Overall, 9 out of 32 studies demonstrated significant increases in testosterone concentrations. There were no statistically-significant increases in testosterone concentrations after 12 wk of supplementation in any of the trials. Three studies were randomized controlled trials (39, 48, 54) and 1 study was a randomized, double-blind, placebo-controlled trial (61). However, conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics.FT or BT (the combination of FT and albumin-bound, “weakly-bound” testosterone) have been suggested as more effective measures for diagnosing AD, particularly as men age (32).A recent narrative review by Clemesha et al. (28) concluded that many supplements claiming “testosterone-boosting” properties, including formulations using herbs, spices, plants, or their extracts, do not appear to be supported by scientific evidence.Three randomized, double-blind, placebo-controlled studies (41, 52, 66) examined the effects of maca on testosterone concentrations.Two studies out of 32 included both male and female participants (2488 participants in total; 2446 males and 42 females). Assessment of studies’ risk of bias A total of 512 male participants were recruited for the studies involving Asian ginseng, with ages ranging from 18 to 79 y and samples sizes ranging from 8 to 143 participants.In an acute study (2 h) conducted in 8 men with a mean age of 21.3 ± 0.7 y, supplementation of 20 g of Korean red ginseng root extract did not increase testosterone concentrations (65), while in 30 healthy, endurance-trained men, aged between 18 and 40 y, Panax ginseng (an ethanolic liquid extract equivalent to 2 g of dried root, daily) did not increase testosterone concentrations after 6 wk of supplementation (38).Two studies used patented extracts, Trib Gold, manufactured by Nerhadou International, standardized to contain up to 45% steroidal saponins (extract source not provided) (39), and Tribestan, manufactured by Sopharma, delivering a minimum of 675 mg furostanol saponins (from overground parts of the herb) (48).The researchers examined testosterone concentrations in 60 stressed, healthy men and women with a mean age of 41 y.One randomized, double-blind, placebo-controlled study was conducted examining the effects of a forskohlii root extract, manufactured to contain a forskolin concentration of 10% (Forslean) daily (extraction process not provided) on testosterone concentrations (40).Three studies used the Testofen® extract, manufactured by GencorTM (also known as Fenu-FG) (details of extract preparation not provided) (57, 58, 63) and the other 3 studies used the extracts IND9, manufactured by Indus Biotech® (53), Furosap®, manufactured by Chemical Resources (CHERESO) (42), and an extract standardized for Grecunin, manufactured by Indus Biotech® (64) (details of all extract preparations not provided).The reference lists of relevant papers were also examined to locate additional studies that were not identified by the initial database search.Another potential mechanism through which herbs may increase testosterone concentrations in males is by ameliorating cortisol production.In this systematic review, many studies were underpowered, making it difficult to obtain statistically significant, between-group differences.For example, saffron has demonstrated antidepressant and anxiolytic effects (23), curcumin appears to offer pain relief for sufferers of arthritis (24), and cinnamon may support blood-sugar regulation in type 2 diabetics (25). Conversely, the study by Rath and Panja (59) was judged to have a high risk of bias since it had some concerns arising from its randomization process (domain 1) and a high risk of bias for its measurement of the outcome (domain 4) and selection of the reported result (domain 5). Six studies (50, 52, 55, 56, 61, 63) out of 32 were judged to have a low risk of bias due to their strong methodological designs. The risk-of-bias assessment (Supplemental Tables 1 and 2) revealed some concerns for most of the included studies. There was no statistically-significant difference in SHBG concentrations between the 2 groups (58). Study durations were from 2 h up to 6 mo, with 2 studies having durations of 2 h and 10 h, respectively, and the remaining studies having durations from 4 wk to 6 mo. Conclusively, testosterone is an essential hormone that is involved in many physiological processes throughout men's lives; in addition to controlling libido, testosterone is closely linked to bone density, muscle growth, and repair; its influence on mental health, especially in reducing symptoms of depression, emphasizes its complex nature. The enzyme aromatase in men can aromatize testosterone into estrogen, which affects a variety of physiological processes, such as bone health and reproductive capabilities; the average testosterone level in healthy men is between 264 and 916 ng/dL . These advantages include better vascular function, mood, muscle strength, bone density, and sexual health in healthy men. Overall, 9 out of 32 studies demonstrated statistically significant increases in testosterone concentrations.Fenugreek seed extracts (positive findings in 4 out of 6 studies) and ashwagandha root and root/leaf extracts (positive findings in 3 out of 4 studies) demonstrated the most consistent increases in testosterone concentrations.Twelve weeks of daily supplementation with 1.0 g of a musali extract in 40 healthy men, aged between 20 and 40 y, did not significantly increase testosterone concentrations compared with the placebo group.The research paper provides a thorough summary of the selection criteria and covers testosterone's effects on depression, vascular endothelium, muscle strength, bone health, and sexual function (Figure 1).Asian ginseng also had 1 study demonstrating its efficacy in increasing testosterone (extract details not provided), but there were 6 studies demonstrating no effect.The dosages used in the included studies varied widely, making an evaluation of safety and efficacy