The eight clinical investigations incorporated in this systematic review were selected according to stringent methodological criteria. Inclusion criteria required: 1) randomized controlled trial (RCT) design; 2) enrollment of healthy adult male participants; 3) explicit documentation of male sexual health; 4) publication in peer-reviewed scientific journals.

Trials addressing different domains of male sexual dysfunction—including erectile dysfunction (ED), late-onset hypogonadism (LOH), and premature ejaculation (PE)—were included to capture the breadth of male sexual health conditions and their potential herbal interventions. This approach reflects the clinical reality that these conditions often co-occur and share overlapping pathophysiological mechanisms. The included studies evaluated diverse herbal interventions, encompassing Eurycoma longifolia (Tongkat Ali), Lepidium meyenii (Maca), Trigonella foenum-graecum (Fenugreek), and a topical multi-herb SS-cream formulation. Key design features, intervention dosages, sample characteristics, and study durations are summarized in Table 1 .

Search Strategy: Literature searches were conducted across major biomedical databases, including PubMed/MEDLINE and Google Scholar. Representative keywords included: “herbal therapy”, “male sexual health”, “testosterone”, “erectile dysfunction”, “randomized controlled trial”, and combinations thereof. Date ranges extended from database inception through 2023.

From each study, we extracted data on study design, participant characteristics, intervention protocols, outcome measures, and adverse events. Primary outcomes included serum testosterone levels (total and free), validated symptom scales such as the aging male symptoms (AMS) questionnaire, the International Index of Erectile Function (IIEF-15), and the Derogatis Interview for Sexual Functioning-Self Report (DISF-SR), as well as libido questionnaires and intravaginal ejaculatory latency time (IELT). Secondary outcomes encompassed quality of life measures, additional hormonal parameters, and safety profiles.

DB-RCT = Double-blind randomized controlled trial; TCM = Traditional Chinese Medicine; Tx = Treatment; mg/d = Milligrams per day; g/d = Grams per day; Ref = Reference. *SS-cream contains: Panax ginseng, Angelica gigas, Cistanche deserticola, Zanthoxylum piperitum, Torilis japonica, Asarum sieboldii, Syzygium aromaticum, Cinnamomum cassia, and Bufo gargarizans.

Two pivotal randomized controlled trials have evaluated Tongkat Ali for male sexual health [11] [12] . In the first trial, Leitão et al. conducted a 6-month, double-blind, placebo-controlled trial with a 2 × 2 factorial design in 45 men with androgen deficiency of aging males. Tongkat Ali supplementation of 200 mg/day significantly increased total testosterone, with the combination of Tongkat Ali and exercise producing the most pronounced effects, including greater improvements in sexual desire and a 15% rise in total testosterone after six months . Complementing these findings, Ismail et al. investigated PHYSTA, a standardized water extract of Tongkat Ali, in 109 healthy men aged 40 - 65 years over 12 weeks. Daily supplementation of 200 mg led to a 14% increase in libido scores, along with improvements in erectile function, quality-of-life measures, and fertility parameters, including a 44% increase in sperm motility and higher semen volume versus placebo. The extract was well tolerated, with adverse events comparable to placebo [11] .

Maca root has demonstrated consistent benefits across diverse populations. Gonzales et al. conducted a 12-week randomized controlled trial (RCT) in 57 healthy

↑ = Significant increase (p < 0.05); ↓ = Significant decrease (p < 0.05); Tx = Treatment; T = Testosterone; QoL = Quality of life; IIEF = International index of erectile function; ADAM = Androgen deficiency in the aging male; DISF-SR = Derogatis interview for sexual functioning-self report; IELT = Intravaginal ejaculatory latency time; Ref = Reference. ^When combined with exercise training. *SS-cream contains: Panax ginseng, Angelica gigas, Cistanche deserticola, Zanthoxylum piperitum, Torilis japonica, Asarum sieboldii, Syzygium aromaticum, Cinnamomum cassia, and Bufo gargarizans.

