Ketoconazole Use in the Treatment of Ovarian Hyperandrogenism

Pepper, Gary M.; Brenner, Sara; Gabrilove, J. Lester

doi:10.1097/00006254-199102000-00025

Cited by 6 publications

(9 citation statements)

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“…Human testicular mono-oxygenase activities in vitro are reduced by 50% from S 310 Environmental antiandrogens and reproductive development 3.1 pmolA ketoconazole. Others (Schurmeyer and Nieschlag, 1984) demonstrated that ketoconazole and other imidazole fungicides inhibited testosterone production in men; it was also reported that ketoconazole was useful in the treatment of ovarian hyperandrogenism in women (Pepper et al, 1990). Ketoconazole also has been shown to alter hepatic steroid catabolism in mice (Wilson and Leblanc, 2000).…”

Section: Ketoconazolementioning

confidence: 99%

Effects of environmental antiandrogens on reproductive development in experimental animals

Gray

Ostby

Furr

et al. 2001

APMIS

108

124

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1Chemicals that act as androgen receptor (AR) agonists and antagonists or inhibit fetal steroidogenesis can induce reproductive malformations in humans and laboratory animals. Several environmental chemicals disrupt development in rats and/or rabbits at fetal concentrations at, or near, exposure levels seen in some segments of the human population. In rats, fetal tissues concentrations of 1 6 2 0 p.p.m. of the DDT metabolite, p,p'-DDE, are correlated with reproductive abnormalities in male offspring. These concentrations are similar to those measured in fist-trimester human fetal tissues in the late 1960s. The pesticides vinclozolin, procymidone, linuron and DDT are AR antagonists. They reduce male rat anogenital distance, and induce areolas at relatively low dosages. Hypospadias, agenesis of the sex accessory tissues and retained nipples are seen in the middle dosages, while undescended testes and epididymal agenesis are seen in the highest doses. Phthalate esters (PE) inhibit testosterone synthesis during fetal life, but do not appear to be AR antagonists. Prenatal administration of a single low dose of dioxin (50-1000 ng TCDDkg) alters the differentiation of androgen-dependent tissues at p.p.t. concentrations, but the mechanism of action likely involves interaction with a hormone-like nuclear transcription factor, the hormone-like receptor AhR, rather than AR. p,p'-DDT and p,p'-DDE, vinclozolin and di-n-butyl phthalate affect reproductive function in rabbits when administered during prenatal and/or neonatal life. Cryptorchidism and carcinoma in situ-like (CIS) testicular lesions were seen in male rabbits treated during development with p,p'-DDT or p,p'-DDE. Extrapolation of effects from rodents to humans would be enhanced if future studies incorporate determination of tissue concentrations of the active metabolites. Knowledge of the tissue concentrations of the active toxicants also would provide an important link to in-vitro studies, which provide more useful mechanistic information when they are executed at relevant concentrations.

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Section: Ketoconazolementioning

confidence: 99%

Effects of environmental antiandrogens on reproductive development in experimental animals

Gray

Ostby

Furr

et al. 2001

APMIS

108

124

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“…Its anticortisolic effect may be useful in most Cushing's syndrome patients. 16,17,18 As the recent report 15 was not a placebo-controlled trial, it was impossible to rule out pla cebo effects. We designed this double blind, controlled study to assess the role of ketoconazole in prevention of multifollicular development, excess ovarian steroidogenesis, and moderate and severe OHSS in patients with polycystic ovary syndrome (PCOS) undergoing superovulation pro gram by gonadotropins.…”

Section: Introductionmentioning

confidence: 99%

A double-blind, randomized, placebo-controlled study to assess the efficacy of ketoconazole for reducing the risk of ovarian hyperstimulation syndrome

Parsanezhad

Alborzi

Pakniat

et al. 2003

Fertility and Sterility

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Background: In order to evaluate the role of ketoconazole in the prevention of ovarian hyperstimulation syndrome (OHSS) in women with polycystic ovary syndrome (PCOS) undergoing ovarian stimulation with gonadotropins, a prospective, random ized, double-blind, placebo controlled study was done on one-hundred and nine PCOS women that had been referred to be treated by gonadotropins.Methods: All 109 women were assigned for random allocation. Group A (50 patients) received two ampoules of hMG beginning on day 2 or 3 of the cycle and ketoconazole (50 mg/every 48 hours) starting on the first day of hMG treatment. Group B (51 patients) received the same protocol of hMG combined with one tablet of pla cebo every 48 hours. Main outcome measures were follicular development, E2 levels, and pregnancy rate.Results: The total number of hMG ampoules and duration of treatment to attain ovarian stimulation was higher in group A (p<0.0001). Serum E2 level and number of patients with dominant follicles on day 9 of the cycle were higher in group B (p<0.0001). There was no significant difference between serum E2 level and total number of follicles at the time of hCG administration in the two groups. The cancellation rate and OHSS rate were similar in the two groups.Conclusion: Ketoconazole has no effect in prevention of OHSS in PCOS pa tients undergoing ovarian stimulation. It may however reduce the rate of folliculogenesis and steroidogenesis.

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“…Azole compounds such as ketoconazole and itraconazole are strong inhibitors of CYP3A (5,17), thereby increasing signi cantly the systemic concentration of inhaled and orally administered glucocorticoids (5). Ketoconazole, an antifungal azole derivative, is also a potent inhibitor of steroidogenesis by inhibition of cytochrome P450 enzymes such as C17-20 desmolase, 17-hydroxylase and 11b-hydroxylase in the steroidogenesis of the adrenals and gonads (18)(19)(20), and therefore is applied in the medical treatment of Cushing's disease (21,22). Ketoconazole can alter the ratio between gonadal secretion of oestrogens and androgens, causing gynaecomastia (23).…”

Section: Discussionmentioning

confidence: 99%

“…A complete absence of all steroid metabolites is not normally seen in patients with Cushing's syndrome or adrenal tumours, or during medication with oral contraceptives. It is known that ketoconazole can suppress androgen synthesis in the adrenals and gonads, an effect that has been used for therapeutic purposes (19,20,23). The effects of itraconazole on steroidogenesis have, however, not been extensively investigated.…”

Section: Discussionmentioning

confidence: 99%

Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient

et al. 2002

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This observation suggests that the metabolic clearance of buDesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge.

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Ketoconazole Use in the Treatment of Ovarian Hyperandrogenism

Cited by 6 publications

References 0 publications

Effects of environmental antiandrogens on reproductive development in experimental animals

Effects of environmental antiandrogens on reproductive development in experimental animals

A double-blind, randomized, placebo-controlled study to assess the efficacy of ketoconazole for reducing the risk of ovarian hyperstimulation syndrome

Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient

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