In a consecutive series of thirty-six male and female patients referred with severe acne, the effect of 3 months' treatment with placebo or spironolactone (50-200 mg daily) on sebum excretion and clinical and endocrine status was evaluated double-blind. Twenty-six patients completed the study. Abnormal free androgen indices were found in 27% of the original nineteen female subjects. Spironolactone reduced sebum excretion in all female subjects, but there was no correlation between sebum response and androgen status. The clinical response was dose-dependent, with maximum subjective and objective benefit when spironolactone doses of 150-200 mg were used.

SUMMARY In a consecutive series of 41 hirsute women clinically classified as benign androgen excess, only 34 %were found to have elevated plasma 'total' testosterone (T), 22 %having subnormal sex hormone binding globulin (SHBG). When expressed as the ratio T jSHBG ('free androgen index'), 85 % of the patients had values above the normal range. It is concluded that this index is more reliable than total testosterone in assessing androgen status in female patients.Total testosterone (nmol/l) x 100 SHBG (nmol DHTII) 24·9 years, range 20-35). Neither group of subjects was receiving the contraceptive pill or other form of medication known to interfere with androgen metabolism. None of the hirsute patients showed evidence of virilism and all were provisionally diagnosed as having 'benign androgen excess'.Plasma total testosterone was measured by the radioimmunoassay of Collins et a[6 using an antiserum donated by Mr Mike Mansfield (Chelsea Hospital for Women). Plasma SHBG was assayed by the two-tier column method of Iqbal and Johnson"; results are expressed in terms of the uptake of 51X-dihydrotestosterone (DHT). Free androgen index (FAl) was calculated as the ratio: ResultsStatistical analysis of results employed Student's t test. Results of grouped data are expressed as the mean ± 1 SEM. Patients and methodsThe results are presented in the Figure. Normal ranges (mean ± 2 SD), calculated from the results obtained in the control group, were as follows: Testosterone 0·8-3·2 nmol/l: SHBG 25-121 nmol DHT/I: FAIl·3-4· 5. Of the 41 hirsute women, only 14 (34 %) had a plasma testosterone which fell outside the normal range, although the group mean Forty-one consecutive premenopausal women (mean (2·5 ± 0·18 nmol/l) was significantly higher than age 27·4 years, range 19-50) referred to the Depart-that of the controls (2·0 ± 0·09 nmol/l)(p

The plasma of normal man and the rat, and an acetone extract of hypothalamus from the rat, have an ability to inhibit Na-K-ATPase which is related directly to salt intake. The ability of the plasma to inhibit Na-K-ATPase is raised in essential hypertension. The ability of plasma and of an acetone extract of hypothalamus from six spontaneously hypertensive (SHR) rats and six normotensive control (WKY) rats to inhibit Na-K-ATPase of fresh guinea-pig kidney was studied using cytochemical bioassay techniques. With a validated assay, which measures the capacity of biological samples to stimulate glucose-6-phosphate dehydrogenase (G6PD) as an index of their capacity to inhibit Na-K-ATPase, the mean G6PD-stimulating ability of the plasma from the SHR and the WKY rat was 772.3 +/- 48.1 units/ml and 12.5 +/- 2.6 units/ml respectively (P less than 0.01) and of the hypothalamic extracts it was 2.2 +/- 1.7 X 10(8) and 4.5 +/- 1.8 X 10(4) units/hypothalamus (P less than 0.01). With a semi-quantitative cytochemical assay, which measures Na-K-ATPase activity directly, plasma and an acetone extract of hypothalamus from the spontaneously hypertensive rat had much greater capacities to inhibit Na-K-ATPase than plasma and extract from the WKY rat. These raised levels of Na-K-ATPase inhibitory activity in the plasma of the SHR rat are similar to the highest values found in the plasma of patients with essential hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

An objective evaluation of the anti-androgen effects of spironolactone was performed in a consecutive series of 12 hirsute patients receiving a daily dose of 150 mg; nine completed the study. Using a computer assisted image analyser, hair diameter on two weekly shavings decreased significantly over a 12 month period in three of the patients, although growth rate and mean diameter did not change in the group as a whole. Plasma testosterone fell significantly to a mean of 53% of basal levels. The mean free testosterone (derived) fell significantly to 64% of basal by the sixth month (P = less than 0.005) and remained significantly depressed the remainder of the study. There was subjective benefit in hair growth and greasiness and a significant reduction in the semi-objective Ferriman-Gallwey index in nine of 10 subjects assessed for at least 9 months. We conclude that although spironolactone was not consistently successful, it may represent effective therapy for a sub group of patients with hirsutism.

Acute volume expansion, increased sodium intake, and restraint on sodium excretion endow the plasma with an increased capacity to inhibit sodium transport. Cytochemical techniques can detect the presence of Na+K+-adenosine triphosphatase (ATPase) inhibitor in the plasma of normal humans and rats, the concentration of which is controlled by salt intake. The substance responsible appears to originate in the hypothalamus, where the concentration is also controlled by salt intake. The plasma concentration of the cytochemically detectable Na+,K+-ATPase inhibitor is substantially raised in the plasma of patients with essential hypertension, spontaneously hypertensive rats (SHR) and of Milan hypertensive rats. The concentration of activity in the hypothalamus of SHR is also considerably raised. These findings demonstrate that these forms of hypertension are associated with a rise in the concentration of a cytochemically detectable circulating Na+,K+-ATPase inhibitor that under normal circumstances is controlled by salt intake.