men, testing two daily doses of Maca (1.5 g and 3.0 g) against placebo. Sexual desire increased significantly from week 8 onward, with a 40% rise in the 1.5 g group and a 42% rise in the 3.0 g group at week 12. By contrast, serum testosterone remained unchanged, suggesting androgen-independent mechanisms [14] . Similarly, Stone et al. reported that trained cyclists receiving 2 g/day for 14 days exhibited enhanced physical performance alongside significant gains in sexual desire inventory scores [15] . More recently, Shin et al. evaluated 6 g/day of gelatinized Maca in 80 men with late-onset hypogonadism over 12 weeks, observing a 3.2-point increase in the International Index of Erectile Function (IIEF), a reduction in Androgen Deficiency in the Aging Male (ADAM) symptoms from 73% to 51%, and improvements in prostate symptom scores, again without altering testosterone levels [13] .

Fenugreek extracts have shown promising results across two studies. First, Steels et al. tested Testofen (600 mg/day) in 54 healthy men over 6 weeks, reporting significant improvements in sexual cognition, arousal, orgasm, libido, and overall well-being, despite no measurable changes in testosterone [16] . Building on this, Rao et al. evaluated Testofen in 111 healthy aging men for 12 weeks. The intervention significantly increased total testosterone (+12.7%) and free testosterone (+14.8%), while also reducing Aging Male Symptom scores, particularly in sexual and somatic domains. In addition, morning erection frequency and sexual activity levels improved compared to placebo [17] .

Choi et al. investigated SS-cream, a topical multi-herbal preparation containing nine traditional herbs such as Ginseng Radix Alba and Angelicae Gigantis Radix, in 106 men with lifelong premature ejaculation. In a double-blind, placebo-controlled parallel trial, the cream was applied 1 - 2 times per week, one hour before intercourse, and it extended intravaginal ejaculatory latency time from 1.37 minutes at baseline to 10.92 minutes after five effective treatments, which is an approximate eightfold increase. Notably, reported side effects were mild, localized, and transient, and overall tolerability was comparable to placebo [18] .

The therapeutic mechanisms proposed for these herbal interventions encompass multiple bioactive pathways, although many require direct experimental validation in future studies.

For Eurycoma longifolia, the therapeutic mechanisms are hypothesized to be mediated through multiple bioactive constituents with distinct but complementary modes of action. Eurypeptides (approximately 4.3 kDa) have been described as putative “phytoandrogens”, potentially facilitating enhanced testosterone biosynthesis in Leydig cells through direct steroidogenic stimulation . Additionally, eurycomanone, a principal quassinoid compound, may exhibit aromatase inhibitory activity, thereby reducing peripheral conversion of testosterone to estradiol . Phosphodiesterase (PDE)-linked mechanisms have been proposed in related phytochemicals (i.e., icariin) rather than demonstrated for eurycomanone within the included trials [25] . These proposed mechanisms suggest a therapeutic profile that combines direct steroidogenic support with enzyme-level modulation, providing complementary pathways for maintaining physiological testosterone concentrations and optimizing sexual function parameters [11] [12] . However, these intermediary mediators were not directly assayed in the included trials.

For Maca, proposed mechanisms appear to involve androgen-independent pathways. Current hypotheses suggest fatty acid amide hydrolase (FAAH) inhibition within the central nervous system and modulation of nitric oxide synthase (NOS) activity as potential mechanisms [13] [14] . FAAH inhibition could theoretically potentiate endocannabinoid signaling cascades relevant to mood, stress response, and sexual behavior, whereas NOS modulation suggests a potential vascular influence on smooth muscle tone and NO-dependent processes [13] [15] . However, these intermediates were not assayed in the included trials, and the precise molecular pathways mediating Maca’s effects on libido and sexual function remain incompletely characterized and require further investigation.

For fenugreek, the bioactivity is primarily attributed to steroidal saponins (notably furostanol glycosides), which are hypothesized to modulate androgen metabolism through specific enzymatic pathways. Specifically, partial inhibition of 5-α-reductase could theoretically attenuate the conversion of testosterone to dihydrotestosterone (DHT), whereas aromatase inhibition would limit peripheral conversion of testosterone to estradiol [17] . This dual enzymatic modulation would be expected to preserve circulating testosterone while enhancing androgen bioavailability. However, these enzymatic intermediates were not directly assayed in the included trials.

