Serum placental protein 14: a novel marker of selective oestrogen receptor modulator action on the postmenopausal endometrium.
The primary objective of this study was to investigate whether changes in the serum level of an endometrial secretory protein, placental protein 14 (PP14), can reflect endometrial adverse events induced by selective oestrogen receptor modulators (SERMs). A randomized, double-blind, placebo-controlled trial was used. Participants were healthy postmenopausal women aged 45-65 years, who received either various doses of raloxifene (30, 60 or 150 mg day-1) or levormeloxifene (1.25, 5, 10 or 20 mg day-1) or placebo for 12 months. Serum PP14 and endometrial thickness (ET) were monitored by radio-immunoassay and transvaginal ultrasonography, respectively. In the levormeloxifene trial, endometrial status at 12 months was assessed by hysteroscopy. Raloxifene induced only slight increases in serum PP14 and ET. Levormeloxifene, however, induced marked increases in both study parameters at all the does tested. The 6 month changes in PP14 showed a positive correlation with both the 6 and 12 month changes in ET (P < 0.001). Marked stromal oedema, pseudocysticity with or without hypervascularity and endometrial proliferation were seen on hysteroscopy in those showing the largest increases in serum PP14. These results suggest that the PP14 assay used on a group basis may provide useful information on the endometrial effects of SERMs administered in a given dose range, and thereby could assist future clinical trials aiming to find the optimal dose range of new SERMs.
Tankó
László B
LB
Centre for Clinical and Basic Research A/S, Ballerup Byvej 222, DK-2750 Ballerup, Denmark. lbt@ccbr.dk
Warming
Lise
L
Bagger
Yu Z
YZ
Byrjalsen
Inger
I
Jensen
Susi
S
Christiansen
Claus
C
D000328:Adult; D000704:Analysis of Variance; D015519:Bone Density / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004717:Endometrium / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D019160:Endosonography / Q000379:methods; D005260:Female; D000071816:Glycodelin; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D017698:Postmenopause; D011257:Pregnancy Proteins / Q000097:blood*; D011759:Pyrrolidines / Q000494:pharmacology*; D011863:Radioimmunoassay / Q000379:methods; D020849:Raloxifene Hydrochloride / Q000494:pharmacology*; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D013997:Time Factors; D014599:Uterus / Q000000981:diagnostic imaging; D014621:Vagina / Q000000981:diagnostic imaging
D000071816:Glycodelin; D006023:Glycoproteins; C045246:PAEP protein, human; D011257:Pregnancy Proteins; D011759:Pyrrolidines; D020845:Selective Estrogen Receptor Modulators; D020849:Raloxifene Hydrochloride; C108255:levormeloxifene