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A Pilot Study of an Investigational Testosterone Transdermal Patch System in Young Women with Spontaneous Premature Ovarian Failure

Developmental Endocrinology Branch (S.N.K., H.G., L.M.N.), National Institute of Child Health and Human Development and Department of Pharmacy (K.A.C.), National Institutes of Health, Bethesda, Maryland 20892; and the Department of Pharmaceutics (N.A.M.), University of Utah, Salt Lake City, Utah 84112

Address all correspondence and requests for reprints to: Karim A. Calis, Pharm.D., M.P.H., B.C.P.S., B.C.N.S.P., F.A.S.H.P., F.C.C.P., Clinical Center Pharmacy Department, National Institutes of Health, Building 10, Room 1S-259, 10 Center Drive (MSC 1196), Bethesda, Maryland 20892. E-mail: kcalis{at}nih.gov.

Context: Evidence suggests that young women with spontaneous premature ovarian failure (sPOF) have significantly lower androgen levels than age-matched regularly menstruating women.

Objective: The objective of the study was to evaluate an investigational testosterone transdermal patch (TTP) designed to deliver the normal ovarian production rate of testosterone.

Design: This was an open-label study (2-month baseline period followed by 2-month treatment period).

Patients: Nine women with sPOF and a history of regular bleeding patterns on standard estrogen/progestogen cyclic treatment participated in the study. One subject with abnormal baseline levels was excluded.

Intervention: Four consecutive 28-d cycles of transdermal estradiol (E₂; 0.1 mg/d) and sequential oral medroxyprogesterone acetate (MPA; 10 mg/d for the last 12 d of each cycle). During cycles 3 and 4, an investigational TTP (nominal delivery 150 µg/d) was applied twice weekly to the abdomen.

Main Outcome Measures: Steady-state pharmacokinetic profiles of free and total testosterone and scheduled vaginal bleeding patterns were studied.

Results: The mean (95% confidence interval) of the time-average free testosterone levels during TTP treatment was 7.5 (4.9–9.9) pg/ml; 26.0 (17.2–34.6) pmol/liter (with E₂), and 6.9 (4.9–8.8) pg/ml; 23.9 (17.2–30.5) pmol/liter (with E₂ and MPA). The confidence intervals of the means include the upper limit of normal for premenopausal women, i.e. 6.8 pg/ml (23.5 pmol/liter), although the mean values are slightly above this.

Conclusions: The addition of TTP to cyclic E₂/MPA therapy in women with sPOF produced mean free testosterone levels that approximate the upper limit of normal. A 3-yr study to assess safety and effectiveness in this population is in progress.