How does a low Body Mass Index (BMI) affect Follicle-Stimulating Hormone (FSH) levels and what are the recommendations for management?

Low BMI and FSH Levels: Clinical Impact and Management

Low BMI (particularly <18.5 kg/m²) suppresses FSH and LH through functional hypothalamic amenorrhea (FHA), where energy deficit disrupts GnRH pulsatility, preferentially reducing LH while FSH remains relatively preserved, and weight restoration to BMI ≥18.5 kg/m² is the primary therapeutic intervention before considering ovulation induction. 1

Mechanism of Hormonal Suppression in Low BMI

• Energy deficit from low body weight suppresses the hypothalamic-pituitary-gonadal axis, leading to decreased GnRH pulsatility that creates a characteristic hormonal pattern 1
• The LH to FSH ratio typically falls below 1 in approximately 82% of FHA patients, which serves as a useful diagnostic marker 1
• This is a central (hypothalamic) problem, not an ovarian dysfunction—the ovaries remain functional, as proven by restoration of ovulation with pulsatile GnRH administration 1

Associated Hormonal Changes Beyond FSH/LH

When energy availability drops below 30 kcal/kg fat-free mass per day, multiple hormonal alterations occur 1:

• Decreased estradiol and progesterone (the primary mechanism of menstrual dysfunction) 1
• Decreased leptin with increased ghrelin and cortisol 1
• Decreased insulin and IGF-1 1
• Decreased thyroid hormones (T3, T4) 1

Critical Diagnostic Distinctions

Do not confuse FHA with other conditions that affect FSH:

• PCOS shows the opposite pattern: LH:FSH ratio >2 (vs. <1 in FHA), with higher testosterone and lower SHBG than FHA patients 1
• Primary ovarian insufficiency and menopause show elevated FSH and LH due to ovarian failure, not suppression 1
• FHA patients lack insulin resistance, which is common in PCOS 1

Clinical Assessment of Low Energy Availability

BMI <17.5 kg/m² or <85% of expected body weight indicates overt signs of low energy availability 2

For adolescents, use BMI percentile method rather than absolute BMI cut-offs, examining weight in relation to the 50th BMI percentile 2

Additional markers of low energy availability include 2:

• Low triiodothyronine (T3)
• Reduced resting metabolic rate (measured RMR/predicted RMR <0.90)
• Recent weight loss or inadequate dietary intake

Management Recommendations

Primary Intervention: Weight Restoration

The Endocrine Society recommends BMI should reach ≥18.5 kg/m² before ovulation induction is offered 1

• Weight restoration is the primary therapeutic intervention for FHA 1
• For breast cancer patients with low BMI (<20) or who have lost ≥10% of usual weight in <6 months, there is increased risk of complications including bone fracture risk 2
• A healthy weight (BMI 20-24.9) must be encouraged 2

Nutritional Support

Adequate dietary protein intake of 1.2-1.5 g/kg/day should be ensured to prevent sarcopenic obesity and maintain muscle mass 2

• Avoid the misinformed tendency to become vegetarian or vegan during treatment, as this limits high-quality dietary protein intake and leads to malnutrition affecting long-term prognosis 2
• Nutritional assessment should be performed immediately after diagnosis and periodically during disease course 2
• Patients should be referred to a registered sports dietitian for comprehensive nutrition assessment 2

Pharmacologic Considerations

Clomiphene citrate is not recommended as first-line treatment for FHA due to uncertain efficacy and lack of randomized trials 1

• Address the underlying energy deficit first before considering ovulation induction 1
• Pulsatile GnRH administration can restore ovulation, proving ovarian functionality is preserved 1

Common Pitfalls to Avoid

• Do not assume weight stability indicates adequate energy availability—athletes in negative energy balance may experience suppression of physiological functions that restores energy balance and weight stability 2
• Do not use BMI alone to determine individual risk—body composition assessment is important as BMI does not account for muscle versus fat mass 2
• Do not overlook psychological stress and excessive exercise as contributing factors to FHA 1
• Do not misinterpret low-normal FSH as normal—in the context of amenorrhea and low BMI, this represents inappropriate suppression 1