Is there any medication that directly lowers sex hormone‑binding globulin (SHBG)?

Medications That Directly Lower SHBG

There are no medications specifically indicated to directly lower SHBG, but certain drugs can reduce SHBG levels as a secondary effect, most notably danazol, androgens (testosterone and anabolic steroids), glucocorticoids, and growth hormone. 1, 2

Medications That Lower SHBG

Danazol

• Danazol causes marked, dose-dependent suppression of SHBG levels and is the most well-documented pharmaceutical agent for this effect 3
• In patients treated with danazol 50-600 mg daily for 6 months, SHBG suppression was dose-related, with corresponding increases in percent free testosterone 3
• The SHBG reduction occurs early in treatment, though the clinical use of danazol is limited to specific conditions like endometriosis, not for SHBG reduction itself 3

Androgens and Anabolic Steroids

• Testosterone and anabolic androgenic steroids decrease SHBG levels but should only be used when clinically indicated for hypogonadism or other approved conditions, not solely to lower SHBG 1, 2
• Androgen administration consistently lowers SHBG in both physiological and supraphysiological doses 4
• In men with high SHBG and low free testosterone, testosterone replacement therapy (TRT) can normalize free testosterone and may reduce elevated SHBG, though this is not the primary therapeutic goal 2

Glucocorticoids

• High-dose glucocorticoids (such as prednisone) lower SHBG levels through metabolic effects 1, 2
• The effect is dose-dependent and occurs as part of the broader metabolic impact of glucocorticoid therapy 2

Growth Hormone

• Growth hormone administration decreases SHBG levels, though this is not a primary indication for its use 1, 2

Critical Clinical Context

Why Direct SHBG Lowering Is Not a Treatment Goal

• The appropriate clinical approach is to identify and treat the underlying cause of elevated SHBG rather than attempting to lower SHBG directly 1
• Common causes of elevated SHBG include hyperthyroidism, hepatic disease, aging, certain medications (anticonvulsants, estrogens, thyroid hormone), smoking, and HIV/AIDS 1, 2

When SHBG Matters Clinically

• High SHBG reduces free testosterone availability, which can cause symptoms of hypogonadism despite normal total testosterone 1, 5
• A free testosterone index (total testosterone/SHBG ratio) <0.3 indicates hypogonadism and warrants evaluation 1, 2
• Measuring both total and free testosterone (or calculating free testosterone index) is essential when SHBG abnormalities are suspected 1, 2

Management Algorithm for High SHBG

Step 1: Identify the Underlying Cause

• Evaluate thyroid function tests for hyperthyroidism 1
• Assess liver function tests for hepatic disease 1
• Review medications (anticonvulsants, estrogens, thyroid hormone) 1, 2
• Consider HIV testing in appropriate clinical contexts 1

Step 2: Treat the Primary Condition

• Correct hyperthyroidism if present 2
• Manage liver disease appropriately 2
• Discontinue or adjust medications that elevate SHBG when feasible 2

Step 3: Consider Testosterone Replacement (If Indicated)

• TRT may be appropriate in symptomatic men with documented low free testosterone, even if total testosterone is normal 2
• Benefits include improved sexual function, well-being, muscle mass, and bone density 2
• Monitor hematocrit/hemoglobin and PSA regularly during therapy 2
• Avoid TRT in men desiring fertility, as it suppresses spermatogenesis; consider selective estrogen receptor modulators instead 2

Important Caveats

Oral Contraceptives Have the Opposite Effect

• Oral contraceptives dramatically increase SHBG levels (approximately 4-fold) and this elevation may persist long after discontinuation 6
• In women with sexual dysfunction who discontinued oral contraceptives, SHBG remained elevated compared to never-users even beyond 120 days 6

SHBG Is Not Just a Transport Protein

• SHBG has its own membrane receptor and can activate adenylate cyclase, suggesting it plays an active regulatory role beyond simply binding steroids 7
• This means that artificially manipulating SHBG without addressing underlying pathology may have unintended metabolic consequences 8