Progestins and the menopausal woman.
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Calcium↗
Biomedical subjects
D R Mishell
Publications and source records attributed to D R Mishell.
Clinical and laboratory predictors of clomiphene response.
A prospective study was carried out on 158 anovulatory women for the purpose of finding parameters that might predict the clomiphene dose at which ovulation would occur. Both body weight and obesity were positively correlated with the dose required to achieve ovulation (P less than 0.05). Once ovulation occurred, obesity did not affect the ability to conceive. Fifty-eight women who ovulated with various doses of clomiphene, including six women who failed to ovulate, had hormonal measurements performed prior to treatment. Compared with normally ovulating controls, serum luteinizing hormone (LH), the ratio of LH to follicle-stimulating hormone (FSH), serum androgens, unbound testosterone, and unbound estradiol were elevated and sex hormone binding globulin-binding capacity (SHBG-BC) significantly lower in women receiving clomiphene. Although the ovulatory dose of clomiphene was positively correlated with both weight and obesity, neither weight nor any laboratory parameter could accurately predict the clomiphene response.
Androgens↗
Functional capacity of the gonadotrophs during pregnancy and the puerperium.
The nature of secretion of gonadotropin during pregnancy and the puerperium was determined by measuring plasma levels of beta-subunit luteinizing hormone (GnRH) during the first, second, third trimesters of pregnancy, and at 10 days post partum in lactating and nonlactating women. The nonlactating subjects were divided into two groups according to whether hormonal suppression of lactation was used. Baseline and response levels of beta-LH and FSH after GnRH were below the limits of assay sensitivity (less than 0.5 ng/ml and less than 1.5 mlU/ml, respectively) in all pregnant subjects. In contrast, postpartum lactating and nonlactating subjects who received no hormonal treatment for suppression of lactation had a small but significant increase in FSH after GnRH. In lactating women, FSH increased from 1.5 +/- 0.3 mlU/ml to 2.7 +/- 0.3 mlU/ml (p less than 0.05); and in nonlactating subjects, FSH increased from undetectable levels to 2.0 +/- 0.4 mlU/ml (p less than 0.001). Patients who received estrogenic compounds for suppression of lactation had undetectable FSH baselines and no response after GnRH. beta-LH in both lactating and nonlactating women had a variable but not a significant response to one administration of GnRH. In conclusion, our findings indicate that the functional capacity of the gonadotrophs recovered earlier (at 10 days) than previously reported (less than 14 days) after term pregnancy, and the recovery of FSH secretion occurs earlier and is more consistent than the recovery of beta-LH.
Female↗
Longitudinal evaluation of patients with untreated prolactin-secreting pituitary adenomas.
A group of 43 patients with galactorrhea, hyperprolactinemia, and radiographic evidence of pituitary adenomas were followed from 3 to 20 years. Initial polytomography and computerized tomographic (CT) scans revealed no evidence of extrasellar extension. Serum levels of prolactin (PRL) were measured at 6 month intervals, and visual fields were assessed annually. Polytomograms and CT scans were repeated every 9 to 36 months. During the period of follow-up, CT scans (but not polytomograms) indicated tumor enlargement in two patients, both of whom underwent selective transsphenoidal removal of the tumor. Polytomograms and CT scans did not show any change in the other 41 patients, and three of them have resumed normal menses, are no longer lactating, and have normal PRL levels. The initial results of this ongoing study indicate that most patients with small pituitary adenomas can be followed with annual CT scans with or without medical therapy, and that surgical treatment should be reserved for those patients with large tumors, those with visual-field loss, and those who show signs of enlargement of the tumor.
Adenoma↗
A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. I-Use effectiveness. An international comparative trial.
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Acne Vulgaris↗
A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. II-Subjective and objective measures of effects. An international comparative trial.
Comparative clinical trials of 2 sizes of contraceptive vaginal rings and of an oral contraceptive were undertaken at 8 investigational sites (9 clinics). More than 500 women enrolled on each of the 3 study regimens. Side effects of the rings and of Nordette, the oral contraceptive, were evaluated by noting spontaneous complaints, by recording medications taken and by physical examination. Inquiries about changes in the frequency of specific conditions were made at the end of the subjects participation in the first year of the study. The incidence of spontaneous complaints was similar among users of the 2 different-sized rings and of the pill.
