Endometrial Polyps in Women Affected by Levothyroxine-Treated Hypothyroidism—Histological Features, Immunohistochemical Findings, and Possible Explanation of Etiopathogenic Mechanism: A Pilot Study

Abstract

The aim of the study was to investigate the possible overexpression of estrogen (ERs) and progesterone (PRs) receptors both in EPs glandular and stromal cells in postmenopausal women with levothyroxine-treated hypothyroidism in comparison to EPs detected in women with physiological thyroid hormone levels. During the study period (January-February 2013) 22 patients were eligible (12 treated, 10 controls). The two groups were homogenous for general, EPs sonographic and hysteroscopic features. None of the cases of atypia was found. Immunohistochemistry showed that the two groups were similar for ERs and PRs intensity rates in EPs glandular cells despite a trend of ERs percentage expression more than 60% in 2/3 of treated patients versus 1/3 of controls. In stromal EPs components, ERs intensity was high positive in 10 (83,3%) treated cases while it was high positive in 1 control (10%). Percentage of ERs stromal expression showed a different trend between the two groups despite a borderline statistical significance. Our hypothesis is based on a possible double action of hypothyroidism and thyroxine intake: the subclinical TSH increased levels and its possible circadian oscillation could stimulate the endometrial TSHRs (increasing type 2 DIO activity); the circulating levels of exogenous thyroxine could be locally metabolized in active form by type 2 DIO stimulating ERs.

Role of thyroid dysimmunity and thyroid hormones in endometriosis

“…From this ex vivo study on thyroid transcripts in patients with endometriosis, an increase in TSH (hypothyroidism) or in thyroid hormone T4 (hyperthyroidism or T4 intake) could be hypothesized as a participating factor for endometriosis aggravation. Interestingly, it has already been shown that thyroid hormone, especially T4, correlated with polyp aggravation without mechanistical evidence (27). Cross-talk between thyroid hormones and estrogens has been suggested by the direct stimulation of estrogen receptors on endometrial cells by thyroid hormones, leading to cell proliferation (28).…”

Does the time interval between hysteroscopic polypectomy and start of in vitro fertilization affect outcomes?

“…Because polyps contain functional endometrium, they can develop in conditions associated with increased or unopposed E 2 levels, as in the case of ovarian stimulation during IVF (10,15,20). Molecular mechanisms, including the overexpression of estrogen and progesterone receptors (25), endometrial aromatase (26,27), and mutations in the HMGIC and HMGI[Y] genes (28,29), also have been implicated in the development of endometrial polyps (20). Polyps may adversely affect fertility by mechanically interfering with sperm transportation or as space-occupying lesions impeding embryo implantation (4,5).…”

Coexistence of adenomyosis and endometrioid endometrial cancer: Role in surgical guidance and prognosis estimation

“…Patients with concurrent primary malignancies, EC of non-endometrioid histological type, previous use of hormone replacement therapy or raloxifene, levothyroxine treatment (16,17), or a history of pelvic irradiation or intrauterine hysteroscopic surgery for metrorrhagia (<1 year prior to EEC diagnosis) (18) were excluded from the study.…”