Metabolic effects of low-dose fluconazole in healthy female users and non-users of oral contraceptives.
1. Azole antifungal agents such as ketoconazole act by inhibiting cytochrome P-450 mediated sterol synthesis in the fungal cell membrane and thus have the potential to interfere with mammalian steroidogenesis. Fluconazole is a novel orally-effective antifungal triazole which has been reported to have more specific effects on the cytochrome P-450 enzymes involved in fungal sterol synthesis. 2. Due to the potential value of systemic antifungal agents in the treatment of infections commonly occurring in women, we assessed the effect of oral fluconazole on the metabolic profile of 18 healthy premenopausal women, 10 of whom were taking combined oral contraceptives (OC). Each woman acted as her own control, being studied both before and 21-28 days after fluconazole therapy (50 mg daily), in the luteal phase of consecutive menstrual cycles. 3. The endocrinological profile included measurement of serum oestradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) concentrations, short tetracosactrin adrenal stimulation test and thyroid function tests. Carbohydrate metabolism was investigated by means of an oral glucose tolerance test with measurement of plasma glucose, insulin and C-peptide concentrations. Serum lipids, lipoproteins and apolipoproteins were analysed on samples taken after an overnight fast. 4. Minor biochemical changes associated with fluconazole treatment included increases in serum thyroxine and testosterone concentrations (but not in women taking OC as well as fluconazole) and in insulin and apolipoprotein B levels (but only in women taking OC as well as fluconazole). In general, these changes were small and of no clinical significance with the values remaining within the laboratory normal range. There were no adverse side-effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Devenport
M H
MH
Metabolic Unit, St Mary's Hospital, London.
Crook
D
D
Wynn
V
V
Lees
L J
LJ
D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects*; D001053:Apolipoproteins / Q000097:blood; D001835:Body Weight / Q000187:drug effects; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects*; D005260:Female; D015725:Fluconazole; D005951:Glucose Tolerance Test; D012739:Gonadal Steroid Hormones / Q000097:blood; D006728:Hormones / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D014230:Triazoles / Q000008:administration & dosage / Q000009:adverse effects*
D000935:Antifungal Agents; D001053:Apolipoproteins; D003278:Contraceptives, Oral, Hormonal; D012739:Gonadal Steroid Hormones; D006728:Hormones; D008055:Lipids; D008074:Lipoproteins; D012738:Sex Hormone-Binding Globulin; D014230:Triazoles; D015725:Fluconazole; D006854:Hydrocortisone