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Objective: To assess the efficacy of a combination of Frank's mold therapy with intercourse as a treatment for congenital vaginal aplasia., Study Design: From 1973-1993, thirty-three patients with congenital aplasia of vagina and uterus were seen by one gynecologist. Patients with a partner were instructed how to create a functional vagina by a modified form of coitus ('interfemoral intercourse'). Mold therapy (using modified molds) was used as a primary treatment when patients had no partner (n = 9) or added to the treatment of nine patients in whom interfemoral intercourse alone had failed. In case of failure of conservative treatment, the surgical creation of a neovagina (McIndoe procedure) was offered., Results: Conservative therapy in patients with a stable sexual relationship (n = 24) gave significantly better (p = 0.0104) results than when patients were single. In the former, a vaginal depth of > 8 cm was reached within six months at most with intercourse alone and four months if combined with mold therapy. With molds alone, 3 out of 9 obtained a satisfactory vagina. Treatment failures occurred (with one exception) only in patients who had no or unstable sexual relationships., Conclusion: Intercourse as a treatment of vaginal atresia can be very successful, especially if practised together with modified mold therapy. A stable sexual relationship--implying a healthy self-concept--appears to be an important determinant of treatment outcome.

Objective: To investigate the effect of dopaminergic drugs on the well being in hyperprolactinemic patients., Design: A psychometric test for well being, the SCL-90, was applied at baseline and in the 24th week of a double-blind randomized prospective study comparing the effectiveness and safety of the new dopamine d2 agonist CV 205-502 with bromocriptine., Setting: Outpatient department of a university clinic for obstetrics and gynecology., Patients: Twenty-four women with hyperprolactinemia, 9 of whom had a prolactinoma. Twenty had been treated before, and 11 were known to react unfavorably to bromocriptine., Results: The effectiveness of CV 205-502 was identical to bromocriptine: its tolerability appeared to be better, especially in the initial phase of treatment. At baseline, the mean scores of the SCL-90 were significantly elevated over the reference values. Sixteen patients had normal scores. The elevations were caused by 8 patients with scores in the range found in psychiatric disease (211 +/- 30 [SD] [CV 205-502] and 182 +/- 32 [bromocriptine]). They were depressed, anxious, and hostile. At 24 weeks, the patients treated with CV 205-502 scored better (130 +/- 23.5) in the SCL-90 than the patients treated with bromocriptine (149.5 +/- 20)., Conclusion: The markedly increased well being in patients treated with CV 205-502 cannot be explained by its better tolerability and is probably caused by a specific central activity of CV 205-502. Further research into the antidepressive properties of this compound is warranted.

Objective: To investigate the clinical course of hyperprolactinemia without demonstrable cause., Design: Prospective study of all patients with idiopathic hyperprolactinemia first seen between 1974 and 1985., Setting: Outpatient Department of University Hospital., Patients: Fifty-nine patients followed for 6 to 190 months (median 78 months). Medical treatment given only in case of anovulatory infertility or hypogonadism., Outcome Measures: Development of pituitary (micro)prolactinoma, prolactin (PRL) levels, and clinical signs of menstrual dysfunction., Results: With exception of one woman in whom it probably had been missed by hypocycloidal tomography, no demonstrable prolactinoma developed. Prolactin levels rose in two patients, one using oral contraceptives and the other with prolactinoma. At the end of follow-up, 15 of 16 patients using a dopaminergic drug had a normal cycle; 13 had normal final PRL levels. From the 43 patients off medication, 28 (66%) had normal PRL levels and 23 (54%) had a normal cycle. There were no significant differences between women who had and had not been pregnant. Dopaminergic medication had no appreciable influence on the course of the disease., Conclusion: In idiopathic hyperprolactinemia, progression to pituitary prolactinoma seldom, if ever, occurs. There is a high tendency to spontaneous cure, and pregnancy or medication have no apparent effect. Frequent pituitary imaging was found to be not necessary in our patient population. It may best be reserved for situations in which the PRL level in symptomatic hyperprolactinemia is inconsistent with pituitary imaging results.

This study describes the use of the ovulation stimulating drugs clomifene, human chorionic gonadotropin (hCG) and human menopausal gonadotropin (hMG) in a representative sample of a population of Dutch women in the child-bearing age group. Clomifene or hMG/hCG are seldom used alone. A considerable percentage of the women received at least four different ovulation-inducing and related drugs during the observation period of two years. Thirty percent of the women who used clomifene were treated for 6 or more cycles. These findings argue for a relative "overuse" and "misuse" of clomifene. Buserelin, a drug not registered for the indication ovulation induction in The Netherlands but used in in vitro fertilization (IVF) programs as inhibitors of pituitary gonadotropin production, was nevertheless prescribed to 38% of the hMG /hCG users and to 11 % of the clomifene users. Our study indicates that, though the potential risks of congenital malformations due to clomifene are difficult to assess, they may be considerable; this, and the fact that different ovulation-inducing drugs are used together with clomifene, emphasizes the need for post-marketing surveillance.

