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The plasma concentrations of immunoreactive luteinizing hormone-releasing hormone (IR-LH-RH) and LH and the peripheral skin temperature of symptomatic menopausal women were recorded continuously and compared with those of asymptomatic menopausal women. These studies were performed by an intermittent withdrawal technique (n = 13) and a continuous withdrawal technique (n = 3). The mean plasma concentration of IR-LH-RH was much higher in symptomatic than in asymptomatic women by both methods of analysis. Large episodic secretory spikes of IR-LH-RH and a temporal correlation between the IR-LH-RH spikes and temperature elevations was found (P less than or equal to 0.025) only in symptomatic women.

Premenstrual syndrome is an extremely common disorder. Prospective documentation of symptoms and their temporal relationship to menstruation establishes the diagnosis of PMS. Because the pathophysiologic mechanisms causing PMS are still undetermined, therapy for PMS is largely empiric. A number of pharmacologic agents may be used to reduce PMS symptomatology, and therapeutic decisions should be tailored to the individual's symptom complex. Many women will be able to lead more productive lives if PMS is properly diagnosed and intelligently treated.

A patient developed hypertension from unilateral hydronephrosis produced by endometriosis. Her blood pressure fell promptly after decompression of the involved kidney.

A specific and sensitive RIA was developed for measuring immunoreactive LHRH (IR-LHRH) in methanol acid-extracted human plasma. Heparinized blood samples were obtained from normal adult women and men, and the plasma was extracted with methanol, acidified, lyophilized, and stored at -20 C until assayed for LHRH. The lowest detectable levels of IR-LHRH in 1.0-3.5 ml methanol acid-extracted plasma ranged from 0.975-1.95 pg/assay tube, and recovery of synthetic LHRH from plasma averaged 88.6 +/- 2.4% (SE). Gel chromatographic separation analysis revealed comparable elution peaks for endogenous, tritiated, and synthetic LHRH. The plasma extract was also effective in evoking the release of LH and FSH in vitro using isolated rat hemipituitaries. IR-LHRH levels in human peripheral plasma rose 50-fold within seconds after an iv bolus injection of 100 micrograms synthetic LHRH with a return to baseline within 60 min. When the pattern of IR-LHRH secretion in peripheral plasma was studied, episodes of IR-LHRH rise were observed approximately every 60 min in both men and women. The physiochemical and biochemical properties of IR-LHRH suggest that it is an authentic LHRH. The presence of pulses of IR-LHRH suggests that its concentration in peripheral blood reflects changes in levels in the pituitary portal blood.

Pregnancy rates following danazol therapy of endometriosis vary widely. In order to reduce variations in patient selection and establish danazol effectiveness, six collaborative centers evaluated 75 infertile patients with normal infertility screening studies and mild (stage I) endometriosis documented by laparoscopy. Following diagnosis and 3 months coital exposure, all patients were treated with danazol for 6 months, and patient surveillance after danazol therapy lasted at least 12 months, with a range of 12 to 34 months. Of the 75 patients treated, 21 (28%) conceived, and the term pregnancy rate was 20% (15 of 75). The low pregnancy rate observed in these patients suggests that the role of danazol therapy for patients with mild endometriosis and infertility should be reconsidered.

In a prospective, randomized, controlled trial, we evaluated the efficacy of intrauterine insemination (IUI) in 54 couples with cervical factor (CF) infertility and in 19 couples with male factor (MF) infertility. The diagnoses were confirmed by strict criteria and all other etiologies of infertility were ruled out prior to entry. Patients served as their own controls with alternating cycles of washed sperm IUI and whole-ejaculate intracervical insemination (ICI). In 113 paired cycles (mean 2.1 pairs/patient; range 1-7 paired cycles), 13% (n = 7) of CF patients became pregnant by IUI, 7% (n = 4) by ICI, and 6% (n = 3) by intercourse after missing inseminations. Seventy-one percent of IUI pregnancies occurred in the first 2 months. In 45 paired cycles for MF patients (mean 2.4 pairs/patient; range 1-6 paired cycles), two patients conceived, both in the first IUI cycle. These data suggest that pregnancies resulting from IUI occur during early treatment cycles.

