Mole modifications following controlled ovarian stimulation for assisted reproduction technologies.

BACKGROUND: The role of estrogens on moles biology remains undefined although estrogenic receptors have been found on melanocytes. It has been postulated that supraphysiological estrogen levels could promote the progression of moles to melanoma. Women undergoing controlled ovarian stimulation (COS) for assisted reproductive technologies (ART) are exposed to high levels of estrogens, produced by the ovary in response to exogenous gonadotropin administration. The aim of this study is to assess whether COS for ART may have an impact on mole structure and/or characteristics. METHODS: Women undergoing to ART for various infertility conditions were included in the study. Personal and clinical data were collected. Dermatoscopic features and scores (total dermoscopy score--TDS) were statistically compared before COS and after a 6-month follow-up period. Statistical correlation was performed between estradiol, FSH blood levels and relative variation in moles dimensions. RESULTS: A total of 46 patients were included in the study. One hundred and seventy-five melanocytic lesions from 31 patients were evaluated at both time points. Although statistically significant differences were found in mole dimension and TDS between the two time points, these differences had no relevance in the clinical setting not suggesting the need for mole excision. Moreover, the only statistically significant correlation with estradiol blood concentration on hCG administration day was found with one-axis dimensional variation. CONCLUSIONS: To our knowledge this is the first work to evaluate the effect of COS on moles. The obtained results do not support a causal relation between the supraphysiological hormone levels stimulation and worsening of clinical and dermoscopical features of moles. Further study is needed to clarify whether estrogens plays a role in melanoma.

Impact of estrogen replacement on letrozole-induced embryopathic effects.

BACKGROUND: The aromatase inhibitor, letrozole, exerts embryo toxic effects in rats, causing increased embryo lethality and anomalies of the axial skeleton at pharmacologically relevant doses. Letrozole acts by inhibiting estrogen biosynthesis. It may thus be feasible that estrogen deprivation is a crucial determinant of the elicited developmental toxic effects. In order to gain insight on this hypothesis, the present study tested the capacity of estrogen replacement in preventing letrozole-mediated embryopathy. METHODS: Pregnant Sprague Dawley rats were exposed to letrozole alone (0.04 mg/kg), or in combination with estradiol cyclopentylpropionate (ECP) at 0.5, 1 or 2 microg/rat. A control group receiving only the vehicles was also included. Animals were exposed during gestation Days 6-16 (corresponding approximately to 3-10 weeks of gestation in the human). Developmental end-points, including intrauterine mortality, fetal growth, placental weight and incidence of structural abnormalities, were evaluated near term gestation. RESULTS: Exposure to letrozole alone was lethal for 41% of conceptuses, and caused minor axial skeletal anomalies in 51% of live fetuses. ECP co-administration effectively prevented letrozole-induced embryolethality, but failed to reduce the incidence of axial skeletal alterations. CONCLUSION: The obtained results support the concept that inhibition of estrogen biosynthesis represents a critical determinant of letrozole-induced embryonic mortality. A mechanism other than estrogen deprivation appears to underlie the initiation of skeletal anomalies.