Endometrial thickness

Studies carried out with transvaginal ultrasound (TVU) in postmenopausal women with breast cancer have shown that the endometrium is thickened more frequently in women receiving tamoxifen than in those not treated with the drug. For example, in a transversal study Cohen et al. observed that 94.6% of women treated with tamoxifen and nonsymptomatic from a gynecological point of view had an endometrial thickness > 5 mm, an observation that was present in only 40% of women who did not receive this treatment (Cohen et al. 1994). 

In contrast to the data from that study, other authors have suggested that the increased endometrial thickness found in postmenopausal women treated with tamoxifen is less frequently associated with endometrial abnormalities, even in the presence of a marked thickening and cystic appearance (Achiron et al. 1996 McGonigle et al. 1998). Those ultrasonographic findings often represent sub endometrial processes such as cysts or stromal edema (Bese et al. 1996 Bornstein et al. 1994 Achiron et al. 1995). 

Fig. 11.1. Effects of raloxifene on endometrial thickness compared to combined continuous Hormones 2 mgr of 17 B-estradiol and 1 mgr of noretisterone acetate for 6 months. (Palacios et al. 2000)...

In preclinical models of postmenopausal osteoporosis, lasofoxifene inhibited bone turnover and prevented bone loss throughout the skeleton (Maeda et al. 2004). The primary indication of lasofoxifene is the treatment and prevention of postmenopausal osteoporosis. In preclinical models, lasofoxifene inhibited breast tumor formation and reduced serum cholesterol (Maeda et al. 2004). Lasofoxifene-treated animals did not differ from ovariectomized controls with respect to endometrial thickness and superficial and basal endometrial gladular epithelial luminal area (Maeda et al. 2004 Ke et al. 2004). 

In a double-blind, placebo-controlled phase I study, ospemifene exerted a very weak estrogenic effect on endometrial histology, and no clinically significant changes were seen in endometrial thickness at any dose level (Voipio et al. 2002). In another double-blind study, ospemifene at daily doses of 30 to 90 mg did not stimulate growth of endometrial thickness (Rutanen et al. 2003). 

Granberg S, Wikland M, Karlsson B, Norstrom A, Friberg L (1991) Endometrial thickness as measured by endovaginal ultrasonography for identifying endometrial abnormality. Am J Obstet Gynecol 164 47-52... 

Holbert TR (1997) Transvaginal ultrasonographic measurement of endometrial thickness in postmenopausal women receiving estrogen replacement therapy. Am J Obstet Gynecol 176 1334-1339... 

No significant effect was observed on endometrial thickness or on the length and severity of uterine bleedings after raloxifene treatment at doses of 60 and 180 mg/d in premenopausal women (Palomba et al. 2002a). Unfortunately,... 

In one of the largest international multicenter studies of raloxifene it was found that, compared with combined hormone replacement therapy (with 17-beta-oestradiol 2 mg + norethisterone acetate 1 mg) 12 months of raloxifene treatment at 60 mg/day was not associated with increased endometrial thickness or uterine volume (31). 

In a prospective study in 77 consecutive women with postmenopausal breast cancer scheduled to start endocrine treatment for breast cancer, using either tamoxifen or an aromatase inhibitor tamoxifen treatment significantly increased endometrial thickness and uterine volume after 3 months (24). In additional, tamoxifen induced endometrial cysts and polyps and increased the size of pre-existing fibroids. In contrast, aromatase inhibitors did not stimulate endometrial growth and were not associated with endometrial pathology. Furthermore, they reduced endometrial thickness and uterine volume in patients who had previously taken tamoxifen. 

Whether one should routinely screen patients for endometrial changes is disputed there seems to be no correlation between endometrial thickness and endometrial pathology, and complications could be easily overlooked (79). 

Okishiro M et al (2009) Genetic polymorphisms of CYP2D6 10 and CYP2C19 2, 3 are not associated with prognosis, endometrial thickness, or bone mineral density in Japanese breast cancer patients treated with adjuvant tamoxifen. Cancer 115 952-961... 

LDL cholesterol and total cholesterol concentrations fell significantly in women taking raloxifene compared with placebo, but there was no change in HDL cholesterol or triglyceride concentrations, nor was endometrial thickness affected the incidence of vaginal bleeding was not increased (18). 

Also, lower doses of estrogen may be associated with a lower risk of endometrial hyperplasia. Raloxifene does not resnlt in endometrial hyperplasia, has no effect on endometrial thickness, is not associated with polyp formation, and has virtnally no proliferative effect on the endometrium. A 4-year trial of raloxifene in women with osteoporosis showed no increased risk of endometrial cancer." ... 

Many PAs and SPRMs display antiproliferative effects in the nonhuman primate endometrium where they suppress estrogen-dependent endometrial proliferation and mitotic activity, secretory activity, and reduce endometrial thickness and wet weight [31, 32]. This antiproliferative effect has been described as noncompetitive [31]. 

Disaccordance between estimation of endometrial thickness as measured by transvaginal ultrasound compared with hysteroscopy and directed biopsy in breast cancer patients treated with tamoxifen. Anticancer Research, 20, 4889-4891. 

Penotti, M. E. Fabio A.B. Modena M. Rinaldi U. Omodei P. Vigano. Effect of soy-derived iso-flavones on hot flushes, endometrial thickness, and the pulsatility index of the uterine and cerebral arteries. Pertil. Steril. 2003, 79, 1112-1117. 

Human clinical trials have indicated a lack of estrogenic effects of black cohosh. In a clinical trial of 400 postmenopausal women, administration of 40 mg of black cohosh extract daily for 1 year did not produce any endometrial hyperplasia or other adverse endometrial outcomes, and no change in endometrial thickness was observed (Raus et al. 2006). Likewise, in a clinical trial of peri- and postmenopausal women, 24 weeks of black cohosh (39 or 127 mg/ day) administration did not produce any changes in vaginal cytology and no systemic estrogenic effects were observed (Liske et al. 2002). 

No changes in mammographic breast density, breast cell proliferation, or endometrial thickness were observed in postmenopausal women who consumed 40 mg daily of iso-propanolic extract of black cohosh for 6 months (Hirschberg etal. 2007). 

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