Circulating androgen levels before and after oophorectomy in premenopausal and postmenopausal women.

OBJECTIVE: This study aimed to determine the effect of oophorectomy on baseline serum levels of androgens and estrogens in premenopausal and postmenopausal women. METHODS: Fourteen premenopausal and 10 postmenopausal women underwent total hysterectomy and bilateral oophorectomy for benign disease of the uterus. Serum levels of dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), testosterone (T), dihydrotestosterone (DHT), 5α-androstane-3α,17ß-diol-17ß-glucuronide (3α-diol G), estrone (E1), estradiol (E2), and sex hormone-binding globulin (SHBG) were measured by highly specific immunoassays prior to surgery and 2 weeks afterward. Free T and free E2 were calculated. Differences were determined between preoperative (preop) and postoperative (postop) samples, and between premenopausal and postmenopausal women. RESULTS: In premenopausal women, postop levels of total and free T, DHT, and total and free E2 decreased significantly from preop. Postop levels of DHEAS, A, 3α-diol G, and SHBG were decreased, but not significantly different from preop. In postmenopausal women, postop levels of total and free T and total and free E2 decreased significantly from preop, but there was little change in the other compounds. Significant differences in the mean change from baseline between premenopausal and postmenopausal women were observed only for E1 and total and free E2. CONCLUSION: The significant decrease in serum T in postmenopausal women following oophorectomy adds to the evidence that the postmenopausal ovary continues to produce T.

Endometrial effect of progesterone delivered by vaginal rings in estrogen-treated postmenopausal women.

AIM: The type of estrogen and progestin as well as their doses, route and regimens of administration may each affect the benefit-risk profile of postmenopausal hormone therapy. The aim of this study was to evaluate the endometrial effect of progesterone released continuously from a vaginal ring, combined with transdermal estradiol in postmenopausal women. METHOD: Forty-four postmenopausal women participated in a randomized, double-blind, dose-finding study evaluating two hormonal treatments, combining 50 microg/day of estradiol delivered by transdermal patches and either 0.5-g or 1-g progesterone vaginal rings (PVR) given for 12 weeks. The effect on the endometrium was assessed by histology and the detection of the proliferative marker Ki-67. We also measured the serum concentration of estradiol and progesterone, the tissue concentration of progesterone and the immunolocalization of estradiol and progesterone receptors in the endometrium. RESULTS: Endometrial thickness was increased after both treatments, although endometrial histology appeared atrophic in most biopsies. A circulating dose-response of serum progesterone levels was observed from the first to the 12th week of PVR use. In the high-progesterone-dose group, the scarce presence of Ki-67 and hormone receptors reflected the predominant action of progesterone in endometrial glands and stroma, in parallel with a lower tissue concentration of progesterone in this group. CONCLUSION: The PVR appears to be a promising method of administering natural progesterone to postmenopausal women treated with estrogen. Estradiol levels corrected the menopausal symptoms, as expected, and the presence of atrophic endometrium in the majority of women indicated that both doses of progesterone oppose the stimulatory estradiol effects, although the percentage of proliferative tissue was not negligible in both groups.

Fine structure of the human ovum in the pronuclear stage.

A penetrated ovum was recovered from the oviduct of a 33 year old surgical patient who had had sexual intercourse 26 hr before the operation. The ovum was in the pronuclear stage. The ooplasmic organelles were mainly represented by mitochondria, endoplasmic reticulum components, and Golgi elements. Small vesicles were found in the space between the two sheets of the pronuclear envelope. These vesicles appeared to be morphologically similar to the ER vesicles in the ooplasm and were considered to be involved in pronuclear development. Numerous annulate lamellae were seen in the ooplasm as well as in the pronuclei. Ooplasmic crystalloids were also observed. These were thought to represent cytoplasmic yolk. Remnants of the penetrating spermatozoon were found in close relation to one of the pronuclei. The fine structure of the first and second polar body is also described. The nuclear complement of the first polar body consisted of isolated chromosomes, whereas the second polar body contained a membrane-bounded nucleus. In consideration of the possibility that polar body fertilization may take place, these differences in nuclear organization could be of importance. Other recognizable differences between the two polar bodies were presence of dense cortical granules and microvilli in the first polar body, and absence of these structures in the second. These dissimilarities were considered to be related to the organization of the egg cytoplasm at the time of polar body separation.

