Body mass index does not influence response to treatment, nor does body weight change with lower doses of conjugated estrogens and medroxyprogesterone acetate in early postmenopausal women.
OBJECTIVE
To determine the effects of lower doses of conjugated estrogens (CE) alone or in combination with medroxyprogesterone acetate (MPA) on body weight and to evaluate the influence of body mass index (BMI) on the effect of lower-dose CE or CE/MPA on vasomotor symptoms, vaginal atrophy, bone mineral density (BMD), endometrial safety, and side effects such as endometrial bleeding and breast pain.


METHODS
In this large clinical trial [the Women's Health, Osteoporosis, Progestin, Estrogen (Women's HOPE) study], 2,673 healthy, postmenopausal women with intact uteri were randomized for 1 year of CE 0.625, CE 0.625/MPA 2.5, CE 0.45, CE 0.45/MPA 2.5, CE 0.45/MPA 1.5, CE 0.3, CE 0.3/MPA 1.5 (all doses mg/d), or placebo. Weight, BMI, number and severity of hot flushes, vaginal atrophy (as determined by the vaginal maturation index), bleeding profiles, breast pain, and endometrial biopsies were evaluated. A subset of 822 women was randomized into a 2-year substudy to evaluate changes in BMD with lower-dose CE or CE/MPA regimens.


RESULTS
After 1 year of treatment, a small but significant (P < 0.05) gain in body weight from baseline was observed in all arms of the study, the largest increase in body weight occurring in the placebo group [1.15 +/- 0.21 (SE) kg]. Body mass index had no significant effect on changes from baseline for vasomotor symptoms, bleeding patterns, vaginal atrophy, BMD, endometrial safety, or breast pain when analyzed both by analysis of covariance with baseline BMI as covariate or when participants were grouped into BMI less than 25 kg/m and BMI of 25 kg/m or greater. In placebo-treated women, vaginal atrophy was significantly greater (P < 0.05) in women with a BMI less than 25 kg/m compared with a BMI of 25 kg/m or greater.


CONCLUSIONS
Lower- and standard-dose regimens of CE or CE/MPA are not associated with greater weight gain than placebo. In addition, BMI does not seem to influence effects of these regimens on vasomotor symptoms, vaginal atrophy, bleeding profiles, BMD, endometrial safety, or breast pain.
Utian
Wulf H
WH
Rapid Medical Research, Cleveland, Ohio, USA. utian@menopause.org
Gass
Margery L S
ML
Pickar
James H
JH
D015992:Body Mass Index; D004311:Double-Blind Method; D015914:Estrogen Replacement Therapy; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage*; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D017258:Medroxyprogesterone Acetate / Q000008:administration & dosage*; D008875:Middle Aged; D017698:Postmenopause; D016896:Treatment Outcome; D014481:United States
D004966:Estrogens, Conjugated (USP); D017258:Medroxyprogesterone Acetate