goserelin and Hirsutism

Thirty-two women with polycystic ovary syndrome (PCOS) were allocated to two antiandrogen treatment regimens; 28 women completed the trial. Twenty women were treated with ethinyloestradiol and cyproterone acetate (EO-CA) cyclically for 6 months and eight women were treated with the gonadotrophin releasing hormone (GnRH) analogue, goserelin for 6 months. Effects on hirsutism, insulin sensitivity (estimated by glucose clamp technique), blood lipids and hormones were measured. Women treated with EO-CA showed a reduction in hirsutism (P <0.05), and decreased serum androgen concentrations (P <0.001) as well as reduced insulin sensitivity (P <0.05). In women treated with goserelin, serum androgen concentrations also decreased (P <0.001), but there was no significant reduction of hirsutism. This group, however, showed an improved insulin sensitivity (P <0.05) despite an unchanged body mass index. Bone mineral density was unaltered in both treatment groups. The reduction in androgen concentrations caused by EO-CA was not paralleled by increased insulin sensitivity, most probably due to the effect of ethinyloestradiol per se. In contrast, the reduction in androgen concentrations by goserelin was accompanied by an improved insulin sensitivity.

Topics: Adult; Androgen Antagonists; Androgens; Cyproterone Acetate; Estradiol Congeners; Ethinyl Estradiol; Female; Goserelin; Hirsutism; Humans; Insulin Resistance; Lipids; Polycystic Ovary Syndrome

We studied 20 hirsute patients with high levels of serum testosterone (T), calculated free T, androstenedione, and dehydroepiandrosterone sulfate and 19 age-matched nonhirsute normoandrogenic control women. The bone mineral density (BMD) in the lumbar spine, femoral neck, and trochanter major region in hirsute patients was higher than that in the controls. BMD in the lumbar spine and proximal femur correlated positively with the body mass index and with serum T and free T in hyperandrogenic women and the whole study group, but not with serum androstenedione or dehydroepiandrosterone sulfate levels. The hirsute women were treated with a GnRH agonist (goserelin, 3.6-mg implant) for 9 months. After the first 3 months of treatment, half of the patients were randomized to receive estrogen-progestin replacement therapy (HRT), and the other half served as controls. After the first 3 months of trial, BMD was unaffected, and the urinary output of collagen pyridinoline, deoxypyridinoline cross-links, and hydroxyproline (all markers of bone resorption) were increased, but serum markers, the carboxy-terminal telopeptide of type I collagen (marker of bone resorption) and that of bone-specific alkaline phosphatase (marker of bone formation) did not change. After 9 months of goserelin treatment, the lumbar spine had lost 5.4% of its BMD (P < 0.01), but regained bone density 6 months after cessation of treatment. Addition of HRT protected the spine and trochanter major against bone loss. The changes in serum telopeptide and urinary output of pyridinoline and deoxypyridinoline after 3 months of treatment (from prestudy levels) correlated with the decrease in BMD in the femoral neck at 9 months. In conclusion, our data show that patients with ovarian androgen excess 1) have high BMD, 2) lose bone during 9 months of treatment with GnRH agonist, 3) show a decrease in bone density preceded by biochemical alterations in bone metabolism at least 6 months earlier, and 4) can have their bone loss prevented by add-back HRT.

Topics: Adult; Alkaline Phosphatase; Bone and Bones; Bone Density; Drug Therapy, Combination; Estradiol; Estrogen Replacement Therapy; Female; Gonadotropin-Releasing Hormone; Goserelin; Hirsutism; Humans; Hydroxyproline; Hyperandrogenism; Medroxyprogesterone Acetate; Testosterone

A multicenter randomized study was carried out to compare the efficacy of combined therapy with a GnRH analog (goserelin) + an oral contraceptive (OC) containing ethinyl estradiol and cyproterone acetate and same OC alone in the treatment of severe hirsutism. The effect of these two therapies was assessed in a subjective and an objective evaluation of hair growth. According to the subjective evaluation, judged by physician and patient. 95% of patients obtained a partial response. The objective response was assessed by measuring the mean diameter of hair from 3 different areas and 1 control area. The decrease in hair diameter compared to pretreatment was statistically significant for both treatments, mainly for the abdomen and face. The difference between the two groups did not reach statistical significance. Therefore, we assume that OC alone remains the treatment of choice for hirsutism. However, the addition of the GnRH analog to OC needs further investigation and could be justified for patients with no response to standard monotherapy.