Endocrinologic and epidemiologic data indicate that cigarette smoking is antiestrogenic. We found that cigarette smoking is significantly associated with the occurrence of cysts of the ovary among 5,398 college alumnae ranging in age from 21 to 80 years. Data on ovarian cysts were obtained in response to the question: "Did you ever have ovarian cysts? If yes, age occurred and treatment." The prevalence (lifetime occurrence) of cysts of the ovary in the entire sample is 10.2%. Never smokers had a lower lifetime occurrence of ovarian cysts in every age decade than did former smokers or current smokers. The age-adjusted odds ratio (OR) for ever smokers compared to never smokers is 1.5 with 95% CL (1.2, 1.8), P less than .001. For former smokers compared to never smokers, the OR is 1.5, 95% CL (1.2, 1.9); for current vs. never smokers, the OR is 1.4, 95% CL (1.1, 1.8). Smoking was also associated with the earlier occurrence of cysts of the ovary. The 2,622 former college athletes in the sample were at significantly lower risk of ovarian cysts than were the 2,776 nonathletes; OR = 0.8, 95% CL (0.6, 0.9). Young women need to be made aware of the possible adverse effect of cigarette smoking on the ovary.

A variety of nutritional factors influence the bioavailability of calcium and increase a woman's risk of osteoporosis. Eight healthy women completed an 8-week metabolic study designed to investigate the effect of nonalcoholic carbonated beverage consumption on calcium metabolism. Compared with women receiving a control diet, women consuming a diet high in nonalcoholic carbonated beverages demonstrated similar mean serum levels of calcium, ionized calcium, phosphorus, alkaline phosphatase, parathyroid hormone, 1,25-dihydroxyvitamin D3, and osteocalcin. Twenty-four-hour urine volume, creatinine clearance, calcium-creatinine ratio, and phosphorus-creatinine ratio were similar during consumption of the diet high in nonalcoholic carbonated beverages and the control diet. Twenty-four-hour cyclic adenosine monophosphate-creatinine ratio was significantly lower in women consuming the diet high in nonalcoholic carbonated beverage compared with women receiving the control diet (342 +/- 27.4 nmol/mmol vs 409 +/- 22.1 nmol/mmol). Consumption of a diet high in nonalcoholic carbonated beverages on a short-term basis does not appear to affect adversely the serum or urinary markers of calcium metabolism.

To study the association between intrauterine devices (IUDs) and pelvic inflammatory disease, we compared contraceptive histories in 4185 while women--283 nulliparous women with primary tubal infertility, 69 women with secondary tubal infertility, and 3833 women admitted for delivery at seven collaborating hospitals from 1981 to 1983. The relative risk of tubal infertility associated with IUD use was calculated by means of multivariate logistic regression to control for confounding factors, including region, year of menarche, religion, education, smoking, and reported number of sexual partners. The adjusted risk of primary tubal infertility associated with any IUD use before a first live birth was 2.0 (95 per cent confidence limits, 1.5 to 2.6) relative to nonuse. Users of the Dalkon Shield had an adjusted risk of 3.3 (1.7 to 6.1), users of the Lippes Loop or Saf-T-Coil had a risk of 2.9 (1.7 to 5.2), and users of copper IUDs had a risk of 1.6 (1.1 to 2.4). Women who reported having only one sexual partner had no increased risk of primary tubal infertility associated with IUD use. The adjusted risk of secondary tubal infertility associated with use of a copper IUD after a first live birth was not statistically significant (1.5; 95 per cent confidence limits, 0.8 to 3.0), whereas the risk from similar use of noncopper devices was significant (2.8; 1.3 to 5.9). We conclude that tubal infertility is associated with IUD use, but less so with copper IUDs.

Data are presented on the prevalence (lifetime occurrence) of bone fractures among 5398 college alumnae, 2622 former college athletes, and 2776 nonathletes, ranging in age from 21 to 80 years. As expected from increased physical activity, the former college athletes in each age decade from 20 to 70 years and over reported a higher lifetime occurrence (i.e., at any age up to the time of reporting) of bone fractures of all types, than that of nonathletes (40.5 versus 31.9%, P less than .001). However, when athletic activity was accounted for, the former college athletes were at no greater risk of fractures in the menopausal years than were nonathletes. Among women 60 years and over who were fracture-free up to age 40, the rate for any fracture at age 40 or over was 29% for former college athletes compared with 32% for nonathletes, a nonsignificant difference.