difficult.Regarding mental health, testosterone may help certain people with their depression symptoms; this is especially important for patients with hypogonadism, such as elderly people, for whom testosterone replacement therapy may be quite beneficial .There were no statistically-significant increases in testosterone concentrations after 12 wk of supplementation in any of the trials. Eight weeks of daily supplementation with 2.4 g of a cordyceps extract in 16 healthy men aged between 19 and 25 y did not significantly increase testosterone concentrations compared with the placebo group. One randomized, double-blind, placebo-controlled study was conducted examining the effects of a longjack extract (Physta®, manufactured by Biotropics; freeze-dried water extract) on testosterone concentrations (45). One randomized, double-blind, placebo-controlled study was conducted examining the effects of reishi extract (dried and chipped with 30% ethanol) on testosterone concentrations (55). One randomized, double-blind, placebo-controlled study was conducted examining the effects of a garcinia extract (standardized to contain 60% hydroxycitric acid; details of extraction process not provided) on testosterone concentrations (43). Twelve weeks of daily supplementation with 1.0 g of a musali extract in 40 healthy men, aged between 20 and 40 y, did not significantly increase testosterone concentrations compared with the placebo group. The final study using Asian ginseng was conducted in 80 infertile men, aged between 25 and 45 y (56). The initial search identified 4384 unique studies, of which 32 randomized controlled trials were identified as eligible following assessment using the selection criteria (Figure 1) (35–66). From the age of 30 onwards, testosterone concentrations in men tend to decline at the rate of ∼1% per year (1–6). Also, some evidence exists for another herb and herbal extract, Asian red ginseng and forskohlii root extract. Currently, there are various approaches to treating patients with testosterone insufficiency, including the use of testosterone pellets and formulations combined with aromatase inhibitors, which need more studies for a better understanding of their effects . The main findings of this review indicate that some herbs, particularly fenugreek seed extracts and ashwagandha extracts, have positive effects on testosterone concentrations in men.Additionally, all studies examining the effect of maca on testosterone concentrations have previously been reviewed by Gonzales et al. (70) and were determined to not affect serum concentrations of testosterone.Summary of randomized controlled trials examining the effects of herbs on testosterone concentrations in men1Finally, matching treatment based on presentation may also clarify populations in whom herbal supplementation may be most beneficial.Further research will better define the function of testosterone in both healthy and deficient men, which will eventually result in more accurate and successful treatment plans.Seven studies were eventually included in the systematic review (Table 1), and all of them showed beneficial impacts on a range of health outcomes, including depression, vascular endothelial function, muscle strength, bone health, and sexual function.Three of the 4 studies demonstrated positive effects of ashwagandha supplementation on testosterone concentrations in men (35, 50, 62), while 1 study (51) showed no effect of supplementation (Table 1). Based on the predetermined criteria, publications that evaluated the effects of testosterone using descriptive, observational, or experimental designs involving human subjects were included. Additionally, testosterone supports endothelial function by increasing nitric oxide production, encouraging endothelial cell growth and repair, and lowering inflammation; it also has a significant impact on the vascular endothelium, the thin layer of cells lining blood vessels, which is essential for preserving cardiovascular health . In men with hypogonadism, including elderly individuals, testosterone replacement therapy may offer antidepressant effects, providing therapeutic benefits for those with testosterone deficiency . It has been demonstrated that testosterone replacement treatment (TRT) improves muscle mass, strength, and physical function in hypogonadal men, while research indicates that men with low testosterone levels have decreased muscle mass and strength . Because it promotes protein synthesis and muscle hypertrophy through androgen receptor binding in muscle cells, testosterone is a critical regulator of muscle mass; this anabolic impact is required for muscle development and repair, making testosterone crucial for preserving muscle mass . For example, reasons for 2 of the 6 fenugreek seed extract studies and 1 of the 4 ashwagandha root/leaf studies not achieving significant differences between groups were not discussed. If future, robustly-designed studies demonstrate consistent positive effects of some of these herbs on testosterone production, further research will also be required to elucidate their potential mechanisms of action. Moreover, fenugreek seed extracts also demonstrated a positive effect on BT concentrations. Additionally, it aims to clarify the effects of testosterone dysregulation on men's mental and physical wellness while advancing clinical procedures and treatment approaches. Specifically, when testosterone levels rise, the body reduces the production of its primary source, while a decline in testosterone levels prompts an increase in its production; this intricate feedback loop plays a critical role in maintaining hormonal balance and is essential for understanding the regulatory mechanisms governing testosterone in men . Testosterone, a steroid hormone predominantly synthesized in the testes, is integral to a wide range of physiological processes that are crucial to male health; the regulation of testosterone levels operates through a feedback mechanism that is essential for understanding