Endocrine Abstracts

Background: Hypogonadotropic hypogonadism (HH) is commonly associated with morbidly obesity. Gynaecomastia is associated feature of hypogonadism and can be deteriorated by testosterone therapy.

History: A 49-year-old gentleman with a BMI of 53.2 kg/m² was referred for management of obesity. He has two children (age 18 and 22). He had obesity associated comorbidities including obstructive sleep apnoea and impaired fasting glucose. He reported lethargy, reduced sexual drive, libido, hair loss, and long standing enlarge breasts. Examination revealed an evidence of hypogonadism with feminine feature, hair loss and large grade IV gynaecomastia (Rohrich et al.); large hypertropic breasts with severe ptosis and redundant skin. Testes size were 25 ml bilaterally.

Investigations: Karyotype 46,XY, total testosterone 4.4 nmol/l, LH 2.4 mU/l, FSH 2.9 mU/l, SHBG 28 nmol/l, and low calculated free testosterone 114 pmol/l confirming HH. Oestradiol (E₂) was elevated in female range 256 pmol/l and serum hCG <1.2 IU/l. The high E₂ with low testosterone indicates increased activity of aromatase enzyme that converts testosterone to E₂ resulting in HH and gynaecomastia. Other pituitary function and Cushing’s investigation were normal. Ultrasound breasts confirmed large bilateral gynaecomastia with no sinister feature.

Management: He was advised on calorie restricted diet and gentle physical activity and lost 6 kg of body weight in 13 weeks. Regarding HH, a trial of aromatase inhibitor was likely to provide more physiological reversal of hormones and potential improvement in gynaecomastia than conventional testosterone therapy. After detail discussion with the patient, he was started on aromatase inhibitor anastrazole 1 mg OD. At 6 weeks, his total testosterone normalised at 19.1 nmol/l with decreasing E₂ at 91 pmol/l. Therapy was planned to continue for 6 months to review effect of his gynaecomastia with a repeat ultrasound.

Conclusions: HH and gynecomastia add significant medical and emotional morbidities to already high-risk individuals with obesity. We demonstrated that a case of high aromatase activity as a cause and successful initial therapy with anastrazole, reversing the hormonal imbalance. Effect on gynaecomatia needs further follow up. With an increasingly obesogenic environment, this is likely become major health risk. A further randomise control trial is needed for long-term effect, dose and duration of therapy and safety in comparison with testosterone.