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Norethisterone acetate and ethinylestradiol in early human pregnancy.

In a double-blind randomized trial, 25 women (8-9 weeks pregnant) received 20 mg norethisterone acetate (NET-AC) and 0.04 mg ethinylestradiol (EE2), 25 women receiving placebo. The patients were followed by ultrasound and the products at curettage studied macroscopically and microscopically. In an open trial, ten patients (5-9 weeks pregnant) received NET-AC + EE2, 11 serving as controls. The concentrations of plasma progesterone, estradiol-17 beta, 17 alpha-hydroxyprogesterone, norethisterone, and FSH were followed. The frequency of intrauterine hemorrhage in early pregnancy was not affected by NET-AC + EE2. Ultrasound was not reliable when studying the occurrence of decidual hemorrhages during early pregnancy. The pharmacokinetics and bioavailability of NET remain unchanged during early pregnancy. The treatment with NET-AC + EE2 had no effect on the heights and the time courses of the mean plasma values of progesterone, estradiol-17 beta, 17 alpha-hydroxyprogesterone, and FSH. No differences were found between treated and nontreated patients in the pathology of the placenta or decidua as determined by both macroscopic and microscopic examinations. The hypothesis of Papp and Gardo, that decidual hemorrhages may be induced in early pregnancy as a consequence of a "withdrawal effect" of hormonal pregnancy tests, is not supported by the results of this investigation.

17-alpha-Hydroxyprogesterone↗

Metabolic changes in women using a long-acting monthly oral contraceptive and return of ovulation on discontinuation.

Metabolic changes were investigated in two groups of women using oral contraceptives for 5 to 16 years. Blood samples were taken during the last cycle of oral contraceptive use and three months post-treatment. One group had used a monthly oral contraceptive (MOC, 3mg quinestrol and 10mg 16-methylene chlormadinone acetate) and the second group a daily oral contraceptive (DOC, 35 micrograms ethynylestradiol and 0.625 mg norethisterone). During treatment there were increases in serum total cholesterol and triglycerides but not HDL-C, in plasma total cortisol but not in renin activity, angiotensin II or urinary free cortisol excretion, in hemoglobin and some coagulation factors but not Factor X or antithrombin III, platelet function or fibrinolysis. The area under the blood glucose concentration-time curve, but not that for serum insulin, was slightly increased and there was no change in fasting blood sugar concentrations. All metabolic parameters, except plasma cortisol, which had shown an increase on treatment, had decreased to control levels within 3 months. Ovulation returned promptly in all women, the mean time being 70 days for Group MOC and 44 days for Group DOC. Thus, in spite of the long duration of use of the oral contraceptives, metabolic changes were minor.

Adult↗

Serum progesterone and norethisterone levels following injection of norethisterone enanthate in different sites and doses.

Serum progesterone (P) and norethisterone (NET) levels following injection of norethisterone enanthate (NETEN) were studied in 11 regularly menstruating women. In 6 subjects 200 mg NETEN was administered to the gluteal (IG) or deltoid (ID) region sequentially. The serum P levels remained anovulatory (less than 4 ng/mL) up to 12 weeks. Serum NET levels were similar whether injection was given IG or ID (paired t - test, NS). In 5 subjects given a 150-mg dose, serum P levels remained anovulatory up to 11 weeks. Serum NET levels declined faster than with the 200-mg dose, but the difference was not significant (Student's t - test, NS). Wide inter-subject variations were seen in both groups. NETEN therefore can effectively be administered in gluteal or deltoid regions. A lower dose of 150 mg may have contraceptive potential on an 8-week schedule.

Adult↗

Maternal plasma estradiol and progesterone levels during therapeutic abortion induced by 16, 16 dimethyl PGE2 p-benzaldehyde semicarbazone ester.

Estradiol and progesterone levels in maternal plasma after administration of 16, 16-dimethyl-PGE2 p-benzaldehyde semicarbazone ester (16,16-PGE2) 6 hourly for abortion were studied in 27 women in the second trimester of pregnancy and in 49 patients with fetal death in utero. Basal maternal plasma levels of estradiol and progesterone measured before prostaglandin injection were significantly lower in cases of fetal death in utero than in the other subjects. After 16,16-PGE2 injection, plasma levels of estradiol and progesterone fell more rapidly and to a greater extent in cases of fetal death in utero than those with normal pregnancy at corresponding gestations; the decline of plasma estradiol levels was quicker and more marked than that of progesterone. Thus, 16,16-PGE2 appears to exert a differential effect on estradiol and progesterone biosynthesis.

16,16-Dimethylprostaglandin E2↗

A clinical pharmacological study of a new type of vaginal delivery system for levonorgestrel.

