Improved bleeding profile and tolerability of tibolone versus transdermal E2/NETA treatment in postmenopausal women with female sexual dysfunction.
OBJECTIVE
To compare the incidence of vaginal spotting/bleeding events and breast pain between therapy with tibolone 2.5 mg and continuous combined transdermal estradiol (E(2))/norethisterone acetate (NETA) 50 microg/140 microg after 24 weeks of treatment.


METHODS
A double-blind, double-dummy, randomized, controlled trial was performed and assessments were performed at baseline, week 12 and week 24. Bleeding/spotting events were recorded in a daily diary. Breast signs and symptoms were collected as adverse events.


RESULTS
A total of 403 women (mean age 56 years) were randomized. Bleeding/spotting events during weeks 1-12 with tibolone and E(2)/NETA were experienced by 16% and 56% of women, respectively (p < 0.001). The corresponding percentages during weeks 13-24 were 12% and 51%, respectively (p < 0.001). E(2)/NETA was significantly more likely than tibolone to be associated with vaginal hemorrhage (11% vs. 0%; p < 0.001) and breast signs and symptoms (11% vs. 4%; p = 0.015). Early discontinuations resulting from adverse events were significantly more common in the E(2)/NETA group than in the tibolone group (20% vs. 12%), primarily related to withdrawal due to vaginal hemorrhage (8% vs. 0%).


CONCLUSIONS
Tibolone has a significantly better tolerability profile than transdermal E(2)/NETA as measured by vaginal bleeding, breast pain and treatment continuation.
Nijland
E A
EA
Department of Obstetrics & Gynecology, Groningen University Medical Center, Groningen, The Netherlands.
Nathorst-Böös
J
J
Palacios
S
S
van de Weijer
P W
PW
Davis
S
S
Stathopoulos
V M
VM
Birkhaeuser
M H
MH
von Mauw
E
E
Mulder
R J
RJ
Schultz
W C M Weijmar
WC
D000279:Administration, Cutaneous; D000368:Aged; D001940:Breast / Q000187:drug effects; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077563:Norethindrone Acetate; D009652:Norpregnenes / Q000009:adverse effects* / Q000627:therapeutic use; D010146:Pain; D017698:Postmenopause; D012735:Sexual Dysfunction, Physiological / Q000188:drug therapy*; D014592:Uterine Hemorrhage / Q000139:chemically induced*
D009652:Norpregnenes; D004958:Estradiol; D000077563:Norethindrone Acetate; C027385:tibolone; D009640:Norethindrone