its physiological control. In addition, many of the studies included in this review have design flaws that adversely affect the strength of conclusions derived from this systematic review. Only 6 out of 32 studies were assessed as having a low risk of bias due to their strong methodological study designs. In this systematic review, many studies were underpowered, making it difficult to obtain statistically significant, between-group differences. The goal of this study is to learn more about the critical and varied roles that testosterone plays in healthy men's physiological functioning. However, conclusions are moderated by the paucity of research for many herbs, the variation in dosages and extracts used, small sample sizes, and the heterogeneity of study characteristics. Moreover, how quickly herbs influence testosterone concentrations in men needs to be elucidated. The paucity of high-quality studies investigating the effects of herbs on testosterone production in men means further research is required. One randomized, double-blind, placebo-controlled study was conducted examining the effects of reishi extract (dried and chipped with 30% ethanol) on testosterone concentrations (55).However, the review of Clemesha et al. (28) had several limitations such as using only a single search term, “testosterone booster,” using only Google to search for existing research, and examining only the top 50 supplements.Additionally, it aims to clarify the effects of testosterone dysregulation on men's mental and physical wellness while advancing clinical procedures and treatment approaches.Specifically, when testosterone levels rise, the body reduces the production of its primary source, while a decline in testosterone levels prompts an increase in its production; this intricate feedback loop plays a critical role in maintaining hormonal balance and is essential for understanding the regulatory mechanisms governing testosterone in men .The aim of this systematic review was to summarize and critically evaluate randomized controlled trials published on the efficacy of single herbal ingredients on testosterone concentrations, in addition to its fractions or binding proteins, in men (≥18 y).It is significant to emphasize that since this study reviews already published studies pertaining to patient data, ethical approval is not necessary.The paucity of high-quality studies investigating the effects of herbs on testosterone production in men means further research is required.One randomized, double-blind, placebo-controlled study was conducted examining the effects of a musali root extract (water extract of dried root tubers) on testosterone concentrations (59).In addition, given the existing controversy regarding the relative importance of “bound” and “unbound” testosterone (34), data for testosterone fractions and binding proteins were extracted and presented in the current review to increase the scope of findings.The Leydig cells of the testes are the main source of testosterone in men; although testosterone is frequently regarded as a male hormone, it is essential for many physiological processes outside of sexual differentiation, including maintaining muscle mass, bone density, mood regulation, and metabolic processes . For example, in an animal study, Asian ginseng reduced the activity of 5α-reductase, the enzyme responsible for the conversion of testosterone into dihydrotestosterone (DHT) (80). Moreover, in animal studies, the administration of 4-hydroxyisoleucine, an extract from fenugreek seeds, lowered serum cortisol concentrations (77). Since cortisol, the body's major stress hormone, is inversely correlated with testosterone concentrations (85), reducing its production may elevate testosterone concentrations. One randomized, double-blind, placebo-controlled study was conducted examining the effects of a rhodiola extract (standardized to 3% rosavins) on testosterone concentrations (46). One randomized, double-blind, placebo-controlled study was conducted examining the effects of cordyceps (manufactured by a submerged culture technique with the mycelia spray-dried to obtain a powder) on testosterone concentrations (44). This systematic review includes randomized controlled trials examining the effects of herbs, spices, plants, and their extracts on testosterone concentrations in men. Moreover, 8 wk of supplementation with an ashwagandha root extract resulted in a significant increase in both muscle strength and testosterone concentrations (62). For example, studies in this review, such as Guo et al. (42), identified a significant increase in lean body mass in addition to a significant increase in testosterone concentrations from 12 wk of supplementation with a fenugreek seed extract. The objective of this systematic review is to critically analyze the various functions of testosterone, including its physiological importance, regulatory processes, and possible repercussions if it is dysregulated in men. Considering the prospective benefits of testosterone therapy, more investigation and clinical testing are necessary to completely comprehend its effects and improve therapeutic modalities. Beyond these physical advantages, testosterone plays a crucial role in male reproductive health by affecting spermatogenesis (the generation of sperm), libido, and erectile function. The development and maintenance of muscular mass, bone density, and general physical strength depend heavily on testosterone, a hormone that plays a complicated and significant role in men's physiology. The authors thank Colin Smith for reviewing and editing the final copy of the manuscript. Tribulus terrestris (tribulus) Two studies used gelatinized maca (41, 52) and 1 study used a dried maca extract (66). A total of 301 participants were recruited for the studies involving Tribulus terrestris, with ages ranging from 18 to 65 y and sample sizes ranging from 21 to 180 participants. Two studies used patented extracts, Trib Gold, manufactured by Nerhadou International, standardized