Topics: Acne Vulgaris; Adult; Contraceptives, Oral; Cyproterone Acetate; Estradiol; Ethinyl Estradiol; Female; Follicle Stimulating Hormone; Goserelin; Hirsutism; Humans; Luteinizing Hormone; Testosterone

The therapies presently available for treating ovarian hirsutism are not uniformly effective, and therefore, much has been expected from GnRH agonists. These inhibit the secretion of gonadotropins and thereby suppress ovarian function, but at the same time cause hypoestrogenic side-effects. We, therefore, administered goserelin, a long-acting GnRH agonist, for treatment of 20 hirsute women (18 with polycystic ovaries) for 9 months; half of them were randomized to receive cyclic estradiol and medroxyprogesterone replacement from the fourth month onward. Seventeen patients completed the study. Goserelin suppressed ovarian function, as evidenced by a profound reduction in serum estradiol levels. The circulating levels of total testosterone, free testosterone, and androstenedione were lowered at 3 months by 29%, 31%, and 38%, respectively, but there was no effect on the levels of sex hormone-binding globulin (SHBG) or dehydroepiandrosterone sulfate. Ovarian suppression, maintained for the duration of the trial, alleviated hirsutism, as evidenced by a decrease in Ferriman-Gallwey hirsutism scores. Estrogen plus progestin replacement restored estradiol levels and increased SHBG levels, but did not potentiate the therapeutic effect of goserelin or reduce free testosterone levels. Replacement therapy abolished or alleviated hypoestrogenic vasomotor symptoms, but it also caused bleeding and premenstrual symptoms, which necessitated the withdrawal of 3 of 10 women from the treatment. Thus, goserelin is an effective treatment for ovarian hyperandrogenism. Simultaneous estrogen replacement abolishes the hypoestrogenic side-effects, but does not potentiate the effect of goserelin on hirsutism. Interestingly, the estrogen-induced increase in SHBG did not affect free testosterone. Thus, the suppression of gonadotropins, rather than the increase in SHBG, appears to be of primary significance in the alleviation of ovarian hyperandrogenism by estrogens.

Topics: Adolescent; Adult; Androgens; Androstenedione; Drug Synergism; Estradiol; Female; Goserelin; Hirsutism; Humans; Medroxyprogesterone Acetate; Sex Hormone-Binding Globulin; Testosterone

Topics: Aged; Androgen Antagonists; Female; Gonadotropin-Releasing Hormone; Goserelin; Hirsutism; Humans; Hyperandrogenism; Postmenopause; Remission Induction; Severity of Illness Index; Testosterone

Topics: Adrenal Hyperplasia, Congenital; Alopecia; Androstenedione; Dehydroepiandrosterone Sulfate; Dexamethasone; Diagnosis, Differential; Female; Gonadotropin-Releasing Hormone; Goserelin; Hirsutism; Humans; Hydrocortisone; Middle Aged; Polycystic Ovary Syndrome; Testosterone; Treatment Outcome

We describe four patients with ovarian hyperthecosis and the effects of gonadotrophin releasing hormone on clinical and metabolic variables.. Open out-patient study.. Four women presented with post-menopausal hirsuties. They had significant hair growth across the chest, upper back and shoulders. Three had histologically proven ovarian hyperthecosis and a fourth had large ovaries visualized on ultrasound. All four women had pronounced risk factors for vascular disease; hypertension, hyperlipidaemia and glucose intolerance, and three had already developed symptomatic vascular disease.. Gonadotrophin releasing hormone agonist therapy resulted in significant reduction in plasma androgens and cosmetic reduction in hair growth but had no effect on hyperlipidaemia.. The post-menopausal women described in this report were clinically considered to have hyperandrogenism due to the pathological pattern of marked body hair over the upper trunk. Treatment with GnRH was very effective at reducing the severity of the hirsuties. The post-menopausal women with hyperthecosis in this report had a high prevalence of cardiovascular disease. Since hyperandrogenism and insulin are considered risk factors for cardiovascular disease in premenopausal women with polycystic ovaries, we discuss the possible relationship between insulin and the post-menopausal ovary.

Topics: Aged; Androgens; Antineoplastic Agents, Hormonal; Diabetes Mellitus, Type 2; Female; Goserelin; Hirsutism; Humans; Hyperlipidemias; Hypertension; Middle Aged; Ovarian Diseases; Ovary; Postmenopause; Smoking

Topics: Androgen Antagonists; Bromocriptine; Contraceptives, Oral, Combined; Dexamethasone; Female; Finasteride; Goserelin; Hirsutism; Humans; Ketoconazole; Leuprolide; Medroxyprogesterone Acetate; Nafarelin