This is a preliminary study of a new orally administered alpha-adrenergic agonist, lofexidine, to establish its effectiveness in the control of vasomotor flushes (VMF) in five post-menopausal women. The initial dose of lofexidine, 0.1 mg b.i.d., was increased by 0.1 mg b.i.d. every two weeks until VMF disappeared, until side-effects became intolerable, or until a maximum dose of 0.6 mg b.i.d. was reached. When the maximum dose for these criteria was reached, there was a patient-blinded crossover to placebo. Each patient recorded her VMF each day and was monitored by finger thermistor for three hours every two weeks to record VMF. At the maximum tolerated dose, the patients had an average 74% (P less than 0.001) decrease in subjectively noted VMF, and a 61% (P less than 0.05) decrease in VMF objectively measured by finger thermistor. The side-effects (dry mouth, fatigue, headache) became intolerable for one patient at 0.3 mg b.i.d. and for one patient at 0.5 mg b.i.d. Two patients tolerated 0.6 mg b.i.d. Four patients had a return to near baseline numbers of VMF with placebo. Preliminary evidence indicates that lofexidine is probably effective in the treatment of VMF; however, at doses which completely eliminate VMF, the side-effects may become intolerable.

The vasomotor flush (VMF) is the most common reason for menopausal women to seek hormonal therapy, but the evaluation of therapeutic regimens has been hampered by the observation that placebo therapy can decrease VMF and, until recently, by a lack of objective criteria of measurement of the VMF. Using the objective criteria of temperature elevations (TEs) and luteinizing hormone (LH) pulses, we evaluated the effect of placebo and medroxyprogesterone acetate (MPA) on VMF. MPA and possibly also placebo were found to reduce not only the subjectively noted VMF but also the frequency of TEs recorded. In addition, MPA, but not placebo, significantly reduced the frequency and amplitude of LH pulses. Possible mechanisms of action of MPA and placebo therapy are discussed.

Lower prevalence of non-reproductive system cancers among former college athletes. Med. Sci. Sports Exerc., Vol. 21, No. 3, pp. 250-253, 1989. The prevalence (lifetime occurrence) rates of cancers of nonreproductive organs and tissues were determined for 5,398 living alumnae, 2,622 of whom were former college athletes and 2,776 who had been nonathletes, from data on medical history, reproductive history, athletic training, and diet. The non-reproductive system cancers were divided into two classes: class I, which included cancers of the digestive system, thyroid, bladder, lung, and other sites and hematopoietic cancers (lymphoma, leukemia, myeloma, and Hodgkin's disease), and class II, which included skin cancers and cutaneous melanoma. The former college athletes had a significantly lower prevalence of class I cancers compared to the nonathletes; the age-adjusted relative risk (RR) equals 3.34, 95% confidence limits (1.35, 8.33), P = 0.009. In contrast, the prevalence rates of malignant melanomas and skin cancers did not differ significantly between the former athletes and nonathletes. The age-adjusted RR did not differ from 1.0. The lower prevalence rate of class I cancers among the former athletes is in accord with previous findings of a significantly lower prevalence rate of breast cancer and cancers of the reproductive system among former college athletes compared to nonathletes.

The frequency and causes of ovarian failure among 182 long-term survivors of childhood cancer were examined. Twenty-two patients (12%) had ovarian failure. Ovarian failure was found in 17 of 25 patients (68%) who had both ovaries within abdominal radiotherapy fields, in five of 35 patients (14%) whose ovaries were at the edge of the treatment field, and in none of 122 patients with one or both ovaries outside of an abdominal treatment field (p < 10(-4)). The odds for ovarian failure in patients with both ovaries in the field are 19.7 higher than those for other irradiated patients (95% confidence interval, 5.3 to 72.8). Covariate and multivariate analyses of tumor type, age at diagnosis, duration of follow-up, abdominal tumor surgery, abdominal radiotherapy, number of chemotherapeutic agents administered, and cumulative doses of several drugs revealed that the location of the ovaries relative to radiation treatment fields was the only risk factor for subsequent ovarian failure.

The characterization of the hyperandrogenism of two sisters with type A insulin-resistant diabetes and hirsutism is presented. Testosterone (T) and androstenedione levels were elevated in peripheral serum. These were not markedly affected by infusion of adrenocorticotropic hormone. In patient 1 glucocorticoid suppression decreased T levels by 50% and androstenedione levels by 30% but had no effect on them in patient 2. Estrogen-progestin suppression markedly reduced testosterone levels in both patients. The blood production of T in patient 1 was 0.8 mg/day and in patient 2 was 4.5 mg/day, both of which are elevated. Selective venous catheterization in patient 2 revealed markedly elevated testosterone levels in the ovarian veins, and polycystic ovaries were found at subsequent laparotomy. These endocrine studies have shown that the source of excessive testosterone in these patients is excessive production by the ovaries, and it can be suppressed by oral contraceptives.