Roles of estradiol and progesterone in eiliciting the midcycle luteinizing hormone and follicle-stimulating hormone surges.

The positive feedback effects of estradiol (E2) and progesterone (P) on LH and FSH release were studied under novel experimental conditions in three women of reproductive age who had undergone oophorectomy and received uninterupted E2 replacement by subdermal implants. Basal serum E2 levels were in the midfollicular phase range, while LH and FSH levels were normal or slightly elevated. Each volunteer underwent seven experiments at 2- to 4-week intervals, receiving im injections of increasing amounts of estradiol benzoate (E2B) alone and in combination with P. The time and dose of P (administered via P-impregnated polysiloxane intravaginal rings) were varied. In two of the seven experiments, P was given without E2B injections. In all three subjects, increasing serum E2 levels mimicking the preovulatory E2 peak were followed by a surge of LH but not of FSH. However, when serum P levels rose after an increase in serum E2 concentrations had occurred, the LH surge occurred earlier and was accompanied by an FSH peak. When serum P levels rose before serum E2 concentrations had risen or when P levels increased without a rise in serum E2, neither a serum LH nor FSH peak was observed. When administered concomitantly, E2B and P suppressed FSH but not LH levels, while P alone did not affect serum LH or FSH concentrations. These data indicate that an acute rise in serum E2 is a necessary condition for the midcycle LH and FSH surges, that P facilitates or blocks the positive feedback response of gonadotropin release in a time-dependent manner, and that P is required for the preovulatory FSH peak.

Classification of secondary amenorrhea based on distinct hormonal patterns.

Patients with secondary amenorrhea have been classified into 4 clincal groups. In order to further investigate these 4 groups, LH, FSH, and estradiol (E2) were measured at 15 min intervals for 4 h in 21 patients with secondary amenorrhea. Patients within each group had similar hormonal patterns, but there was a distinct variation among the groups. Three patients in group 1 (polycystic ovaries [PCO]) had elevated basal levels of only LH with marked irregular fluctuations. Seven patients in group II (hypothalamic-pituitary dysfunction) had normal basal levels of LH, FSH, and E2. Only LH showed oscillations of varying mahnitude and frequency. Eight patients in group III (hypothalamic-pituitary failure) had low or low-normal levels of LH, FSH, and low E2 with minimal or absent fluctuations. Three patients in group IV (ovarian failure) had high basal levels of FSH and LH and irregular fluctuations. This study confirmed the rationality of separating patients with secondary amenorrhea into 4 different groups. In addition, it was found that in group III patients, the total amount of LH secreted in a 4-hour period of time appears to be insufficient to stimulate E2 production from the ovary even when a single sample was found to be in the normal range.

PIP: Patients with secondary amenorrhea were classified into 4 groups based on clinical evidence. The patients were classified according to the presence of polycystic ovaries (Group 1), hypothalamic-pituitary dysfunction (Group 2), hypothalamic-pituitary failure (Group 3), and ovarian failure (group 4). These groups were further characterized by measurement of luteinizing hormone (LH), follicle stimulating hormone (FSH), and estradiol (E2) every 15 minutes for 4 hours. 3 patients in Group 1 showed elevated basal levels of LH with inconsistent fluctuations. Normal basal levels of LH, FSH, and E2 were observed in 7 patients in Group 2, though there were oscillations in LH levels of varying magnitude and frequency. Low or low-normal levels of LH, FSH and E2, with minimal or no fluctuations, were found in 8 patients in Group 3. In this group, the total amount of LH secreted over the 4-hour period was insufficient to stimulate E2 production from the ovary. 3 patient in Group 4 showed high basal levels of FSH and LH, with irregular fluctuations. The results support the approach of classifying patients with secondary amenorrhea in 4 groups.

The modulating role of obesity and 17 beta-estradiol (E2) on bound and unbound E2 and adrenal androgens in oophorectomized women.

