Efficacy and safety of a constant-estrogen, pulsed-progestin regimen in hormone replacement therapy.
OBJECTIVE
Two studies (Studies A and B) were conducted to measure efficacy and safety of constant 17beta-estradiol (E2), pulsed norgestimate (NGM) hormone replacement therapy on bleeding and vasomotor symptoms in postmenopausal women. NGM was pulsed in a 3-days-off/3-days-on fashion. Study A also assessed effects of treatment on vaginal cytology.


METHODS
In two 360-day, multicenter, double-blind, parallel-group studies, 1,253 subjects were randomized to receive daily, unopposed E2 1 mg or one of three constant estrogen, pulsed progestin regimens: E2 1 mg/NGM 30 microg, E2 1 mg/NGM 90 microg, or E2 1 mg/NGM 180 microg.


RESULTS
Bleeding control improved over time in women treated with E2 1 mg/NGM 90 microg: 69% of women were free of bleeding (irrespective of spotting) during month 1, 71% during month 6, and 80% during month 12. E2 1 mg/NGM 30 microg had a lower incidence of bleeding but provided inadequate endometrial protection. Among subjects with vasomotor symptoms at baseline, the percentage of asymptomatic subjects at the end of 3 months was 70% in the E2 1-mg group and 76% in the E2 1-mg/NGM 90-microg group. E2 1 mg/NGM 90 microg was at least as effective as E2 1 mg alone in causing maturation of vaginal epithelial cells. All regimens were well tolerated.


CONCLUSIONS
Pulsed dosing of NGM 90 microg for 3 days off and 3 days on along with continuous administration of E2 is effective in treating vasomotor symptoms and vulvovaginal atrophy, provides endometrial protection (i.e., no cases of endometrial hyperplasia or cancer), and has a bleeding profile acceptable to the majority of women studied.
Sulak
P J
PJ
Scott & White Memorial Hospital, Temple, Texas 76508, USA.
Caubel
P
P
Lane
R
R
D000328:Adult; D000368:Aged; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004958:Estradiol / Q000008:administration & dosage* / Q000009:adverse effects*; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D008875:Middle Aged; D009644:Norgestrel / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D017698:Postmenopause; D014481:United States; D014592:Uterine Hemorrhage / Q000139:chemically induced / Q000517:prevention & control*; D014621:Vagina / Q000166:cytology / Q000187:drug effects*
D009644:Norgestrel; D004958:Estradiol; C017576:norgestimate