Endometrial Expression of Estrogen Receptors and the Androgen Receptor in Women With Polycystic Ovary Syndrome: A Lifestyle Intervention Study

Hulchiy, Mariana; Nybacka, Åsa; Sahlin, Lena; Hirschberg, Angelica Lindén

doi:10.1210/jc.2015-3803

Cited by 37 publications

(18 citation statements)

References 29 publications

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“…38,39 Recently, it has been shown that the level of ERa and ERa/ERb were decreased in proliferative endometrium, whereas the level of androgen receptor was increased. 40 Therefore, the thin uterine lining in PCOS may result from changes in steroid hormones and receptors. Tamoxifen improves EMT and pregnancy outcomes in PCOS mainly through the ER pathway.…”

Section: Discussionmentioning

confidence: 99%

The Effect of Tamoxifen on Thin Endometrium in Patients Undergoing Frozen—Thawed Embryo Transfer

Jiang

Xia

et al. 2018

Reprod. Sci.

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Tamoxifen has played a vital role in endocrine therapy for the treatment of estrogen receptor-positive breast cancer. We examined the effect of tamoxifen in patients with a thin endometrium in frozen-thawed embryo transfer (FET) cycles and compared the improvement in endometrial thickness (EMT) and pregnancy outcomes stratified by different etiologies of thin endometrium. A total of 226 women were recruited for a new tamoxifen protocol; all had an EMT of less than 7.5 mm in previous cycles, including natural cycle (NC), hormone replacement treatment (HRT), and ovulation induction (OI) cycles. Compared with previous cycles, tamoxifen cycles showed a significantly increased EMT (from 6.11 ± 0.98 mm to 7.87 ± 1.48 mm in the NC group, from 6.24 ± 1.01 mm to 8.22 ± 1.67 mm in the HRT group, and from 6.34 ± 1.03 mm to 8.05 ± 1.58 mm in the OI group; all P < .001). Patients were further divided into 3 groups based on the causes of their thin endometrium: (1) history of intrauterine adhesion (n = 34), (2) history of uterine curettage (n = 141), and (3) polycystic ovary syndrome (PCOS; n = 51). Patients with PCOS obtained the thickest EMT (9.31 ± 1.55 mm), the lowest cycle cancellation rate (11.76%), and the highest rate of clinical pregnancy (60%) and live birth (55.56%) per transfer ( P < .001). Multivariable regression analysis showed that EMT was related to live birth (odds ratio: 1.487; 95% confidence interval: 1.172-1.887). A tamoxifen protocol improves EMT in patients after NC, HRT, and OI cycles during FET. Patients with PCOS show the most benefit from tamoxifen and achieve better pregnancy outcomes.

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Section: Discussionmentioning

confidence: 99%

The Effect of Tamoxifen on Thin Endometrium in Patients Undergoing Frozen—Thawed Embryo Transfer

Jiang

Xia

et al. 2018

Reprod. Sci.

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“…Of interest, female ERα -/- but not ERβ -/- mice develop obesity and insulin resistance (2). Hulchiy et al (62) have reported that endometrial ERα but not ERβ mRNA is decreased in overweight/obese patients with PCOS compared with controls, which is in contrast to the increased endometrial ERα and ERβ mRNA and/or protein expression observed in patients with hyperandrogenic PCOS (18,19). Thus, it remains unclear how insulin resistance and hyperandrogenism differentially affect ER subtype-mediated regulation of glycolysis in the endometrium in patients with PCOS.…”

Section: Resultsmentioning

confidence: 96%

Uterine glycolytic enzyme expression is affected by knockout of different estrogen receptor subtypes

