Literature Review of Sex Hormones and Cataract Development, With Modern Implications.

Sparse data exist regarding the relationship between androgens and cataract development.

• The literature review found limited evidence specifically examining androgen effects on the crystalline lens.
• Gender-affirming hormone therapy (GAHT) has been associated with increasing ocular manifestations, but cataracts have not been previously reported in this context.
• GAHT is increasingly used in young individuals, raising questions about long-term ocular implications.

Animal studies have provided evidence regarding oestrogen's effects on the lens, including possible biomechanisms.

• The review incorporated findings from animal studies to assess oestrogen's effects on the crystalline lens.
• Possible biomechanisms for oestrogen's protective role on the lens were identified through animal research.
• These animal-derived findings were used to contextualize observational data on cataract incidence in humans.

Data surrounding parity, menarche, menopause, and hormone replacement therapy generally supports a protective role of endogenous and exogenous estrogen on the crystalline lens.

• Observational data on cataract incidence with varying estrogen levels were reviewed.
• Both endogenous estrogen (associated with parity and menarche) and exogenous estrogen (hormone replacement therapy) showed associations with lens protection.
• Menopause-related estrogen decline was among the factors correlating with changes in cataract incidence.
• The protective role was observed across multiple lines of evidence including reproductive milestones and therapeutic hormone use.

Long-term gender-affirming hormone therapy could potentially suppress estrogen's protective effect on the crystalline lens in susceptible individuals.

• Testosterone-based GAHT in transgender men may reduce circulating estrogen levels, potentially removing its lens-protective effects.
• No studies currently exist examining cataract risk specifically in individuals undergoing GAHT.
• The authors identified this as a potential cataractogenic risk factor warranting further investigation.
• The concern is particularly relevant given that GAHT is increasingly administered to young individuals who may be exposed over long durations.

Further research via population-based studies is needed to identify potential cataractogenic risk factors from gender-affirming hormone therapy.

• The authors recommend population-based studies as the appropriate methodology to assess cataract risk in GAHT users.
• No relevant studies currently exist regarding cataract risk in the context of GAHT.
• The gap in evidence exists despite increasing clinical use of GAHT and known associations between GAHT and other ocular manifestations.