What's the best approach for a patient with consistent Sex Hormone-Binding Globulin (SHBG) levels of 15nmol/l, despite changes in weight and total testosterone, and who also has osteopenia and significant weight gain?

Approach to Persistently Low SHBG with Osteopenia and Weight Gain

Your consistently low SHBG of 15 nmol/L requires measurement of free testosterone by equilibrium dialysis to determine true hypogonadal status, as low SHBG in obesity falsely lowers total testosterone without necessarily indicating true androgen deficiency. 1

Diagnostic Workup Required

Measure free testosterone by equilibrium dialysis - this is the critical test you need, as your low SHBG (normal range typically 20-60 nmol/L) means total testosterone measurements are unreliable for determining true hypogonadal status. 1, 2

Morning hormone panel (8-10 AM on two separate occasions):

• Free testosterone by equilibrium dialysis 1, 2
• Total testosterone (for calculating free testosterone index) 1
• LH and FSH (to distinguish primary vs. secondary hypogonadism) 1, 2
• Calculate free testosterone index: total testosterone/SHBG ratio <0.3 indicates true hypogonadism 1

For your osteopenia specifically:

• 25-hydroxyvitamin D level 1
• Corrected serum calcium and phosphate 1
• Thyroid function tests 1
• Parathyroid hormone if calcium remains low despite supplementation 1

Understanding Your Low SHBG

Obesity-related decreases in testosterone are frequently attributable to low SHBG concentrations - men with obesity and low total testosterone due solely to low SHBG have normal free testosterone levels and do not have true hypogonadism. 1 However, a subset will have frankly low free testosterone due to increased aromatization of testosterone to estradiol in adipose tissue, causing estradiol-mediated negative feedback that suppresses pituitary LH secretion. 1

Your SHBG remaining at 15 nmol/L despite weight changes suggests this is your baseline set point, making free testosterone measurement absolutely essential before any treatment decisions. 1, 2

Treatment Algorithm Based on Free Testosterone Results

If Free Testosterone is Normal (You Don't Have True Hypogonadism):

Focus on weight loss and osteopenia management without testosterone therapy, as testosterone is contraindicated in eugonadal men even with symptoms. 1, 2

For weight loss:

• Low-calorie diet with calcium 1 g/day + vitamin D3 800 IU/day 1
• Regular exercise program 1
• Consider pharmacotherapy: liraglutide 3.0 mg daily (8% weight loss) or naltrexone/bupropion ER 16/180 mg twice daily (6.1% weight loss) 1

For osteopenia (T-score -1.0 to -2.5):

• Repeat DXA in two years 1
• Ensure adequate nutrition as low BMI is an independent risk factor 1
• Calcium 1 g/day + vitamin D3 800 IU/day 1
• Stop smoking if applicable 1

If Free Testosterone is Low (True Hypogonadism Confirmed):

Treat both the hypogonadism and osteopenia simultaneously, as testosterone therapy alone is insufficient for fracture risk reduction in established osteopenia. 1

First-line testosterone therapy:

• Transdermal testosterone gel 1.62% at 40.5 mg daily (preferred for stable levels) 2
• Alternative: testosterone cypionate 100-200 mg IM every 2 weeks if cost is a concern 2
• Target mid-normal testosterone levels (500-600 ng/dL) 2

Concurrent osteopenia treatment:

• Oral bisphosphonate (alendronate or risedronate) as first-line therapy for your osteopenia, as testosterone therapy provides only modest bone benefits and you need established anti-osteoporosis medication regardless. 1
• Continue calcium 1 g/day + vitamin D3 800 IU/day 1
• Minimum five years of bisphosphonate therapy, with repeat DXA after two years 1

Expected outcomes with testosterone therapy:

• Small improvements in sexual function and libido (standardized mean difference 0.35) 2
• Modest improvements in bone mineral density (7% increase in lumbar spine trabecular volumetric BMD after 1 year) 1
• Improvements in fasting glucose, insulin resistance, triglycerides, and HDL cholesterol 1
• Little to no effect on energy, vitality, physical function, or cognition 2

Monitoring Requirements

Initial phase (first 3 months):

• Testosterone levels at 2-3 months after starting therapy 2, 3
• Hematocrit (withhold if >54%) 1, 2, 3
• PSA if over 40 years old 1, 2, 3

Maintenance phase:

• Testosterone levels every 6-12 months once stable 2
• Hematocrit monitoring periodically 2, 3
• PSA annually in men over 40 2, 3
• Repeat DXA in two years 1

Critical Pitfalls to Avoid

Never start testosterone therapy based on total testosterone alone when SHBG is low - you will overtreate eugonadal men with obesity-related low SHBG but normal free testosterone. 1, 2

Never rely on testosterone therapy alone for osteopenia management - hypogonadal men with osteopenia should receive established anti-osteoporosis medication (bisphosphonates) regardless of testosterone therapy to most effectively reduce fracture risk. 1

Never assume symptoms of fatigue or low energy will improve with testosterone - even in confirmed hypogonadism, testosterone produces minimal improvements in energy (SMD 0.17) and less-than-small improvements in depressive symptoms (SMD -0.19). 2

If you desire fertility preservation, testosterone therapy is absolutely contraindicated - you would need gonadotropin therapy (hCG plus FSH) instead. 1, 2