Testosterone-secreting adrenal adenoma that contained crystalloids of Reinke in an adult female patient.

We describe a testosterone-secreting adrenal adenoma that contained crystalloids characteristic of Leydig cells in a 55-year-old woman with virilization, in whom results of a steroid biochemical profile were normal except for a substantially increased serum testosterone level. After right adrenalectomy, the serum testosterone level returned to normal and has remained within the normal range 2 years postoperatively. Histologic examination confirmed the diagnosis of a testosterone-secreting adrenal adenoma with crystalloids of Reinke specific for Leydig cells. The exact pathogenesis of these testosterone-secreting adrenal adenomas is still unclear. Although crystalloids of Reinke have been identified in only three cases, their absence does not exclude a Leydig cell character in the rest of the reported cases. Our case provides additional support for the hypothesis that Leydig cells are present in the adrenal gland and may have an active role in the pathogenesis of testosterone-secreting adrenal tumors; thus, such cells should be sought in every case.

Peritoneal fluid from patients with unexplained infertility inhibits growth of 2-cell mouse embryos.

A significantly higher DHEAS concentration was measured in the peritoneal fluid of unexplained infertility patients (1171.4 +/- 155 ng/mL) in comparison to normal controls (667.6 +/- 82 ng/mL). Since the androgenic male serum does not promote blastocyst formation in the mouse embryo assay system, the potential of growth impairment by peritoneal fluid (PF) obtained from 22 women with unexplained infertility and 10 fertile controls was assessed. Where peritoneal fluid and serum from unexplained infertile (UI) patients were used as media supplement in mouse embryo culture, a significant inhibition of growth was observed in dishes containing PF but not serum. When DHEAS was added in varying concentrations to the culture media, a dose-dependent inhibition of embryo growth was observed. These findings show that the elevated DHEAS concentrations in the PF of UI patients adversely effect embryo growth and further suggest that increased DHEAS levels in the cul-de-sac fluid may be a causative factor for infertility.

Episodic luteinizing hormone release in idiopathic oligospermia.

The pathophysiology of idiopathic oligospermia (IO) is not fully understood. As some males with IO, particularly those with low normal testosterone (T), may respond favorably to human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG), aberration in gonadotropin release may be implied in these subjects. Therefore, episodic luteinizing hormone (LH) was studied in five males with IO and normal T and compared to six normal control males. Blood samples were obtained every 20 minutes, commencing at 8 A.M. over a period of six to eight hours and assayed for FSH and LH. T was determined at 0, 100, 180, 300, 360, and 480 minutes. Mean LH of 44.6 +/- 4.8 ng/mL (mean + standard error of the mean) in IO was higher than the mean LH of 32.2 + 3.1 ng/mL in the control group (P less than .025). Mean FSH of 204.2 +/- 20.3 ng/mL in IO was higher than mean FSH of 143.1 +/- 22.0 ng/mL in the control group (P less than .05). Mean T of 430 + 56 ng/dL in IO was comparable to 471 +/- 59.2 in the control group. The frequency of LH pulses was similar in both groups. The mean pulse amplitude of LH, 27 +/- 5.5 ng/mL, in IO was significantly higher than in the control group (15 +/- 2.2 ng/mL) (P less than .05). Although a central mechanism cannot be excluded, our data support a possible abnormality in testicular function in some males with IO.

Pain relief in hysterosalpingography. A comparison of analgesics.

Hysterosalpingography provides important information in the evaluation of infertility but is generally considered an uncomfortable and painful procedure. We evaluated various analgesics for decreasing or eliminating the discomfort from this procedure. Two types of analgesia were required to give maximum pain relief during and after the examination in the 180 patients evaluated. The best results were achieved with a combination of naproxen sodium, 550 mg, given orally two hours before the examination, and 20% benzocaine, applied to the cervix.

Continuous estrogen/progestin therapy in menopause.