Adolescent↗
A multicenter study of levonorgestrel-estradiol contraceptive vaginal rings. III-Menstrual patterns. An international comparative trial.
Menstrual events among users of contraceptive vaginal rings (CVRs), releasing levonorgestrel and estradiol, were studied in comparison with a combined oral contraceptive, Nordette, in multicentered trials. CVRs were made with outside diameters of 50 and 58 mm and released about 250 micrograms and 290 microgram of levonorgestrel and 150 microgram and 180 microgram of estradiol per day, respectively. The CVRs were used continuously for 3 weeks and then removed for 1 week. Both the CVRs and Nordette were perceived to reduce menstrual flow and days of menstrual bleeding. Twenty to 25% of CVR users perceived increased intermenstrual bleeding or spotting. Diaries indicate, however, that on average, CVR users experienced about 1 day per month of bleeding or spotting with the ring in place. CVRs and Nordette produced approximately the same total number of bleeding and spotting days during 6 cycles of use, 27-29, but the small (50-mm OD) ring was associated with somewhat more spotting. This ring was also associated with somewhat more prolonged bleeding and spotting runs and with more prolonged nonbleeding intervals than reported by users of the larger (58-mm OD) ring or of Nordette. Differences among regimens, however, tended to be small even when statistically significant. Evidence from menstrual diaries indicates that these CVRs, and in particular 58-mm ring, provide control over the menstrual cycle comparable to the Nordette.
Adolescent↗
The effect on lipids and lipoproteins of a contraceptive vaginal ring containing levonorgestrel and estradiol.
Lipids and lipoproteins were studied in controls and women using contraceptive vaginal rings (CVRs). The groups were comparable for race, age, parity, obesity indices, alcohol ingestion, smoking, diet and exercise. Fasting blood samples were obtained twice before CVR treatment, after 2 and 7 weeks of treatment and 1 week thereafter. The women using the CVR had a significant incremental reduction of cholesterol from baseline to treatment which was distributed among all the lipoprotein classes. The cholesterol/HDL-C ratio was significantly increased with treatment. All mena changes were within the reference range. The reduction in HDL and especially in the subclasses HDL 2a and HDL 2b were significant and outside the reference range. The LDL/HDL ratio increased significantly, while the LDL/HDL 2a+2b ratio increased significantly outside the reference range with treatment. Of the lipid and lipoprotein measurements that changed significantly with treatment, HDL-C, HDL, HDL 2a LDL/HDL and LDL/HDL 2a+2b changed significantly towards baseline in the 1-week-off treatment. The potential reduction in predicted coronary risk with the use of the CVR suggested by a reduction in cholesterol was counterbalanced by a reduction in HDL-C and increases in the cholesterol/HDL-C and LDL/HDL ratios. The potential clinical implications of these findings remain to be determined.
Adult↗
The effect of a contraceptive vaginal ring and oral contraceptives on the vaginal flora.
Premenopausal women seeking a steroid contraceptive method were allowed to choose between a contraceptive vaginal ring (CVR) containing levonorgestrel and estradiol used in a 3-week in, 1-week out regimen (n=20) and an oral contraceptive (OC) containing levonorgestrel and ethinyl estradiol in a 28-day regimen (n = 10). Cultures from the posterior vaginal fornix were obtained before therapy in both groups and monthly for 6 months for the CVR group and after 1, 3, and 6 months for the OC group. These cultures were streaked on specific media to provide quantitative aerobic and anaerobic, lactobacillus, Candida sp., Gardnerella vaginalis and Neisseria gonorrhoeae counts in micro-organisms per milliliter. A comparison of the number and types of organisms isolated from vaginal cultures obtained initially and at 6 months demonstrated no statistically significant differences in colony counts between CVR and OC users. The results of this study suggest that the use of the CVR is not associated with a greater growth of pathogens than is oral administration of a progestin and estrogen combination.