to contain up to 45% steroidal saponins (extract source not provided) (39), and Tribestan, manufactured by Sopharma, delivering a minimum of 675 mg furostanol saponins (from overground parts of the herb) (48). Two of the studies demonstrating positive effects recruited men with no known clinical conditions (50, 62). Associated Data Conclusively, testosterone is an essential hormone that is involved in many physiological processes throughout men's lives; in addition to controlling libido, testosterone is closely linked to bone density, muscle growth, and repair; its influence on mental health, especially in reducing symptoms of depression, emphasizes its complex nature.It has an effect on many body systems, underscoring its importance for men's physical health and fertility.The remaining studies (25/32) were judged as having some concerns for their risk of bias due to potential biases arising from the randomization process (domain 1) (35–49, 51, 53, 54, 57, 58, 60, 62, 64–66), with Gaffney et al. (38) also being judged as having some concerns for its risk of bias due to missing outcome data (domain 3).A total of 301 participants were recruited for the studies involving Tribulus terrestris, with ages ranging from 18 to 65 y and sample sizes ranging from 21 to 180 participants.Moreover, several studies did not provide specific details of extracts as recommended by the National Center for Complementary and Integrative Health (88), making duplication of those studies difficult. Two studies out of 32 included both male and female participants (2488 participants in total; 2446 males and 42 females). Risk of bias of the included studies was assessed using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials (30). “Herbs, spices, plants, or their extracts” will henceforth be referred to as “herbs.” However, the review of Clemesha et al. (28) had several limitations such as using only a single search term, “testosterone booster,” using only Google to search for existing research, and examining only the top 50 supplements. Therefore, the use of alternative options, such as herbs, spices, plants, or their extracts, has been explored as a potential treatment option for AD. A higher level of evidence would be provided by a well-conducted RCT, improving the consistency and dependability of the results and providing a more thorough knowledge of the effects seen across studies, so we could find more evidence in the future. It is significant to emphasize that since this study reviews already published studies pertaining to patient data, ethical approval is not necessary. The likelihood of sarcopenia (age-related muscle loss) and diminished muscle strength rises as testosterone levels naturally fall with age; however, research indicates that testosterone therapy may mitigate these effects in older men, enhancing physical performance, sexual drive, and muscle mass . The Leydig cells of the testes are the main source of testosterone in men; although testosterone is frequently regarded as a male hormone, it is essential for many physiological processes outside of sexual differentiation, including maintaining muscle mass, bone density, mood regulation, and metabolic processes . The 2 studies that showed no effect of fenugreek supplementation on TT concentrations (57, 63) recruited healthy men, with participants in the Rao and Grant (57) study including men with benign prostate hyperplasia (BPH). Six studies (42, 53, 57, 58, 63, 64) were conducted examining the effects of fenugreek seed extracts on testosterone concentrations. The main findings of this review indicate that 2 herbal extracts, fenugreek seed extracts and ashwagandha root and root/leaf extracts, have positive effects on testosterone concentrations in men. This systematic review provides some evidence that certain herbs and herbal extracts increase testosterone concentrations in men. However, this review identified 1 study having significant positive effects on testosterone concentrations with acute use (10 h, fenugreek seed extract) (53). Following the recommendations outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we conducted a literature search . Libido, or sexual desire, is significantly influenced by testosterone, which regulates various brain regions involved in sexual motivation, including the hypothalamus; in men, testosterone plays a crucial role in sexual desire and arousal . DHT has a stronger androgenic effect and is essential for the maintenance of prostate health and the development of secondary sexual traits in men . The hypothalamic-pituitary-gonadal (HPG) axis, a crucial part of the endocrine system, controls the production of testosterone. Impact of Testosterone on Male Health: A Systematic Review These included TT, (calculated) free testosterone (FT), measurement of FT, bioavailable testosterone (BT), and sex hormone–binding globulin (SHBG). Testosterone, its fractions, and binding proteins were all examined in this systematic review. Each study was scored based upon its risk of bias being low, with some concerns, or high for each criterion. The reference lists of relevant papers were also examined to locate additional studies that were not identified by the initial database search. Essential for bone maturation, testosterone helps bones reach maximal mass and preserves bone density, all during adulthood; it also promotes skeletal growth by improving mechanical loading . The increase in sex steroid production during puberty speeds up bone mineral accumulation and causes sex-specific variations in bone growth; after mid-puberty, the male population experiences a greater increase in periosteal bone growth than the female population, who shows more pronounced endocortical bone formation . As a primary hormone influencing bone metabolism, testosterone directly affects osteoclasts, osteoblasts, and osteocytes, promoting periosteal bone formation during puberty and decreasing bone resorption during adulthood; testosterone is also strongly correlated