Puts · Hormones and behavior 2018 · expert commentary / response letter · n=?

Is human brain masculinization estrogen receptor-mediated? Reply to Luoto and Rantala.

Cited 20 times in the scientific literature.

Level 5 - mechanism / opinion, no new human data

Commentary/expert opinion and narrative rebuttal with no original empirical data

PubMed 28818501 · doi:10.1016/j.yhbeh.2017.07.018 · record verified 2026-08-26

What was done

This commentary responded to arguments regarding the role of estrogen receptors in human brain masculinization. The authors synthesized existing literature comparing human and rodent sex differentiation, analyzed human genetic conditions (such as androgen receptor and estrogen receptor functioning), and reviewed findings from genetic females prenatally exposed to synthetic estrogens like diethylstilbestrol (DES).

What was found

The abstract provides no quantitative data or effect sizes. The authors argue that functional androgen receptors, rather than testosterone aromatization or estrogen receptors, are necessary for male-typical behavior in genetic males. Furthermore, they note that the totality of evidence from females exposed to DES in utero indicates little to no effect of estrogens on sexuality, supporting the view that estrogen plays a limited role in masculinizing human brain and behavior.

Why it matters

Rodent models demonstrate a critical aromatase- and estrogen-mediated pathway for brain masculinization; this commentary clarifies why those mechanisms do not readily generalize to human sexual differentiation, where androgen receptor pathways dominate.

Limits

This is an opinion letter without a systematic search methodology, meta-analysis, or new primary empirical data. Specific sample sizes, effect estimates, and statistical certainty cannot be evaluated from the abstract.

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