Adult↗
Termination of early gestation with (15S)-15-methyl prostaglandin F2 alpha methyl ester vaginal suppositories.
Vaginal suppositories containing (15S)-15-methyl prostaglandin F2 alpha methyl ester were administered to 40 subjects, in an attempt to induce an early abortion. All subjects were 49 days or less from their last menstrual period. Ten subjects received a 3-mg suppository followed in 3 hours by a 1 mg suppository, ten subjects received the 1-mg suppository followed in 3 hours by a 3-mg suppository, and twenty subjects received the 3-mg suppository followed in 1 hour by the 1-mg suppository. Twenty-four subjects (60%) had a successful termination of their pregnancy using the two vaginal prostaglandin suppository regimen. All subjects who aborted had 10 percent or less of their pretreatment levels of beta-hCG 7 to 22 days after therapy. Sixteen subjects (40%) did not abort. One of the subjects who failed treatment refused the second suppository due to gastrointestinal side effects and uterine cramping following the insertion of the 1-mg suppository. A second subject had an incomplete abortion and developed mild endometritis. Sixteen subjects reported side effects which included nausea, emesis, diarrhea, uterine cramping requiring analgesia, restlessness, shakiness, and dizziness. The addition of the second vaginal suppository containing this particular prostaglandin analogue did not significantly increase the overall abortifacient activity of this method.
Abortion, Induced↗
Correlation of Ovutron readings and the basal body temperature (BBT) with serum sex-hormone and luteinizing hormone levels.
Prior studies have produced conflicting results about whether a change in electric potential occurs at the time of ovulation. This study was undertaken to determine whether the Ovutron, a digital voltmeter which displays the sign and magnitude of voltage measured when the index fingers are applied to the electrodes, would produce a mix in polarity, some positive and some negative voltages, with 5 consecutive measurements preceding ovulation. This device was used daily in 10 normally ovulating women to determine whether such a mix in polarity occurred during the menstrual cycle and its relationship to the corresponding daily measurements of luteinizing hormone, total immunoreactive estrogen (IRE) and progesterone heralding and confirming ovulation. In addition, the Ovutron readings were compared to the basal body temperature (BBT) measurements. In 8 of 10 women studied with the Ovutron device, a mix in polarity was observed in 2 of 3 consecutive days preceding ovulation and was associated in all but 2 subjects with a 50 pg/ml/day incremental increase in IRE. By comparison, only 4 of the 10 subjects had a "classic" biphasic BBT curve. This novel device should be evaluated in a large group of women employing these and other additional parameters (e.g., ultrasonography) in order to determine its efficacy and whether it has a role in the treatment of infertility as well as contraception.
Adolescent↗
Changes in physiologically free circulating estradiol and testosterone during exposure to levonorgestrel.
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Adult↗
Elevations in unbound serum estradiol as a possible mechanism for inappropriate gonadotropin secretion in women with PCO.
Twenty-three women considered to have polycystic ovarian disease (PCO) were studied in an effort to better understand the mechanism of inappropriate secretion (IGS) which is so characteristic of these women. Criteria for PCO included oligomenorrhea, infertility, an obesity index (ponderal index, PI) < 12, and an LH:FSH ratio > 3. The mean +/- SE weight and PI for this group were 175 +/- 7.5 lbs. and 11.2 +/- 0.2 respectively. Weight was not correlated with steroid levels in PCO or control women. The mean (+/- SE) of serum androgen concentrations (DHEA-S: 2.9 +/- 0.5 micrograms/ml; androstenedione: 2.6 +/- 0.3 ng/ml; and testosterone: 47 +/- 5 ng%) were all significantly higher than those in control women (p < .05). Total serum estradiol (E2) was comparable to those of controls in the follicular phase, while estrone (E1): E2 ratios averaged 2:1. Serum sex hormone binding globulin-binding capacity (SHBG-BC) averaged 56.8 +/- 4.2 nM which was significantly lower than that of controls (p < .05). The percent unbound E2 was significantly elevated in PCO (62% vs 37%). The mass of unbound E2 was also significantly higher in PCO women (40 +/- 3 pg/ml) than in controls (17 +/- 2 pg/ml) (p < .005). Serum LH:FSH ratios had a positive correlation with the relative and absolute concentration of unbound E2. In control women, unbound E2 correlated significantly with LH levels. This suggests that IGS characteristically found in PCO patients and exemplified by elevated LH;FSH ratios, is the result of the feedback response to elevated levels of unbound (i.e., biologically active) E2.
