Banca de DEFESA: Ariane Bocaletto Frare

Uma banca de DEFESA de DOUTORADO foi cadastrada pelo programa.
STUDENT : Ariane Bocaletto Frare
DATE: 09/01/2026
TIME: 14:30
LOCAL: Plataform Teams
TITLE:

Study of the effects of estrogenic hormone replacement on the physical capacity of cross-sex female mice

KEY WORDS:

Transgender Women in Sport, Gender-Affirming Hormone Therapy, Capacidade Física, Dismorfismo Sexual, Animal Models.

PAGES: 100
BIG AREA: Ciências da Saúde
AREA: Farmácia
SUMMARY:

The participation of transgender women in elite sports is a complex debate centered on biological differences, such as muscle mass and bone density, accentuated by exposure to testosterone post-puberty in individuals designated as male. Organizations like the International Olympic Committee (IOC) seek to balance inclusion and competitive fairness by establishing hormonal limits for trans athletes. This study sought to fill a research gap by investigating, using an animal model, the effects of Gender Affirming Hormone Therapy (GAHT) on physical capacity, aiming to support the discussion about the equality of biological conditions for competition. Using castrated male mice subjected to estrogen replacement (crosssex group), we compared their performance to cisgender male and female mice. The hormonal protocol was effective, drastically reducing testosterone and increasing plasma estradiol levels in the cross-sex group. After eight weeks of high-intensity interval training, the exercised cross-sex group demonstrated a substantial disadvantage in physical endurance performance, registering the lowest percentage increment in endurance capacity (59%) and the shortest distance covered, compared to the trained cis and hypogonadal groups. This disparity was morphologically reflected: the gastrocnemius muscle (fast-twitch) of exercised cis males remained significantly heavier than that of the cross-sex group, indicating the persistence of a previous anabolic advantage. Although estrogen replacement reversed the accumulation of Visceral White Adipose Tissue (WATV) in hypogonadal males, histomorphometric analysis detected short-term cellular morphological resistance in adipose tissue. At the molecular level, the treatment induced a tissue-specific "functional feminization". Brown Adipose Tissue (BAT) and the gastrocnemius muscle showed successful oxidative remodeling, with an increase in slow muscle fibers (Myh7) similar to the pattern of cis females. However, GAHT in male mice (cross-sex), via castration and estradiol replacement, induced notable functional molecular feminization in BAT and the gastrocnemius muscle. In BAT, the treatment demonstrated success in oxidative and energetic remodeling. The expression of essential mitochondrial genes, such as ATPmc3 and Cox7a2, and the antioxidant defense gene Sod1, was significantly increased in the cross-sex group, reaching levels similar to the physiological pattern of Cis Females. This finding suggests a complete functional conversion of metabolism in adipose tissue. In the gastrocnemius muscle (fast-twitch), the treatment was also successful in remodeling the muscle fiber profile: the expression of the Myh7 gene (characteristic of slow/oxidative fibers) significantly increased, indicating a transition toward a more oxidative muscle phenotype. However, GAHT revealed resistance in the mitochondrial regulation of the muscle. The expression of ATPmc3 in the cross-sex group significantly differed from the Cis Female pattern. Furthermore, markers of total mitochondrial biogenesis, such as Cs, maintained expression levels similar to those of Cis Males. In summary, GAHT achieved functional feminization in several metabolic genes but encountered biological barriers in the complete structural conversion of the muscle, establishing a unique molecular profile.

COMMITTEE MEMBERS:
Presidente - 3320778 - ALEXANDRE DE GOES MARTINI
Interna - 2329402 - ANGELICA AMORIM AMATO
Externa à Instituição - CINTHIA GABRIEL MEIRELES - HMS
Interna - 1125771 - PAULA MARIA QUAGLIO BELLOZI
Externo à Instituição - SIDNEY ALCANTARA PEREIRA - HMS