Short and long duration testosterone treatments induce reversable subfertility in female mice using a gestational model of gender-affirming hormone therapy DOI
Daniel R. Pfau,

Evelyn Cho,

Julia Clark

et al.

Human Reproduction, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Abstract STUDY QUESTION How does testosterone gender-affirming hormone therapy (T-GAHT) impact breeding success in female mice? SUMMARY ANSWER T-GAHT causes reversible subfertility mice and persistent changes to reproductive tract anatomy, gene expression, receptors. WHAT IS KNOWN ALREADY Adult implanted with capsules containing 10 mg of mimic many aspects phenotypes patients, who may desire future gestation while pausing T-GAHT. In mice, oocytes retrieved from had decreased IVF rates, T cessation prior stimulation improved these outcomes. However, the effects on have not been examined. DESIGN, SIZE, DURATION CD1 were subcutaneously or blank controls. separate studies, removed after 6 (‘short’) 12 weeks (‘long’ n = 15/group), then paired proven-breeder males. Breeding pair pup development (15–20/group) measured for first second litters, terminal measurements taken dams their adult offspring (10/group). PARTICIPANTS/MATERIALS, SETTING, METHODS The explanted control was investigated by pairing them Regular observations litters enabled analysis fertility male pups two litters. Terminal measures and/or focused endpoints tied function gestation, including hormones, vaginal cytology, sperm ovarian uterine histology, expression. MAIN RESULTS AND THE ROLE OF CHANCE All but one gave birth, time between birth longer than controls long (22.3 ± 1.3 days vs 24.5 3.1) short (23.2 1.4 25.5 4) treatments. Dams given treatment fewer (11.9 2.7 7.8 number unaltered (11.5 2.4 11.4 3.7). Further, displayed accelerated puberty. Fertility differences developmental absent gestations Despite rescue, several anatomical, genetic, histological persisted Offspring system outcomes significantly altered once dam restored. This study powerfully demonstrates a subfertile phenotype T-GAHT-treated animals that is rescued over identifies gonadotropin steroid signaling as potential mechanisms further investigation. LARGE SCALE DATA No large-scale data generated this study. LIMITATIONS, REASONS FOR CAUTION Significant be unrelated subfertility, similar must examined during period identify fully understand roles T-GAHT-dependent changes. WIDER IMPLICATIONS FINDINGS assumption irreversible damage reproduction has harmfully informed public opinion, medical practice, government policies. finding are permanently impacted translational relevance opens avenues tested non-human primate models humans. FUNDING/COMPETING INTEREST(S) NIH R01 HD098233, T32 DK071212. authors declare no competing interests.

Language: Английский

Fertilitätsprotektion bei Personen mit Geschlechtsinkongruenz und männlichem Zuweisungsgeschlecht DOI
Florian Schneider,

Bettina Scheffer,

Sabine Kliesch

et al.

