Differential effects on the androgen status of postmenopausal women treated with tibolone and continuous combined estradiol and norethindrone acetate replacement therapy.
OBJECTIVE
To determine serum parameters reflective of androgen status in postmenopausal women using two types of hormone replacement therapy (HRT).


METHODS
Randomized, double-blind, prospective 1-year trial of two oral HRT regimens.


METHODS
University hospital, department of obstetrics and gynecology, menopause clinic.


METHODS
100 postmenopausal women > or = 45 years.


METHODS
Daily use of the progestogen tibolone (2.5 mg; n = 50) or continuous combined 17-beta-estradiol (2 mg) and norethindrone acetate (E+NA, 1 mg; n = 50).


METHODS
Measurements of total testosterone (total T), dehydroepiandrosterone sulfate (DHEAS), androstenedione (A), FSH, and sex-hormone-binding globulin (SHBG), and calculations of free testosterone (free T). Assessment of changes from baseline within and between groups after 6 and 12 months.


RESULTS
We found significant differences (% changes) in the tibolone group compared to baseline within the groups after both 6 and 12 months, respectively. Levels of free T doubled, total T decreased slightly, and SHBG decreased by half; DHEAS increased by approximately 20%; and FSH decreased. In the E+NA group, levels of free T, total T, androstenedione, and FSH all decreased, and SHBG increased. Pre-trial levels of DHEAS, A, and total T were significantly higher in the E+NA group. Between groups throughout the study, the changes from baseline were significant due to the different extent of FSH reduction, and opposite changes of free T, SHBG, and DHEAS.


CONCLUSIONS
Both regimens modify plasma androgens, DHEAS, and SHBG differently. Tibolone decreased the levels of SHBG, and substantially increased free T and to a lesser extent increased DHEAS; this may reflect a modification of adrenal androgen production. Continuous combined estradiol and norethindrone acetate HRT suppressed the peripheral plasma androgens mediated by increased levels of SHBG.
Department of Obstetrics and Gynecology, Westfällische Wilhelms-Universität, Münster, Germany. doeren@ukbf.fu-berlin.de
M
M
Dören
A
A
Rübig
H J
HJ
Coelingh Bennink
W
W
Holzgreve
D000728:Androgens / Q000097:blood*; D000735:Androstenedione / Q000097:blood; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000627:therapeutic use; D015914:Estrogen Replacement Therapy; D005260:Female; D005640:Follicle Stimulating Hormone / Q000097:blood; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage* / Q000031:analogs & derivatives / Q000627:therapeutic use; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000008:administration & dosage / Q000627:therapeutic use*; D017698:Postmenopause; D011446:Prospective Studies; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood
D000728:Androgens; D009652:Norpregnenes; D012738:Sex Hormone-Binding Globulin; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D005640:Follicle Stimulating Hormone; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone