Hyperestrogenemia

Hyperestrogenemia is the condition in which circulating levels of estrogens, particularly estradiol, are higher than normal for a person’s age and sex. It can result from endogenous overproduction, exogenous exposure to estrogens, or impaired metabolism and clearance. Diagnosis is typically based on hormonal assays showing elevated estrogen levels, often interpreted in the context of sex hormone–binding globulin (SHBG) levels and the individual’s clinical situation.

Causes fall into several broad categories. Endogenous sources include estrogen-secreting tumors such as granulosa cell tumors, other ovarian pathology, and certain adrenal or testicular disorders. Functional ovarian hyperstimulation and obesity, which increases peripheral aromatization of androgens to estrogens, are common non-tumor causes. Exogenous sources include estrogen-containing medications such as hormone replacement therapy and combined oral contraceptives, as well as supplements or substances with estrogenic activity. Liver disease can impair estrogen metabolism and clearance, contributing to elevated levels. Pregnancy also involves high estrogen production but is usually considered a physiological condition rather than a disorder.

Clinical features reflect estrogen effects on tissues. In women, hyperestrogenemia can cause abnormal uterine bleeding, menorrhagia or menometorrhagia, endometrial hyperplasia, breast tenderness, and fibrocystic breast changes. In men, excess estrogen commonly presents with gynecomastia, reduced libido, erectile dysfunction, and potential infertility. Some patients experience edema or other nonspecific symptoms.

Evaluation includes a thorough history and physical examination, pregnancy testing, and laboratory assays for estradiol with supportive tests (liver and thyroid function, prolactin, SHBG) as indicated. Imaging or tissue biopsy may be pursued to identify an estrogen-secreting tumor. Management targets the underlying cause: discontinue or modify exogenous estrogens, surgically treat estrogen-producing tumors, or address obesity and liver disease; in symptomatic men, antiestrogen therapies or aromatase inhibitors may be used in selected cases. The prognosis depends on the underlying cause and response to treatment.