A clinical trial using danazol for the treatment of premenstrual tension.

Forty women with premenstrual tension received either placebo, 100, 200 or 400 mg danazol daily for 3 months in a pilot study arranged as a double-blind trial. Thirteen patients withdrew by the third month usually because they complained of no improvement. They had significantly higher pretrial symptom scores than those who continued. In patients treated with danazol, symptom scores for breast pain during the second and third months and for irritability, anxiety and lethargy during the third month were significantly (P less than 0.05) lower than scores in those given placebo. Most symptoms improved on placebo in the first month but by the third month only three remained improved. In contrast eight symptoms were improved on 200 mg danazol by the third month. By the end of the trial more than 75% of patients who were still taking danazol were essentially free of breast pain, lethargy, anxiety and increased appetite, but results for other common symptoms were no better than with placebo.

Hormonal studies in women with premenstrual tension.

Serum hormone concentrations were determined at intervals during the last 17 days of the menstrual cycle in 35 patients with premenstrual tension (PMT) and 11 control subjects without symptoms. The maximum mean concentration of oestradiol occurred 17 days before menstruation in the patients and 14 days before in the controls. The maximum concentrations of progesterone were similar in the two groups but the mean concentrations rose earlier in the cycle in the patients with PMT. These results suggested that the patients tended to ovulate earlier in the cycle than the controls and on the basis of the ovulatory surge in gonadotrophins two groups could be identified, group A who showed signs of ovulation 14 days or less before menstruation (17 patients, 9 controls) and group B who ovulated more than 14 days before menstruation (18 patients, 2 controls). There were no significant differences between the groups in prolactin, thyroid stimulating hormone or testosterone levels, but cortisol concentrations were uniformly higher in both groups of patients compared with those in the controls. Follicular growth was assessed with ultrasound in 18 patients and 16 control subjects. Mean follicular diameters were significantly lower in the patients than in the control group at the time of ovulation. Oestradiol determinations done at the same time correlated with the diameters and were also significantly lower in the patient group. The results suggest that ovulation tends to occur prematurely in women with PMT.

Acth function in women with the polycystic ovarian syndrome.

Serum androgen levels, including dehydroepiandrosterone sulphate (DHAS) which is thought to be solely of adrenal origin, are elevated in women with the polycystic ovarian syndrome. We have investigated the possibility that this may be due to a mild form of congenital adrenal hyperplasia by measuring basal and stimulated levels of ACTH in women with this condition and have compared them to levels in normal women. We found no difference in the diurnal rhythm of ACTH between patients and normal subjects nor any difference in stimulated levels achieved after a single-dose oral metyrapone test. Thus there is no evidence from this study to support the idea that these patients might have congenital adrenal hyperplasia. There are two alternative hypotheses to explain the elevated DHAS levels. They may be associated with the high oestrogen levels, which interfere with the enzyme 3 beta-hydroxysteroid dehydrogenase, or there may be alteration of the factors controlling adrenal androgen secretion.

A survey of 100 patients who had laparoscopic ventrosuspensions.

The technique for and results of 100 laparoscopic ventrosuspensions are described; patients were followed for an average of 40 months and in all but 11 the uterus was anteverted at the end of the follow-up period. The presenting symptoms of dyspareunia, dysmenorrhoea or sacral backache were almost always improved as a result of the operation.

Modification by sex steroids of LHRH response in the polycystic ovary syndrome.

Exogenously administered oestradiol or progesterone was found to induce augmentation of LH and FSH release in response to LHRH administration in patients with the polycystic ovary (PCO) syndrome. The effect of oestradiol upon LH release in the patients was significantly less than the augmented release induced in normal women (P less than 0-02). In contrast, progesterone induced a significantly greater LH release in PCO patients than normal women studied during the early follicular phase (P less than 0-001) but less than that in normal women studied during the mid-follicular phase of the cycle (P less than 0-01). The effects on FSH release in the PCO patients were less marked but similar to those in normal women with comparable basal steroid levels. The results suggest that both oestradiol and progesterone can modify the hypothalamic-pituitary axis in the PCO syndrome in a manner similar to that observed in normal women and a failure of these 'positive feedback' mechanisms does not appear to be the cause of the ovulatory deficiency in this syndrome.

The control of gonadotrophin release in women with hyperprolactinaemic amenorrhoea: effect of oestrogen and progesterone on the LH and FSH response to LHRH.

The effect of the administration of oestradiol benzoate and of progesterone on the subsequent response to LHRH has been investigated in women with hyperprolactinaemia. There was an amplification in the release of LH in four out of ten patients and of FSH in one out of ten patients at 44 h after the administration of 2-5 mg oestradiol benzoate. The average amount of LH released before and after oestrogen did not change, but there was a significant decrease in the amount of FSH released. There was no correlation between the LH released and the oestradiol concentration in serum at the time of the LHRH tests but there was a negative correlation between the FSH released and the oestradiol concentration (r = 0-507;P less than 0-05). These results contrast with those obtained in normal subjects in the follicular phase of the cycle when there is a positive correlation of oestrogen concentrations and the amount of LH and FSH released. As in normal subjects, however, a significant suppression of basal FSH concentrations, persisting until 44 h, was produced by the oestrogen (P less than 0-01). Seven out of eleven patients showed an amplification of LH response and six out of eleven an FSH response 20 h after the administration of 25 mg progesterone. The mean amplifications are not significantly different from those of normal subjects tested in the early follicular phase of the cycle, but are significantly less than those tested in the mid follicular phase of the cycle (LH P less than 0-001; FSH P less than 0-01). This may be related to the serum concentrations of oestradiol which in patients with hyperprolactinaemia are significantly less than those found in the mid follicular phase of the cycle (P less than 0-05). These results indicate that in women with hyperprolactinaemia oestrogen negative feedback, necessary for cycle initiation, is normal: failure of ovulation may be related to failure of positive feedback to oestroen. Oestrogen-negative feedback is unopposed and this may explain the follicullar development and lack of oestrogen in the mid-follicular phase.

Sex hormone levels and gonadotrophin release in the polycystic ovary syndrome.

The response to synthetic luteinizing hormone-releasing hormone was studied in eighteen patients with the polycystic ovary syndrome. The release of follicle-stimulating hormone was similar to that found in normal women. The mean response of luteinizing hormone was similar to that found in the luteal phase, but significantly greater (P less than 0-02) than that found in the early follicular phase of the normal menstrual cycle. Basal serum levels of FSH and LH, estimated in twenty-five patients, were similar to those found in normal subjects. The sex hormone binding globulin capacity was reduced in twenty-four of them. Basal serum testosterone levels were elevated in twelve of twenty-two patients and the mean level was significantly greater (P less than 0-01) than the mean level of normal women. Basal serum androstenecione levels were elevated in nine of twenty-two patients and the mean level was also significantly greater (P leess than 0-001) between basal testosterone and LH levels. These data suggest the pituitary gland of patients with the polycystic ovary syndrome contains adequate amounts of LH but that the ovulatory surge of LH which occurs in normal women is inhibited by testosterone acting on either the pituitary or, more probably, on the hypothalamus.