Is there a correlation between hypogonadism and hyperparathyroidism?

Correlation Between Hypogonadism and Hyperparathyroidism

Yes, there is a significant correlation between hypogonadism and hyperparathyroidism, with GnRH agonists used in androgen deprivation therapy increasing parathyroid hormone-mediated osteoclast activation and bone turnover. 1

Pathophysiological Relationship

• GnRH agonists used in androgen deprivation therapy (ADT) for prostate cancer increase parathyroid hormone-mediated osteoclast activation, leading to increased bone turnover 1
• Testosterone deficiency from hypogonadism results in bone loss through decreased testosterone levels and reduced aromatization of testosterone to estrogen 1
• In patients with congenital hypogonadotropic hypogonadism, inadequate hormone replacement therapy is associated with reduced bone mineral density (BMD) 2

Clinical Evidence

• Men with prostate cancer receiving ADT experience significant bone loss, with the highest magnitude occurring during the first year of treatment, though losses continue with long-term therapy 1
• Within 6 months of diagnosis, men treated with ADT or those who undergo bilateral orchiectomy have a 5-year fracture risk of 19% versus 12% in matched controls 1
• In cardiac transplant patients, hypogonadism (present in 20% of patients) was associated with significantly lower BMD (78±12% vs. 88±12%) compared to normogonadal patients 3

Bone Health in Hypogonadism and Hyperparathyroidism

• Hypogonadism is recognized as a condition associated with secondary osteoporosis and is listed as a risk factor requiring bone mineral density assessment 1
• In postmenopausal women with primary hyperparathyroidism, the concomitant presence of growth hormone deficiency (often associated with hypogonadism) leads to more severe reductions in BMD compared to those with normal GH secretion 4
• Chronic exposure to high PTH levels in primary hyperparathyroidism causes increased bone remodeling with predominant bone resorption, leading to reduced BMD and increased fracture risk 5

Screening and Monitoring Recommendations

• Men with hypogonadism over age 18, especially those with surgically or chemotherapeutically induced castration, should undergo bone mineral density assessment 1
• In men with diabetes who have symptoms or signs of hypogonadism, morning total testosterone levels should be measured using an accurate and reliable assay 1
• For patients with hypogonadism, monitoring for secondary hyperparathyroidism is recommended as both conditions can contribute to long-term bone loss 3

Treatment Considerations

• Bisphosphonate therapy and RANK-L monoclonal antibody therapy (denosumab) are the most commonly used agents for managing bone loss during androgen deprivation therapy 1
• Sex hormone replacement in hypogonadal patients with hyperparathyroidism has shown a 35% increase in BMD compared to normogonadal patients 3
• Calcium supplementation (1000mg daily) combined with sex hormone replacement in hypogonadism has proven effective for long-term prevention of decreased BMD and fractures 3
• Parathyroid hormone (PTH) therapy has shown benefits in improving bone strength, trabecular connectivity, and mineral content in orchiectomized rat models of hypogonadism 6

Clinical Implications

• Patients with hypogonadism require lifelong follow-up to avoid inadequate hormone replacement therapy, treatment pauses, and further morbidity related to bone health 2
• Androgen deprivation therapy for prostate cancer is associated with increased risk for osteoporotic fracture in a dose-dependent manner, with relative risks of 1.45 and 1.54 for men who received 9 or more doses of GnRH agonist or underwent orchiectomy, respectively 1
• When treating patients with both conditions, addressing both the hypogonadism and hyperparathyroidism is essential for optimal bone health outcomes 3