What are the effects of obesity-related hypogonadism on Luteinizing Hormone (LH) and Follicle-Stimulating Hormone (FSH) levels?

LH and FSH Levels in Obesity-Related Hypogonadism

In obesity-related hypogonadism, both LH and FSH levels are characteristically low or inappropriately normal (hypogonadotropic pattern), creating a state of secondary hypogonadism where gonadotropins fail to rise appropriately despite reduced testosterone levels. 1

Pathophysiologic Mechanism

The suppression of gonadotropins in obese men occurs through a well-defined mechanism:

• Increased aromatization of testosterone to estradiol in adipose tissue leads to enhanced estradiol-mediated negative feedback on the hypothalamic-pituitary axis, suppressing both LH and FSH secretion 1
• This creates hypogonadotropic hypogonadism where both gonadotropins are inappropriately low relative to the reduced testosterone levels 1
• The pituitary remains responsive to GnRH stimulation, indicating the defect is primarily at the hypothalamic level with excessive negative feedback rather than intrinsic pituitary failure 2

Specific Gonadotropin Patterns

LH Levels

• Basal LH levels are significantly lower in obese men compared to normal-weight controls 2
• LH pulse amplitude is reduced by approximately 50% in untreated obese men 3
• When estradiol negative feedback is interrupted (e.g., with aromatase inhibitors), LH secretion doubles and normalizes to levels seen in normal-weight men 3

FSH Levels

• FSH levels are also suppressed in obesity, though the reduction may be less pronounced than LH 2
• Obese males demonstrate significantly lower basal and GnRH-stimulated FSH levels compared to normal-weight controls 2
• FSH increases significantly with weight loss interventions such as GLP-1 receptor agonists 4, 5

Clinical Diagnostic Implications

When evaluating low testosterone in obese men, the gonadotropin pattern is critical for diagnosis:

• Measure serum LH and FSH concentrations to distinguish primary (testicular) from secondary (pituitary-hypothalamic) hypogonadism 6, 7
• Low testosterone with concomitantly low or inappropriately normal LH/FSH indicates secondary hypogonadism related to obesity 1, 7
• This pattern contrasts with primary hypogonadism, where LH and FSH would be elevated in response to testicular failure 6

Reversibility with Weight Loss

The hypogonadotropic state in obesity is potentially reversible:

• GLP-1 receptor agonist liraglutide significantly increases both LH and FSH levels (P < 0.001) while promoting weight loss 4
• Tirzepatide treatment results in significant increases in LH, FSH, and testosterone levels after just 2 months, alongside improvements in body composition 5
• Aromatase inhibition normalizes LH secretion in obese women, demonstrating that the suppression is mediated by estradiol negative feedback at the pituitary level 3

Important Clinical Caveats

Distinguishing Obesity-Related from Other Causes

• If LH/FSH remain persistently low despite weight loss, further evaluation for other causes of hypothalamic or pituitary dysfunction is warranted, including serum prolactin, iron saturation, comprehensive pituitary function testing, and potentially MRI of the sella turcica 1
• The pituitary retains normal responsiveness to GnRH in obesity-related hypogonadism, which can help distinguish it from intrinsic pituitary pathology 2

Estradiol Levels

• Contrary to older hypotheses, estradiol levels may not be significantly elevated in obese men with BMI up to 39 kg/m², though the increased aromatase activity in adipose tissue still mediates the negative feedback effect 8
• The mechanism appears more related to altered feedback sensitivity rather than absolute estradiol elevation 8

LH:FSH Ratio

• While an LH:FSH ratio >2 suggests PCOS in women, a ratio <1 is found in approximately 82% of patients with functional hypothalamic amenorrhea, which shares pathophysiologic similarities with obesity-related hypogonadism 6