Twenty-five symptomatic postmenopausal women with an intact uterus were assigned in random double-blind fashion to receive 0.625 mg of conjugated estrogens on either a cyclic (3 weeks on, 1 week off) or continuous (daily) basis. The incidence of endometrial hyperplasia as demonstrated by screening biopsies at 6 and 12 months of therapy was 4.5 per 100 woman-months in the cyclic group and 3.7 per 100 woman-months in the continuous group (a difference not statistically significant). Thus, in this study, cyclic therapy was found to offer no advantage over continuous therapy. In our opinion, the rate of hyperplasia development in both groups unacceptably high, and efforts must be directed at reducing its incidence primarily.

Hormone levels, physiologic parameters, electroencephalographic (EEG) activity, and changes in subjective feelings recorded using a nonverbal instrumental device were assessed following the double-blind intravenous administration of 500 micrograms of gonadotropin-releasing hormone (GnRH) or placebo to five normal males. Within 30 minutes of GnRH administration, prolactin (PRL) levels had risen by 4.3 +/- 1.2 ng/ml (mean +/- SEM) from a baseline of 8.5 +/- 0.9 ng/ml (overall increase P less than 0.005 vs. baseline, P less than 0.001 vs. placebo); maximally stimulated values had a mean of 16.7 +/- 2.3 ng/ml. The PRL elevations measured in absolute terms significantly correlated with increases in luteinizing hormone (LH) (r = 0.97) and follicle stimulating hormone (FSH) (r = 0.89). No changes in physiologic parameters or EEG activity occurred in response to GnRH, nor were any behavioral responses found. The increase in PRL following GnRH was specifically shown to be unrelated to experimental stress or the behavioral effects of GnRH.

As part of an investigation of the role of gonadal steroid concentrations and testicular function, testosterone (T), estradiol (E2) and dehydroepiandrosterone sulfate (DHEA-S) were measured in bilateral testicular biopsies from infertile men with varicoceles. The biopsies were performed randomly either immediately before or 1 hour after varicocelectomy in an effort to detect acute changes in testicular hormone concentrations. No significant differences were noted between these two groups nor was there consistent evidence of disturbed in vivo Leydig cell function. A wide range of testicular hormone concentrations was found in these biopsies, which did not correlate well with morphologic findings. This suggests that many different pathophysiologic conditions may exist in association with the presence of a varicocele.

During the examination to confirm premature rupture of membranes, amniotic fluid unavoidably contaminated with cervical mucus and other vaginal debris can often be obtained from the posterior fornix. This study was undertaken to determine the validity of phospholipid measurements on contaminated amniotic fluid. Fifteen paired amniocentesis and vaginally contaminated samples of amniotic fluid were used to measure the lecithin/sphingomyelin ratio and saturated phosphatidylcholine (SPC). The amniocentesis specimens had a mean L/S ratio of 3.94 +/- 0.22 (mean +/- SEM), and contaminated samples had a mean L/S ratio of 3.82 +/- 0.29 (mean +/- SEM). Paired t-test was unable to demonstrate a significant difference (p greater than 0.10), and the correlation coefficient between paired L/S samples was r = 0.79. SPC measurements on the amniocentesis fluid had a mean value of 1,243 microgram/DL +/- 217 (mean +/- SEM) as compared to the contaminated-specimen mean of 1.375 micrograms/dl 223 (mean +/- SEM). Paired t-test likewise was unable to demonstrate a significant difference (p greater than 0.10), and the correlation coefficient between paired SPC samples was r = 0.93. Within the design of this study, we were unable to demonstrate a statistically significant effect of brief vaginal contamination on the measurement of the L/S ratio or SPC.

Estrogen replacement therapy at accepted doses is not fully effective in preventing bone loss and fractures in postmenopausal women. Bone densitometry is useful for monitoring estrogen replacement therapy to assess dose, foster compliance, and check for secondary bone loss. The most appropriate site for bone loss monitoring is probably the spine because it shows larger decreases at the menopause than appendicular sites, it shows larger increases with therapy, and it has clinical import in terms of fracture. Both dual-photon absorptiometry (or dual-energy x-ray absorptiometry) and computed tomography are the preferred monitoring methods. The precision of these densitometry methods is generally adequate to permit interim decisions with regard to continuing therapy, as well as conclusive decisions on therapeutic efficacy after 1 to 2 years of monitoring. Judicious use of densitometry in combination with biochemical determinations can enhance therapeutic control and provide both patient and physician confidence in long-term estrogen replacement therapy.