Adolescent↗
A separate mechanism of gonadotropin recovery after pregnancy termination.
To further elucidate the mechanism of return of pituitary secretory function after gestation, eight women were studied for up to 55 days after pregnancy termination. As long as serum estradiol (E2) and progesterone (P) levels were elevated, serum FSH remained low. Four to 6 days after abortion, serum E2 and P decreased to levels seen in the early follicular phase, and thereafter the initial increase in FSH occurred while serum beta-LH remained undetectable. After the initiation of FSH secretion, the levels fluctuated within the normal follicular phase range, resulting in a steady increase of E2 to a mean preovulatory peak of 257 +/- 37 pg/ml at a mean time of 21 +/- 1.3 days after pregnancy termination. This E2 peak was followed by FSH and LH peaks and subsequent ovulation. In contrast to FSH, serum beta-LH levels increased only after PRL-concentrations diminished to 30 ng/ml or less. This initiation of beta-LH secretion followed the advent of FSH secretion in six of eight patients. Therefore, a temporally separate mechanism of FSH and LH secretion after pregnancy termination is theorized. The theory of FSH occurs soon after the E2 and P levels decline while PRL levels are still elevated. However, the secretion of beta-LH increases only after levels have risen from the postabortion decline.
Abortion, Induced↗
Clinical and laboratory evaluation of patients with primary amenorrhea.
Sixty-two patients with primary amenorrhea were retrospectively categorized into 4 groups: 1) breast development absent and uterus present (29 patients), 2) breast development present and uterus absent (9 patients), 3) both breast development and uterus absent (2 patients), and 4) both breast development and uterus present (22 patients). Patients in category 1 were diagnosed as having hypogonadotropic hypogonadism (low or normal follicle-stimulating hormone [FSH]) or gonadal dysgenesis (elevated FSH). Patients in category 2 were diagnosed as having congenital absence of the uterus (female range testosterone [T] or testicular feminization [male range T]). In the 2 patients in category 3, a 46,XY karyotype occurred with an enzyme defect (17,20 desmolase) in 1 and the other had agonadism. In category 4, 5 patients with elevated prolactin and a pituitary adenoma were identified. The remaining 17 patients were divided into 2 groups based on progesterone withdrawal bleeding. Patients who had withdrawal bleeding and had elevated luteinizing hormone level were diagnosed as having polycystic ovaries and patients with normal gonadotropins as having hypothalamic dysfunction. Patients who did not bleed were diagnosed as having hypothalamic failure (normal or low FSH) or primary ovarian failure (elevated FSH). This study demonstrates that it is possible to classify patients with primary amenorrhea into 4 useful diagnostic categories based on physical examination and a minimal laboratory investigation.
Adenoma↗
Feedback effects of estradiol and progesterone upon gonadotropin and prolactin release.
The relationship between estradiol- and progesterone-mediated gonadotropin release and steroid-induced changes in prolactin levels was investigated in an improved human experimental model. Three women who had undergone bilateral ovariectomy were studied after they had received a subcutaneous implant of one 25-mg estradiol (E2) pellet. Serum E2 levels remained between 60 and 125 pg/ml, and serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) concentrations were within the normal or slightly elevated range. Serum prolactin (PRL) levels were normal. Each woman received intramuscular injections of gradually increasing doses of estradiol benzoate (E2B) alone and in combination with progesterone (P) in 7 different experiments. An E2B-induced rise in E2 levels comparable to that observed at midcycle elicited a clearly defined LH surge but no change in FSH and PRL. Rising E2 concentrations followed by increasing P levels caused LH and FSH release but no change in PRL. When only P was administered or when serum P levels rose concomitantly with E2 levels, PRL and gonadotropin levels remained unchanged. These data indicate that a surge of E2 similar to that observed at midcycle triggers an acute release of LH only. Moreover, P levels commensurate with those found at mid-cycle facilitate an E2-mediated LH release and induce a concomitant peak in FSH. The lack of a significant increase in PRL levels suggests that different mechanisms are responsible for the pituitary release of PRL and gonadotropins.
