Women with polycystic ovary syndrome wedge resected in 1956 to 1965: a long-term follow-up focusing on natural history and circulating hormones.

OBJECTIVE: To determine if the hormonal imbalance in women with polycystic ovary syndrome (PCOS) continues into and after menopause and to analyze factors constituting an increased risk for developing metabolic disorders. DESIGN: The study was a transectional retrospective cohort follow-up of patients with PCOS. SETTING: The women with PCOS were recruited from hospital clinics, and referents were randomized from a population study of women. PARTICIPANTS: Thirty-three women ages 40 to 59 years with ovarian histopathology typical of PCOS at wedge resection 22 to 31 years previously; 132 age-matched referents were analyzed. MAIN OUTCOME MEASURES: Clinical data were collected via a questionnaire supplemented with an interview in connection to a clinical examination that also included fasting venous sampling. RESULTS: Infertility, hirsutism, and oligomenorrhea were more common among the subjects with PCOS, but there was a considerable spontaneous restitution of cyclic regularity with time. Women with PCOS were more often hysterectomized and entered menopause later compared with referents. The hormone data show a typical profile for PCOS. Compared with referents women with PCOS showed marked increase in prevalence of central obesity, higher basal serum insulin concentrations, and a higher prevalence of diabetes mellitus and hypertension. CONCLUSION: Perimenopausal women with PCOS have an increased morbidity in hypertension and diabetes mellitus that adds to the classic symptoms, such as anovulation, hirsutism, and infertility.

Human granulosa cell tumor: stimulation of steroidogenesis by gonadotropins in vitro.

A 59-year-old previously oophorectomized woman underwent surgery for a recurrent malignant granulosa cell tumor. Specimens and dispersed cells from the tumor tissue were incubated for 2 hr and cultured for 48 hr, respectively, with and without gonadotropins. Steroids and cyclic AMP (cAMP) concentrations were measured in the incubation and culture media. Incubated specimens from the tumor tissue released measurable amounts of cAMP, progesterone, and estradiol into the medium. Human follicle-stimulating hormone (FSH) 1 microgram/ml significantly stimulated the formation of cAMP and both steroids. Human luteinizing hormone (LH) 1 microgram/ml stimulated cAMP and progesterone but not estradiol release. Human chorionic gonadotropin (hCG) 10 micrograms/ml stimulated cAMP and progesterone formation in tumor tissue but was totally devoid of effect on estradiol release. In the tissue culture experiments progesterone and estradiol were formed in considerable amounts, with a higher capacity for progesterone than for estradiol. Progesterone formation was stimulated by FSH and hCG, while estradiol release was stimulated only by hCG. The addition of testosterone significantly enhanced estradiol formation in both incubation and culture experiments. It is concluded that the steroidogenesis of this granulosa cell tumor is sensitive to gonadotropins.

Vaginal administration of low-dose oestradiol--effects on the endometrium and vaginal cytology.

Twenty (20) post-menopausal women, mean age 62.4 yr, presenting with symptoms associated with urogenital atrophy were treated intravaginally with daily doses of 25 and 50 micrograms oestradiol (E2) in a double-blind, cross-over study. After randomization, the patients started daily treatment with pessaries containing either 25 or 50 micrograms E2 for 3 wk, followed by a maintenance period of 6 wk during which the pessaries were used only twice a week. A 4-wk wash-out period was followed by another treatment period of 9 wk. The effects on the karyopyknotic index (KPI) and on endometrial histopathology were assessed before and after 3, 9, 16 and 22 wk of treatment. In the case of the 25 micrograms dose the mean KPI values were 34.7 and 20.9% after 3 and 9 weeks of treatment, respectively, the corresponding figures after treatment with 50 micrograms E2 being 39.2 and 22.7%. No dose-effect relationship was apparent from the vaginal cytology findings. Endometrial biopsies could not be taken systematically in all patients. Weak proliferation of the endometrium was observed in 1 woman after 3 wk of daily treatment with the 50 micrograms dose. No endometrial stimulation was detected in any of the patients after treatment with 25 micrograms daily. Beneficial clinical and cytological effects were obtained with both dosage regimens. Daily intravaginal administration of 25 micrograms E2 can accordingly be advocated for the treatment of urogenital symptoms attributable to oestrogen deficiency in post-menopausal women.

