Abstract
Testosterone (T) is the most abundant biologically active hormone in women. It has a direct effect at the androgen receptor in every major organ system. Local aromatization of T is a major source of bioavailable estradiol. Adequate amounts of bioavailable T are essential for optimal health, immune function, and disease prevention. More than 80% of bioavailable T in women is from the local intracrine production of T from the adrenal precursor steroids androstenedione and dehydroepiandrosterone (sulfate). Serum T levels reflect <20% of the total androgen pool in women, which limits its usefulness in diagnosing or treating androgen deficiency. The gradual decline of androgens associated with aging is responsible for many of the adverse signs and symptoms of aging, including mental and physical deterioration. Decades of evidence support the safety and efficacy of T therapy in women. We have found that subcutaneous T implant therapy relieves symptoms of hormone deficiency in women with and without breast cancer, improves their quality of life, and maintains overall health and well-being. T does not increase and may lower the risk of breast cancer. The combination of T with an aromatase inhibitor prevents the conversion of androgens to estrogens, limiting their stimulatory effect in estrogen-sensitive diseases, including breast cancer. Adequate doses of T therapy should provide adequate levels of bioavailable T in the target organs—determined by clinical response (benefits) versus adverse side effects (risks). Pharmacological dosing of T implants in women is safe and necessary for physiological effect.
Highlights
Androgens are critical for immune function and overall health in both sexes
We have found that subcutaneous T implant therapy relieves symptoms of hormone deficiency in women with and without breast cancer, improves their quality of life, and maintains overall health and wellbeing
Recent pharmaceutical sponsored studies have focused on topical T formulations and recent narratives have argued against the use of T pellet implants.[7]
Summary
Androgens are critical for immune function and overall health in both sexes. Androgens decline with age, adversely affecting mental and physical health. Doses and therapeutic ranges for exogenous therapy with T pellet implants have been published in the peerreviewed literature (Table 2).[11,14,20,23] Trough (nadir) levels, measured when symptoms returned,[11] support that T levels on exogenous therapy cannot be compared with, monitored by, or dosed based on endogenous T ranges in serum.[8,9,77] In addition, there is a significant interindividual variation (coefficient of variation [CV] >40%) as well an intraindividual variation (CV 25%) in T levels on therapy suggesting that a single T level is extremely variable and of little or no value in clinical decision making, further supporting ACOG’s position on hormone testing.[11,75]. Evidence suggests that hyperandrogenism is secondary to hyperinsulinemia—insulin stimulates the production of androgens and treating hyperinsulinemia ameliorates hyperandrogenism.[90,91] The absence of significant ‘‘therapy-related’’ adverse health events is consistent with our long-term experience
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