Conditions and Medications That Cause Low Sex Hormone Levels
Multiple medical conditions and long-term medications can cause estrogen, progesterone, and testosterone to remain abnormally low, leading to significant health consequences including bone loss, sexual dysfunction, and reduced quality of life. Understanding these causes is essential for proper diagnosis and treatment.
Medical Conditions That Cause Low Sex Hormones
Primary Endocrine Disorders
- Female Athlete Triad: Characterized by low energy availability, menstrual dysfunction, and decreased bone mineral density 1
- Functional Hypothalamic Amenorrhea (FHA): Results from energy deficiency leading to suppressed gonadotropin pulsatility and hypogonadism 1
- Premature Ovarian Insufficiency (POI): Especially iatrogenic POI following chemotherapy or radiation therapy 1
- Hyperthyroidism: Causes elevated SHBG levels, reducing bioavailable testosterone 2
- Liver Disease/Cirrhosis: Increases SHBG production, reducing free hormone levels 2
Nutritional and Metabolic Factors
- Low Energy Availability: Inadequate caloric intake relative to energy expenditure 1
- Malnutrition: Severe weight loss or eating disorders 2
- Low Body Mass Index (BMI): Associated with elevated SHBG and reduced free hormone levels 2
Other Conditions
- Acute Hepatic Porphyrias: Associated with cyclic attacks during the luteal phase when progesterone levels are highest 1
- Aging: Natural decline in hormone production, particularly testosterone in men 1
Medications That Cause Low Sex Hormone Levels
Hormone-Suppressing Medications
- GnRH Analogs: Used to treat cyclic attacks in porphyrias and other conditions, these suppress ovulation and corpus luteum formation, reducing progesterone and estrogen 1
- Combined Oral Contraceptives: Particularly those containing ethinylestradiol, which suppress endogenous hormone production and increase SHBG 1
Other Medications
- Certain Progestins with Anti-Androgenic Effects: Can worsen hypoandrogenism in patients with iatrogenic POI 1
- Medications That Elevate SHBG: Reduce bioavailable testosterone and estrogen 2
Diagnostic Approach
Essential Laboratory Tests
- Morning measurements of total testosterone, estrogen, and progesterone on at least two occasions 2
- Free testosterone levels (calculated free testosterone preferred over free androgen index) 2
- SHBG levels 2
- FSH and LH to assess hypothalamic-pituitary function 2
- Thyroid function tests (TSH, free T4) 2
Clinical Assessment
- Evaluate for symptoms of hypogonadism (fatigue, decreased libido, mood changes)
- Assess for signs of specific conditions (e.g., weight loss, amenorrhea)
- Review medication history thoroughly
Treatment Considerations
Non-Pharmacological Approaches
- Increase Energy Availability: Primary treatment for female athlete triad and FHA 1
- Weight Management: Regular physical activity and dietary modifications to normalize SHBG levels 2
- Nutritional Optimization: Ensure sufficient zinc and vitamin D intake to support hormone production 2
Pharmacological Options
- Hormone Replacement Therapy: For POI patients, 17β-estradiol (preferably transdermal) with cyclical or continuous progestin 1
- Testosterone Therapy: For men with confirmed low testosterone levels (<300 ng/dL) and symptoms 1
- Clomiphene Citrate: Increases endogenous testosterone while preserving fertility 2
- Human Chorionic Gonadotropin (hCG): Stimulates testicular testosterone production 2
Special Considerations
- For cyclic attacks related to menstrual cycle in porphyrias, GnRH analogs may be beneficial but should not be used beyond 6 months without low-dose estrogen supplementation 1
- Oral estrogen replacement is not effective for improving bone mineral density in low-weight conditions due to suppressive effects on hepatic IGF-1 production 1
Monitoring
- SHBG and free hormone levels every 3-6 months 2
- Bone mineral density in patients with prolonged hypogonadism
- Hematocrit in patients receiving testosterone therapy 2
- Symptom improvement through targeted questioning 2
Understanding these complex interactions between medical conditions, medications, and sex hormone levels is crucial for proper diagnosis and management of patients with suspected hormonal deficiencies.