The effects of combined raloxifene and oral estrogen on vasomotor symptoms and endometrial safety.
OBJECTIVE
To compare effects of 52 weeks' treatment with either raloxifene 60 mg/day alone (RLX) or in combination with 17beta-estradiol 1 mg/day (RLX + E) on vasomotor symptoms (n = 83) and endometrial safety (n = 123) in postmenopausal women who transitioned from estrogen-progestin therapy.


METHODS
In this randomized, double-blind clinical trial, the frequency of vasomotor symptoms, hot flashes, and night sweats was assessed for up to 52 weeks. Endometrial thickness was assessed by transvaginal ultrasonography at baseline and at 12 and 52 weeks. An exit endometrial biopsy was performed at study completion or early termination.


RESULTS
The frequency of vasomotor symptoms, hot flashes, and night sweats was unchanged from baseline with RLX but was significantly reduced in women treated with RLX + E, from baseline (all P < 0.001) and the RLX group at 6, 12, 24, 36, and 52 weeks (all P < 0.01). Women in the RLX + E group had significantly increased endometrial thickness (0.74 +/- 0.28 mm, mean +/- SEM) at 52 weeks, from baseline and RLX (P < 0.05), with no statistically significant changes in women treated with RLX. Two women, both in the RLX + E group, had endometrial hyperplasia (one with atypia) on the exit biopsy.


CONCLUSIONS
In women transitioning from estrogen-progestin therapy, occurrence of vasomotor symptoms was unchanged from baseline with RLX treatment, but these symptoms were significantly reduced with combined RLX + E therapy. Signs of endometrial stimulation were observed in the RLX + E group. Further studies using different estrogen doses and preparations are needed before concomitant use of raloxifene with systemic estrogens can be recommended.
Stovall
Dale W
DW
Virginia Commonwealth University Medical Center, Richmond 23235, USA. dwstoval@vcu.edu
Utian
Wulf H
WH
Gass
Margery L S
ML
Qu
Yongming
Y
Muram
David
D
Wong
Mayme
M
Plouffe
Leo
L
D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004958:Estradiol / Q000008:administration & dosage* / Q000494:pharmacology; D015914:Estrogen Replacement Therapy / Q000379:methods; D005260:Female; D019584:Hot Flashes / Q000188:drug therapy*; D006801:Humans; D008875:Middle Aged; D020849:Raloxifene Hydrochloride / Q000008:administration & dosage* / Q000494:pharmacology; D018570:Risk Assessment; D020845:Selective Estrogen Receptor Modulators / Q000008:administration & dosage* / Q000494:pharmacology; D012720:Severity of Illness Index; D016037:Single-Blind Method; D016896:Treatment Outcome; D014666:Vasomotor System / Q000187:drug effects*
D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol