Efficacy and safety of low-dose regimens of conjugated estrogens cream administered vaginally.
OBJECTIVE
The aim of this study was to evaluate the efficacy and safety of low-dose conjugated estrogens (CE) cream for treatment of atrophic vaginitis.


METHODS
Postmenopausal women (N = 423) with moderate-to-severe vaginal atrophy were randomized to CE cream 0.3 mg or placebo once daily (21 days on/7 days off) or twice weekly for 12 weeks, followed by open-label treatment with CE cream for 40 weeks consistent with their prior regimen. Primary endpoints were changes in vaginal maturation index (VMI; percentage of superficial cells), vaginal pH, and severity of participant-reported most bothersome symptom (vaginal dryness, itching, burning, or dyspareunia) at week 12. Endometrial safety was assessed by transvaginal ultrasound and endometrial biopsy for 52 weeks.


RESULTS
At week 12, improvements in VMI with daily and twice-weekly use of low-dose CE cream (27.9% and 25.8%, respectively) were significantly greater compared with placebo (3.0% and 1.0%, respectively; P < 0.001). Improvements in vaginal pH with daily and twice-weekly CE cream (-1.6 for both) were also significantly greater relative to placebo (-0.4 and -0.3, respectively; P < 0.001). VMI and vaginal pH responses were sustained through 52 weeks. Both CE cream regimens significantly reduced most bothersome symptom scores compared with placebo (P < or = 0.001), including those for dyspareunia (P < or = 0.01). There was no report of endometrial hyperplasia or carcinoma. Adverse events occurred with similar frequency among the active and placebo groups during the double-blind phase.


CONCLUSIONS
Daily and twice-weekly use of low-dose CE cream was equally effective in relieving symptoms of vulvovaginal atrophy. Both regimens showed endometrial safety and sustained efficacy during 1 year of therapy.
University of Medicine and Dentistry of New Jersey-Robert Wood Johnson Medical School, New Brunswick, NJ 08901, USA. bachmaga@umdnj.edu
Gloria
G
Bachmann
Céline
C
Bouchard
Diana
D
Hoppe
Radhika
R
Ranganath
Corrado
C
Altomare
Alberta
A
Vieweg
Jay
J
Graepel
Eileen
E
Helzner
D000282:Administration, Intravaginal; D000368:Aged; D000369:Aged, 80 and over; D004311:Double-Blind Method; D004714:Endometrial Hyperplasia / Q000139:chemically induced / Q000000981:diagnostic imaging / Q000473:pathology; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects / Q000473:pathology; D004966:Estrogens, Conjugated (USP) / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008875:Middle Aged; D010919:Placebos; D017698:Postmenopause; D014463:Ultrasonography; D014622:Vaginal Creams, Foams, and Jellies / Q000008:administration & dosage; D014627:Vaginitis / Q000188:drug therapy*
D004966:Estrogens, Conjugated (USP); D010919:Placebos; D014622:Vaginal Creams, Foams, and Jellies