A pilot study of an investigational testosterone transdermal patch system in young women with spontaneous premature ovarian failure.
BACKGROUND
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.


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


METHODS
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.


METHODS
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 microg/d) was applied twice weekly to the abdomen.


METHODS
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.
Kalantaridou
Sophia N
SN
Developmental Endocrinology Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA.
Calis
Karim A
KA
Mazer
Norman A
NA
Godoy
Heidy
H
Nelson
Lawrence M
LM
D000279:Administration, Cutaneous; D000328:Adult; D000728:Androgens / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D005260:Female; D006728:Hormones / Q000097:blood; D006801:Humans; D008597:Menstrual Cycle / Q000187:drug effects; D010865:Pilot Projects; D016649:Primary Ovarian Insufficiency / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D013739:Testosterone / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use
D000728:Androgens; D006728:Hormones; D013739:Testosterone