High prevalence of cervical dysplasia in female consorts of men with genital warts.

Altogether 51 regular female consorts of men attending a venereal disease clinic for genital warts were examined using colposcopy, vaginal cytology and--when needed--surgical biopsy. Abnormal cytological smears were found in 18 out of 49 consorts (37%), which should be compared with 8 out of 124 (6%) matched female controls from a family planning clinic (p less than 0.001). Possibly premalignant lesions, i.e. atypical condylomata and/or frank dysplasia, were found in 14 (27%) out of 51 consorts. The prevalence of abnormal smears or biopsy-proven dysplasia was approximately the same in consorts with and without external warts. These findings call for close attention to the risk of development of cervical dysplasia in female consorts of men with genital warts.

A new combination of conjugated equine oestrogens and medroxyprogesterone for treatment of climacteric complaints.

Thirty-four post-menopausal women with climacteric complaints were given conjugated equine oestrogens (1.25 mg/day) for 21 days followed by 2 days without hormones and then 5 mg medroxyprogesteroneacetate daily for 5 days. The present trial was designed to study effects on vasomotor symptoms, bleeding patterns and endometrial histopathology. Vasomotor disturbances were completely relieved. No recurrence of symptoms was recorded in the oestrogen-free week. Withdrawal bleedings were regular and slight, which was a positive experience for those women who had previously been treated with other oestrogen-progestogen regimens. In most patients inactive or weak secretory endometrial epithelium was found during treatment. Two women developed differing degrees of hyperplasia after 2.5 and 3 yr, respectively. This fact emphasizes the necessity of adding progestogens for at least 10 days each month even if the oestrogens and progestogens are administered separately. It may also be wise to perform an endometrial biopsy when sex hormones are administered on a long-term basis.

Hilus cells from human postmenopausal ovaries: gonadotrophin sensitivity, steroid and cyclic AMP production.

Strips of ovarian hilar tissue taken from 11 post-menopausal women were examined histologically and found to contain clusters of hilus cells in contiguity with non-myelinated nerve fibers. No other steroidogenically active structures were found. Specimens from these strips were incubated for 30 and 240 minutes in Krebs bicarbonate buffer containing 5.5 mM glucose and 1% bovine serum albumin. The specimens produced measureable amounts of androstenedione, estradiol-17 beta and progesterone in vitro. The major steroid formed was androstenedione, and this pattern of steroidogenesis appeared similar to that of postmenopausal ovarian stroma. However, the amounts of steroids formed were considerably higher than in stromal tissue. This implies that the hilus cells possibly may be of greater importance, qualitatively, than the stroma cells for steroidogenesis in the postmenopausal ovary. Addition of hCG to the incubated specimens elicited increase in both cyclic AMP formation and steroid synthesis, especially of estradiol-17 beta, indicating a preserved responsiveness to gonadotrophin in hilus cells from postmenopasual ovaries.

Microscopic studies of curvature-causing structures in hypospadias.

Microscopical studies were performed in a consecutive series of 20 hypospadiacs (3 crypto-hypospadias; 9 glandular; 7 penile; and 1 perineal) with curvature, 3 of whom also exhibited torsion. Specimens for the investigation were dissected free at the first operation and it was found that the binding tissues on the ventral side of the penis reached about half of the circumference of the penile shaft, stretching longitudinally from the coronal sulcus, passing the original meatus and extending proximally on the shaft. The specimens from the 17 hypospadias with curvature only exhibited a symmetric pattern in the tissue plate, while in 3 hypospadias with curvature and torsion an asymmetry was found, with longer lateral tissue plates in the contralateral direction to the torsion. With two exceptions, the microscopical investigation showed the same principal lesions: proximally the urethra had a normal circular corpus spongiosum, but at varying distances distally the ventral parts of the corpus spongiosum were thinned out, and disappeared and the lateral parts were disorganized, penetrating out laterally in the plate of connective tissue. The dorsal part of the corpus spongiosum was thinned and was found to continue distally from the meatus to the coronal sulcus. In the 3 hypospadias with curvature and torsion the microscopical findings were principally the same as in the cases with curvature only, but with longer lateral penetration on the side contralateral to the direction of the torsion.