with bone density; lower testosterone levels result in decreased bone density . The production of testosterone in men is primarily controlled by negative feedback mechanisms, whereby high levels of testosterone prevent the release of GnRH from the hypothalamus and LH from the pituitary, thereby limiting further testosterone synthesis; testosterone is made from cholesterol by a variety of enzymatic pathways in the testes . Examining the Effects of Herbs on Testosterone Concentrations in Men: A Systematic Review Seven studies were eventually included in the systematic review (Table 1), and all of them showed beneficial impacts on a range of health outcomes, including depression, vascular endothelial function, muscle strength, bone health, and sexual function. The research paper provides a thorough summary of the selection criteria and covers testosterone's effects on depression, vascular endothelium, muscle strength, bone health, and sexual function (Figure 1). In addition to having significant effects on health and illness, these hormonal changes are necessary for preserving physiological balance; one particularly significant time of hormonal change is during puberty, when a rise in sex hormones, such as testosterone, promotes the growth of secondary sexual traits like increased muscle mass, body and facial hair, and a deeper voice . Descriptive, observational, and experimental studies including healthy men-more especially, those assessing the effects of testosterone therapy-were required for inclusion. In men, testosterone is primarily synthesized in the testes and the adrenal gland, with smaller amounts produced in the ovaries and adrenal glands in women . The synthesis and regulation of testosterone, a vital steroid hormone, are highly complicated procedures that involve intricate interactions among multiple endocrine glands, including the hypothalamus, pituitary gland, and gonads, as well as feedback mechanisms that maintain homeostasis within the body. Dysregulation of this feedback mechanism can lead to a variety of pathophysiological conditions, particularly testosterone deficiency; such disruptions may occur due to aging, disease processes, or lifestyle factors, underscoring the importance of accurate diagnosis and appropriate therapeutic interventions . An outline of the major hormonal changes that take place in men throughout their lives is given in this introduction, with special attention to testosterone's crucial role in controlling a wide range of physiological processes. This means that testosterone may have a greater physiological effect in the body when concentrations of these biomarkers are elevated. Three out of 4 studies also demonstrated positive effects on (calculated) FT (53, 58, 63), and the 2 fenugreek studies that included BT as an outcome measure demonstrated positive effects (53, 64). All herbal extracts were well tolerated, and the incidence of adverse events was low. Fenugreek seed extracts (positive findings in 4 out of 6 studies) and ashwagandha root and root/leaf extracts (positive findings in 3 out of 4 studies) demonstrated the most consistent increases in testosterone concentrations. Three randomized, double-blind, placebo-controlled studies (41, 52, 66) examined the effects of maca on testosterone concentrations. Daily supplementation with 800 mg of a tribulus extract for 30 d did not increase testosterone concentrations, while in the Neychev and Mitev study (54) in 21 participants aged 20 to 36 y, a tribulus extract at 2 doses, 10 mg ⸱ kg−1 ⸱ d−1 (3 divided doses) or 20 mg ⸱ kg−1 ⸱ d−1 (3 divided doses), did not increase testosterone concentrations after 4 wk of supplementation. In support of the findings of this review, a recent meta-analysis of clinical trials on fenugreek seed extract supplementation reported a significant increase in testosterone concentrations (68). The main findings of this review indicate that some herbs, particularly fenugreek seed extracts and ashwagandha extracts, have positive effects on testosterone concentrations in men. Twelve weeks of daily supplementation with 1667 mg of garcinia, equivalent to 1000 mg of hydroxycitric acid, in 25 overweight or obese men aged between 20 and 65 y did not significantly increase testosterone concentrations compared with men in the placebo group. The dosages used in the included studies varied widely, making an evaluation of safety and efficacy difficult. Similarly, in vitro studies demonstrated reishi's ability to inhibit the activity of 5α-reductase (79, 86, 87). For example, inflammation and oxidative stress have an inverse relationship with testosterone, as demonstrated by several human and animal trials (9, 81–83). The remaining studies (25/32) were judged as having some concerns for their risk of bias due to potential biases arising from the randomization process (domain 1) (35–49, 51, 53, 54, 57, 58, 60, 62, 64–66), with Gaffney et al. (38) also being judged as having some concerns for its risk of bias due to missing outcome data (domain 3). Despite a lack of robust support for herbal supplementation increasing testosterone concentrations in men, there are potential mechanisms of action. This outcome was similar to that of an 8-wk study in 143 men (33–79 y) with erectile dysfunction, using a slightly higher dose (2 g/d) of tissue-cultured mountain (Asian) ginseng (root) extract (49), as well as another study using a longer intervention (12 wk, 3 g/d, Korean red ginseng; details of extract preparation not provided) in 60 men (26–70 y) with mild-to-moderate erectile dysfunction (37). A total of 512 male participants were recruited for the studies involving Asian ginseng, with ages ranging from 18 to 79 y and samples sizes ranging from 8 to 143 participants. A recent narrative review by Clemesha et al. (28) concluded that many supplements claiming “testosterone-boosting” properties, including formulations using herbs, spices, plants, or their extracts, do not appear to be supported by scientific evidence. Given the