In order to study estrogen absorption from the vagina, 0.5 mg of unconjugated estrone (E1) or 17beta-estradiol (E2) was administered vaginally to 10 postmenopausal patients. A 29-fold increase in plasma E2 and a 4-fold increase in plasma E1 concentrations were observed 1 hour following the vaginal deposition of 0.5 mg of E2. Maximal decreases of 25% and 37% in plasma levels of follicle-stimulating hormone (FSH) and luteinizing hormone (LH), respectively, were observed at 5 hours following treatment. One hour after vaginal administration of 0.5 mg of E1, a 24-fold increase in plasma E1 and a 3.7-fold increase in E2 were observed. These increases were associated with a 30% decrease in plasma FSH and LH. These data indicate that the vaginal administration of E2 or E1 may be used to achieve physiologic blood levels of these estrogens. They further suggest that vaginal estrogens not be used in patients in whom systemic estrogen therapy is contraindicated.

A randomized, double-blind study was performed on 16 women to compare the efficacy of daily subcutaneous (SC) injections of leuprolide acetate (LA; TAP Pharmaceuticals, North Chicago, IL) plus oral placebo tablets (group A, n = 7) with SC LA plus oral medroxyprogesterone acetate (The Upjohn Company, Kalamazoo, MI; group B, n = 9) in the treatment of leiomyomata uteri. Patients in group A had a significant reduction in uterine size from a pretreatment volume of 601 +/- 62 cm3 (mean +/- standard error) to a mean uterine volume of 294 +/- 46 cm3 at 24 weeks of therapy (P less than 0.01). Group B patients had a reduction in uterine volume from 811 +/- 174 cm3 to 688 +/- 154 cm3, which was not statistically significant. However, only one patient in group B experienced hot flashes, whereas six patients in group A had this symptom (P less than 0.01). Both groups demonstrated significant increases in mean hemoglobin concentrations, hematocrits, and serum iron levels at 24 weeks of therapy compared with pretreatment levels.

Eighteen patients with poor reproductive histories and 2 patients with primary infertility underwent Tompkins metroplasty for a septate uterus. There were 19 pregnancies within 2 years of surgery, and 11 patients had at least 1 viable pregnancy, for an overall success rate of 55%. One of the infertile patients conceived and delivered. The average fecundability rate for the first 24 months was 0.078 (normal, 0.20). The cumulative pregnancy rate at 27 months was 94% by the life-table method. The group of patients (n = 14) with two or more losses and no other major risk factors for reproductive failure had higher fecundability and a better success rate (71%). The Tompkins metroplasty is a technically simple procedure with a success rate similar to that of the Jones procedure.

Plasma levels of LH, FSH, prolactin (PRL), and testosterone (T) were assessed in six normal men following administration of a pharmacologic dose of gonadotropin releasing hormone (GnRH) (500 micrograms iv over a one-min period) with concomitant oral administration of either ethanol (0.695 g/kg of body weight over a 15-min period) or ethanol placebo. Acute ethanol administration had no effect on the response of either LH or FSH to GnRH. PRL levels increased following GnRH and administration of both ethanol and ethanol placebo. Ethanol administration enhanced the T response to GnRH (p less than 0.001 vs placebo). During the placebo condition, T levels did not rise significantly until 100 min after GnRH administration, at which time the mean increment over baseline was 101 +/- 20 ng/dl (+/- SEM). In contrast, following ethanol intake, T levels were significantly elevated within 30 min after GnRH administration, at which time the mean increment over baseline was 187 +/- 42 ng/dl. The mean T increments were 304 +/- 62 and 472 +/- 77 ng/dl, respectively, 60 and 105 min following GnRH and ethanol administration. The increase in T levels following acute ethanol intake and concomitant gonadotropin stimulation is in contrast to the well-documented effect of chronic ethanol intake on suppression of testosterone synthesis by testicular Leydig cells.

The prevalence (lifetime occurrence) rate of cancers of the reproductive system (uterus, ovary, cervix, and vagina) and breast was determined for 5,398 living college alumnae, 2,622 of whom were former college athletes and 2,776 nonathletes, from data on medical and reproductive history, athletic training, and diet. The former athletes had a significantly lower risk of cancer of the breast and reproductive system than did the nonathletes. The relative risk (RR), nonathletes/athletes, for cancers of the reproductive system was 2.53, 95% confidence limits (CL) (1.17, 5.47). The RR for breast cancer was 1.86, 95% CL (1.00, 3.47). The analysis controlled for potential confounding factors, including age, family history of cancer, age at menarche, number of pregnancies, use of oral contraceptives, use of estrogen in the menopausal period, smoking, and leanness. Of the college athletes, 82.4% had been on precollege teams compared with 24.9% of the college nonathletes. We conclude that long-term athletic training lowers the risk of breast cancer and cancers of the reproductive system. The lowered risk may be related to changes in estrogen metabolism associated with increased leanness.

