Netherlands: According to a research article published in Endocrinology, Diabetes & Metabolism, the study has provided supporting evidence explaining the long-term efficacy of Clomiphene citrate (CC) in hypogonadal males with increases in total testosterone, free testosterone and gonadotrophins and total biochemical increase in TT in 89% of the patients. The researchers highlighted the importance of CC therapy in hypogonadal symptoms showing improvement in 74 % of patients. Both biochemical and clinical response was observed in 81% of patients.
Hypogonadism causes sexual, physical and mental problems in men. The first treatment choice is testosterone, but it has many side effects. An alternative off-label therapy for a particular group of hypogonadal males is Clomiphene citrate (CC), especially for those with an active or future child wish. There needs to be more data regarding CC usage in males with hypogonadism.
Considering this background, a retrospective study was done to evaluate the effectiveness and safety of CC for hypogonadal males measuring the Primary outcome of the hormonal evaluation.
The hormonal evaluation included total testosterone (TT), free testosterone (FT), luteinizing hormone (LH) and follicle-stimulating hormone (FSH).
Haemoglobin (Hb), haematocrit (Ht), prostate-specific antigen (PSA), side effects, the effect of a trial without medication and potential predictors for biochemical and clinical response were also reported by the researchers.
The study results could be summarised as follows:
One hundred fifty-three hypogonadal men were treated with CC.There was an increase in Mean TT, FT, LH and FSH.TT increased from 9 to 16 nmol/L.There was a biochemical increase in 89% of patients.After eight years of treatment, an increased level of TT persisted in patients who continued CC treatment.74% of the patients showed symptom improvement with CC treatment.LH at the lower normal range before CC treatment was predictive for better TT response.Few side effects were recorded during CC usage.No clinically meaningful changes in PSA, Hb, and Ht were recorded.
They said that our study is the first large retrospective cohort study on both clinical and biochemical effects of CC in hypogonadal males with extended follow-up.
They concluded Clomiphene citrate has effectiveness in both the short and long term. In the present study, CC improved clinical symptoms and biochemical markers of male hypogonadism. From a safety point of view, only a few side effects were recorded, thereby confirming overall good safety aspects.
The study’s limitations include retrospective character, data obtained manually from patient files, lack of strict inclusion criteria with predefined baseline and outcome measurements, absence of validated instrument and underestimation.
Huijben M, Lock MTWT, de Kemp VF, Beck JJH, De Kort LMO, van Breda HMK. Clomiphene citrate: A potential alternative for testosterone therapy in hypogonadal males. Endocrinol Diabetes Metab. 2023 Mar 30:e416. Doi: 10.1002/edm2.416. Epub ahead of print. PMID: 36998229.