increasing body of research on herbal supplementation to support natural hormone production, it presents as a potential treatment option for AD. For example, saffron has demonstrated antidepressant and anxiolytic effects (23), curcumin appears to offer pain relief for sufferers of arthritis (24), and cinnamon may support blood-sugar regulation in type 2 diabetics (25). Plants and plant-based products, including herbs and spices, have been used for millennia to improve the flavor of food as well as to treat disease and improve overall health and well-being (22). The final study using Asian ginseng was conducted in 80 infertile men, aged between 25 and 45 y (56).A total of 197 male participants were recruited for the studies, with ages ranging from 18 to 70 y and sample sizes ranging from 46 to 60 participants.The paucity of high-quality randomized controlled trials examining the effects of herbs on testosterone concentrations in men, along with the heterogeneous cohorts assessed in these trials, precludes definitive conclusions being made.Moreover, by encouraging the synthesis of nitric oxide, aiding in the development and repair of endothelial cells, and lowering inflammation, testosterone improves endothelial function, which is essential for preserving vascular health and underscoring testosterone's complex role in general physiological well-being .The objective of this systematic review is to critically analyze the various functions of testosterone, including its physiological importance, regulatory processes, and possible repercussions if it is dysregulated in men.This systematic review includes randomized controlled trials examining the effects of herbs, spices, plants, and their extracts on testosterone concentrations in men.Therefore, the aim of this systematic review was to summarize and critically evaluate randomized controlled trials conducted to assess the efficacy of single herbal ingredients on testosterone concentrations, in addition to their fractions or binding proteins, in men.The production of testosterone in men is primarily controlled by negative feedback mechanisms, whereby high levels of testosterone prevent the release of GnRH from the hypothalamus and LH from the pituitary, thereby limiting further testosterone synthesis; testosterone is made from cholesterol by a variety of enzymatic pathways in the testes . Moreover, several studies did not provide specific details of extracts as recommended by the National Center for Complementary and Integrative Health (88), making duplication of those studies difficult. Also, the studies on fenugreek used 4 different extracts, with dosages ranging from 250 mg/d up to 600 mg/d. The heterogeneity of herbal extracts, various dosages used, and differences in sample types (serum, plasma, and saliva samples) make comparing studies and conducting a meta-analysis difficult. A key component of human physiology is hormonal regulation, which intricately regulates a wide range of biological processes and maintains homeostasis across multiple systems; from the many hormones that regulate bodily functions, testosterone stands out for its significant and complex effects on male health . Further research will better define the function of testosterone in both healthy and deficient men, which will eventually result in more accurate and successful treatment plans. Small sample sizes and a dearth of studies, however, limit these findings, highlighting the need for more investigation to completely comprehend the wider impacts of testosterone on men's health. Testosterone supplements can have a good impact on a number of important aspects of men's health, such as vascular endothelial function, mood (particularly in lowering depression), muscle strength, bone health, and sexual function. Examining the safety and efficacy of an herb in different populations, such as healthy, aging men; men with comorbid medical conditions such as metabolic syndrome, obesity, or diabetes; men engaging in regular exercise; and in men taking concurrent medications, will also help to determine the most suitable groups to target for its use. Sample sizes ranged from 7 to 620 and ages of the male participants ranged from 18 to 79 y. FT or BT (the combination of FT and albumin-bound, “weakly-bound” testosterone) have been suggested as more effective measures for diagnosing AD, particularly as men age (32). The inclusion of the testosterone fractions and binding proteins were deemed important since only ∼2% is “free” testosterone, with the remaining testosterone “bound” to proteins (predominantly SHBG, ∼40–45%) (31–33) and controversy existing regarding the relative importance of “bound” and “unbound” testosterone (34). Examining the safety and efficacy of an herb in different populations, such as healthy, aging men; men with comorbid medical conditions such as metabolic syndrome, obesity, or diabetes; men engaging in regular exercise; and in men taking concurrent medications, will also help to determine the most suitable groups to target for its use.Despite a lack of robust support for herbal supplementation increasing testosterone concentrations in men, there are potential mechanisms of action.Testosterone replacement therapy (TRT), on the other hand, was found to significantly increase survival rates of hypogonadal men (15, 16).Two of the studies demonstrating positive effects recruited men with no known clinical conditions (50, 62).Moreover, how quickly herbs influence testosterone concentrations in men needs to be elucidated.One randomized, double-blind, placebo-controlled study was conducted examining the effects of cordyceps (manufactured by a submerged culture technique with the mycelia spray-dried to obtain a powder) on testosterone concentrations (44).However, this review identified 1 study having significant positive effects on testosterone concentrations with acute use (10 h, fenugreek seed extract) (53). Summary of randomized controlled trials examining the effects of herbs on testosterone concentrations