For SS-cream, the formulation is proposed to act through peripheral desensitization of penile sensory nerves, thereby raising the threshold for tactile stimulation and prolonging ejaculatory latency. Its polyherbal composition may provide bioactive compounds such as bufadienolides, bufosteroids, and eugenol, which could exert local anesthetic effects via sodium-channel blockade in sensory terminals [18] . This localized neural modulation would theoretically deliver therapeutic benefit while limiting systemic exposure. However, the clinical trial did not include mechanistic assays , and this mechanism should be viewed as explanatory context rather than direct evidence.

In aging men prioritizing androgen augmentation, fenugreek (Testofen) may be considered, given its observed increases in total and free testosterone and sexual activity measures [17] . Eurycoma longifolia can be deployed to address erectile function and sexual desire. Evidence from a factorial RCT suggests greater benefit when combined with structured exercise in men with ADAM [12] , whereas PHYSTA may be useful when hormone levels are within the normal range [11] . Maca offers an androgen-sparing option when the goal is to improve sexual desire or LOH symptoms without altering testosterone [13] - [15] . For subjects with lifelong premature ejaculation, topical SS-cream provides a non-systemic alternative with clinically meaningful gains in latency and local, transient adverse effects [18] ( Table 3 ). Clinicians should monitor clinical outcomes and routine laboratory parameters and should avoid extrapolating efficacy or safety beyond the studied durations.

Safety was generally favorable across intervention periods of 6 - 24 weeks. Reported adverse events were primarily mild and transient: 1) stomach discomfort with fenugreek when taken without food and occasional headache/dizziness in aging men [16] [17] ; 2) local burning (~15%) and other minor local reactions with SS-cream that resolved spontaneously [18] ; and 3) rare, mild gastrointestinal complaints with Maca, with hormonal profiles remaining stable [13] - [15] . In the Tongkat Ali trials, scattered mild symptoms occurred at rates comparable to placebo, and where assessed, laboratory parameters remained stable [11] [12] . No serious adverse events were attributed to any intervention.

Key limitations across the included trials encompass modest sample sizes, heterogeneity of herbal preparations and dosing regimens, short- to medium-term follow-up periods, and limited mechanistic assessment ( Table 1 ). Trial quality considerations, including these factors, influence the strength of evidence and require caution when interpreting clinical implications. The heterogeneity of outcome domains (erectile dysfunction, hypogonadism, premature ejaculation) reflects the breadth of male sexual dysfunction but limits direct comparisons across interventions. To address these gaps, future research should prioritize adequately powered, multi-center randomized controlled trials that employ standardized herbal extracts, adhere to Consolidated Standards of Reporting Trials (CONSORT) guidelines, and extend follow-up beyond 12 months to establish therapeutic durability and detect rare adverse events. Comparative-effectiveness study designs incorporating head-to-head comparisons with conventional therapies and dose-response or factorial methodologies should be prioritized.

Beyond study design, future studies should integrate prespecified mechanistic and pharmacokinetic endpoints, including comprehensive androgen panels, semen parameters, endothelial function, nitric-oxide pathway surrogates, and local absorption with sensory metrics for topical agents such as SS-cream. Moreover, investigations should evaluate combination herbal formulas with planned statistical interaction analyses. In addition, stratifying participants by baseline androgen status, age, body mass index (BMI), physical activity, and health status will facilitate the identification of optimal responder subgroups. Finally, to minimize nutritional confounding and address tolerability, protocols should standardize daily energy and nutrient intake.

In parallel, informed by emerging literature on mind-body interconnections and immune-neuroendocrine regulatory mechanisms [34] - [37] , pragmatic clinical studies may investigate adjunctive stress-reduction interventions, meditation practices, or structured movement therapies administered alongside herbal interventions. Such integrative research should be explicitly framed as hypothesis-generating to guide subsequent confirmatory trials.