In order to determine whether serum-immunoreactive inhibin could constitute a biochemical marker for the presence and progression of ovarian granulosa cell tumors and their metastases, we measured immunoreactive inhibin concentrations in series of serum samples obtained from 8 patients with granulosa cell tumor. Six series were tested in retrospect. From these, three came from patients who had been treated with an abdominal hysterectomy and bilateral salpingo-oophorectomy. In the 2 patients with residual or recurrent disease, inhibin was elevated, 4 and 20 months respectively before clinical manifestations of recurrence became evident; it reflected the effects of secondary therapy. Inhibin remained undetectable in one patient who was free of disease during 11 years of follow-up. Inhibin concentrations were also inappropriately increased in 2 of 3 women with amenorrhea and infertility resulting from small granulosa cell tumors. After removal, inhibin concentrations became normal and fertility resumed. Fertility also returned in the third patient. There was a significant negative correlation between the serum inhibin and FSH concentrations, consistent with autonomous production of inhibin by granulosa cell tumors. It is concluded that granulosa cell tumors have the capacity to produce inhibin. In retrospect, inhibin proved to be a marker for both primary and also recurrent and residual disease.

Inhibin is a peptide hormone normally produced by ovarian granulosa cells. It reaches a peak of 772 +/- 38 U per liter in the follicular phase of the menstrual cycle and is undetectable in the serum of menopausal women. To determine whether measurements of serum inhibin levels would provide a biochemical marker of the presence or progression of ovarian granulosa-cell tumors and their metastases, we measured the serum immunoreactive inhibin concentrations in six women with such tumors. Three women had been treated by hysterectomy and bilateral salpingo-oophorectomy. In the two women with residual or recurrent disease, the serum inhibin levels were abnormally elevated 5 and 20 months before the clinical manifestations of recurrence became evident. The maximal concentrations approached 3000 U per liter. The serum inhibin level remained undetectable in one patient who was disease-free for 11 years. Serum inhibin concentrations were also elevated in three women with amenorrhea and infertility that resulted from small granulosa-cell tumors. After the removal of the tumors, the serum inhibin levels in these women became normal, and fertility returned. There was a significant negative correlation between the serum concentrations of inhibin and follicle-stimulating hormone, in a manner consistent with the autonomous production of inhibin by granulosa-cell tumors. We conclude that granulosa-cell tumors produce inhibin. Since serum inhibin levels reflect the size of the tumor, measurements of inhibin can be used as a marker for primary as well as recurrent disease.

The immediate and long term fertility after bilateral ovarian wedge resection in 53 women with clomiphene citrate-resistant hyperandrogenic chronic anovulation is related to the histology of the ovarian wedges. Patients with polycystic ovaries and hyperplastic stromal abnormalities had most spontaneous conceptions and a normal fertility during follow-up. Apparently, chronic anovulation in these cases had been caused by ovarian disease in the face of normal hypothalamic function. Patients with polycystic ovaries without stromal abnormalities often needed postoperative stimulation of ovulation in order to conceive, which may indicate hypothalamic involvement. Patients with large ovaries, normal stroma, and small follicles, who as a group had the lowest serum levels of luteinizing hormone, and patients whose ovaries contained large follicles and cysts without theca cell activity did not benefit from the bilateral ovarian wedge resection. Generally, their postoperative response to medical induction of ovulation did not improve either. Measures to prevent adhesions were not completely successful. Nevertheless, our results suggest that anovulation rather than formation of adhesions causes persistent infertility after bilateral ovarian wedge resection.

Forty-one hyperprolactinemic women (prolactin [PRL] greater than 2,000 mU/L) were treated between 12 and 52 weeks with the new nonergot, long-acting dopamine agonist octahydrobenzo [g] quinoline (CV 205-502). The treatment resulted in normalization of PRL secretion in 71% of the women at a once-daily dose of less than or equal to 0.100 mg. All women responded with a significant decrease in serum PRL. Menstrual function normalized in all women except 1, whereas galactorrhea disappeared in all but 2 patients. During the observation period, four pregnancies were recorded with an additional three in the immediate posttreatment period. Until now, four healthy children have been born. Regarding tolerability, women with fair or poor response bromocriptine (Parlodel) in the past tolerated CV 205-502 better. Two women with no PRL decrease while on Parlodel responded with a decrease while on CV 205-502. All safety parameters remained normal while on treatment, and no significant changes were observed in blood pressure (supine and standing), pulse rate, or electrocardiogram (ECG) recordings. CV 205-502 therefore seems to be a valuable new compound in the management of patients with hyperprolactinemia.

In a retrospective international study 223 pregnancies induced with pulsatile hormone-releasing hormone (LH-RH) were evaluated. In patients with hypothalamic amenorrhea (HA) and polycystic ovarian disease (PCOD) the abortion rate was similar (10% vs 8.7%). The premature delivery rate was significantly higher, however, in the patients with HA, but this could be explained by the higher incidence of multiple pregnancies in this group. Thirty multiple pregnancies were observed in the HA group (n = 174) compared with none in the PCOD group (n = 24; p less than 0.05). The incidence of multiple pregnancies in the HA group correlated to the pulse dose (p less than 0.05). The 1st treatment cycle resulted in more multiple pregnancies than did subsequent cycles (p less than 0.05). Difference in pulse interval did not affect the incidence of multiple pregnancies, nor did the route of administration (intravenous or subcutaneous). The incidence of congenital anomalies was comparable to that with spontaneously achieved pregnancies.

Five phenotypic female patients with primary amenorrhoea, mild hypertension, and hypokalaemia are described. The condition originates from 17-hydroxylase deficiency in both adrenals and gonads. Two cases had a XY chromosome pattern, two cases were familial. It is suggested to determine serum potassium in all cases with unexplained primary amenorrhoea.