Ketoconazole therapy: hormonal and clinical effects in non-tumoral hyperandrogenism.
The aim of this study was to assess the usefulness of ketoconazole as a therapeutic alternative to polycystic ovary syndrome. The study group comprised 37 women with signs of hyperandrogenism (hirsutism, acne) and oligomenorrhea. A low dose (400 mg/day) of ketoconazole was tested in a 9-month prospective clinical study. Clinical response (Ferriman & Gallway score, acne) and modifications in hormone pattern (luteinizing hormone, follicle-stimulating hormone, estradiol, testosterone, prolactin, 17-hydroxy-progesterone, androstenedione, steroid hormone-binding globulin, dehydroepiandrosterone sulfate, cortisol, adrenocorticotropin (ACTH) and free testesterone index) were measured, and ACTH stimulation tests were performed. Tolerance and side-effect also were assessed. After 9 months of ketoconazole treatment, the patients' Ferriman & Gallway scores (18.26 +/- 4.6 vs 12.4 +/- 4.1; p < 0.001) and acne had improved markedly. Hormone patterns also became more favorable, with decreases in androgenic steroids (testosterone, androstenedione, free testosterone index and dehydroepiandrosterone sulfate; p < 0.01) and increases in estradiol (p < 0.01). Basal cortisol levels and cortisol after ACTH stimulation were not changed significantly, remaining within the reference range. Increases in ACTH were observed only in the 3rd month (p < 0.01). Initial levels of androgenic steroids were correlated inversely with their percentage decrease in successive samplings. Decreases in adrenal androgenic steroids were associated with an increase in steroid hormone-binding globulin. The side-effects of treatment, although not severe, caused some discomfort and led to a high drop-out rate (30%).(ABSTRACT TRUNCATED AT 250 WORDS)
Vidal-Puig
A J
AJ
Department of Internal Medicine I (Endocrine Division), University of Granada Hospital, Spain.
Muñoz-Torres
M
M
Jódar-Gimeno
E
E
García-Calvente
C J
CJ
Lardelli
P
P
Ruiz-Requena
M E
ME
Escobar-Jiménez
F
F
D000152:Acne Vulgaris; D000293:Adolescent; D000328:Adult; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D012739:Gonadal Steroid Hormones / Q000097:blood; D006628:Hirsutism; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D017588:Hyperandrogenism / Q000188:drug therapy* / Q000378:metabolism; D007654:Ketoconazole / Q000009:adverse effects / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D007986:Luteinizing Hormone / Q000097:blood; D009839:Oligomenorrhea; D011446:Prospective Studies; D000637:Transaminases / Q000097:blood
D012739:Gonadal Steroid Hormones; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D000637:Transaminases; D007654:Ketoconazole; D006854:Hydrocortisone