Evaluation of the Role of Luteinizing Hormone (LH) and Human Chorionic Gonadotropin (hCG) in Adult Patients Undergoing Assessment for Endocrine Disorders

The hormonal changes that occur during the menopausal transition and after menopause affect multiple organ systems and are associated with a range of symptoms and chronic diseases. The prevalence of several endocrine disorders, including hypothyroidism, primary hyperparathyroidism, osteoporosis, and adrenal tumors, increases markedly during and after menopause. In addition, postmenopausal women are at increased risk of obesity, type 2 diabetes, hypertension, cardiovascular disease, and osteoporosis. While menopausal hormone therapy can alleviate symptoms and reduce bone loss, concerns regarding breast cancer and thromboembolic risk limit its use, highlighting the need for a better understanding of the biological mechanisms underlying menopausal symptoms and long-term health complications.

Menopause is characterized not only by declining estrogen concentrations but also by a marked increase in circulating luteinizing hormone (LH). Most metabolic and skeletal changes associated with menopause have traditionally been attributed to estrogen deficiency. However, several important changes, including accelerated bone loss and weight gain, often begin during perimenopause when estrogen concentrations remain relatively stable but LH levels increase substantially. This observation suggests that elevated LH may have physiological effects beyond its established role in the reproductive system.

LH exerts its biological effects through the luteinizing hormone/choriogonadotropin receptor (LHCGR), which is also activated by human chorionic gonadotropin (hCG). Although hCG is generally considered a pregnancy-associated hormone, measurable concentrations are frequently observed in postmenopausal women and in men with hypergonadotropic hypogonadism. Emerging evidence from our group suggests that LH and hCG have previously unrecognized effects on calcium homeostasis, adipose tissue, thyroid hormone metabolism, adrenal function, and potentially the development and progression of endocrine diseases.

Experimental and clinical studies conducted by our group indicate that LH and hCG stimulate urinary calcium excretion, leading to compensatory increases in parathyroid hormone (PTH) and increased bone resorption. These findings suggest the existence of a novel physiological interaction between the hypothalamic-pituitary-gonadal axis and mineral metabolism. Such mechanisms may contribute to osteoporosis development and other disorders of calcium homeostasis, particularly in postmenopausal women exposed to prolonged elevations in LH.

In addition to skeletal effects, our data indicate that adipose tissue expresses LHCGR and responds directly to LH stimulation. Elevated LH levels may influence adipocyte function, brown adipose tissue activity, energy expenditure, weight regulation, and thyroid hormone activation through inhibition of type II iodothyronine deiodinase (DIO2). These findings suggest that LH may contribute to metabolic alterations associated with aging and menopause.