Xenoestrogen
Xenoestrogens are clinically significant because they can mimic the effects of endogenous estrogen and thus have been implicated in precocious puberty and other disorders of the reproductive system.
Transgender hormone therapy (male-to-female)
Prior to orchiectomy (surgical removal of the gonads) or sex reassignment surgery, the doses of estrogens used in transgender women are often higher than replacement doses used in cisgender women. This is to help suppress testosterone levels. The Endocrine Society (2017) recommends maintaining estradiol levels roughly within the normal average range for premenopausal women of about 100 to 200 pg/mL. However, it notes that these physiological levels of estradiol are usually unable to suppress testosterone levels into the female range. A 2018 Cochrane review proposal questioned the notion of keeping estradiol levels lower in transgender women, which results in incomplete suppression of testosterone levels and necessitates the addition of antiandrogens, and noted that high-dose parenteral estradiol is known to be safe. The Endocrine Society itself recommends dosages of injected estradiol esters that result in estradiol levels that can markedly exceed the normal female range; for instance, 10 mg per week estradiol valerate by intramuscular injection, with a single such injection resulting in estradiol levels of about 1,250 pg/mL at peak and levels of about 200 pg/mL still after 7 days. Dosages of estrogens can be reduced after an orchiectomy or sex reassignment surgery, when gonadal testosterone suppression is no longer needed.