The effects of six months of treatment with a low-dose of conjugated oestrogens in menopausal women.
OBJECTIVE
Hormone replacement therapy (HRT) is usually prescribed as medium- to high-dose formulations. Little is known, however, about dose-dependency of oestrogen effects on plasma hormone levels, markers of cardiovascular risk in lipid metabolism and the haemostatic system, or markers of bone turnover.


METHODS
In an open trial, three groups of 12 or 13 healthy, non-obese postmenopausal women received conjugated equine oestrogens (CEE) for 6 months at doses of 0.3 mg/day (group 1), 0.6 mg/day (group 2) or 1.25 mg/day (group 3). From day 1 to day 10, CEE was administered alone, and from day 11 to day 21, in combination with 5 mg of medrogestone. Each treatment cycle was followed by a pause of 7 days. Fasting blood samples were obtained before treatment as well as on days 10, 21 and 28 of the first, third and sixth months on treatment. All results obtained on day 10 were grouped together as phase A, on day 21 as phase B, and on day 28 as phase C.


METHODS
Plasma concentrations of oestradiol (E), dehydroepiandrosterone sulphate (DHEA-S), total testosterone (T), FSH, PRL, sex hormone binding globulin (SHBG), type I procollagen propeptide (PICP) and the cross-linked carboxyterminal telopeptide of type I collagen (ICTP), total cholesterol, HDL-cholesterol, triglycerides (TG), apolipoprotein (apo) A-1, apo B, lipoprotein(a)[Lp (a)], fibrinogen, factor VIIc and plasminogen activator inhibitor 1 (PAI-1) were evaluated with commercially available kits.


RESULTS
Dose-dependently, the three regimens increased E, SHBG and factor VIIc activity and decreased FSH, DHEAS, cholesterol, LDL-cholesterol and apoB. HDL-cholesterol and apoA-1 were slightly decreased in group 1 but increased in groups 2 and 3. The high CEE dosage in group 3 resulted in a significant increase of TG and decrease of Lp(a) and PAI-1. Markers of bone turnover were not significantly changed by any CEE dosage.


CONCLUSIONS
Six months of treatment with 0.3 mg/day of conjugated equine oestrogen significantly lowers serum levels of total cholesterol and LDL-cholesterol without causing the adverse increases of triglycerides or factor VIIc, which were observed at higher doses. However, this low-dose treatment did not yield the maximal LDL-cholesterol lowering effect. Moreover, the positive effects of HRT on HDL-cholesterol, apolipoprotein A-I, lipoprotein (a) and plasminogen activator inhibitor-1 required at least the medium dose of 0.6 mg conjugated equine oestrogens per day. Therefore, further studies are needed to determine which dose of conjugated equine oestrogens has the optimal effect on cardiovascular risk and bone turnover.
Schlegel
W
W
Department of Obstetrics and Gynaecology, Wesfälische Wilhelms-Universität, Münster, Germany.
Petersdorf
L I
LI
Junker
R
R
Schulte
H
H
Ebert
C
C
Von Eckardstein
A
A
D015415:Biomarkers / Q000097:blood; D016723:Bone Remodeling / Q000187:drug effects*; D003094:Collagen / Q000097:blood; D024042:Collagen Type I; D019314:Dehydroepiandrosterone Sulfate / Q000097:blood; D004334:Drug Administration Schedule; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000097:blood / Q000627:therapeutic use; D005167:Factor VII / Q000032:analysis; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D005640:Follicle Stimulating Hormone / Q000097:blood*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008593:Menopause / Q000097:blood; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011347:Procollagen / Q000097:blood; D011388:Prolactin / Q000097:blood; D012738:Sex Hormone-Binding Globulin / Q000032:analysis; D013739:Testosterone / Q000097:blood
D015415:Biomarkers; D024042:Collagen Type I; D004966:Estrogens, Conjugated (USP); D008055:Lipids; D010446:Peptide Fragments; D010455:Peptides; D017395:Plasminogen Activator Inhibitor 1; D011347:Procollagen; D012738:Sex Hormone-Binding Globulin; C052929:collagen type I trimeric cross-linked peptide; C042813:procollagen type I carboxy terminal peptide; D013739:Testosterone; D019314:Dehydroepiandrosterone Sulfate; D005167:Factor VII; D005340:Fibrinogen; D011388:Prolactin; D005640:Follicle Stimulating Hormone; D003094:Collagen