The incidence of vaginal bleeding, endometrial histology, menopausal symptoms, blood pressure, and serum lipid concentrations were evaluated in 26 women who received either continuous conjugated equine estrogens and medroxyprogesterone acetate (group I, N = 16) or cyclic conjugated equine estrogen + medroxyprogesterone acetate (group II, N = 10) over a 9-month treatment period. At the end of therapy, endometrial biopsy specimens in group I revealed inactive endometrium, whereas one of ten biopsy specimens in group II showed proliferative endometrium. Blood pressure, serum total cholesterol, high-density and low-density lipoprotein cholesterol, and triglyceride levels were not significantly altered from baseline in either group during the 9-month treatment. Vaginal bleeding was virtually eliminated in group I by the end of the study, while 80% of the patients in group II continued to have cyclic menses (p less than 0.001). This pilot study suggests that continuous conjugated equine estrogen plus medroxyprogesterone acetate therapy appears to be a satisfactory method of postmenopausal hormone replacement, effectively reducing menopausal symptoms without any apparent short-term alterations in serum lipids. It has the added benefit of eliminating cyclic menstrual flow.

Serum oestradiol, progesterone, chorionic gonadotrophin and prolactin concentrations during pregnancy in the Bolivian squirrel monkey (Saimiri sciureus).

Concentrations of chorionic gonadotrophin gradually increased during early pregnancy, reached maximum values at mid-gestation, then declined to low levels. Oestradiol-17 beta concentrations were relatively low (300-600 pg/ml) during early pregnancy, increased thereafter to high levels (10-35 ng/ml), and then appeared to decline towards term. Concentrations of progesterone were constant (100-200 ng/ml) for the first 15 weeks of gestation, suggesting that sequential measurements of progesterone could be used to diagnose early pregnancy. Prolactin concentrations rose during pregnancy, reaching maximum values at term.

Evidence for a possible cytosol estrogen receptor deficiency in endocervical glands of infertile women with poor cervical mucus.

Endocervical gland estrogen receptor (ER) deficiency has been proposed as a possible cause for the poor cervical mucus (CM) in some infertile women with cervical factor. Cytosol ERs were measured in endocervical tissue obtained by biopsy within 3 days of ovulation (determined by the endogenous luteinizing hormone [LH] surge) in five infertile women with persistent poor preovulatory CM (group 1) and in endocervical tissue obtained in the late follicular phase in eight ovulatory women with excellent CM (group 2). ER concentrations were measured in Fmol/mg protein by the dextran-coated charcoal separation method (New England Nuclear Kit, Boston, MA). CM score evaluation and measurement of serum estradiol (E2) and progesterone (P) levels were performed concomitantly. Serum E2 levels of 123.4 +/- 29.3 pg/ml (mean +/- standard error of the mean [SEM]) in group 1 were comparable to E2 levels of 123.3 +/- 15.0 pg/ml in group 2. Serum P concentrations of 0.9 +/- 0.27 ng/ml in group 1 were comparable to 0.79 +/- 0.29 in group 2. A CM score of 4.6 +/- 0.69 in group 1 was significantly lower than 11.6 +/- 0.53 in group 2 (P less than 0.01). The cytosol ER was negative in four of five women in group 1, whereas in group 2, ER was positive in six, borderline in one, and negative in one subject. This study suggests that cytosol ER may be deficient in some women with cervical factor.

Effects of clomiphene citrate on cytosolic estradiol and progesterone receptor concentrations in secretory endometrium.

Cytosolic estradiol and progesterone receptor concentrations were measured in luteal phase endometrial biopsy samples obtained from 12 anovulatory or oligoovulatory women on clomiphene citrate therapy and from 40 normal control subjects. Clomiphene citrate treatment (250 to 750 mg per cycle) decreased both endometrial estradiol and progesterone receptor concentrations. Estradiol receptor levels were nondetectable in seven tissue samples and progesterone receptor levels in four samples from the 12 subjects given clomiphene citrate compared to nondetectable estradiol receptor concentrations in one tissue sample and progesterone receptor concentrations in two samples from the 40 normal control subjects. In histologically dated endometrium, mean estradiol receptor concentrations on days 20 to 23 and progesterone receptor levels on days to 24 to 27 were lower than the values observed in the comparable dated endometrium of normal ovulatory women. Steroid receptor concentrations correlated negatively with the duration of clomiphene citrate therapy, which implies a time-dependent suppressive effect of clomiphene citrate on measurable cytosolic estradiol and progesterone receptor concentrations during the luteal phase of the cycle.