17 beta-Estradiol (E2) pellet replacement therapy for oophorectomized women has been shown to be safe and effective. Some investigators have advocated the addition of testosterone (T) pellets for oophorectomized women. This study was carried out to measure the level of androgens in oophorectomized women with and without E2 pellets. The possible modulating role of E2 upon adrenal androgens was investigated as well as the effects of obesity on bound and unbound serum levels of E2 and T. Seven obese patients and eight nonobese normal patients with E2 pellets were compared to nine oophorectomized age- and weight-matched control women not receiving estrogen. Obese patients had higher levels of androstenediol (Adiol) and androstenedione (A) than nonobese patients, yet compared to oophorectomized controls, nonobese patients had higher levels of dehydroepiandrosterone sulfate (DHEA-S) and Adiol. As a group, patients with E2 pellets had higher levels of DHEA-S, Adiol A, and unbound T compared to oophorectomized controls, and their Adiol and total and unbound T levels were similar to those of premenopausal females. Obese patients had lower levels of total E2, yet a higher percentage of unbound E2, resulting in unbound E2 levels which were similar to those of the nonobese women. Unbound T was higher in obese patients compared to the nonobese women and oophorectomized controls. In conclusion, these data suggest that 1) there may be a modulating role of E2 on adrenal androgens exemplified by an increased serum level of delta 5-3 beta-ol androgens in women with E2 pellets, 2) supplemental T implants for oophorectomized women may not be necessary, and 3) obese women with pellets have higher levels of Adiol, A, and unbound T then nonobese women and therefore have a higher ratio of androgen to estrogen.

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.

Changes in physiologically free circulating estradiol and testosterone during exposure to levonorgestrel.

PIP: The biological activity of circulating sex steroids is dependent upon the relative binding to (SHBG) sex hormone-binding globulin. Only that fraction which is not specifically bound to the high affinity binding protein is available to the receptors or for metabolism. (D-Ng) Levonorgestrel, a synthetic gestagen used for contraception decreases the hepatic production of SHBG. Volunteers wearing contraceptive vaginal rings containing (E2) estradiol and d-Ng were studied to determine the changes in sex steroid binding which occur when d-Ng is administered in a sustained release fashion. The % of steroids not specifically bound to SHBG was measured by fractionating the serum proteins with ammonium sulfate precipitation. A binding capacity assay was used to quantitate SHBG. During the normal menstrual cycle in control subjects, the unbound fractions of both E2 and (T) testosterone remained constant at about 25% of total E2 and 10% of total T. During treatment with d-Ng, however, the % of unbound E2 increased to about 80% of the total, and that of T increased to about 55% of the total, significantly greater than that in the control cycles (p 0.01). SHBG was constant during the normal menstrual cycle, averaging 85.9 + or - 1.92 nM but was suppressed during the administration of d-Ng to 10.0 + or - 2.6 nM. When SHBG concentration was greater than 50 nM, the % binding of both E2 and T were independent of the concentration of this binding protein. When SHBG was suppressed below 50 nM, the % binding of E2 and T was directly related to the concentration of the binding protein. The affinity of SHBG for d-Ng allows competition with E2 and T for SHBG-binding sites at concentrations of SHBG below 50 nM. The increase in physiologically free E2 and T, therefore, may be a result of both the suppression of SHBG concentration by d-Ng as well as the competition between d-Ng and endogenous sex steroids for the decreased number of available binding sites on SHBG.^ieng

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.

Gonadotropin insufficiency in patients with thalassemia major.

To elucidate whether the cause of sexual maturational arrest in thalassemia major is of hypothalamic or pituitary etiology, three female and two male patients were extensively studied. After the iv administration of 150 micrograms gonadotropin-releasing hormone (GnRH) and 500 micrograms of TRH, all patients demonstrated a minimal LH and no FSH response, with variable PRL and TSH responses. The test was repeated after the patients received 100 micrograms GnRH im daily for 7 days. The LH, FSH, PRL, and TSH responses were similar to those obtained previously. The female patients were then retested twice, after priming with 17 beta-estradiol (2 mg daily for 7 days) and again after treatment with human menopausal gonadotropins. The male patients were treated with hCG and, after testosterone reached normal adult male values, the GnRH-TRH stimulation test was repeated. In both the female and male patients, the pituitary responses remained unchanged. These results demonstrate the presence of primary gonadotropin insufficiency as well as the lack of positive estrogen feedback mechanism in patients with thalassemia major. The site of this abnormality has been demonstrated to be the pituitary gland, since hemosiderosis of the pituitary without hypothalamic involvement has been found at autopsy in one patient.

Transitory hCG-like activity in the urine of some IUD users.

Using an antiserum (H-93) specific to the COOH-terminal peptide of hCG beta and gel chromatography, we found the transitory (1-2 days) presence of a gonadotropin having immunological, biological, and physical similarity to hCG, but not typical hLH, in the late luteal phase (days 24-29) urine of some (5 of 26) IUD users. We did not detect hCG in sera from any of the women. Although the source of the hCG-like gonadotropin is unknown, the data suggest that late luteal phase implantation may have occurred transiently.

