Uterine effects of estrogen plus progestin therapy and raloxifene: adjudicated results from the EURALOX study.
OBJECTIVE
To compare the incident rate of abnormal endometrial findings in postmenopausal women receiving treatment with either 60 mg of raloxifene or a continuous combined estrogen plus progestin therapy containing 2 mg of 17 beta-estradiol plus 1 mg of norethisterone acetate for a duration of up to 12 months.


METHODS
One thousand eight asymptomatic postmenopausal women with osteoporosis or cardiovascular risk factors with an endometrial thickness of less than 5 mm at baseline participated in this prospective, randomized, double-blind trial that lasted 6 months; 347 of these women also participated in a 6-month extension. Women with repeated bleeding or an increase in endometrial thickness to above 5 mm were subjected to saline-infused sonohysterography or hysteroscopy with biopsy. Sonographic, histologic, and clinical findings were adjudicated by a panel of 4 experts blinded with respect to patients' treatments. All adjudicated patients were grouped into 15 diagnostic categories according to predefined criteria.


RESULTS
Three hundred thirty-four women needed adjudication during the core phase, 73 (14.7%) of those taking raloxifene and 261 (50.9%) taking continuous combined estrogen plus progestin therapy (P <.001). Compared with raloxifene, women using continuous combined estrogen plus progestin therapy had significantly higher rates of benign endometrial proliferation (8.8 versus 1.2%, P <.001), endometrial polyps (4.3 versus 2.0%, P =.048), and cystic atrophy (5.5 versus 1.2%, P <.001).


CONCLUSIONS
Women using continuous combined estrogen plus progestin therapy more often have benign endometrial pathology and, in our study, more often required the protocol-specific gynecological follow-up assessments for safety reasons, as compared with those using raloxifene. These findings are of clinical relevance when choosing the most appropriate therapy for postmenopausal health risks such as osteoporosis.
Neven
Patrick
P
Department of Gynaecological Oncology, Univesity of Leuven, Leuven, Belgium. Patrick.neven@zu.kuleuven.ac.be
Quail
Deborah
D
Lévrier
Marc
M
Aguas
Fernanda
F
Thé
Hok Sien
HS
De Geyter
Christian
C
Glant
Michael D
MD
Beck
Heike
H
Bosio-LeGoux
Brigitte
B
Schmitt
Henri
H
Hottgenroth
Antje
A
Nickelsen
Thomas
T
D000465:Algorithms; D004311:Double-Blind Method; D004958:Estradiol / Q000627:therapeutic use*; D004967:Estrogens / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008875:Middle Aged; D009640:Norethindrone / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000077563:Norethindrone Acetate; D011446:Prospective Studies; D020849:Raloxifene Hydrochloride / Q000627:therapeutic use*; D020845:Selective Estrogen Receptor Modulators / Q000627:therapeutic use*; D014599:Uterus / Q000187:drug effects*
D004967:Estrogens; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; D004958:Estradiol; D000077563:Norethindrone Acetate; D009640:Norethindrone