Monoclonal antibodies identifying leukocytes subpopulations were applied to smears of laparoscopically collected peritoneal fluid leukocytes and parallel samples of peripheral blood leukocytes from women with endometriosis (n = 33), those with unexplained infertility (n = 9), and fertile controls (n = 8). Peripheral blood leukocyte profiles in all groups were indistinguishable from reported normal values. Peritoneal fluid leukocyte profiles were observed to be different between groups. The most significant elevations in total leukocytes, macrophages, helper T lymphocytes and natural-killer cells were observed in women with stage I and II endometriosis. Significantly elevated levels of total leukocytes, macrophages, and T lymphocytes were also observed in peritoneal fluid from women with unexplained infertility. The results from this study indicate that the peritoneal environment is immunologically dynamic and suggest that cellular immune mechanisms may contribute to reproductive failure in women with endometriosis and unexplained infertility.

Most studies of circulating PTH levels using traditional RIAs have supported the concept of physiological hyperparathyroidism of pregnancy, with pregnant women having serum immunoreactive PTH levels significantly higher than those in nonpregnant subjects. However, such RIAs are insensitive and often detect inactive PTH fragments, so that the correlation between PTH immunoreactivity and bioactivity is poor. Employing a new intact PTH immunoradiometric assay (Allegro-Nichols), we reassessed the effects of pregnancy on parathyroid function. The mean serum PTH level in 81 pregnant women was 14.4 +/- 6.3 (+/- SD) compared to 24.8 +/- 9.0 ng/L in 11 normally cycling nonpregnant women (P less than 0.001). The mean serum total and ionized calcium levels in the 2 groups were similar. In 5 of the pregnant women, serum bioactive PTH, determined by cytochemical bioassay, was slightly lower (7.7 +/- 3.4 ng/L) than in normal individuals (11.1 +/- 1.9 ng/L). Our findings suggest, in contrast with the results of most previous studies, that serum intact PTH may decline during pregnancy.

Seventeen healthy postmenopausal women who had subjectively noted eight or more hot flashes per day and who objectively demonstrated four or more vasomotor flushes of 1.0C or more during eight hours of continuous thermography were studied. They were randomly allocated in a double-blind fashion to either 50 micrograms/day of transdermal estradiol (E2) patch or placebo. Application of the first patch was followed immediately by repeat eight-hour thermography, with hourly measurements of E2 and luteinizing hormone (LH). In the transdermal E2 group only, significant elevations of E2 (mean 91 pg/mL) were noted at two hours, and LH was suppressed after eight hours (P less than .05). There was no immediate effect on vasomotor flushes. Treatment was continued for six weeks, with daily subjective recording of hot flash frequency. Patients on transdermal E2 reported a significant (P less than .001) fall in hot flashes over four weeks, after which the rate stabilized. An initial decline in the placebo group was not statistically different from baseline. Eight-hour thermography was repeated after six weeks of treatment. Patients on transdermal E2 demonstrated an 85% decrease from baseline in vasomotor flushes (P less than .01). No effect on total cholesterol or its subfractions, renin substrate, or aldosterone was found. Serum E2 levels fell by 50% in 24 hours after patch removal. Endometrial histology and vaginal cytology showed an estrogen effect.

We report on data relating to nonalcoholic carbonated beverage consumption and bone fractures in 5,398 college alumnae, 2,622 former college athletes and 2,776 nonathletes, who responded to a detailed mailed questionnaire. A statistically significant association between nonalcoholic carbonated beverage consumption and bone fractures was found only in the former athletes, not the nonathletes. Among the athletes, the age-adjusted odds ratio (OR) for the association of drinkers (yes/no) with any fracture (yes/no) was 1.35, 95% confidence limits (CL) (1.14, 1.59). The dose-response relationship between the amount of carbonated beverages consumed daily and the number of bone fractures of the athletes was also statistically significant. Results of multiple logistic regression analysis, which included only alumnae greater than or equal to 50 years of age and which controlled for current exercise and other potential confounding factors, were as follows: (a) for athletes, the OR for the association of drinking nonalcoholic carbonated beverages and a first bone fracture at or after age 40 was 2.28, 95% CL (1.36, 3.84); (b) for all alumnae, a low milk diet was a risk factor for first bone fractures at or after age 40, OR = 1.92, 95% CL (1.15, 3.16); (c) former college athletes had a significantly lower risk of first fractures at or after age 40 than did nonathletes; OR = 0.63, 95% CL (0.40, 0.99). The deleterious effect of nonalcoholic carbonated beverage consumption on the risk of bone fractures has not been reported, as far as we know.(ABSTRACT TRUNCATED AT 250 WORDS)

