What is the management approach for a female athlete with elevated sex hormone-binding globulin (SHBG) levels?

Management of Elevated SHBG in Female Athletes

The primary concern with elevated SHBG in female athletes is identifying and treating underlying Relative Energy Deficiency in Sport (RED-S) or functional hypothalamic amenorrhea (FHA), as elevated SHBG typically reflects low energy availability and hypoestrogenism that threatens bone health, cardiovascular function, and reproductive capacity. 1

Understanding the Clinical Context

Elevated SHBG in female athletes is not a primary disorder requiring direct treatment—rather, it serves as a biomarker indicating metabolic and hormonal dysfunction. 2, 3 The key pathophysiologic mechanism involves:

• Low energy availability (EA < 30 kcal/kg fat-free mass/day) suppresses the hypothalamic-pituitary-gonadal axis, leading to hypoestrogenism and functional hypothalamic amenorrhea. 1
• Hypoestrogenism reduces hepatic SHBG suppression, resulting in elevated SHBG levels that further reduce bioavailable sex hormones. 2, 4
• This creates a cascade of adverse effects on bone mineral density, cardiovascular health, and metabolic function. 1, 5

Initial Assessment Algorithm

Step 1: Evaluate for RED-S and Energy Availability

• Document menstrual history: oligomenorrhea (cycles >35 days) or amenorrhea (>3 months absent menses) strongly suggests FHA. 1, 6
• Calculate energy availability: Target EA = energy intake minus exercise energy expenditure, normalized to fat-free mass. Optimal EA is ≥45 kcal/kg FFM/day; values <30 kcal/kg FFM/day suppress bone formation. 1
• Assess for disordered eating patterns: inadvertent undereating, restrictive dietary habits, or frank eating disorders occur in 6-45% of female athletes. 1
• Evaluate training volume and intensity: endurance, aesthetic, and weight-class sports carry highest risk. 1

Step 2: Obtain Confirmatory Laboratory Testing

• Pregnancy test first to exclude pregnancy as cause of amenorrhea. 6
• Hormonal panel: FSH, LH, estradiol, TSH, prolactin measured on cycle days 3-6 (or anytime if amenorrheic). 6
  • Low estradiol (<50 pg/mL) with low-normal FSH/LH confirms FHA. 6, 5
  • LH/FSH ratio <1 seen in 82% of FHA cases (versus >2 in PCOS). 6
• Bone mineral density via DEXA scan: FHA carries 2-fold increased fracture risk; obtain baseline assessment. 5
• Vitamin D and calcium levels: deficiency common in female athletes and compounds bone health risks. 1

Step 3: Rule Out Alternative Diagnoses

• Thyroid dysfunction: TSH abnormalities alter SHBG independent of energy availability. 6, 2
• Hyperprolactinemia: prolactin >20 μg/L suggests pituitary adenoma or medication effect. 6
• PCOS: distinguished by LH/FSH >2, normal/elevated estradiol, and clinical hyperandrogenism. 6
• Primary ovarian insufficiency: FSH >40 mIU/mL on two occasions 4 weeks apart. 6

Treatment Approach: Prioritize Non-Pharmacological Intervention

First-Line Management: Restore Energy Availability

Non-pharmacological management must continue even if pharmacological therapy is initiated. 1, 5

• Increase energy intake to achieve EA ≥45 kcal/kg FFM/day: this is the cornerstone of treatment and the only intervention that addresses the underlying pathophysiology. 1, 5
• Modify exercise volume/intensity: goal is positive energy balance, not elimination of physical activity. 5
• Nutritional counseling by sports dietitian: essential component of comprehensive care for menstrual dysfunction. 1
• Address psychological factors: stress reduction, treatment of eating disorders if present. 1, 5
• Timeline: may require >6 months for menstrual recovery; continue lifestyle modifications for at least 6 months before considering additional interventions. 1, 5

Micronutrient Optimization

• Calcium: 1000-1300 mg/day from food sources or supplementation. 1
• Vitamin D: maintain 25-OH-vitamin D >50 nM (>32-50 ng/mL); supplement with 1000-2000 IU daily or 50,000 IU weekly for 8 weeks if deficient (<50 nmol/L). 1
• Iron: screen for deficiency, particularly common in female athletes. 1

What NOT to Do: Critical Pitfalls

Combined Oral Contraceptives Are Contraindicated

Do not prescribe combined oral contraceptives (COCs) for FHA—they mask the underlying condition, create false reassurance with withdrawal bleeding, and worsen bone health by suppressing hepatic IGF-1 production. 1, 5

• COCs do not restore spontaneous menses or correct the metabolic derangements of FHA. 1, 5
• They suppress an already-low bone trophic hormone (IGF-1) in FHA patients. 5
• Withdrawal bleeding on COCs does not indicate resolution of hypoestrogenism. 1, 5

Pharmacological Options: Only After Non-Pharmacological Failure

If Pregnancy Is Desired

• Letrozole for ovulation induction: appropriate when pregnancy is immediate goal, but does not treat underlying FHA or restore metabolic/bone health. 5
• Monitor endometrial thickness: target ≥7-8 mm at ovulation via transvaginal ultrasound. 5
• Pulsatile GnRH therapy: directly addresses GnRH pulsatility defect; consider if spontaneous menses absent after 6 months of adequate EA. 5

If Bone Protection Is Priority (After ≥6 Months Failed Non-Pharmacological Treatment)

• Transdermal estradiol (100 μg patch twice weekly) with cyclic micronized progesterone (200 mg for 12 days/month): preferred over COCs for bone protection in FHA. 1
• This regimen is NOT contraception; rule out thrombophilic disorders before initiating. 1
• Bisphosphonates or teriparatide: reserved for osteoporosis with recurrent fractures after failed estrogen therapy ≥18-24 months; requires endocrinologist referral. 1

Monitoring and Return-to-Play Considerations

Ongoing Assessment

• Reassess menstrual status monthly: return of spontaneous menses indicates improved energy availability. 1, 5
• Repeat DEXA scan: if initial scan shows low BMD or after 12-24 months of treatment. 1, 5
• Monitor for cardiovascular dysfunction: FHA patients demonstrate endothelial dysfunction despite normal weight. 5

Clearance for Competition

• Risk stratification based on cumulative factors: menstrual status, BMD, nutrition status, and injury history determine clearance level (full, provisional/limited, or restricted). 1
• Athletes with multiple RED-S risk factors require provisional clearance with modified training until metabolic normalization. 1

Key Takeaway

Elevated SHBG in a female athlete is a red flag for energy deficiency and hypoestrogenism, not a condition requiring direct SHBG-lowering therapy. The only effective treatment is restoring adequate energy availability through increased caloric intake and/or reduced exercise energy expenditure—pharmacological interventions are adjuncts at best and harmful (COCs) at worst. 1, 5