What causes low levels of Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH)?

Causes of Low FSH and LH Levels

Low levels of Follicle-Stimulating Hormone (FSH) and Luteinizing Hormone (LH) are primarily caused by hypothalamic-pituitary dysfunction, most commonly seen in hypogonadotropic hypogonadism, which requires prompt evaluation and treatment to prevent complications related to reproductive health and quality of life.

Primary Causes of Low FSH and LH

Hypothalamic Causes

• Functional Hypothalamic Amenorrhea (FHA) - Occurs in approximately 3-4% of women in the general population 1
  • Stress and stress sensitivity
  • Vigorous exercise/endurance exercise
  • Weight loss and eating disorders
  • Psychological disorders
  • Energy deficit

Pituitary Causes

• Pituitary tumors - Most common organic cause 1, 2
  • Prolactinoma (most frequent)
  • Other sellar tumors
• Hyperprolactinemia - Can be functional or tumor-related 1
• Pituitary surgery or trauma 2
• Cranial/pituitary radiation therapy 2

Systemic Conditions

• Chronic systemic diseases 1
  • Type 2 diabetes mellitus/metabolic syndrome
  • HIV infection
  • Chronic organ failure (particularly liver disease)
  • Chronic inflammatory arthritis

Other Important Causes

• Medications 1
  • Glucocorticoids
  • Anticonvulsants (can affect hormone metabolism)
  • Opioids
  • Antipsychotics
• Endocrine disorders
  • Cushing syndrome (glucocorticoid excess) 1
  • Hypothyroidism
• Advanced liver disease - Alters estrogen metabolism and disrupts the hypothalamic-pituitary axis 1
• Critical illness 1

Diagnostic Approach

Initial Evaluation

1. Hormone panel assessment

   • FSH and LH levels
   • Estradiol/testosterone levels
   • Prolactin levels
   • Thyroid function tests

2. Clinical context evaluation

   • In women: Menstrual irregularities (oligomenorrhea, amenorrhea)
   • In men: Decreased libido, erectile dysfunction, reduced stamina 2
   • Weight changes, exercise patterns, stress levels

3. Differential diagnosis considerations

   • Polycystic Ovary Syndrome (PCOS) - Can be confused with FHA with polycystic ovarian morphology (FHA-PCOM) 1
   • Primary gonadal failure - Shows high FSH/LH (unlike hypogonadotropic hypogonadism)

Imaging

• MRI of brain/pituitary - Essential when organic cause is suspected 2

Treatment Approach

For Functional Causes

1. Address underlying factors

   • Reduce psychological stress
   • Normalize exercise patterns
   • Ensure adequate nutrition
   • Treat any underlying systemic disease

2. Hormone Replacement

   • Consider hormone therapy if symptoms of deficiency develop
   • In women: Low-dose estradiol with cyclical progestin 3
   • In men: Testosterone replacement therapy for symptom relief 4, 2

For Fertility Concerns

• Pulsatile GnRH therapy
  • Highly effective for inducing spermatogenesis in men 5
  • Effective for ovulation in women with FHA 1
• Gonadotropin therapy (alternative approach) 2

Monitoring and Follow-up

• Regular hormonal assessment (3-6 months initially)
• Bone mineral density testing if prolonged low hormone state
• Monitoring for improvement in symptoms

Important Caveats and Pitfalls

1. Don't miss organic causes - Always consider pituitary tumors, especially prolactinomas, which require specific treatment

2. Distinguish between primary and secondary hypogonadism - Low FSH/LH with low sex hormones indicates secondary (hypogonadotropic) hypogonadism, while high FSH/LH with low sex hormones indicates primary gonadal failure 4

3. Consider medication effects - Many medications can suppress the hypothalamic-pituitary axis

4. Recognize the impact of chronic illness - Particularly liver disease, which affects 25% of premenopausal women with advanced liver disease 1

5. Be aware of diagnostic challenges - Distinguishing between FHA-PCOM and PCOS can be difficult but important for treatment decisions 1

By systematically evaluating these causes and implementing appropriate treatment, most patients with low FSH and LH can achieve significant improvement in symptoms and quality of life.