Thirty-eight premenopausal women with uterine leiomyomata were enrolled in a randomized, double-blind, placebo-controlled study evaluating the efficacy of depot leuprolide acetate (LA), a gonadotropin-releasing hormone agonist, in decreasing uterine volume. Eighteen women received intramuscular (IM) depot LA 3.75 mg every 4 weeks for 24 weeks (group A); 20 women received IM placebo with the same injection schedule (group B). Group A patients had a mean reduction in pretreatment uterine volume from 505 +/- 93 cu cm (mean +/- standard error of the mean) to 305 +/- 57 cu cm after 12 weeks (P less than 0.05 versus pretreatment) and 307 +/- 57 cu cm after 24 weeks of therapy (P less than 0.05 versus therapy (P less than 0.05 versus pretreatment). At 3 months after cessation of therapy, the mean uterine volume in group A had increased to 446 +/- 92 cu cm (P less than 0.05 versus week 24). Group B patients had no significant change in uterine volume over the 24-week treatment period. These results suggest that depot LA therapy may significantly decrease uterine volume in patients with leiomyomata, but that regrowth of uterine size occurs shortly after cessation of therapy.

In a case of ectopic pregnancy, ultrasound findings showed a pseudogestational sac in the uterus containing debris that mimicked a fetal pole. Ultrasonography done one week before had revealed no intrauterine gestational sac. The progression in one week of an "empty" uterus to a seven-week-sized intrauterine gestational sac with the appearance of a fetal pole without a heartbeat should suggest to the sonographer the possibility of a pseudosac and ectopic pregnancy.

The plasma concentrations of testosterone (T), dehydroepiandrosterone (D), androstenedione (A), pregnenolone (delta 5P), progesterone (P), 17-hydroxypregnenolone (17-delta 5P), 17-hydroxyprogesterone (17-P), 11-deoxycortisol (S), and cortisol (F) were measured before, and 30 and 60 minutes after, a bolus intravenous injection of 25 units of adrenocorticotropic hormone (ACTH) in nine normal women and in fifteen patients with a variety of manifestations of androgen excess. Patients with androgen excess demonstrated significantly higher mean baseline levels of T, D, A, delta 5P, 17-delta 5P, and 17-P. After a bolus intravenous injection of 25 units of ACTH, higher-than-normal increments were noted for the following steroids: delta 5P (one patient), 17-delta 5P (one patient), D (two patients), P (one patients), 17-P (two patients), and S (two patients). Following ACTH injections, the ratios of increments in plasma steroid pairs were computed to estimate the efficiency of several adrenal enzymes, and evidence suggesting partial deficiency of 3 beta-hydroxysteroid dehydrogenase delta 4-5 isomerase (five patients) and 11 beta-hydroxylase (five patients) was found. In addition, 6 of the 15 patients with androgen excess exhibited an abnormally high increment in D relative to the increment in F. The data show that apparent abnormalities in adrenal steroid biosynthesis are a frequent occurrence in patients with hyperandrogenism.

Studied was the peripheral bone density of 39 women (ages 18 to 43) with the diagnosis of secondary amenorrhea in an effort to define the population of amenorrheic women at risk for osteoporosis. Eight women had exercise-induced amenorrhea (athletes), 20 women had amenorrhea associated with weight loss, and 11 women had premature menopause. These diagnoses were made on the basis of history, physical examination, and luteinizing hormone (LH), follicle-stimulating hormone (FSH), and prolactin levels, and failure to have withdrawal bleeding after the administration of progestin. Twenty-five nonathletic, normally menstruating women served as control subjects. The peripheral bone density of the amenorrheic athletes (0.738 g/cm2 +/- 0.047) was not significantly different from that of the controls (0.726 g/cm2 +/- 0.044). The average bone density of the group with weight loss-associated amenorrhea (0.672 g/cm2 +/- 0.066) was significantly less than controls (P less than .005) as was that of the women with premature menopause (0.616 g/cm2 +/- 0.048, P less than .001). There was a significant correlation between months of amenorrhea and decrease in bone density (r = 0.506, P less than .001). From this study it was concluded that women with exercise-associated amenorrhea are not at significant risk for cortical bone loss as measured by direct photon absorptiometry. Women with weight loss-associated amenorrhea and women with premature menopause are at significant risk for bone loss when compared with normal controls.