Episodic luteinizing hormone release in hyperprolactinemic women.

Episodic luteinizing hormone (LH) secretion was studied in 16 hyperprolactinemic women (microprolactinoma, 12; idiopathic, 4) with amenorrhea of 1.4 to 7 years' duration. Blood samples obtained through an indwelling venous catheter at 20-minute intervals over 5 hours were assayed for LH, follicle-stimulating hormone (FSH), prolactin (PRL), and estrogen (E) (selected samples). LH pulse patterns were divided arbitrarily into high-amplitude release (LH pulse greater than 10 mIU/ml) (n = 7), low-amplitude release (LH pulse less than 10 mIU/ml (n = 6), and no release (n = 3). Mean pulse frequencies in women with high-amplitude and low-amplitude release were 2.4 +/- 0.3 (mean +/- standard error) and 1.3 +/- 0.2 pulses/5 hours and differed significantly (P greater than 0.02), whereas mean percentages of secretory increment were 155% and 62%, respectively. Mean LH concentrations in the high-amplitude (18.0 +/- 0.8 mIU/ml), low-amplitude (13.2 +/- 0.6 mIU/ml), and no-pulse groups (7.5 +/- 0.2 mIU/ml) differed significantly (P greater than 0.02). Despite the different pulse patterns, mean serum FSH, PRL, and total E concentrations were similar. The lack of episodic LH release and/or low infrequent LH release could account for the absence of cyclic hypothalamic pituitary ovarian function, although other mechanism(s) may be operative in women with augmented LH secretory pulses.

Endometrial estradiol and progesterone receptors in patients with luteal phase defects and endometriosis.

Endometrial cytosol estrogen receptors (ERs) and progesterone receptors (PgRs) were quantitated in postovulatory endometrial biopsy samples of patients with luteal phase defect (LPD), those with endometriosis, and normal control subjects. Serum levels of estradiol (E2) and progesterone (P), obtained on the day of the biopsy, were also measured. No significant differences among endometrial ER, PgR, serum E2, and P levels were detected between the patients with endometriosis and normal control subjects. Although ER concentrations in the luteal defect group did not differ from those of control subjects, the PgR levels in day 20 to 23 endometrium were significantly higher. Mean serum E2 and P levels in the group with luteal insufficiency were significantly lower than those of the control subjects. Our data suggest that in patients with LPD the increase in PgR levels during the midluteal days is compatible with a relative deficiency of P secretion by the corpus luteum.

Progesterone as a predictor of cyclicity in Bolivian squirrel monkeys during the breeding season.

In a squirrel monkey breeding colony, two distinct groups of females were observed during the breeding season, December through March. One had low and the other had high estradiol (E2) and progesterone (P) concentrations. The conception rate in females with high E2 and P values was 74%. However, only 25% of monkeys with low steroid concentrations became pregnant during the breeding season. This study showed that all mature females in a colony may not be cycling concurrently and that two serum P measurements obtained at four-day intervals may be utilized to detect noncycling monkeys during the breeding season.

Effect of an oral contraceptive on adrenal and ovarian androgenic steroids.

Seven women with hirsutism (five with polycystic ovarian disease, two with eumenorrheic hirsutism) were studied before and during the fourth and sixth cycles of oral contraceptive treatment (norethindrone/mestranol, 1 mg/0.05 mg). Plasma testosterone, androstenedione, and dehydroepiandrosterone sulfate were measured before and during treatment. Testosterone was reduced 72%, androstenedione was reduced 68.5%, and dehydroepiandrosterone sulfate was reduced 41.25% during therapy. Plasma dehydroepiandrosterone sulfate normalized in all patients with pretreatment elevation of this steroid. Norethindrone/mestranol, 1 mg/0.05 mg is capable of suppressing both ovarian and adrenal androgens in hirsute women with modest elevation of these steroids.

