Introduction: Secondary, or late onset, hypogonadism (LOH) is a common problem in the ageing male population. It is significantly associated with various co morbidities such as obesity, type 2 diabetes, hypertension, osteoporosis and metabolic syndrome. The standard therapy for hypogonadism is testosterone replacement therapy (TRT) which is not suitable for men seeking fertility – a major problem in many men from the Gulf States.
Objectives: We wished to compare the efficacy of single agent clomiphene citrate (CC), human chorionic gonadtrophin (HCG), and a combination of the two in symptomatic patients of LOH wishing to preserve fertility.
Patients & Methods: In this unblinded multicentre RCT, a total of 287 hypogonadal patients were randomly enrolled 2:2:1 into 3 groups. Group A (n = 88) were given HCG 5000 international units (i.u) intramuscularly once a week; group Group B (n = 82) took CC 50 mg daily, and group C (n = 41) took both HCG&CC (our previous standard treatment) A non-randomized control group of consecutive patients (D: n = 76) who did not wish to preserve fertility were commenced on Testosterone undecanoate (TU). All patients had physical examination, T measurements & glycosylated haemoglobin(HbA1c) at baseline, 1 month and 3 months, as were Quantitative ADAM questionnaire (qADAM) scores. LH and FSH levels were checked at baseline and three months.
Results: The average age of patients were 42 being 47 for TU group, 40 for HCG, 38 for CC and 41 for combination group. The mean body mass index (BMI) of all patients was 30,9 All three treatments increased serum testosterone levels as shown in table 1:
treatment Baseline T T after1 m T after 3 m
HCG 2.53 3.31 4.53
CC 2.58 3.78 5.55
Combination 2,24 3.22 5.18
Significant improvements were seen in the qADAM score in all groups. Improvements were seen in HbA1c and BMI in all groups, although not always reaching significance. The increases in all metrics, while not directly comparable, were similar to those seen in the TU group.
Conclusion: CC and HCG alone or in combination are good alternative therapy in LOH with comparable results and rapid onset subjectively and objectively in hypogonadal men irrespective of their age but the outcome is less in obese patients. These results would suggest a larger RCT between CC, HCG and TRT.