Aktuelle Urologie, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 5, 2025

Zusammenfassung Nach aktuellen Leitlinien muss bei Behandlungssuchenden mit Geschlechtsinkongruenz eine adäquate Aufklärung über die verschiedenen Möglichkeiten einer Fertilitätsprotektion durch medizinisches Fachpersonal stattfinden. Durch geschlechtsangleichende Hormontherapie männlichem Zuweisungsgeschlecht kommt es zu Reduktion von LH, FSH und Testosteron damit einhergehend Regression der Spermatogenese (bis hin zum vollständigen Ausbleiben) konsekutiven Hodenatrophie. Behandlungssuchende, geschlechtsangleichenden nach durchlebten männlichen Pubertät beginnen, können Ejakulatprobe abgeben, um Spermien kryokonservieren. Falls im Ejakulat unter geschlechtsangleichender keine finden sind oder das Abgeben nicht mehr möglich psychisch belastend ist, sollte (mikrochirurgische) testikuläre Spermienextraktion ([m]TESE), angeboten werden. Eine Elektroejakulation Narkose ist eher selten zielführend, da Samenzellbildung Hormonbehandlung gestört. Aus diesem Grund auch mikrochirurgische epididymale Spermienaspirtation (MESA) zielführend. Wird Jugendlichen Pubertätsblockade und/oder bereits in einem frühen Stadium (ab Tanner-Stadium 2 möglich) begonnen, wird Ausreifung spermatogonialer Stammzellen reifen verhindert. Die GnRH führt LH Hirnanhangsdrüse. Konsekutiv Testosteronproduktion den Leydig-Zellen Stimulation Hoden statt. In diesen Fällen Kryokonservierung spermatogonialen Stammzellen, wie sie einigen Ländern für peripubertäre Patienten vor notwendigen keimzellschädigenden Therapie wird, möglich. Deutschland existiert ein entsprechendes Netzwerk (Androprotect), 2012 Münster gegründet wurde. Dieses Vorgehen Androprotect jugendliche Behandlungssuchende angeboten. Das gilt als experimentell, derzeit noch etablierte spätere Refertilisierung betroffenen Erwachsenen gibt, wenngleich mehrere Verfahren In-vitro-Spermienreifung Gewebetransplantation Entwicklung sind. Bei Betreuung Menschen sollten interdisziplinären Behandlungsteam individuelle Beratung erfahrenes stattfinden Sinne partizipativen Entscheidungsfindung (informed consent) Behandlungsansätze werden, jeden richtigen Weg zur Entscheidung gegen finden.

Citations

0
Short and long duration testosterone treatments induce reversable subfertility in female mice using a gestational model of gender-affirming hormone therapy DOI
Daniel R. Pfau,

Evelyn Cho,

Julia Clark

et al.

Human Reproduction, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 11, 2025

Abstract STUDY QUESTION How does testosterone gender-affirming hormone therapy (T-GAHT) impact breeding success in female mice? SUMMARY ANSWER T-GAHT causes reversible subfertility mice and persistent changes to reproductive tract anatomy, gene expression, receptors. WHAT IS KNOWN ALREADY Adult implanted with capsules containing 10 mg of mimic many aspects phenotypes patients, who may desire future gestation while pausing T-GAHT. In mice, oocytes retrieved from had decreased IVF rates, T cessation prior stimulation improved these outcomes. However, the effects on have not been examined. DESIGN, SIZE, DURATION CD1 were subcutaneously or blank controls. separate studies, removed after 6 (‘short’) 12 weeks (‘long’ n = 15/group), then paired proven-breeder males. Breeding pair pup development (15–20/group) measured for first second litters, terminal measurements taken dams their adult offspring (10/group). PARTICIPANTS/MATERIALS, SETTING, METHODS The explanted control was investigated by pairing them Regular observations litters enabled analysis fertility male pups two litters. Terminal measures and/or focused endpoints tied function gestation, including hormones, vaginal cytology, sperm ovarian uterine histology, expression. MAIN RESULTS AND THE ROLE OF CHANCE All but one gave birth, time between birth longer than controls long (22.3 ± 1.3 days vs 24.5 3.1) short (23.2 1.4 25.5 4) treatments. Dams given treatment fewer (11.9 2.7 7.8 number unaltered (11.5 2.4 11.4 3.7). Further, displayed accelerated puberty. Fertility differences developmental absent gestations Despite rescue, several anatomical, genetic, histological persisted Offspring system outcomes significantly altered once dam restored. This study powerfully demonstrates a subfertile phenotype T-GAHT-treated animals that is rescued over identifies gonadotropin steroid signaling as potential mechanisms further investigation. LARGE SCALE DATA No large-scale data generated this study. LIMITATIONS, REASONS FOR CAUTION Significant be unrelated subfertility, similar must examined during period identify fully understand roles T-GAHT-dependent changes. WIDER IMPLICATIONS FINDINGS assumption irreversible damage reproduction has harmfully informed public opinion, medical practice, government policies. finding are permanently impacted translational relevance opens avenues tested non-human primate models humans. FUNDING/COMPETING INTEREST(S) NIH R01 HD098233, T32 DK071212. authors declare no competing interests.

Language: Английский

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0