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Hair Loss Study Abstract: Low dose ketoconazole attenuates serum androgen levels in patients with polycystic ovary syndrome and inhibits ovarian steroidogenesis in vitro.
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Title
Low dose ketoconazole attenuates serum androgen levels in patients with polycystic ovary
syndrome and inhibits ovarian steroidogenesis in vitro.
Author
Gal M; Orly J; Barr I; Algur N; Boldes R; Diamant YZ
Address
Department of Obstetrics and Gynecology, Shaare Zedek Medical Center, Jerusalem, Israel.
Source
Fertil Steril, 61: 5, 1994 May, 823-32
Abstract
OBJECTIVE: To investigate the effects of a low-dose ketoconazole on ovarian
steroidogenesis and on serum androgen levels in polycystic ovary syndrome (PCOS). DESIGN:
In vitro, human granulosa-luteal cells were incubated with ketoconazole and radiolabeled
steroid substrates, to follow their metabolic fate by thin-layer chromatography analysis.
In vivo, normally cycling women (n = 7) in their luteal phase were administered one tablet
of 200 mg ketoconazole at 8 A.M. Serum steroid levels, sampled basally and at 12 P.M., 4
P.M., and 8 A.M. the next morning, were compared with untreated control group (n = 7)
values. Polycystic ovary syndrome women (n = 11) were similarly administered ketoconazole
6 to 10 days after occurrence of spontaneous menses. Adrenal origin of hyperandrogenemia
was excluded by stimulation with ACTH and a normal basal DHEAS. The steroid diurnal
variation was determined in the same patients a day before treatment. RESULTS: In vitro,
ketoconazole selectively inhibited the key steroidogenic cytochromes, namely P450scc,
P45017 alpha, and P450arom (IC50 = 0.5 to 1.0 microgram/mL). In vivo, in the luteal phase,
ketoconazole transiently decreased serum values (mean +/- SE) of E2 (19.2% +/- 2.1%) and P
(38.3% +/- 8.5%) within 4 to 8 hours. The same low-dose ketoconazole, administered to PCOS
women, decreased serum values of androstenedione (17.6% +/- 4.7%), T (24.6% +/- 7.6%), and
free T (30.7% +/- 7.7%). In contrast, 17 alpha-hydroxyprogesterone increased concomitantly
(78.5% +/- 10.8%), suggesting a greater suppressibility of the P45017 alpha lyase
activity. The E2 levels in PCOS patients were slightly elevated (29.1% +/- 5.6%),
resulting in a 1.7- to 2.3-fold increase of the E2:T ratio. CONCLUSIONS: These findings
suggest that a low-dose ketoconazole may facilitate a decreased intraovarian T:E2 ratio,
which may prove favorable for follicular maturation in PCOS.
Language of Publication
English
Unique Identifier
94229255
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