(095) Comparative Analysis of Absolute Risk in Testosterone versus Clomiphene Therapy: A Bayesian Analysis of Adverse Effects
Authors: Saffati G , Naeem T , Guhan M , Iacobucci A , Green C , Lipshultz LI , Khera M 
Published: February 2024

Abstract

Introduction
Clomiphene is a selective estrogen receptor modulator used to induce ovulation by increasing luteinizing (LH) and follicle-stimulating hormone (FSH) levels. Since the 1970’s, it has been used in males with hypogonadism as an alternative to testosterone therapy as it does not suppress the hypothalamic-pituitary-gonadal axis.

Objective
While there have been systematic reviews looking at the effectiveness of clomiphene, we sought to better characterize the average testosterone levels, as well as the rate of deep venous thrombosis (DVT), myocardial infarction (MI), stroke, and polycythemia in clomiphene vs. testosterone users.

Methods
We performed a retrospective chart review for 537 men with a hypogonadism diagnosis that were seen by two urology providers at our center. Of these 537 patients, 84 presented with prior use or were prescribed clomiphene. We measured the incidence of DVT, MI, stroke, polycythemia and average testosterone levels with clomiphene. Statistical analysis was conducted using both a beta binomial and linear model.

Results
Patients receiving testosterone (n=217) versus clomiphene (n=84) demonstrated a 99% chance of higher mean levels of testosterone (Difference=216.55, 95% CrI = 20.67-408.16). Among those taking testosterone or clomiphene at the final visit (N=237; testosterone n=185; clomiphene=52) adverse events included, polycythemia (n=28), one DVT, VTE’s (n=4), MI’s (n=4), and strokes (n=4). The absolute risk (AR) of experiencing at least one of these events (i.e. polycythemia, DVT, VTE, MI or stroke) was 13.8% (95% CrI = 10.1-17.9%) and 3.1% (95% CrI = 0.44-9.4%) for testosterone and clomiphene respectively (Absolute Risk Difference (ARD) = 10.5% (95% CrI = 3.4-15.7%); Posterior Probability (ARD&gt;0) &gt; 0.99. The AR of polycythemia was 12.6% (95% CrI = 8.9-16.7%) and 1.5% (95% CrI = 0.1-7.4%) for testosterone and clomiphene respectively (ARD = 10.7% (95% CrI = 4.3-15.6%); Posterior Probability (ARD &gt; 0) &gt; 0.99. The AR of stroke was 0.94% (95% CrI = 0.14-2.98%) and 1.56% (95% CrI = 0.1-7.4%) for testosterone and clomiphene respectively (ARD = -0.6% (95% CrI = -6.5-2.1%); Posterior Probability (ARD &lt; 0) = 0.64. The AR of MI was 1.4% (95% CrI=0.33-3.8%) and 1.5% (95% CrI=0.1-7.4%) for testosterone and clomiphene respectively (ARD = 1.3% (95% CrI = -0.36-3.73%); Posterior Probability (ARD &gt; 0) = 0.96. The AR of DVT was 0.37% (95% CrI = 0.01-1.99%) and &lt;0.00001% (95% CrI = &lt;0.00001-1.6%) for testosterone and clomid respectively (ARD = 0.30% (95% CrI = -1.24-1.92%); Posterior Probability (ARD &gt; 0) = 0.88.

Conclusions
The absolute risk of experiencing at least one of the events was found to be significantly higher in patients receiving testosterone compared to those receiving clomiphene. The results should be interpreted with caution, given the broad credible intervals due to its small size.

Disclosure
Any of the authors act as a consultant, employee or shareholder of an industry for: Consultant for AbbVie, Marius, Tolmar, Endo, Petros, Boston Scientific, Coloplast Investor: Sprout.