Zhang

Egecioglu

et al. 2019

biom rep

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The estrogen signaling pathway via nuclear estrogen receptors (ER) α and β is considered to be the master regulator of the cellular glucose metabolism in the uterus. While in vivo animal studies have demonstrated that 17β-estradiol (E2) treatment increases the expression levels and activities of several glycolytic enzymes in the uterus, the specific ER subtype-dependent regulation of key glycolytic enzymes in the uterus has not been experimentally verified. In this study, the localization of ERα and ERβ in human and mouse endometria were evaluated using immunohistology. Given that ERα and ERβ are not functionally equivalent, ERα, ERβ and ERαβ knockout (ERα-/-, ERβ-/- and ERαβ-/-) mice were utilized to determine the expression pattern of glycolytic enzymes in the uterus. It was found that the level of ERα was higher than that of ERβ in the human and mouse endometrial epithelial and stromal cells, and both receptors were downregulated by E2 treatment in the mouse uterus. The expression of the hexokinase 1 and GAPDH was increased in ERα-/- and ERβ-/- mice compared with wild-type controls. Increased phosphofructokinase expression was observed in ERα-/- and ERαβ-/- mice, whereas increased pyruvate kinase isozyme M2 and pyruvate dehydrogenase expression was observed in ERβ-/- and ERαβ-/- mice. The findings indicated for the first time that while estrogen regulates ERα and ERβ expression in the uterus, ERα and ERβ selectively regulate uterine glycolytic enzyme expression during glycolysis. Additionally, the link between endometrial ER subtypes and glycolysis in women with polycystic ovary syndrome (PCOS) is discussed. The findings suggested that the E2-dependent ER-mediated regulation of glycolysis may be involved in the disturbance of the glucose metabolism in patients with PCOS with endometrial dysfunction.

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“…While these reports may suggest a role of abnormal FoxO1 signaling in the development of restricted progesterone-dependent uterine receptivity and decidualization in PCOS, further molecular studies into the mechanistic association between the endometrial PGR and other transcriptional mediators of endometrial receptivity, particularly the Indian hedgehog (IHH) signaling pathway, are warranted. Notably, the fact that the persistence of the abovementioned endometrial irregularities despite adequate metabolic control, lifestyle interventions and the restoration of regular ovulatory cycles [47,69] underpins the need to further examine the link between chronic inflammation and related immunological abnormalities in the development of P4 resistivity in PCOS.…”

Section: Evidence Of Endometrial Progesterone Resistance In Pcosmentioning

confidence: 99%

Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome

Albaghdadi

Kan

2021

IJMS

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Polycystic ovary syndrome (PCOS) is a major anovulatory infertility affecting a great proportion of women of childbearing age and is associated with obesity, insulin resistance and chronic inflammation. Poor endometrial receptivity and recurrent implantation failure are major hurdles to the establishment of pregnancy in women with PCOS. The accumulating body of evidence obtained from experimental and clinical studies suggests a link between inherent adaptive and innate immune irregularities and aberrant endometrial features in PCOS. The use of conventional therapeutic interventions such as lifestyle modification, metformin and ovarian stimulation has achieved limited clinical success in restoring ovulation and endometrial receptivity in women with PCOS. Unlike other immunosuppressive drugs prescribed in the clinical management of autoimmune and inflammatory disorders that may have deleterious effects on fertility and fetal development, preclinical studies in mice and in women without PCOS but with repeated implantation failure revealed potential therapeutic benefits for the use of low-dose tacrolimus in treating female infertility. Improved systemic and ovarian immune functions, endometrial progesterone receptor and coreceptor expressions and uterine vascular adaptation to pregnancy were among features of enhanced progesterone-receptor sensitivity in the low-dose tacrolimus-treated mouse model of the disease. In this review, we have compiled available experimental and clinical data in literature on endometrial progesterone resistance and current therapeutic options, as well as mechanisms of actions and reported outcomes relevant to the potential therapeutic benefits for the use of low-dose tacrolimus in treating PCOS-associated female infertility.

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Endometrial Expression of Estrogen Receptors and the Androgen Receptor in Women With Polycystic Ovary Syndrome: A Lifestyle Intervention Study

Abstract: Lifestyle intervention alters, but does not fully restore, ER and AR expression in proliferative and secretory endometrium of obese women with PCOS.

Cited by 37 publications

References 29 publications

The Effect of Tamoxifen on Thin Endometrium in Patients Undergoing Frozen—Thawed Embryo Transfer

The Effect of Tamoxifen on Thin Endometrium in Patients Undergoing Frozen—Thawed Embryo Transfer

Uterine glycolytic enzyme expression is affected by knockout of different estrogen receptor subtypes

Therapeutic Potentials of Low-Dose Tacrolimus for Aberrant Endometrial Features in Polycystic Ovary Syndrome

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