What causes increased conversion of testosterone into estrogen?

From the Guidelines

Increased conversion of testosterone into estrogen is primarily caused by excess body fat, as adipose tissue contains high levels of aromatase, the enzyme responsible for this conversion. Several factors can enhance this conversion, including:

• Excess body fat, which is a major contributor due to the high levels of aromatase in adipose tissue 1
• Aging, which naturally increases aromatization in men, leading to higher estrogen levels as they get older
• Certain medications, such as some antibiotics, antifungals, and antidepressants, which can affect this conversion
• Alcohol consumption, which stimulates aromatase activity, particularly with chronic use
• Liver dysfunction, which impairs hormone metabolism, potentially increasing estrogen conversion
• Medical conditions like hypogonadism and certain tumors, which can disrupt hormone balance
• Environmental factors, including exposure to xenoestrogens found in plastics, pesticides, and industrial chemicals, which may also influence this process
• Nutritional factors, such as zinc deficiency, which can increase aromatization since zinc normally helps inhibit the aromatase enzyme 1

As noted in the study on pharmacotherapy for obesity, increased aromatization of testosterone to estradiol in adipose tissue is a key factor in the development of low free testosterone levels in men with obesity 1. This highlights the importance of managing excess body fat to regulate testosterone-to-estrogen conversion. By maintaining a healthy body weight, moderating alcohol intake, and addressing underlying medical conditions, individuals can help regulate this conversion and mitigate the risks associated with increased estrogen levels.

From the FDA Drug Label

The growth of many cancers of the breast is stimulated or maintained by estrogens. In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol

• The aromatase enzyme is responsible for converting testosterone into estrogen (estrone and estradiol) in postmenopausal women.
• Therefore, increased activity of the aromatase enzyme can cause increased conversion of testosterone into estrogen 2.

From the Research

Causes of Increased Conversion of Testosterone into Estrogen

• Aromatase expression in adipose tissue and possibly the skin primarily accounts for the extraglandular (peripheral) formation of estrogen and increases as a function of body weight and advancing age 3
• The enzyme aromatase is found in a number of human tissues and cells, including ovarian granulosa cells, the placental syncytiotrophoblast, adipose and skin fibroblasts, bone, and the brain, and it locally catalyzes the conversion of C(19) steroids to estrogens 3
• Extraglandular aromatase expression in adipose tissue and skin (via increasing circulating levels of estradiol) and bone (via increasing local estrogen concentrations) is of paramount importance in slowing the rate of postmenopausal bone loss 3
• Testosterone replacement improves quality of life and is aromatized in men in adipose tissues to estrogen, and hyperestrogenism is believed to be harmful to male sexuality 4
• High estradiol levels were found in 20.2% of men treated with injectable testosterone, and the correlation coefficient of serum estradiol to age was .53, SD = 8.21 4

Factors Influencing Aromatase Expression

• Aromatase expression is under the control of the classically located proximal promoter II in the ovary and a far distal promoter I.1 (40 kilobases upstream of the translation initiation site) in the placenta 3
• In skin, the promoter is I.4, and in adipose tissue, 2 other promoters (I.4 and I.3) located between I.1 and II are used in addition to the ovarian-type promoter II 3
• Promoter use in adipose fibroblasts switches between promoters II/I.3 and I.4 upon treatments of these cells with PGE(2) versus glucocorticoids plus cytokines 3
• The presence of a carcinoma in breast adipose tissue also causes a switch of promoter use from I.4 to II/I.3 3

Relationship Between Testosterone and Estrogen

• Testosterone is converted to estradiol by the enzyme aromatase, and this conversion is increased in adipose tissue and skin with advancing age and body weight 3, 5
• Testosterone inhibits expression of lipogenic genes in visceral fat by an estrogen-dependent mechanism, and aromatase inhibition constrains testosterone-induced visceral fat loss and the downregulation of key lipogenic genes at the mRNA level 6
• The acute endocrine response to a bout of heavy resistance exercise generally includes increased secretion of various catabolic (breakdown-related) and anabolic (growth-related) hormones including testosterone, which can be converted to estrogen by aromatase 7