Adult↗
Subdermal estradiol pellets following hysterectomy and oophorectomy. Effect upon serum estrone, estradiol, luteinizing hormone, follicle-stimulating hormone, corticosteroid binding globulin-binding capacity, testosterone-estradiol binding globulin-binding capacity, lipids, and hot flushes.
Subderman estradiol (E2) pellets (25 mg) were inserted immediately after hysterectomy and oophorectomy in 22 menstruating women, ages 29 to 50 years. Serum samples were obtained daily for 7 days, weekly for 4 weeks, and at monthly intervals for 6 months. Although there was significant variation between patients, E2 levels remained within the follicular phase range, averaging 50 to 70 pg/ml for 3 months, and then slowly declining to a mean of 37 pg/ml at 6 months, when new pellets were inserted. Over the entire study period, the E2:estrone (E1) ratio was greater than unity. Subdermal E2 pellets limited the rise in luteinzing hormone (LH) and follicle-stimulating hormone (FSH) after gonadectomy and the levels of LH and FSH 6 months after the insertion of E2 pellets were significantly lower (p < 0.01) than in 20 postmenopausal women who had undergone oophorectomy and whose serum E2 levels were less than 20 pg/ml. Serum corticosteroid binding globulin-binding capacity (CBG-BC) and serum testosterone-estradiol binding globulin-binding capacity (TeBG-BC) remained unchanged with E2 pellets. Although high-density lipoprotein-cholesterol increased significantly (p < 0.05), low-density lipoprotein-cholesterol, total cholesterol, and triglycerides were unaffected, except for a rise in triglycerides in three older women with diabetes mellitus and hypertension. There were no complaints of severe hot flushes. Women who had vasomotor symptaoms had mild or moderate flushes that occurred at 5 or 6 months after replacements of the pellets. Thus, E2 pellets are an effective form of parenteral estrogen replacement therapy and offer both practical and theorteical advantages over other forms of estrogen.
Adult↗
Comparison of metabolic and clinical effects of four oral contraceptive formulations and a contraceptive vaginal ring.
A group of 100 women desiring OC received one of the following four formulations on a randomized basis: (1) mestranol 50 micrograms and norethindrone 1 mg, , (2) ethinyl estradiol 50 micrograms and norethindrone 1 mg, (3) ethinyl estradiol 35 micrograms and norethindrone 1 mg, and (4) ethinyl estradiol 30 micrograms and levonorgestrel 150 mg. An additional 10 women received a CVR containing levonorgestrel and estradiol. Measurement of a large number of serum chemistries, lipids, proteins, clotting factors, and liver enzymes was obtained before and 3 and 6 months after starting medication. Clinical factors such as weight, blood pressure, bleeding or spotting, or any adverse side effects were also recorded. There was no significant difference in the metabolic parameters measured among the four oral contraceptives except the increase in angiotensinogen was slightly less in the groups receiving the compounds with 30 or 35 micrograms estrogen and the groups receiving the norgestrel compound had no increase in triglycerides and a slight decrease in cholesterol levels. When the CVR was compared with all oral contraceptives it was found to produce no change in angiotensinogen levels and a decrease in triglycerides. Some of each group of OC users had a lowering of antithrombin III to abnormal levels but none of the CVR users had his amount of decrease. As oral steroids with 30 or 35 micrograms of estrogen do not produce significantly less metabolic alteration than do compounds with 50 micrograms of estrogen, it is unlikely that their use will reduce the incidence of the uncommon serious adverse effects associated with OC use. However, since the CVR's did not increase angiotensinogen, their use as contraceptives will most likely not produce hypertension and possibly the other serious circulatory problems which are increased in some OC users.
Adolescent↗