The pharmacokinetic and pharmacodynamic effects of a new type of levonorgestrel-releasing vaginal device (with an in vitro release rate of 25 micrograms/24 h) were studied in a group of 18 normally menstruating women during a period of 90 days of continuous use. Peripheral blood samples were drawn three times weekly (Mondays, Wednesdays, Fridays) during a pretreatment (control) cycle and during the 90 days (3 segments) of exposure to levonorgestrel and the levels of levonorgestrel, progesterone and estradiol were analyzed. Blood samples were also drawn at frequent intervals during the first day and daily during the first week with the devices in situ. In addition, endometrial biopsy specimens were obtained during days 20-22 of the control cycle and then 6 and 10 weeks following the insertion of the devices for morphometric analysis and for the assay of progesterone and estradiol levels. Following insertion of the devices, plasma levels rapidly rose to 1 nmol/l in 12 hours; a plateau of approximately 1.6 nmol/l was reached in 3-4 days, after which the plasma levels declined in a linear fashion with a daily average rate of 7.4 pmol/l to 60% of the initial level in 90 days' time. Of the 54 treatment segments of 30 days, 68% were anovulatory and 24% showed normal, ovulatory-like estradiol and progesterone levels. A complete set of three biopsies were obtained from 15 of the 18 subjects. Of the biopsies obtained during exposure to levonorgestrel only one exhibited signs of atrophy, 80% showed suppressed or arrested proliferation, and 10% had a normal cyclic appearance.(ABSTRACT TRUNCATED AT 250 WORDS)

Clinical Trials as Topic↗

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

OBJECTIVE: 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. DATA SOURCES: 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. STUDY SELECTION: 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). DATA EXTRACTION: 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. DATA SYNTHESIS: 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. CONCLUSIONS: 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.

Adult↗

Pharmaceutical effect of contraceptive pills on the skin.

Described are the various effects of birth control methods on the skin-mainly those of the contraceptive pill. The equilibrium of healthy skins and mucosa might be affected by these chemicals or pharmaceutical agents, causing different manifestations. The skin and mucosa should be looked upon as integral parts of the human body and its functions even where localized symptoms arise.

Contraceptive Agents↗

Neurology of sex steroids and oral contraceptives.

Under normal circumstances, sex steroids interact with diverse neural substrates to modulate a host of activities essential to the preservation of the individual and the species. In addition, sex hormones play an important role in various human neurologic conditions including strokes, migraine, certain movement disorders and peripheral neuropathies, and possibly even the behavior of CNS neoplasms.

Animals↗

Selection of steroid combinations for oral contraceptives of maximum benefit.

Low-dose oral contraceptives differ in the specific progestin component. Our review of available animal and human data revealed differences between the progestins as to their potencies for estrogenic, anti-estrogenic, androgenic and progesterone effects. Ideally, oral contraceptive formulations should have the minimal effective dose, sufficient to prevent pregnancy but with the fewest metabolic changes. The risk of cardiovascular disease may be predicted by changes in the composition and amount of circulating lipoproteins. Progestins with significant androgenic potency can lower high-density lipoprotein2; that is a possible adverse effect. Randomized, blind, comparative trials of the new multiphasic preparations are needed to determine which ones truly cause the fewest metabolic changes that might be of clinical significance.

Animals↗

Ovarian response in superovulated cycles after suppression with oral contraceptive steroids.

The endocrine response to controlled ovarian hyperstimulation was reviewed in 94 women undergoing in vitro fertilization during 114 cycles. The purpose of this review was to evaluate the effect of short-term oral contraceptive suppression on the recovery of pituitary gonadotropin function and subsequent controlled ovarian hyperstimulation. Seventy-three cycles (64%) were adequate for oocyte retrieval. In 41 cycles (36%) hyperstimulation was discontinued. The serum 17 beta-estradiol value in women with a poor response was 57 +/- 50 pg/ml on day 8 compared with 376 +/- 334 pg/ml in the women who completed in vitro fertilization (p less than 0.05). The majority of women (84.2%) had a prompt response to controlled ovarian hyperstimulation after short-term oral contraceptive suppression. Most discontinuations were due to dominant follicle selection or luteinizing hormone surge and not to oversuppression by short-term oral contraceptives. Clinical pregnancies occurred in 15 women (20.5% of harvests).

Chorionic Gonadotropin↗

Clinical and endocrinologic study of continuous levonorgestrel administration from subcutaneous solid polydimethylsiloxane rods.

Three solid polydimethylsiloxane (Silastic) rods containing levonorgestrel were inserted into the subcutaneous tissue of the volar aspect of the forearm of 8 women. Serum samples were drawn three times a week for 2 months and weekly thereafter for 2 years in 3 of the subjects. The other subjects had serum drawn during the twelfth and last treatment months. Levonorgestrel, estradiol and progesterone were measured in all samples. The subject kept a bleeding record. In comparison to an earlier clinical trial in which 6 hollow capsules of Silastic filled with levonorgestrel were used, the 3 solid levonorgestrel-containing rods provided higher serum levels of levonorgestrel, fewer serum estradiol peaks, only a single episode of ovulation and better bleeding performance.

Adult↗