidence of ovulation was obtained by determining the LH surge and the subsequent progesterone peak. In 18 of the 20, disappearance of the dominant follicle was also documented. Ovulation was predicted in 17 of the 20 subjects by both TestPack and Ovustick. Both tests were effective in predicting the day of ovulation, but TestPack provided a more easily defined end point and required less time and effort to perform.
Adolescent↗
Correcting misconceptions about oral contraceptives.
Although the majority of American women believe that oral contraceptives can cause serious health problems such as cancer or heart disease, the scientific literature does not support these beliefs. Oral contraceptives actually protect against endometrial and ovarian cancer. The increased incidence of cardiovascular disease in oral contraceptive users, including myocardial infarction, appears to be caused by thrombosis and not atherosclerosis. The studies suggesting an increased risk of cardiovascular disease in oral contraceptive users were published in the late 1970s and therefore used a data base of women ingesting formulations containing 50 micrograms of estrogen or more. More recently published data involving healthy women taking mainly lower estrogen dose preparations suggest that there is no increased incidence of myocardial infarction or stroke. Nearly all published studies indicate that there is no increased risk of myocardial infarction in former users of oral contraceptives. Animal data actually suggest that oral contraceptives may have a protective effect against atherosclerosis, even in the presence of lowered high-density lipoprotein levels. The low-dose triphasic and monophasic formulations are effective, safe methods of contraception that can be used by most healthy women of reproductive age.
Contraceptives, Oral↗
Estrogen replacement therapy: an overview.
Levels of circulating estrogen fall during the perimenopausal period, resulting in changes in the postmenopausal woman's genitourinary tract, central nervous and cardiovascular systems, skin, and bone. Exogenous estrogen minimizes the benign symptoms and prevents the increased incidence of osteoporosis and atherosclerotic heart disease that accompany estrogen deficiency. Thus to avoid the recognized problems of estrogen deficiency, nearly all women should begin a lifelong course of estrogen replacement therapy during the perimenopausal period.
Estrogen Replacement Therapy↗
Norplant: subdermal implant system for long-term contraception.
Norplant offers long-term contraception through the use of subdermal capsules filled with levonorgestrel. The six capsules are implanted in the inside part of the upper arm. The levonorgestrel is released from the capsules gradually, providing contraception for about 5 years. The primary mechanism of action of Norplant is suppression of ovulation. Studies have shown a pregnancy rate of 0.6/100 woman-years after 1 year and a cumulative rate of 1.5/100 woman-years at 5 years. Principal side effects are irregular menstrual bleeding and headaches. No changes in carbohydrate metabolism, blood coagulation, or liver function have been reported. Lipid levels have decreased 5% to 15%. After removal of Norplant, fertility returns rapidly, and there have been no adverse effects on infants. Norplant is currently approved in 12 countries; clinical trials are being conducted in 37 countries.
Administration, Cutaneous↗
Use of progestins.
The question that still remains today is, What is an ideal formulation for administering estrogens? There have been no large-scale, long term studies to answer this question. But the pendulum appears to be swinging from cyclic combination therapy, or sequential combination therapy, to continuous therapy. There is less bleeding and compliance is better. There is no difference in the effects on lipids, and it looks as though the endometrium maintains its atrophy. The future in developing the ideal formulation may lie in this direction; however, more studies need to be coordinated and done in several centers.
Cholesterol, HDL↗
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↗
Correlation of endometrial maturation with four methods of estimating day of ovulation.
Dating of maturity of the endometrium by histologic examination was correlated with four methods of ovulation detection in 13 cycling parous women. Histologic dating was assessed independently by two pathologists and correlated with the postovulatory duration as determined by daily transvaginal ultrasound scanning, serum LH measurements, basal body temperature (BBT), and subtraction of 14 days from the onset of menses. In addition, progesterone and estradiol (E2) were measured in daily serum samples. Dating of the endometrial biopsy was highly correlated (P less than .002) with the day of ovulation as determined by ultrasound, and was found to be within 2 days of the correct postovulatory day on evaluation of 25 of 26 (96.1%) of the interpretations. The accuracy of dating using the LH surge was 84.6% (22 of 26 interpretations), and with the BBT thermogenic shift was 76.9% (20 of 26 interpretations). However, dating of the endometrium was within 2 days of the correct day in only 17 of the 26 interpretations as determined by subtracting 14 days from the onset of the subsequent menses. The accuracy of dating was significantly better correlated (P less than .025) with days from ovulation as determined by ultrasound than as calculated from the onset of menses. There was a significant correlation between endometrial dating and the amount of progesterone (P less than .01) and E2 (P less than .01) secreted from the day of ovulation, as determined by transvaginal ultrasound, to the day of biopsy. These data confirm a strong correlation between endometrial dating and ovarian hormone secretion during the postovulatory phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Response to the antiprogestagen RU 486 (mifepristone) during early pregnancy and the menstrual cycle in women.
RU 486 has wide potential utility as an abortifacient drug when used within the first 6 weeks of pregnancy and has the ability to induce an abortion in about 80% of subjects. Administration of low doses of prostaglandins together with RU 486 increases the success rate. It is possible that alterations in metabolism of RU 486 may explain non-responsiveness to the drug in some women. Mid-luteal phase administration of RU 486 produces bleeding within 72 h and in one-third of subjects there was luteolysis with decrease in serum FSH, oestradiol and progesterone concentrations. Administration of RU 486 in the late luteal phase does not disturb menstrual cycle length, bleeding patterns, ovulation, or hormonal parameters in treatment or posttreatment cycles. However, the drug alone cannot be used as a 'menses regulator' or 'once monthly pill' since some pregnancies do continue. Possibly the efficacy of RU 486 may be enhanced when it is combined with prostaglandins or other agents. Administration of RU 486 in the follicular phase blocks ovulation, delays the LH surge, and is associated with low concentrations of oestradiol. This is presumably the result of gonadotrophin inhibition.
