Prolonged use of letrozole causes morphological changes on gonads in Galea spixii.

Maria Angelica Machado Arroyo,Antônio Chaves De Assis Neto,Paulo Ramos Da Silva Santos,Moacir Franco De Oliveira

doi:10.1590/1984-3143-ar2020-0029

Maria Angelica Machado Arroyo, Antônio Chaves De Assis Neto + Show 2 more

Open Access

https://doi.org/10.1590/1984-3143-ar2020-0029

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Abstract

Letrozole is used as a therapeutic agent in reproductive disorders caused by high estrogen levels. Letrozole inhibits cytochrome P450 aromatase and reduces estrogen levels. However, the effects of long-term use on reproductive traits are unknown. The aim of this study was to evaluate the prolonged use of letrozole in the gonads of rodents (Spix's yellow-toothed cavy; Galea spixii). Forty-eight rodents (24 males and 24 females) were randomly divided into the treated and control groups. Letrozole administration started at 15 days of age and continued weekly until 30, 45, 90, and 120 days of age. The body, testis, and ovary weights were analyzed, as well as the morphological progression of spermatogenesis and folliculogenesis. Macroscopically, body weight gain and gonads weight were increased in the letrozole group. Microscopically, the ovaries of treated females showed stratified epithelium and a cellular disorder of the tunica albuginea. In the testes of treated males, the development of seminiferous tubules was delayed and sperm was absent. The collective findings indicate that the prolonged use of letrozole alters secondary sexual characteristics, and causes weight gain, reproductive changes, and male infertility.

Highlights

Letrozole is a selective P450 aromatase inhibitor that decreases the amount of estrogen produced without changes in other steroidogenic pathways (Lephart, 1996; Bhatnagar, 2007)
Body weight gain was greater in the group that received letrozole in both sexes and at all ages (Figure 2)
Letrozole causes an imbalance in the sex hormone steroid ratio, because it induces the reduction of estrogen levels by blocking the action of cytochrome P450 aromatase (Bhatnagar, 2007)

Summary

Introduction

Letrozole is a selective P450 aromatase inhibitor that decreases the amount of estrogen produced without changes in other steroidogenic pathways (Lephart, 1996; Bhatnagar, 2007). Aromatase is responsible for the biosynthesis of estrone and estradiol from androgenic hormones, such as androstenedione and testosterone, respectively (Santos et al, 2017b) (Figure 1). The use of letrozole allows the evaluation of aromatase activity in vivo, as well as the possible effects of the inhibition of aromatase caused by an imbalance in the ratio of androgens to estrogens (Bhatnagar, 2007)

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