A study was designed to compared the metabolic fate and the biologic effects of 4 mg of estriol (E3) administered either orally or vaginally to six postmenopausal women. Blood samples were collected every hour for 6 hours and five different estriol fractions as well as gonadotropins were measured. Vaginal E3 administration resulted in a decline of 45% in luteinizing hormone (LH) levels and 17% in follicle-stimulating hormone (FSH) levels at 6 hours after treatment (p < 0.05). In contrast, the administration of 4 mg of E3 orally did not produce a decline of LH and FSH, despite the fact that the serum levels of E3-3-sulfate, E3-3-sulfate-16-glucosiduronate, estriol-3-glucosiduronate, and estriol-16-glucosiduronate were all fourfold to 24-fold higher after oral administration than after vaginal estriol administration. However, since the levels of unconjugated E3 were higher after the vaginal than after the oral administration of estriol, we conclude that only unconjugated E3 suppresses gonadotropins.

Factors influencing the probability of conception following artificial insemination with donor semen (AID) have been investigated in a series of 124 married females. Overall, 79 conceptions were achieved, for a cumulative rate of conception of 85.1% at the end of 1 year and an average fecundability of 15%, using life-table analysis. Women aged 30 or over or those with evidence of tubal or ovulatory problems had decreased probability of conception, although not to a significant extent. Women whose husbands were azoospermic had 20% fecundability in response to AID, significantly better than the 10% fecundability after AID observed in the women whose mates were oligospermic. Cycles during which AID was successful were significantly more likely to have had a positive postcoital test observed, compared with unsuccessful AID cycles.

There is evidence to suggest that abnormalities in the secretion of prolactin (PRL) in patients with the hyperprolactinemia-amenorrhea syndrome are due to hypothalamic dysfunction. In an attempt to further define the inhibitory effect of excessive PRL release on luteinizing hormone releasing hormone (LHRH) and luteinizing hormone (LH) secretory patterns in human plasma, four amenorrheic women with known hyperprolactinemia were studied before and during bromocriptine (BRCR) therapy. Ten-minute blood samples collected with a continuous withdrawal pump for two hours were analyzed for immunoreactive LHRH (IR-LHRH), LH and PRL using previously established radioimmunoassay procedures. Three patients showed a significant rise in mean IR-LHRH plasma levels coincident with a significant decrease in mean PRL concentrations five days to two weeks following BRCR therapy, whereas mean LH titers increased significantly in only one patient. One patient showed no increase in IR-LHRH or LH with BRCR therapy and failed to show a decrease in serum PRL to normal levels after five days of this treatment. A defect in the control of PRL release in these patients seemed to result from the inability of dopaminergic inhibition to be mediated effectively and seemed to be associated with altered secretion of LHRH.

The status of oocytes, the follicular fluid concentrations of steroids, and the in vitro steroidogenic capacities of stromal tissue, thecal tissue, and granulosa cells from a 15-yr-old girl with primary amenorrhea, ovarian hyperandrogenism, insulin-resistant diabetes mellitus, and acanthosis nigricans were compared to those from normal adult human ovaries. Most oocytes (95%) in the antral follicles recovered from the hyperandrogenic ovaries were degenerative, and the antral fluid levels of testosterone were 30- to 200-fold higher than those in normal ovaries. Granulosa cells from the hyperandrogenic ovaries produced mainly estradiol as did those from normal healthy follicles. The thecal tissues produced 2- to 6-fold more androgen than similar tissues from normal ovaries. However, the stroma from the hyperandrogenic ovaries produced 49- to 250-fold more testosterone than that generated by normal tissues. These data suggest that the removal of stromal tissue as well as follicular tissue from patients with certain types of hyperandrogenism may sometimes contribute to a reduction in androgen secretion.

A higher risk of reproductive system disorders, (which include benign tumors, endometriosis, dilation and curettage, hysterectomy, and other disorders requiring gynecologic biopsies) exist among women with cutaneous melanoma as compared to women with skin cancers: The odds ratio (OR) is 3.2, 95% confidence limits (1.0, 10.1), p = 0.049; as compared to a random sample of women with no melanoma or skin cancers, the OR is 3.9, 95% confidence limits (1.2, 12.4), p = 0.021. Confirming the observations of others, the authors found that melanoma was associated with red hair. The data also confirmed the finding that melanoma is associated with significantly fewer pregnancies. The mean numbers of pregnancies in the melanoma group is 1.83 +/- 1.6 (mean and standard deviation) compared to 2.99 +/- 1.9 in the skin cancer group and 2.93 +/- 1.9 in the random sample (p less than or equal to 0.05).