Subcutaneous Testosterone Anastrozole Therapy in Men: Rationale, Dosing, and Levels on Therapy.

This analysis was designed to determine the efficacy of anastrozole, an aromatase inhibitor, combined with testosterone in a subcutaneous implant in preventing elevated estradiol levels and the subsequent side effects of excess estrogen associated with testosterone therapy. It also allowed for the establishment of normative ranges of serum testosterone levels on subcutaneous implant therapy. The study participants were 344 men who were accrued to an institutional review board-approved cohort study between April 2014 and 2017. Efficacy of the subcutaneous combination implant in maintaining low estradiol levels was evaluated. Serum levels of testosterone and estradiol were measured throughout the implant cycle, at week 4, and when symptoms returned. Correlations between patient demographics, dosing, and serum levels on therapy were evaluated. Mean testosterone dose was 1827 ± 262 mg. Mean anastrozole dose was 15.3 ± 3.2 mg with the majority of men receiving 16 mg of subcutaneous anastrozole. The mean interval of insertion was 4.8 months. Low estradiol levels were maintained throughout the implant cycle. Mean T level at week 4 was 1183 ± 315 ng/dl and 553 ± 239 ng/dl when symptoms returned. Levels of testosterone on therapy inversely correlated with body mass index. There were no adverse events attributed to testosterone or anastrozole therapy. Subcutaneous anastrozole delivered simultaneously with testosterone allowed for higher dosing of testosterone and less frequent intervals of insertion. Low-dose anastrozole released from the combination implant maintained low estradiol levels throughout the implant cycle and prevented clinical side effects attributed to excess estrogen.

Incidence of invasive breast cancer in women treated with testosterone implants: a prospective 10-year cohort study.

BACKGROUND: Testosterone implants have been used for over eighty years to treat symptoms of hormone deficiency in pre and postmenopausal women. Evidence supports that androgens are breast protective. However, there is a lack of data on the long-term effect of testosterone therapy on the incidence of invasive breast cancer (IBC). This study was specifically designed to investigate the incidence of IBC in pre and postmenopausal women (presenting with symptoms of androgen deficiency) treated with subcutaneous testosterone implants or testosterone implants combined with anastrozole. METHODS: The 10-year prospective cohort study was approved in March 2008 at which time recruitment was initiated. Recruitment was closed March 2013. Pre and postmenopausal women receiving at least two pellet insertions were eligible for analysis (N = 1267). Breast cancer incidence rates were reported as an unadjusted, un-weighted value of newly diagnosed cases divided by the sum of 'person-time of observation' for the at-risk population. Incidence rates on testosterone therapy were compared to age-specific Surveillance Epidemiology and End Results (SEER) incidence rates and historical controls. Bootstrap sampling distributions were constructed to verify comparisons and tests of significance that existed between our results and SEER data. RESULTS: As of March 2018, a total of 11 (versus 18 expected) cases of IBC were diagnosed in patients within 240-days following their last testosterone insertion equating to an incidence rate of 165/100000 p-y, which is significantly less than the age-matched SEER expected incidence rate of 271/100000 p-y (p < 0.001) and historical controls. CONCLUSION: Long term therapy with subcutaneous testosterone, or testosterone combined with anastrozole, did not increase the incidence of IBC. Testosterone should be further investigated for hormone therapy and breast cancer prevention.

Subcutaneous testosterone-letrozole therapy before and concurrent with neoadjuvant breast chemotherapy: clinical response and therapeutic implications.

OBJECTIVE: Hormone receptor-positive breast cancers respond favorably to subcutaneous testosterone combined with an aromatase inhibitor. However, the effect of testosterone combined with an aromatase inhibitor on tumor response to chemotherapy was unknown. This study investigated the effect of testosterone-letrozole implants on breast cancer tumor response before and during neoadjuvant chemotherapy. METHODS: A 51-year-old woman on testosterone replacement therapy was diagnosed with hormone receptor-positive invasive breast cancer. Six weeks before starting neoadjuvant chemotherapy, the patient was treated with subcutaneous testosterone-letrozole implants and instructed to follow a low-glycemic diet. Clinical status was followed. Tumor response to "testosterone-letrozole" and subsequently, "testosterone-letrozole with chemotherapy" was monitored using serial ultrasounds and calculating tumor volume. Response to therapy was determined by change in tumor volume. Cost of therapy was evaluated. RESULTS: There was a 43% reduction in tumor volume 41 days after the insertion of testosterone-letrozole implants, before starting chemotherapy. After the initiation of concurrent chemotherapy, the tumor responded at an increased rate, resulting in a complete pathologic response. Chemotherapy was tolerated. Blood counts and weight remained stable. There were no neurologic or cardiac complications from the chemotherapy. Cost of therapy is reported. CONCLUSIONS: Subcutaneous testosterone-letrozole was an effective treatment for this patient's breast cancer and did not interfere with chemotherapy. This novel combination implant has the potential to prevent side effects from chemotherapy, improve quality of life, and warrants further investigation.

Beneficial effects of testosterone therapy in women measured by the validated Menopause Rating Scale (MRS).

OBJECTIVES: This study was designed to measure the beneficial effects of continuous testosterone therapy, delivered by subcutaneous implant, in the relief of somatic, psychological and urogenital symptoms in both pre- and post-menopausal patients, utilizing the validated Health Related Quality of Life (HRQOL), Menopause Rating Scale (MRS). STUDY DESIGN: 300 pre- and post-menopausal women with symptoms of relative androgen deficiency, were asked to self-administer the 11-item MRS, at baseline and 3 months after their first insertion of the subcutaneous testosterone implant. Baseline hormone measurements, menopausal status and BMI, were assessed to determine correlation with symptoms and clinical outcome. MAIN OUTCOME MEASUREMENTS: Changes related to therapy were determined. Total MRS scores as well as psychological, somatic and urogenital subscale scores were compared prior to therapy and following testosterone implant therapy. RESULTS: Pre-menopausal and post-menopausal females reported similar hormone deficiency symptoms. Both groups demonstrated similar improvement in total score, as well as psychological, somatic and urogenital subscale scores with testosterone therapy. Better effect was noted in women with more severe complaints. Higher doses of testosterone correlated with greater improvement in symptoms. CONCLUSION: Continuous testosterone alone, delivered by subcutaneous implant, was effective for the relief of hormone deficiency symptoms in both pre- and post-menopausal patients. The validated, HRQOL questionnaire, Menopause Rating Scale (MRS), proved a valuable tool in the measurement of the beneficial effects of testosterone therapy in both cohorts.