in men1 The aim of this systematic review was to summarize and critically evaluate randomized controlled trials published on the efficacy of single herbal ingredients on testosterone concentrations, in addition to its fractions or binding proteins, in men (≥18 y). Asian ginseng also has antioxidant properties, which reduce lipid peroxidation and increase glutathione peroxidase concentrations (74), and it is noteworthy that the only study demonstrating benefits of Asian ginseng recruited individuals with metabolic syndrome (47). Additionally, all studies examining the effect of maca on testosterone concentrations have previously been reviewed by Gonzales et al. (70) and were determined to not affect serum concentrations of testosterone. Asian ginseng also had 1 study demonstrating its efficacy in increasing testosterone (extract details not provided), but there were 6 studies demonstrating no effect. Currently, the primary treatment for AD is testosterone replacement therapy (TRT), which may exacerbate pre-existing medical conditions. Adverse effects of 24 hours of sleep deprivation on cognition and stress hormones. By identifying limitations in existing studies and suggesting directions for future investigations, we hope to encourage the research community to pursue more robust and methodologically sound studies that will further strengthen the evidence base. It is also critical to comprehend how the Free Androgen Index (FAI), which is connected with bone density, is used; a low FAI indicates a higher likelihood of bone density loss . The selection, screening, and assessment of the chosen studies were assisted by the remaining authors, AR and AFR. Participants supplemented with 2.4 g of maca (pulverized, dehydrated maca root) daily did not increase testosterone concentrations compared with the placebo group. Three of the 4 studies demonstrated positive effects of ashwagandha supplementation on testosterone concentrations in men (35, 50, 62), while 1 study (51) showed no effect of supplementation (Table 1). Seven studies were conducted examining the effects of Asian ginseng on testosterone concentrations (36–38, 47, 49, 56, 65). Therefore, the aim of this systematic review was to summarize and critically evaluate randomized controlled trials conducted to assess the efficacy of single herbal ingredients on testosterone concentrations, in addition to their fractions or binding proteins, in men. Study characteristics Additionally, testosterone plays a vital role in vascular health by improving endothelial function, which is crucial for maintaining cardiovascular health in men. Moreover, by encouraging the synthesis of nitric oxide, aiding in the development and repair of endothelial cells, and lowering inflammation, testosterone improves endothelial function, which is essential for preserving vascular health and underscoring testosterone's complex role in general physiological well-being . Regarding mental health, testosterone may help certain people with their depression symptoms; this is especially important for patients with hypogonadism, such as elderly people, for whom testosterone replacement therapy may be quite beneficial . In an acute study (2 h) conducted in 8 men with a mean age of 21.3 ± 0.7 y, supplementation of 20 g of Korean red ginseng root extract did not increase testosterone concentrations (65), while in 30 healthy, endurance-trained men, aged between 18 and 40 y, Panax ginseng (an ethanolic liquid extract equivalent to 2 g of dried root, daily) did not increase testosterone concentrations after 6 wk of supplementation (38). One randomized, double-blind, placebo-controlled study was conducted examining the effects of a forskohlii root extract, manufactured to contain a forskolin concentration of 10% (Forslean) daily (extraction process not provided) on testosterone concentrations (40). One randomized, double-blind, placebo-controlled, partial-crossover study was conducted examining the effects of a stinging nettle root extract (synthesized from the roots via a fractional percolation process and standardization) on testosterone concentrations (60). One randomized, double-blind, placebo-controlled study was conducted examining the effects of a musali root extract (water extract of dried root tubers) on testosterone concentrations (59). The 1 study that showed no effect of an ashwagandha extract, Shoden®, on testosterone concentrations in men was conducted by Lopresti et al. (51). Four studies were conducted examining the effects of ashwagandha on testosterone concentrations (35, 50, 51, 62). Four of the 6 studies demonstrated increased testosterone concentrations with fenugreek supplementation (42, 53, 58, 64), while 2 studies (57, 63) showed no effect of supplementation (Table 1). Only 1 study demonstrated positive effects of Asian ginseng supplementation on testosterone (47), while 6 studies showed no effect of supplementation (Table 1). In addition to identifying the effects of herbal supplementation during use, it will be useful to determine the duration of effects once supplementation ceases. Moreover, there was significant variability in the herbal extracts used, which may impact safety and potency. For example, the studies on ashwagandha used dosages ranging from 240 to 675 mg/d, with varying standardization and extraction processes and different sample types. A strength of this systematic review is the inclusion of only randomized controlled trials investigating the effect of a single herb on testosterone concentrations in men. In this review, Asian ginseng only had 1 study out of 7 demonstrating a positive effect on testosterone concentrations in men; however, its administration reduced cortisol concentrations in adults experiencing high work stress (78). This meta-analysis included 4 studies (42, 58, 63, 64) but did not include 2 of the studies included in this review because it was conducted in late 2018 and excluded studies with a duration 69) conducted a systematic review on all tribulus studies