A randomized, open-label, crossover study comparing the effects of oral versus transdermal estrogen therapy on serum androgens, thyroid hormones, and adrenal hormones in naturally menopausal women.
OBJECTIVE
To compare the changes induced by oral versus transdermal estrogen therapy on the total and free serum concentrations of testosterone (T), thyroxine (T4), and cortisol (C) and the concentrations of their serum binding globulins sex hormone-binding globulin, thyroxine-binding globulin, and cortisol-binding globulin in naturally menopausal women.


METHODS
Randomized, open-label, crossover. Interventions included a 6-week withdrawal from previous hormone therapy (baseline), followed in randomized order by 12 weeks of oral conjugated equine estrogens (CEE) (0.625 mg/d) and 12 weeks of transdermal estradiol (TD E2) (0.05 mg/d), with oral micronized progesterone (100 mg/d) given continuously during both transdermal estrogen therapy regimens.


RESULTS
Twenty-seven women were enrolled in the study, and 25 completed both treatment periods. The mean(SD) percentage changes from baseline of sex hormone-binding globulin, total T, and free T with oral CEE were +132.1% (74.5%), +16.4% (43.8%), and -32.7% (25.9%), respectively, versus +12.0% (25.1%), +1.2% (43.7%), and +1.0% (45.0%) with TD E2. The mean (SD) percentage changes of thyroxine-binding globulin, total T4, and free T4 with oral CEE were +39.9% (20.1%), +28.4% (29.2%), and -10.4% (22.3%), respectively, versus +0.4% (11.1%), -0.7% (16.5%), and +0.2% (26.6%) with TD E2. The mean (SD) percentage changes of cortisol-binding globulin, total C, and free C with oral CEE were +18.0% (19.5%), +29.2% (46.3%), and +50.4% (126.5%), respectively, versus -2.2% (11.3%), -6.7% (30.8%), and +1.8% (77.1%) with TD E2. Concentrations of all hormones and binding globulins were significantly different (P < or = 0.003) during administration of oral versus transdermal estrogen therapy, except for free T4 and free C.


CONCLUSIONS
Compared with oral CEE, TD E2 exerts minimal effects on the total and free concentrations of T, T4, and C and their binding proteins.
Shifren
Jan L
JL
Vincent Obstetrics and Gynecology Service, Massachusetts General Hospital, Boston, MA 02114, USA. jshifren@partners.org
Desindes
Sophie
S
McIlwain
Marilyn
M
Doros
Gheorghe
G
Mazer
Norman A
NA
D000279:Administration, Cutaneous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D002352:Carrier Proteins / Q000097:blood; D018592:Cross-Over Studies; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008593:Menopause; D008875:Middle Aged; D011374:Progesterone / Q000008:administration & dosage*; D013739:Testosterone / Q000097:blood; D013974:Thyroxine / Q000097:blood; D016896:Treatment Outcome
D002352:Carrier Proteins; D004966:Estrogens, Conjugated (USP); C027091:cortisol binding globulin; D013739:Testosterone; D011374:Progesterone; D013974:Thyroxine