Pharmacokinetics of a testosterone gel in healthy postmenopausal women.
BACKGROUND
The paucity of pharmacokinetic data on androgen formulations in women has hindered clinical trials of testosterone supplementation in women.


OBJECTIVE
The objective of this study was to determine the time course and profile of serum testosterone concentrations during treatment with different doses of testosterone gel in postmenopausal women and assess whether estrogen treatment affects the pharmacokinetics of testosterone gel.


METHODS
Postmenopausal women with total testosterone levels less than 33 ng/dl after baseline 24-h sampling were treated with 4.4, 8.8, or 13.2 mg testosterone gel daily for 7 d each in random order, with a 7-d washout period between doses. We studied 13 women who had not received estrogen therapy (group I) and 13 who had received stable estrogen therapy for 3 months or more (group II). Total and free testosterone concentrations were measured for 48 h on the seventh day of each dose administration.


RESULTS
Twenty-six women were randomized; of these, 24 were evaluable, 13 in group I and 11 in group II. The average steady-state concentrations (Cav) of serum total and free testosterone increased with increasing testosterone dose and were highly correlated with the dose (dose effect, P < 0.00001), but were not affected by estrogen therapy (P = 0.43). In both groups, the 4.4-mg dose increased Cav total and free testosterone into the mid- to high-normal range, whereas 8.8- and 13.2-mg doses raised total (Cav: 22.3, 51.6, 80.3, and 92.0 ng/dl in group I; 22.7, 59.8, 82.0, and 114.3 ng/dl in group II at 0, 4.4, 8.8, and 13. 2 mg, respectively) and free testosterone (5.9, 8.4, 11.5,12.8 pg/ml in group I and 5.0,7.6,11.1,10.8 in group II, respectively, at the various doses) above the physiological range. The area under the curve, maximum and minimum concentrations, and the change in Cav for total and free testosterone were dose related and significantly higher during administration of the 13.2-mg dose than during the 0- or 4.4-mg dose; estrogen therapy had no significant effect on these measures. Serum estradiol, LH, FSH, and SHBG levels did not change significantly at any dose. Testosterone gel was well tolerated.


CONCLUSIONS
Administration of testosterone gel to postmenopausal women raised total and free testosterone concentrations in proportion to the administered dose without affecting estradiol levels. A 4.4-mg dose raised testosterone levels into the mid- to high-normal range. Previous estrogen therapy had no significant effect on testosterone pharmacokinetics over this short duration.
Singh
Atam B
AB
Division of Endocrinology, Metabolism, and Molecular Medicine, Drew-University of California-Los Angeles Reproductive Science Research Center, Charles R. Drew University of Medicine and Science, Los Angeles, California 90059, USA.
Lee
Martin L
ML
Sinha-Hikim
Indrani
I
Kushnir
Mark
M
Meikle
Wayne
W
Rockwood
Al
A
Afework
Sebhat
S
Bhasin
Shalender
S
D000287:Administration, Topical; D000368:Aged; D019540:Area Under Curve; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D043373:Follicle Stimulating Hormone, Human / Q000097:blood; D005782:Gels; D006801:Humans; D007986:Luteinizing Hormone / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause / Q000378:metabolism*; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism; D013739:Testosterone / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics*; D016896:Treatment Outcome
D043373:Follicle Stimulating Hormone, Human; D005782:Gels; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D007986:Luteinizing Hormone