The effects of spironolactone on testosterone fractions and sex-hormone binding globulin binding capacity in hirsute women.

This study explored the effect of the anti-androgen spironolactone on sex-hormone binding globulin (SHBG) and the distribution of circulating testosterone (T) into various free and bound fractions in seven women with hirsutism assessed before and then monthly for three months on a regimen of spironolactone, 100 mg bid as the sole therapeutic agent. Blood samples were taken at each assessment time for a battery of androgen parameters and serum T fractions studies. None of the women were judged obese based upon body mass index values. After three months of spironolactone therapy, there was little change in the hirsutism index, and measurement of serum T, androstenedione, DHEA-S and 17 beta-estradiol showed no significant changes, the same occurring with SHBG-binding capacity. However, there was a shift in the distribution of circulating T, with a decrease in SHBG-bound T and an increase in albumin-bound and free T (non-SHBG-bound fractions). As previous reports suggest that non-SHBG-bound fractions represent bioavailable fractions, the current data suggests that T fraction studies may not be clinically useful parameters of hyperandrogenism in women receiving antiandrogen therapy.

Serum testosterone fractions in women: normal and abnormal clinical states.

The potential usefulness of determining serum testosterone (T) fractions in women, ie, sex hormone-binding globulin (SHBG)-bound T, albumin-bound T (Alb-T), and free T (FT) fractions, was explored in a variety of clinical situations. Serum T, SHBG, and albumin concentrations were measured by standardized methods and using binding constants of T to SHBG and albumin, we calculated serum T fractions, which agreed remarkably with measured values of SHBG-T and nonbound T. Serum T levels did not change in normal women examined during the follicular and luteal phases of the menstrual cycle, but SHBG levels were elevated in the luteal phase, changing the distribution of T, with increased SHBG-T and less T distributed to other fractions. Women taking oral contraceptives had decreased serum T levels, but use of androgen-like oral contraceptives decreased SHBG levels and T distribution to this binding protein, whereas use of non-androgen-like oral contraceptives increased SHBG levels, resulting in the expected shift of T fractions. Women receiving phenytoin for seizure disorders and women with Graves' disease exhibited increased SHBG levels with concomitant increased SHBG-T and decreased distribution of T to nonbound fractions. Women with hirsutism exhibited decreased SHBG levels irrespective of total serum T levels, and the T/SHBG ratio was elevated in this population. However, of interest were women with morbid obesity (nonhirsute) who had similar low levels of SHBG and T/SHBG ratios that were indistinguishable from those of hirsute women.(ABSTRACT TRUNCATED AT 250 WORDS)

Treatment of hirsutism in women with flutamide.

OBJECTIVE: To explore the clinical usefulness of the antiandrogen flutamide in the treatment modality for hirsutism in women. DESIGN: Nine women with hirsutism were assessed before and then monthly for 3 months on a regimen of flutamide 250 mg three times a day as the sole therapeutic agent. Blood samples were taken at each assessment time for a battery of androgenic parameters. SETTING: Patients were followed in the Out-Patient Department of the Hospital das Clinicas, Sao Paulo, Brazil. Hormonal assays were performed in the Hormone Laboratories of Hospital das Clinicas and the Endocrine Research Laboratory at Newark Beth Israel Medical Center, Newark, New Jersey. PATIENTS: Nine women with moderate hirsutism were treated with flutamide. Six women were previously diagnosed as having idiopathic hirsutism, and three women were diagnosed as having polycystic ovary syndrome. INTERVENTION: All women were treated with flutamide 250 mg three times a day for 3 months. MAIN OUTCOME MEASURE: Improvement of hirsutism was assessed using the Ferriman-Gallwey hair density index. Side effects of drug therapy (deterioration of menses and dry skin) were explored. Androgen parameters included testosterone (T), sex hormone-binding globulin, bound, nonbound, and free T, androstanediol glucuronide, and others. RESULTS: After 3 months of flutamide alone, Ferriman-Gallwey scores improved in seven of nine women with mean scores decreasing from 28.1 +/- 0.6 to 24.5 +/- 0.6. None of the androgenic parameters changed during this period of time. Follicle-stimulating hormone and luteinizing hormone response to gonadotropin-releasing hormone was unchanged after flutamide. CONCLUSION: Flutamide favorably influenced hirsutism in women, with differences noted after only 3 months of therapy. More prolonged and detailed studies of this drug as the sole therapeutic agent for treatment of hirsutism seems warranted.