Measurement of serum LH, FSH, progesterone, 17-hydroxy-progesterone and estradiol-17beta levels at 4-hour intervals during the periovulatory phase of the menstrual cycle.

PIP: Measurement of serum luteinizing hormone (LH), follicle stimulating hormone (FSH), progesterone, 17-hydroxyprogesterone, and estradiol-17beta in 4 women every 4 hours during the midcycle LH peaks preceded by estradiol peaks and followed by ovulatory levels of serum progesterone (greater than 3 ng/ml). 48 hours was the average length of the LH peak, and 36-62 hours later progesterone rose to ovulatory levels. 17-hydroxyprogesterone rose after the initial onset of the midcycle LH surge in 2 subjects and concomitant with the onset in the other two. The estradiol peak occurred prior to the midcycle rise in 17-hydroxyprogesterone in all subjects. It was postulated that the incr ease in 17-hydroxyprogesterone secretion occurs as a result of the LH surge. In 2 subjects estradiol levels were declining prior to the initiation of the LH surge and in 2 they were not; therefore, it was suggested that estradiol may not be the mechanism for the midcycle release of LH.^ieng

Serum medroxyprogesterone acetate (MPA) concentrations and ovarian function following intramuscular injection of depo-MPA.

A sensitive radioimmunoassay measuring serum medroxyprogesterone acetate (MPA) has been developed in order to measure and correlate serum MPA concentrations and ovarian function in women following im administration of deop-MPA (DMPA), employing goat anti-MPA-3-(O-carboxymethyl) oxime-bovine serum albumin and MPA-3-(O-carboxymethyl) imino-125I-iodohistamine. In the 3 women studied, im injection of 150 mg of DMPA yielded brief initial serum MPA concentrations ranging from 1.5 to 3 ng/ml for a few days. Serum MPA concentrations gradually declined and remained relatively constant at about 1 ng/ml for 2 to 3 months, declined gradually thereafter reaching 0.2 ng/ml during the 6th month and became undetectable (less than 0.02 ng/ml) about 7-1/2 to 9 months following administration. Serum estradiol remained at early to midfollicular phase levels for 4 to 6 months after DMPA injection and rose to preovulatory levels when serum MPA levels fell below 0.5 to 0.25 ng/ml. Ovulation, however, as evidenced by serum progesterone concentrations did not occur, apparently due to suppression of the LH peak by positive feedback inhibition. Prolonged inhibition of cyclic ovarian function following DMPA injection is caused by slow MPA absorption and persists until serum MPA levels have decreased below 0.1 ng/ml or become undetectable about 7 to 9 months after DMPA administration.

PIP: Serum medroxyprogesterone acetate (MPA) concentrations were measured by a newly developed, highly sensitive, radioimmunoassay technique, and ovarian function was evaluated in 3 women after a single im injection of MPA (150 mg). Initial MPA concentrations ranged from 1.5 to 3 ng/ml for the 1st few days, and then gradually declined to a relatively constant level of about 1 ng/ml for 2-3 months. During the 6th month, MPA concentrations had declined to about .2 ng/ml, and became undetectable between 7!-9 months. Serum estradiol levels remained at early or midfollicurlar phase values for 4-6 months following injection, and then increased to preovulatory values (.25-.5 ng/ml). However, ovulation did not occur as determined by serum progesterone concentrations. Prolonged suppression of ovarian function by depo-MPA is due to the slow release of MPA; from the injection site.

The effect of olestra on systemic levels of oral contraceptives.

The effect of olestra, a nonabsorbable, noncaloric fat replacement, on the absorption and efficacy of a highly lipophilic oral contraceptive was investigated in a double-blind, placebo-controlled crossover study with 28 women. Subjects consumed 18 gm/day olestra for 28 days while taking an oral contraceptive containing 300 micrograms of norgestrel and 30 micrograms ethinyl estradiol (Lo/Ovral-28). Blood taken on days 12 to 14 of the treatment cycles was analyzed for ethinyl estradiol and norgestrel. There was no statistically significant difference in time to attain maximum concentration, maximum concentration, or area under the concentration-time curve between the olestra and placebo treatments for either drug component. Measurements of serum progesterone indicated that olestra ingestion did not reduce efficacy as indicated by ovulation. The data show that ingestion of 18 gm/day olestra did not affect the absorption or efficacy of the highly lipophilic oral contraceptive.