The outcome of pregnancy in patients with treated and untreated prolactin-secreting pituitary tumors.

Few data document pregnancy risks in patients with prolactin-secreting pituitary tumors, particularly risks relating to the likelihood and severity of increased tumor size. This study presents three groups of women with such lesions. Group 1 consisted of 47 women with transsphenoidal resection who were euprolactinemic postoperatively. Of this group 20 of 22 previously infertile women conceived 25 pregnancies. Group 2 was composed of 17 women who were operated upon but in whom prolactin was still raised (greater than 50 ng/ml) postoperatively and bromocriptine was subsequently used. Seven of these 17 patients were previously infertile, and six of the seven have conceived. In group 3 22 infertile women with small pituitary tumors were not operated upon but received bromocriptine. Eighteen of these patients have achieved 24 pregnancies. Methods of diagnosis, surveillance during pregnancy, and medical and surgical management are presented. Only two patients, both in group 3, developed signs of expanding tumor size in pregnancy.

The effect of hyperprolactinemia on the diurnal variation of adrenal androgens.

Morning and evening plasma cortisol, dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S) were measured in ten women with hyperprolactinemia secondary to pituitary adenomas and in seven control subjects with cyclic menses and normal prolactin (PRL) levels. Plasma cortisol and DHEA-S levels were comparable in both groups. A diurnal variation for cortisol and DHEA was identified and comparable in both groups. These findings indicate that PRL may not be an important physiologic regulator of adrenal androgen secretion.

Failure of acute changes in prolactin to affect DHEA-S secretion in the human.

To investigate whether acute changes in prolactin secretion affect adrenal androgen secretion, serum prolactin and dehydroepiandrosterone sulfate (DHEA-S) concentrations were determined in seven normal women following the administration of chlorpromazine and L-dopa. The changes in plasma prolactin and DHEA-S concentrations over a four-hour period were compared to those in control experiments in which four of the women received placebo alone. Following the administration of chlorpromazine, plasma prolactin concentrations increased four-fold above pretreatment concentrations, reaching a maximum at 120 minutes. Following L-dopa, plasma prolactin concentrations decreased by greater than 50%, with the nadir noted within 90 minutes. Despite these acute changes in prolactin secretion, plasma DHEA-S concentrations remained unchanged. These results, therefore, strongly suggest that acute changes in prolactin secretion have no affect on adrenal androgen secretion.

Testosterone/androstenedione ratio in the evaluation of women with ovarian androgen excess.

A plasma testosterone/androstenedione (T/A) ratio was calculated in 15 women with possible ovarian neoplasms and androgen excess and whose mean plasma concentration of testosterone approached or was greater than a twofold elevation. The T/A ratio approached unity in eight of nine patients with polycystic ovarian disease, whereas all patients with hyperthecosis and two of three patients with androgen-secreting tumors had a testosterone/androstenedione ratio above 1.5. In 13 of 16 patients with androgen-secreting tumors of the ovary reported in the literature, the testosterone/androstenedione ratio was above 1.5. An elevated testosterone/androstenedione ratio should raise the suspicion of either an ovarian androgen-secreting tumor or hyperthecosis.

Spontaneous regression of prolactin-producing pituitary adenomas.

Two women evaluated for amenorrhea, galactorrhea, and hyperprolactinemia had radiographic changes of the sella turcica (localized erosion on trispiral tomography) suggestive of a pituitary tumor. Both patients experienced spontaneous regression of apparent prolactin-secreting adenomas with a marked decrease in the quantity of galactorrhea and a reduction of serum prolactin concentrations to the normal range. One patient noted a marked improvement of headaches and spontaneous menses resumed in the other patient.