Continuous combined hormone replacement therapy with oral 17beta-estradiol and norethisterone acetate improves homocysteine metabolism in postmenopausal women.
OBJECTIVE
To evaluate the effect of a continuous combined oral hormone replacement therapy (HRT) on basal and post-methionine load homocysteine levels in postmenopausal women.


METHODS
Twenty-two postmenopausal women (PMW) were randomly allocated to receive either continuous combined oral HRT (2 mg of estradiol plus 1 mg of norethisterone acetate; n = 11) or no treatment (controls, n = 11) for 6 months. A methionine oral load (0.1 g/kg body weight) was performed in each subject at time 0 and after 6 months. Serum homocysteine levels were measured by high-performance liquid chromatography in samples collected at time 0 and at 4, 8, and 24 h after the methionine load, while levels of vitamin B6 (by high-performance liquid chromatography) and B12 and folate (both by ELISA) were assayed in samples collected at time 0.


RESULTS
Serum levels of glucose and body mass index increased in treated PMW, whereas folate decreased in controls. In treated PMW, basal homocysteine tended to decrease (10.6 +/- 3.3 micromol/L vs. 9.62 +/- 2.8 micromol/L, p = 0.062), whereas in controls it significantly increased (10.7 +/- 2.65 micromol/L vs. 12.17 +/- 3.89 micromol/L, p < 0.05). This increase was not significant after correction for vitamin status (p = 0.072). Homocysteine values 4 h (31.9 +/- 13.53 micromol/L vs. 39.83 +/- 22.53 micromol/L, p < 0.05) and 8 h (35.1 +/- 13.13 vs. 43.34 +/- 22.15 micromol/L) after methionine, and integrated homocysteine response to methionine (392.5 +/- 133.8 micromol/24 h vs. 458.8 +/- 104.8 micromol/24 h; p < 0.05), were significantly reduced in HRT-treated, but not in untreated, PMW.


CONCLUSIONS
Continuous combined oral HRT with17beta-estradiol plus norethisterone acetate reduces homocysteine levels, mainly after a methionine load. This effect seems to be independent of vitamin status and may have positive implications for the prevention of cardiovascular diseases in PMW.
Ventura
P
P
Department of Internal Medicine, Division of Geriatrics and Gerontology, University of Modena and Reggio Emilia, Italy. paoloven@unimo.it
Cagnacci
A
A
Malmusi
S
S
Panini
R
R
Baldassari
F
F
Arangino
S
S
Volpe
A
A
Salvioli
G
G
D000284:Administration, Oral; D001786:Blood Glucose / Q000032:analysis / Q000187:drug effects; D015992:Body Mass Index; D002851:Chromatography, High Pressure Liquid; D004958:Estradiol / Q000494:pharmacology / Q000627:therapeutic use*; D015914:Estrogen Replacement Therapy / Q000379:methods*; D005260:Female; D005492:Folic Acid / Q000097:blood; D006710:Homocysteine / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D008715:Methionine; D008875:Middle Aged; D009640:Norethindrone / Q000494:pharmacology / Q000627:therapeutic use*; D017698:Postmenopause / Q000187:drug effects* / Q000378:metabolism*; D045167:Progesterone Congeners / Q000494:pharmacology / Q000627:therapeutic use*; D011736:Pyridoxine / Q000097:blood; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000097:blood
D001786:Blood Glucose; D045167:Progesterone Congeners; D006710:Homocysteine; D004958:Estradiol; D005492:Folic Acid; D008715:Methionine; D011736:Pyridoxine; D014805:Vitamin B 12; D009640:Norethindrone