Monthly cyproterone acetate in the treatment of hirsute women: clinical and laboratory effects.

Cyproterone acetate given as a single intramuscular dose of 300 mg monthly for 6 months resulted in significant reduction of hirsutism without appreciable side effects. This regimen resulted in decreased levels of luteinizing hormone (LH) and estradiol in the eight women studied. No significant changes were observed in total serum testosterone (T) levels, however, there was a reduction in sex hormone binding globulin (SHBG), resulting in lowered SHBG-bound T, and an increase in non-SHBG-T over this time. Serum androstanediol glucuronide levels decreased in three of four women, although not to normal levels.

Comparison of the subacute effects of a new glucocorticoid, deflazacort, and prednisone on the hypothalamic-pituitary-adrenal axis of normal subjects.

The effects of deflazacort (DFL), a new oxazoline derivative of prednisolone, were compared with those of prednisone (Pd) by measuring plasma cortisol (F) levels as an index of the function of the hypothalamic-pituitary-adrenal (HPA) axis. Twelve normal volunteers received each glucocorticoid for 16 to 24 days in a double-blind cross-over trial with random allocation of subjects to treatment with DFL (24 mg/day) and Pd (20 mg/day) in clinically equivalent doses, with a washout period from 20 to 45 days between administration of the glucocorticoids. The following tests were performed in a randomized sequence: cortisol (F) circadian rhythm, insulin tolerance test (ITT), lysine-vasopressin (LVP) and B1-24 ACTH stimulation. Despite basal F suppression by DFL, the relative maximum F response (maximum F increment above basal/basal x 100) was significantly greater than control for the ITT and ACTH tests and was similar to the control after intramuscular injection of LVP, suggesting that the responses were appropriate for the basal F levels, with the HPA being reset at a lower level. After Pd, despite higher basal F levels, the F diurnal rhythm disappeared and there was no significant response to ITT, LVP or ACTH, indicating that the limiting factor in the HPA response was the reduced adrenal F production independent of the effects on the steroid-sensitive tissues of the brain including the pituitary.

Salivary cortisol for the evaluation of Cushing's syndrome.

Cortisol concentrations were measured in matched plasma and salivary samples from 8 healthy controls, 8 patients with Cushing's syndrome and 4 patients suspected of having spontaneous hypercortisolism. In healthy subjects, the circadian rhythm in salivary cortisol paralleled that in plasma. Absence of the diurnal rhythm in Cushing's syndrome was seen in saliva as well as in plasma. After ACTH stimulation, mean peak cortisol in saliva showed a 3-fold increase while in plasma there was a 2.5-fold increment above baseline. Cushing's syndrome, due to pituitary or adrenal adenoma was diagnosed equally well by measuring the cortisol response to cosyntropin in either plasma or saliva. Finally, the low- and high-dose dexamethasone suppression test was reflected equally well in both plasma and saliva. In patients suspected of having Cushing's syndrome dynamic tests can be performed in both plasma and saliva. However, in some samples, the salivary cortisol measurement appears advantageous over plasma cortisol determination.

Tear calcium levels in normal subjects.

Tear calcium contents were measured in 30 normal subjects divided into six groups of 5 individuals each, age ranging from the second to the seventh decade. No significant difference was found among the age groups. A mean of 4.40 mg of calcium/100 ml was determined for the 30 subjects with a standard deviation of 1.22 and a range 2.60-7.60 mg/100 ml. The tear calcium as percentage of the serum calcium was similar in the six groups and a mean of 45.68 was found for the 30 subjects. This figure is quite similar to that of serum ionised calcium as percentage of the total serum calcium values obtained by different authors.