Abstract

Gynecomastia is a rare side effect associated with testosterone replacement therapy (TRT), which has traditionally been treated surgically by irradiating or stopping testosterone supplements. Here we present our experience of two cases of gynecomastia in men undergoing TRT who were successfully treated with anastrozole, an aromatase inhibitor.

introduction

Testosterone replacement therapy (TRT) is increasingly common among men with hypogonadism as caregivers are increasingly aware of andropause and the benefits of treatment. However, exogenous administration of testosterone may be associated with side effects, including effects on the prostate, hematocrit, fertility, and the development of gynecomastia. Gynecomastia is believed to be caused by the peripheral conversion of testosterone to estradiol via the enzyme aromatase. This condition is embarrassing for men and can lead to the discontinuation of otherwise successful testosterone treatment.

Male gynecomastia has traditionally been treated with radiation therapy or surgical resection of breast tissue.2 The introduction of a new generation of aromatase inhibitors has created an opportunity to treat testosterone-induced gynecomastia with oral drugs alone.

Here we present our experience with the use of an aromatase inhibitor, anastrozole, in the treatment of gynecomastia in hypogonadic men receiving testosterone supplements.

Case reports

Fall 1

The 61-year-old man had a history of erectile dysfunction, decreased libido and difficulty reaching orgasm. The clinical left gynecomastia in adolescence, which was treated surgically without further recurrence, previously showed a clinical history. The current physical examination was not remarkable. Blood tests showed TF 0.8 ng / dl, TT 295 ng / dl, luteinizing hormone (LH) 3.4 mIU / l (normally: 2-18 mIU / l), follicle stimulating hormone (FSH) 3.4 mIU / l (normal: 2 – 18 mIU / l) and PSA 1.5 ng / l (normal: 0-4 ng / l). The NPTR observed a decrease in maximum stiffness. Intramuscular injections of testosterone enanthate 400 mg / 3 weeks were initiated. The lowest total testosterone level was 287 ng / dl. The patient showed significant symptomatic improvement with testosterone supplementation.

Six months after the start of treatment, the patient noticed gynecomastia on the right side, which had not been operated on earlier as a teenager. TRT was stopped and one month later the patient reported complete resolution of the gynecomastia. Testosterone supplementation was resumed according to the same schedule as before and oral administration of anastrozole (Arimidex®, AstraZeneca, London, UK) was also started at 1 mg / day. After 3 years, the patient benefits from the clinical benefit of TRT without recurrence of gynecomastia.

Fall 2

A 30-year-old man had a history of erectile dysfunction, decreased libido and fatigue. The physical examination was normal, except for moderate obesity and mild bilateral gynecomastia. Blood tests revealed TT 220 ng / ml, FT 1.1 ng / ml, FSH 0.9 mIU / l, LH 3.7 mIU / l and prolactin (PRL) 8.2 ng / ml (2.1- 17.7 ng / ml). Erections with NPTR deficiency have been observed. Treatment was started with intramuscular injections of testosterone enanthate 200 mg / 2 weeks. After 6 months, the patient reported worsening of the bilateral basal sinus enlargement and new pain on palpation of the nipple. The peak serum levels of -FT were 4 ng / dl. Estradiol levels reached 103 pg / ml (normally: 10-52 pg / ml). Testosterone replacement was discontinued and anastrozole (Arimidex®, AstraZeneca, London, UK) started at 1 mg / day. After 1 month, the patient reported a decrease in breast size and resolution of nipple tenderness. TRT was then reintroduced. After 5 months, the patient reported significant improvement in initial symptoms without recurrence of breast changes.

In men, aromatase inhibitors are used to treat male infertility in the hope of achieving a better testosterone / estradiol ratio. Raman and Schlegel3 observed a significant improvement in sperm concentration, motility and morphology in the group of men treated with anastrozole. No benefit was observed in individuals with azoosperm. Gillam et al6 recently reported a case of large prolactinoma treated with bromocriptine and cabergoline. Associated hypogonadism has been successfully treated with TRT and anastrozole. Herzog et al7 reported beneficial effects on sexual function and seizure control in men using the aromatase inhibitor testolactone with TRT.

Theoretical adverse effects of aromatase inhibition in men include effects on body composition, carbohydrate / fat metabolism, muscle strength, bone density and infertility.7,8 It has been shown that estrogen has significant beneficial effects on bone density, even in men; However, the long-term effects on bone density in men receiving both testosterone supplements and antiestrogens such as anastrozole are uncertain. However, there are no comprehensive studies of anastrozole in men, so there is little information on its side effects in this population. In a series of infertile men treated with anastrozole, asymptomatic elevations in serum liver enzymes were observed in 7.4% of cases and returned to baseline3 after discontinuation of treatment3.

The development of gynecomastia in hypogonadic men on TRT can be a major problem for those affected and may lead to discontinuation of treatment. Because TRT is generally considered voluntary because it is given to improve quality of life and not a life-threatening disease, radiation therapy and surgery are often viewed by patients and physicians as too invasive treatment for gynecomastia and gynecomastia. testosterone. Patients often stop treatment if they feel embarrassed about their breast augmentation. Effective treatment with oral drugs, such as an aromatase inhibitor, is therefore an attractive therapeutic alternative and should be considered in symptomatic men.