Vitrectomy for the treatment of full-thickness stage 3 or 4 macular holes. Results of a multicentered randomized clinical trial. The Vitrectomy for Treatment of Macular Hole Study Group.

OBJECTIVE: To prospectively assess the risks and benefits of vitrectomy surgery for eyes with stage 3 or 4 macular holes. DESIGN: A multicentered, controlled, randomized clinical trial. SETTING: Community- and university-based ophthalmology clinics. PATIENTS: One hundred twenty patients (129 eyes) with stage 3 or 4 macular holes. INTERVENTIONS: Standardized macular hole surgery vs observation alone. MAIN OUTCOME MEASURES: Four measures of best-corrected visual function, standardized photographic evaluation of the extent of hole closure, evaluation of lens opacification, and determination of adverse events. Outcomes were determined at 6 months after randomization. RESULTS: Compared with observation alone, a significant benefit due to surgery was found in the rate of hole closure (4% vs 69%, P < .001). After adjusting for baseline visual acuity, hole duration, and maximum hole diameter, a significant benefit due to surgery was found in visual acuity for the Bailey-Lovie Word Reading (P = .02) and the Potential Acuity Meter (P < .01) tests; a marginally significant benefit due to surgery was found in visual acuity for the Early Treatment Diabetic Retinopathy Study chart (P = .05). Although the proportion of eyes achieving a change in visual acuity of 2 or more lines on the Early Treatment Diabetic Retinopathy Study chart was significantly greater for the surgery group vs the observed group (11 [19%] of 59 eyes vs 3 [5%] of 58 eyes, adjusted P = .05), 20 (34%) of 59 eyes randomized to surgery had a loss in visual acuity of 1 or more lines. Compared with the observation group, eyes randomized to surgery had higher nuclear sclerosis scores (2.4 vs 1.3, P < .001). Fourteen adverse events were noted in the surgery group; none were noted in the observed group. CONCLUSIONS: Some visual benefit of vitrectomy surgery for macular holes exists, despite a notable incidence of adverse events. The large variability in visual acuity outcome in the surgical group may be because of complications or progressive cataract. A study of the long-term outcome after macular hole surgery is needed.

Methotrexate prophylaxis for persistent ectopic pregnancy after conservative treatment by salpingostomy.

OBJECTIVE: To investigate whether the incidence of persistent ectopic pregnancy after linear salpingostomy can be reduced by prophylactic administration of a single dose of methotrexate postoperatively. METHODS: Women who underwent linear salpingostomy for treatment of unruptured ectopic pregnancy and who agreed to participate in the study (n = 129) were randomly assigned to the prophylaxis or control group. Women with anemia, renal insufficiency, or liver disease were excluded. In the prophylaxis group, patients received a single dose of methotrexate, 1 mg/kg intramuscularly, within 24 hours postoperatively. No treatment was used in the control group. Both groups were followed with serial serum beta-hCG titers; titers were measured on the seventh postoperative day, then every 72 hours until levels were lower than 15 mIU/mL. A blood count and chemistry panel were also obtained on postoperative day 7, and any side effects related to methotrexate were noted. Persistent ectopic pregnancy was defined as a rise in the serum beta-hCG level or a decline of less than 20% between two consecutive measurements taken 3 days apart. RESULTS: A total of 116 women completed the postoperative follow-up: 54 in the prophylaxis group and 62 in the control group. Ten women had persistent ectopic pregnancy, one in the prophylaxis group (1.9%) and nine among the controls (14.5%); this difference was statistically significant (P < .05). The relative risk of developing persistent ectopic pregnancy after prophylactic methotrexate was 0.13 (95% confidence interval 0.02, 0.97). Three women (5.5%) reported mild side effects after methotrexate, but these resolved spontaneously. CONCLUSION: The incidence of persistent ectopic pregnancy was significantly reduced after a single prophylactic dose of systemic methotrexate administered postoperatively. This regimen is safe and can be used to decrease the extent of postoperative monitoring after conservative treatment of unruptured ectopic pregnancy.

Progesterone and estradiol patterns in women using an intrauterine contraceptive device.

