E-Poster 63rd Endocrine Society of Australia Annual Scientific Meeting 2020

Dose-Dependent Response to Long-term Clomiphene Citrate in Male Functional Hypogonadotropic Hypogonadism: A Case study (#90)

Beryl Lin 1 2 , Stephen M Twigg 1 2
  1. Endocrinology, Royal Prince Alfred Hospital, Sydney
  2. Sydney Medical School, University of Sydney, Sydney

INTRODUCTION: Functional hypogonadotropic hypogonadism is a relatively common condition in middle-aged to elderly men that can significantly impair quality of life.1,2 Although its aetiology is incompletely understood, the phenotype is characterized by clinical androgen deficiency in the absence of structural hypothalamic-pituitary pathology. In addition to lifestyle optimisation, androgen replacement remains the treatment mainstay; however it can cause azoospermia and testicular atrophy.3

 Clomiphene citrate is a serum estrogen receptor modulator that acts centrally to increase testosterone production without affecting fertility. It has demonstrated efficacy in short-duration studies, but longer-term data is lacking.3

CASE REPORT: An otherwise well 42-year-old male presented with a 6-year history of generalised fatigue, reduced libido and insomnia. Hormonal profile demonstrated secondary hypogonadism: low total testosterone 8.5(9.5-28)nmol/L, low-normal LH 1.0(0.6-12)IU/L, low FSH 0.9(1.0-12)IU/L. Semen analysis was normal. A dedicated pituitary MRI did not identify any focal abnormality.

A biopsychosocial approach to management was employed. Due to patient preference, clomiphene citrate was trialled. After six weeks at 25mg daily, all symptoms including libido, erectile dysfunction and cognition improved. Blood total testosterone increased to the upper limit of normal 20.3nmol/L with corresponding increases in LH 1.7IU/L and FSH 3.5IU/L. Despite adherence to intensive lifestyle practices, clomiphene dose reductions below 15mg daily precipitated symptom recurrence. Thus, clomiphene was continued with dose titrations on regular follow up every 4-6 months.

Over five years to date, our patient has demonstrated a linear correlation between clomiphene dose and blood testosterone, oestradiol, LH and FSH levels (p<0.001). He has sustained an excellent clinical response with no known adverse effects.

CONCLUSION: Clomiphene induces a dose-dependent response in pituitary function and endogenous testosterone production. It has potential as a safe and efficacious longer-term treatment option for male functional hypogonadism. Further studies including randomized controlled trials comparing clomiphene to conventional androgen replacement are indicated to inform evidence-based therapy.

  1. Mulligan T, Frick MF, Zuraw QC, Stemhagen A, McWhirter C. Prevalence of hypogonadism in males aged at least 45 years: the HIM study. International journal of clinical practice. 2006;60(7):762-9.
  2. Araujo AB, Esche GR, Kupelian V, O’Donnell AB, Travison TG, Williams RE, Clark RV, McKinlay JB. Prevalence of symptomatic androgen deficiency in men. The Journal of Clinical Endocrinology & Metabolism. 2007;92(11):4241-7.
  3. Wheeler KM, Sharma D, Kavoussi PK, Smith RP, Costabile R. Clomiphene citrate for the treatment of hypogonadism. Sexual medicine reviews. 2019;7(2):272-6.