Management of Elevated Estradiol in Men

Men with elevated baseline estradiol should be referred to an endocrinologist for evaluation and management. 1

Initial Assessment and Referral

The American Urological Association (AUA) provides clear guidance on this issue:

Measure serum estradiol in testosterone-deficient men who present with breast symptoms or gynecomastia prior to starting testosterone therapy 1
Any man found to have elevated baseline estradiol measurements requires endocrinology referral 1
This recommendation applies regardless of whether testosterone therapy is being considered 1

The endocrinologist will evaluate several potential etiologies:

Obesity is the most common cause of elevated estradiol in men, as adipose tissue contains aromatase enzyme that converts testosterone to estradiol 2, 3, 4
Estradiol production increases proportionally with body weight and fat mass, particularly subcutaneous abdominal fat 5
Obese men can have estradiol production rates as high as 127-157 micrograms/day (compared to normal ranges) 4
Other causes include medications, liver disease, and rarely, estrogen-secreting tumors 1

Measure luteinizing hormone (LH) levels in all men with hormonal abnormalities to determine if the issue is primary (testicular) or secondary (hypothalamic-pituitary) 1
Men with low testosterone AND low/normal LH may be candidates for selective estrogen receptor modulator (SERM) therapy, particularly if fertility preservation is desired 1
Check prolactin levels if LH is low or low-normal, as hyperprolactinemia can cause hormonal imbalances 1

For obese men with elevated estradiol, lifestyle intervention with diet-induced weight loss is the primary non-pharmacologic approach:

Weight loss of approximately 10% body weight significantly decreases total estradiol levels (mean reduction of 2.5 pg/mL) 2
Free estradiol index also decreases significantly with weight loss 2
This approach simultaneously increases total testosterone levels (mean increase of 71 ng/dL with diet alone) 2
Lifestyle modifications include: smoking cessation, regular dynamic exercise, weight loss, Mediterranean diet, and moderate alcohol consumption 1

When weight loss alone is insufficient or inappropriate:

Aromatase inhibitors (such as anastrozole) can reduce estradiol by 70% within 24 hours and 80% after 14 days 6
Anastrozole 1 mg daily is the standard dose that suppresses estradiol to lower limits of detection in postmenopausal women; dosing in men requires endocrinology expertise 6
Selective estrogen receptor modulators (SERMs) like clomiphene citrate may be appropriate for men with secondary hypogonadism and low/normal LH 1, 7
Clomiphene works by blocking estrogen receptors at the hypothalamus, increasing gonadotropin release and subsequently testosterone production 7

Do not attempt to manage elevated estradiol without specialist input, as the underlying cause must be identified first 1
Men on testosterone therapy commonly experience estradiol increases as testosterone rises; this is often physiologic and does not always require intervention 1
For men who develop gynecomastia or breast symptoms on testosterone therapy, a period of clinical monitoring is appropriate as symptoms sometimes resolve spontaneously 1
The European Association of Urology notes that breast cancer growth is influenced by testosterone conversion to estradiol, making active or treated male breast cancer an absolute contraindication to testosterone therapy 1

Estradiol suppression with anastrozole is maintained for up to 6 days after cessation of daily dosing 6
Regular monitoring of both estradiol and testosterone levels is necessary to avoid over-suppression 6
Physical function improvements from lifestyle intervention occur regardless of hormonal changes, suggesting benefits beyond hormone normalization 2