Purpose: Male hypogonadism, characterized by decreased functionality of the testicles and evidenced by low testosterone levels, requires treatment strategies tailored to the specific type of hypogonadism. Primary hypogonadism, resulting from direct testicular impairment, is typically addressed with testosterone replacement therapy (TRT). In contrast, secondary hypogonadism, stemming from dysfunction in the hypothalamic-pituitary axis, often necessitates alternative treatments aimed at preserving fertility markers. These include Selective Estrogen Receptor Modulators (SERMs), Aromatase Inhibitors, and human chorionic gonadotropin (hCG). Although all treatment options can be effective, TRT uniquely offers dose-dependent benefits, which are not as achievable with alternatives due to their inability to bypass the body's natural testosterone production controls. However, the choice of TRT, particularly for individuals with secondary hypogonadism, involves a trade-off between maximizing treatment efficacy and preserving fertility markers. Our study addresses this dilemma by exploring a novel therapeutic approach, dubbed 'Oral TRT Plus,' which combines two oral medications: oral native testosterone and enclomiphene citrate. This approach aims to provide the dose-dependent benefits of exogenous testosterone while also preserving fertility markers.Materials and Methods: 79 male patients, encompassing both hypogonadal and eugonadal men, participated in a sequence of four distinct experiments. These experiments were designed to determine the ideal dosing, assess the necessity of fat intake for enhanced drug absorption, and identify the most effective timing for blood tests to capture peak testosterone levels. Measurements of various blood markers, including total testosterone, free testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol (E2), and sex hormone-binding globulin (SHBG), were obtained using both at-home lab testing kits and in-person venipuncture. In addition, participants completed subjective questionnaires—the quantitative Androgen Deficiency in the Aging Male (qADAM) and the Patient Health Questionnaire-4 (PHQ-4)—to evaluate subjective improvements in hypogonadal symptoms during the treatment.Results: With optimized dosing, total testosterone levels in both eugonadal and hypogonadal men increased fourfold and free testosterone fivefold (both p < 0.025), surpassing the 99th percentile for both measurements in all participants. Meanwhile, LH and FSH levels remained within normal ranges across all participants (p < 0.025), demonstrating the treatment's ability to preserve fertility markers irrespective of the increased testosterone dosing. Estrogen levels significantly decreased but stayed within normal limits. Subjective health measures improved notably; over 70% of participants reported enhanced energy, strength/endurance, improved work performance, and quality of life according to qADAM scores, with significant reductions in anxiety and depression symptoms evidenced by 97% of participants reporting normal function (both p<0.001). Conclusions: Both eugonadal and hypogonadal men utilizing the “Oral TRT Plus Protocol” demonstrated a fivefold increase in free testosterone levels on average, while simultaneously mitigating endogenous suppression and preserving fertility markers. This protocol elicited significant improvements across various subjective health metrics, including quality of life, energy, strength, mood, libido, and work performance, alongside a marked decrease in anxiety and depression symptoms. Furthermore, the protocol effectively regulated estrogen levels within normal physiological ranges, eliminating the necessity for adjunctive medications. The “Oral TRT Plus Protocol” aligns with the evolving landscape of telemedicine by demonstrating how advanced hormonal treatment regimens can be effectively administered and monitored remotely, offering an innovative, non-invasive strategy for enhancing men's mental, physical, and hormonal health while preserving fertility markers.