Changes in Serum Testosterone After Sublingual Enclomiphene Citrate Combined With a Mineral Oxide Delivery System: A...

Background Declining testosterone levels in adult males represent a significant clinical burden. Conventional testosterone replacement therapy (TRT) with exogenous androgens suppresses the hypothalamic-pituitary-gonadal (HPG) axis, causes testicular atrophy, and impairs spermatogenesis, outcomes that are unacceptable for many patients. Enclomiphene citrate, a selective estrogen receptor modulator (SERM), stimulates endogenous gonadotropin release and has been studied as an alternative to exogenous TRT. Objective This study aims to describe 60-day changes in serum total testosterone in 15 adult men treated with a compounded sublingual formulation, TBooster 365 (Best 365 Labs, Salt Lake City, UT), containing enclomiphene citrate 25 mg, boron 10 mg, vitamin C 10 mg, spermidine 10 mg, and the MODS MAX mineral oxide delivery system per 1 mL dose. Methods This is a retrospective case series of 15 consecutive adult male patients with symptomatic hypogonadism, enrolled regardless of baseline total testosterone level, treated at a single private longevity medicine practice located at an elevation of 4,500 to 5,500 feet. All blood draws were fasting morning samples analyzed at reference laboratories by liquid chromatography tandem mass spectrometry (LC-MS/MS) or immunoassay. The primary outcome was the change in total serum testosterone at 60 days. Results All 15 patients demonstrated increased total testosterone at 60 days. Mean total testosterone increased from 347.0 ng/dL to 805.0 ng/dL (mean change: +458.0 ng/dL; 95% CI (326.3, 589.6); t(14) = 7.46; p < 0.0001 by paired t-test; Wilcoxon signed-rank W = 0, p = 0.0001). The paired-samples Cohen's dz was 1.93; the pooled-SD Cohen's d was 2.37. The mean body weight change across the cohort was -0.5 lb (range: -40 to +15 lb), with individual patients gaining, losing, or maintaining weight without a standardized diet or exercise protocol. Sensitivity analyses excluding the largest responder (Patient 4, who was also on concurrent GLP-1 receptor agonist therapy with substantial weight loss) and restricting to patients with a body weight change of 10 lb or less both preserved the primary finding (dz 2.35 and 2.31, respectively). No serious adverse events were documented during the 60-day period. Conclusion In this retrospective uncontrolled case series of 15 symptomatic men, a compounded sublingual protocol containing enclomiphene citrate, boron, vitamin C, spermidine, and MODS MAX was associated with increased total testosterone after 60 days. Because the study lacked a control group, standardized symptom assessment, luteinizing hormone (LH)/follicle-stimulating hormone (FSH) measurements, and long-term safety monitoring, causality, clinical efficacy, fertility preservation, HPG-axis effects, and the independent contribution of MODS MAX cannot be determined. Prospective controlled studies are needed.