Abortion, Induced↗
Relative frequency of primary ovarian neoplasms: a 10-year review.
The relative frequency of ovarian neoplasms varies according to information in different texts. In an attempt to clarify the distribution of primary ovarian neoplasms by decades of life, a 10-year retrospective review of 861 women with a postoperative diagnosis of an ovarian neoplasm was undertaken. Benign cystic teratoma was the single most common ovarian neoplasm, accounting for 44% of all neoplasms, and was 57% more frequent than benign serous tumors. Germ cell neoplasms were the most common group of benign ovarian neoplasms; epithelial neoplasms were the most common malignant neoplasm. Stromal neoplasms and neoplasms of low malignant potential were uncommon at all ages. The risk that an ovarian neoplasm was malignant increased 12-fold from ages 20-29 to 60-69. The overall risk that an ovarian neoplasm was malignant was 13% in premenopausal women and 45% in postmenopausal women.
Adult↗
Is routine use of estrogen indicated in postmenopausal women? An affirmative view.
A study of age-adjusted all causes of mortality has shown that estrogen nonusers are three times as likely to die of all causes compared with users. The benefit of estrogen is greatest in women who have had their ovaries removed, but benefit also occurs in those who have had a hysterectomy as well as those with intact pelvic organs. A recent British study also reported that women taking estrogen were less likely to die of all causes. Because of the many benefits of estrogen replacement therapy improving both the quality and quantity of life, all women who have this postmenopausal hormone deficiency, except possibly those who are obese, should receive estrogen replacement. The beneficial effects of estrogen replacement therapy are many and there are very few adverse effects.
Attitude of Health Personnel↗
Congenital limb reduction deformities and oral contraceptives.
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Abnormalities, Drug-Induced↗
Use of oral contraceptives in women of older reproductive age.
Evidence of increased risk for cardiovascular disease in oral contraceptive users of older reproductive age is based on early data involving formulations containing higher doses of estrogen and progestin than those in use today. In addition, early studies included patients who would not receive oral contraceptives with today's more stringent prescribing criteria. When these data were carefully analyzed, a significant increase in myocardial infarction was noted only in oral contraceptive users with concomitant risk factors for cardiovascular disease. Analysis of other studies also showed a significant increase in the incidence of cardiovascular disease and mortality only in oral contraceptive users older than age 35 years who smoked. A recent long-term cohort study of women without risk factors for cardiovascular disease who mainly used oral contraceptives containing less than or equal to 50 micrograms estrogen showed no increased risk of myocardial infarction or cerebrovascular accident with oral contraceptive use. Use of oral contraceptives containing less than 50 micrograms estrogen has not been shown to be associated with an increased risk of cardiovascular disease in healthy, nonsmoking women 35 to 45 years of age.
Adult↗
A 9% decrease in cholesterol levels led to a 19% reduction in cardiovascular disease.
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Adult↗
Cholesterol treatment recommendations for adults: highlights of the 1987 report from the National Cholesterol Education Program Adult Treatment Panel.
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Adult↗
Early abortion with a single dose of the antiprogestin RU-486.
RU-486 is a synthetic progesterone antagonist that is abortifacient in early pregnancy. This trial evaluated the effectiveness and safety of a single 600 mg oral dose given to 50 healthy women less than or equal to 49 days from their last menstrual period. Efficacy was inversely related to the initial beta-subunit of human chorionic gonadotropin level, ranging from 100% at less than 5000 mIU/ml to 81% at greater than 20,000 mIU/ml (p less than 0.05). Uterine bleeding was the most serious side effect. However, the mean change in the hemoglobin value 14 days after treatment was -0.4 gm/dl, and no patient required blood transfusion. This regimen appears to be simple, effective, and safe.
Abortifacient Agents↗
Termination of early gestation with the anti-progestin steroid RU 486: medium versus low dose.
RU 486 is a synthetic steroid which has antiprogesterone and antiglucocorticoid activity. In order to determine the optimal dosage of this drug to terminate early pregnancy, we treated 106 healthy women with normal pregnancies by real time ultrasound examination whose gestational duration was less than 49 days from onset of last menses with either a medium or low dose treatment regimen. A total of 66 patients received the medium dose regimen (100 mg/day X 7 days). Another 10 patients received ergonovine (0.2 mg/day X 6 doses) on Day 4 of the same RU 486 treatment regimen. In the first group, 48 (73%) aborted successfully and, of the second group, 6 (60%) aborted. Eighty percent of the subjects in this group of 76 patients reported side effects of nausea and vomiting, heavy bleeding, severe menstrual cramps or headache. All these side effects were successfully treated with analgesic and antiemetic medication. The remaining 30 subjects were treated with a low dose regimen (50 mg/day X 7 days). Of these 30, 15 (50%) aborted; this incidence was significantly less (p less than 0.05). Following the medium dose treatment regimen, the AM cortisol levels were significantly elevated on treatment Days 4 and 8, as compared to baseline (p less than 0.001), although the mean levels were still within the normal range. With the low dose, there was a non-significant rise in AM cortisol values. Thus the rise in cortisol was significantly greater in the former group than the latter (p less than 0.05). With the medium dose regimen, the women who aborted had significantly lower (p less than 0.05) pretreatment mean B-HCG and progesterone levels than the group that failed to abort. Mean serum levels of RU 486 were not significantly different between the group who aborted and those who did not. RU 486 is a promising agent for termination of early pregnancy.
Abortion, Induced↗