Estrone Sulfate Source of Estrone and Estradiol Formation in Isolated Human Hair Roots: Identification of a Pathway Linked to Hair Growth Phase and Subject to Site-, Gender-, and Age-Related Modulations

Background: The present study investigated the metabolism of estrone sulfate into bioactive estrogens in the human hair root, including the effects of hair growth phase, anatomical site, gender, and age. Methods: Healthy male (n = 18) and female (n = 20) subjects were investigated. Growing (anagen) and resting (telogen) hair roots were collected from selected scalp and body sites. Results: Estrone sulfate metabolism in the hair root yielded substantial levels of estrone and estradiol. Estrogen synthesis exceeded that associated with aromatization of androgens in a previous study. In subjects <50 years old, estrogen synthesis in scalp hair was lower in menthan in women. Comparable levels of estrogen formation were observed in 1) male and female axillary and pubic hair and 2) male beard hair. These levels were higher than the estrogen levels detected in the in scalp hair of men <50 years old. With increasing age, estrogen synthesis increased in men and decreased in women. In telogen hair from all body sites, the capacity to form estrone from estrone sulfate remained unaffected, whereas the ability to form estradiol decreased by 62% and 86% in men and women, respectively. Conclusions: Estrogen formation from estrone sulfate in sexually dimorphic hair is linked to the hair growth phase and is subject to gender- and age-related modulations. The magnitude of the in situ estrogen synthesis from estrone sulfate and the selective arrest of estradiol synthesis at the end of the hair cycle suggest that this pathway plays a crucial role in the regulation of human hair growth.