Levels of progesterone, estradiol, LH, and FSH were measured in daily serum samples obtained from 4 subjects during a control cycle and during the first and fourth menstrual cycles after insertion of an intrauterine device (IUD). In addition, progesterone and estradiol were measured in serum samples obtained from 6 women 3, 4, or 5 months after IUD insertion, and from 6 women more than 1 year after IUD insertion. These measurements were compared to the data obtained from study of a large group of normal cycles. The results indicated that the IUD does not influence follicular maturation, time of ovulation, or corpus luteum function. The IUD did exert a local effect on the endometrium, causing the onset of menses to take place when steroid levels were higher than in control cycles.

PIP: In an attempt to resolve differing results on the effect of the IUD on steroid and gonadotropic levels in women wearing the IUD, levels of progesterone, estradiol, luteinizing hormone, and follicle stimulating hormone were measured in daily serum samples obtained from 4 subjects during a control cycle and during the 1st and 4th menstrual cycles after insertion of an IUD (Lippes loop D or TCu 200). Progesterone and estradiol were measured in serum samples obtained from 6 other women 3, 4, or 5 months after IUD insertion (Copper T) and from these another group of 6 women 1 year or more after insertion. These measurements were compared to data obtained from study of a large group of normal cycles. The results indicated that influence on follicular maturation, time of ovulation, or corpus luteum function by an IUD is absent. The IUD exerted a local effect on the endometrium, causing the onset of the menses to take place when steroid levels were higher than in control cycles.

Size and weight determinations of nongravid enlarged uteri.

Uterine size was estimated in 66 women before hysterectomy by bimanual examination, uterine sounding, and pelvic ultrasound. The results were compared with weight and dimensions recorded after removal. There was greater error in estimation of uterine size using bimanual examination (standard error of the estimate [SEE] = 2.6 weeks) or uterine sounding (SEE = 2.2 weeks) than with ultrasound (SEE = 1.06 weeks). A close correlation existed between uterine size and weight (r = 0.95).

Metabolic parameters and steroid levels in postmenopausal women receiving lower doses of natural estrogen replacement.

This study was carried out to determine whether some of the lowest doses of natural estrogens currently prescribed for postmenopausal women result in significant changes in plasma lipids, urinary calcium, urinary free cortisol, or level of androgens. Twenty-four postmenopausal women were studied and the estrogens ingested were either conjugated estrogens (0.3 or 0.6 mg), piperazine estrone sulfate (0.6 or 1.2 mg), or micronized estradiol (1 mg). Plasma lipids were unaltered, with the exception of a decrease in low-density lipoprotein cholesterol in women receiving conjugated estrogens, 0.625 mg, and micronized estradiol. The fasting calcium: creatinine ratio, which was significantly higher than that of premenopausal women, decreased significantly after treatment with all the prescribed doses. There was no correlation between the initial calcium: creatinine ratio and urinary free cortisol or androgen levels. Urinary free cortisol was in the premenopausal range and did not change with treatment; levels of dehydroepiandrosterone sulfate and testosterone were significantly lower than premenopausal levels but did not change with treatment. In conclusion, these natural estrogens have no effect on lipids, urinary free cortisol, and androgen levels, but they appear to reduce the urinary loss of calcium in the fasting state.

Ovulation induction in amenorrheic women.

Seventy-six patients with primary or secondary amenorrhea who wished to conceive were treated with clomiphene citrate, 2-Br-alpha-ergocryptine, and/or human menopausal gonadotropins (hMG). Of these 71 patients who received clomiphene citrate, 39 (55%) ovulated. Of these 71 patients, 52 had withdrawal uterine bleeding following IM progesterone, and 38 (73%) ovulated; only 1 of the 19 who did not bleed ovulated (P less than 0.001). Ovulation occurred in the former group of patients whether or not they had galactorrhea. Of the 32 patients who failed to ovulate despite treatment with the maximal dose of clomiphene, 250 mg/day for 5 days, 26 received hMG-hCG. All 26 ovulated and 15 conceived. All 8 patients with amenorrhea-galactorrhea who were treated either primarily or secondarily with bromergocryptine ovulated, and 4 conceived. Therefore, the drug of choice for ovulation induction in amenorrheic patients depends on 1) the presence of withdrawal bleeding after progesterone and 2) the presence of galactorrhea. In all patients with progesterone withdrawal bleeding with or without galactorrhea, the initial treatment of choice is clomiphene citrate. In the absence of withdrawal bleeding, hMG should be administered if galactorrhea is absent, and bromergocryptine should be administered if galactorrhea is present.