History and Benefits of Testosterone Therapy in Women

Testosterone therapy has long been recognized as breast-protective in both pre- and post-menopausal women. For over 80 years, it has been used to alleviate symptoms associated with perimenopause and menopause. In countries like England and Australia, testosterone has been officially approved for use in women for more than 60 years.

Androgens, including testosterone, interact with multiple tissues and receptor sites throughout the body, offering significant benefits, especially for the central nervous system. In the brain, certain biochemical changes linked to Alzheimer’s disease—such as increased beta-amyloid, reduced glucose metabolism, and diminished blood flow—can be mitigated by testosterone and estradiol. Research has shown that these hormones can reduce beta-amyloid deposits, improve glucose metabolism in brain cells, and enhance cerebral blood flow, potentially lowering the risk of neurodegenerative conditions.

The conversation around osteoporosis and testosterone has traditionally focused on men, with most peer-reviewed studies and cited papers addressing male osteoporosis. However, osteoporosis affects approximately 10 million people in the United States, 80% of whom are women. This metabolic bone disease, characterized by low bone density and the deterioration of bone structure, significantly increases fracture risk. 1 in 7 women will develop osteoporosis after age 50, and over 50% of those with significant bone mineral density loss will sustain a fracture in their lifetime. While estrogen deficiency due to menopause is often blamed for osteoporosis in women and age-related testosterone deficiency in men, this view oversimplifies the multifaceted nature of the disease.

Osteoporosis treatments often include bisphosphonates, RANK ligand inhibitors, estrogen agonists/antagonists, parathyroid hormone analogs, and monoclonal antibodies. However, testosterone, which has been used for decades to treat osteoporosis, is notably absent from this list. Studies consistently show that androgens upregulate androgen receptor expression in osteoblasts, promoting their differentiation. Mature osteoblasts increase bone formation and bone mineral density in both women and men. Interestingly, the 2012 Endocrine Society osteoporosis guidelines recommend testosterone therapy for men with symptomatic low testosterone at high risk of fractures but fail to address its use in women.

Moreover, testosterone receptors are found in other peripheral tissues, such as the breast, skeletal muscle, adipose, and genital tissues. Despite this, many physicians remain hesitant to treat women with testosterone due to concerns about potential unknown effects. They argue that only FDA-approved preparations designed for men should be used for hormone therapy. This perspective stems from several misconceptions, including the belief that bioidentical hormones are unregulated, a lack of awareness about the safety and efficacy of testosterone in women, a preference for administration, and the FDA’s assumption that risks associated with estrogen and progesterone apply similarly to testosterone.

It is crucial to dispel myths and enhance awareness about the safety and efficacy of testosterone in women.

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