Positive effects on cardiovascular and breast metabolic markers of oral estradiol and dydrogesterone in comparison with transdermal estradiol and norethisterone acetate.
OBJECTIVE
To assess differences in two sequential combined hormone replacement therapy (HRT) products on selected cardiovascular and breast metabolic markers. The products were different concerning the route of administration of estradiol and its combined progestin, either oral or transdermal, and the androgenic properties of progestogens, respectively, dydrogesterone and norethisterone acetate.


METHODS
One hundred and nineteen healthy non-hysterectomized postmenopausal women were included in this open, multi-center, two parallel group trial. They were randomized to a treatment of six 28-day cycles with oral estradiol sequentially combined with dydrogesterone (oE2/D10) or a sequential combination patch of estradiol plus norethisterone acetate (tdE/NETA). At baseline and after six cycles the high-density lipoprotein cholesterol (HDL-C), the sex hormone binding globulin (SHBG) and the total insulin-like growth factor-I (IGF-I) blood levels were determined by a central laboratory. A total of 89 women were compliant to the protocol.


RESULTS
After six cycles, a statistically significant difference (P<0.001) concerning HDL-C, SHBG and IGF-I levels was found between the two treatment groups. The HDL-C levels were increased in the oE2/D10 group and decreased in the tdE/NETA group, with a final difference of about 0.3 mmol/l. The oE2/D10 treatment induced a sharp increase (about 57 mmol/l) in SHBG levels. IGF-I levels decreased with both the products, but the difference in favor of the oE2/D10 treatment was of about 30 ng/ml. Moreover, patients on tdE/NETA with an IGF-I baseline value below the median showed an increase.


CONCLUSIONS
Oral estradiol sequentially combined with dydrogesterone, a non-androgenic progestogen, induced positive changes of some cardiovascular (HDL-C) and breast (SHBG and IGF-I) metabolic markers. These effects were significantly different from those obtained with a transdermal estradiol associated to an androgenic progestogen.
Campagnoli
Carlo
C
Unit of Endocrinological Gynaecology, Azienda Ospedaliera O.I.R.M./Sant'Anna, c.so Spezia, 60-10127 Torino, Italy.
Colombo
Paola
P
De Aloysio
Domenico
D
Gambacciani
Marco
M
Grazioli
Irene
I
Nappi
Carmine
C
Serra
Giovan Battista
GB
Genazzani
Andrea Riccardo
AR
D000279:Administration, Cutaneous; D000284:Administration, Oral; D008076:Cholesterol, HDL / Q000097:blood*; D004958:Estradiol / Q000008:administration & dosage / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077563:Norethindrone Acetate; D017698:Postmenopause; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*
D008076:Cholesterol, HDL; D012738:Sex Hormone-Binding Globulin; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; D000077563:Norethindrone Acetate; D009640:Norethindrone