examining various forms of testosterone in animals and humans and concluded that the evidence indicated that it is ineffective at increasing testosterone concentrations in humans. The paucity of high-quality randomized controlled trials examining the effects of herbs on testosterone concentrations in men, along with the heterogeneous cohorts assessed in these trials, precludes definitive conclusions being made. A total of 197 male participants were recruited for the studies, with ages ranging from 18 to 70 y and sample sizes ranging from 46 to 60 participants. A total of 366 male participants were recruited for the studies, with ages ranging from 18 to 72 y and samples sizes ranging from 16 to 120 participants. Three studies used the Testofen® extract, manufactured by GencorTM (also known as Fenu-FG) (details of extract preparation not provided) (57, 58, 63) and the other 3 studies used the extracts IND9, manufactured by Indus Biotech® (53), Furosap®, manufactured by Chemical Resources (CHERESO) (42), and an extract standardized for Grecunin, manufactured by Indus Biotech® (64) (details of all extract preparations not provided). Our understanding of the relative advantages of both physiological and pharmacological therapies for aging men is greatly improved by the effects of testosterone treatment and exercise on factors such as strength, aerobic fitness, and body composition . Furthermore, via binding to androgen receptors in muscle cells, testosterone stimulates protein synthesis and muscular growth, which is crucial for the regulation of muscle mass . Additionally, there is a significant correlation between bone density and testosterone levels; a decrease in testosterone can result in decreased bone density . However, the use of a carefully planned randomized controlled trial (RCT) is advised in order to bolster the evidence even further and offer more conclusive findings. Daily supplementation with 1.5 g Korean red ginseng (6-y-old ginseng, steamed, dried, and powdered) over 12 wk resulted in no significant between-group differences in testosterone concentrations. Six studies used a randomized, double-blind, placebo-controlled study design (36–38, 47, 49, 56), and 1 study used a randomized, controlled crossover study design (65). All studies used berry or root extracts of Asian ginseng (Panax ginseng), with the root reported as Korean red ginseng, a processed form (67). Overall, 9 out of 32 studies demonstrated statistically significant increases in testosterone concentrations. Therefore, herbs with anti-inflammatory and antioxidant properties may have a positive effect on testosterone concentrations. Fenugreek seed extracts also demonstrated efficacy for increasing (calculated) FT and BT concentrations. A total of 126 male participants were recruited for the studies, with ages ranging from 20 to 56 y and sample sizes ranging from 20 to 56 participants. Using standardized, replicable herbal extracts or, where appropriate, reporting the concentration of the active ingredient, can ameliorate some of these problems since different parts of the plant (e.g., leaf, stem, or root), the time of the year the herbs are harvested, how they are stored, and how they are processed can all affect concentrations of active ingredients (89). In addition, given the existing controversy regarding the relative importance of “bound” and “unbound” testosterone (34), data for testosterone fractions and binding proteins were extracted and presented in the current review to increase the scope of findings. Another potential mechanism through which herbs may increase testosterone concentrations in males is by ameliorating cortisol production. Moreover, the testosterone-enhancing effects identified in the single study on forskohlii (40) are consistent with the results of an animal study where reproductive toxicity in rats, induced by the pro-oxidant mancozeb, was attenuated by forskohlii supplementation, potentially resulting from its antioxidant properties (84). One randomized, double-blind, placebo-controlled, partial-crossover study was conducted examining the effects of a stinging nettle root extract (synthesized from the roots via a fractional percolation process and standardization) on testosterone concentrations (60).Six studies used a randomized, double-blind, placebo-controlled study design (36–38, 47, 49, 56), and 1 study used a randomized, controlled crossover study design (65).If future, robustly-designed studies demonstrate consistent positive effects of some of these herbs on testosterone production, further research will also be required to elucidate their potential mechanisms of action.Eight weeks of daily supplementation with 2.4 g of a cordyceps extract in 16 healthy men aged between 19 and 25 y did not significantly increase testosterone concentrations compared with the placebo group.In men with hypogonadism, including elderly individuals, testosterone replacement therapy may offer antidepressant effects, providing therapeutic benefits for those with testosterone deficiency .Five studies were randomized, double-blind, placebo-controlled trials (42, 57, 58, 63, 64) and one was a randomized, double-blind, placebo-controlled crossover study (53).One randomized, double-blind, placebo-controlled study was conducted examining the effects of a longjack extract (Physta®, manufactured by Biotropics; freeze-dried water extract) on testosterone concentrations (45).Each study was scored based upon its risk of bias being low, with some concerns, or high for each criterion. Four studies (39, 48, 54, 61) examined the effects of Tribulus terrestris on testosterone concentrations. The researchers examined testosterone concentrations in 60 stressed, healthy men and women with a mean age of 41 y. Three studies used a randomized, double-blind, placebo-controlled study design (35, 51, 62), and 1 study used a randomized, double-blind, placebo-controlled, crossover study design (50). Five studies were randomized, double-blind, placebo-controlled trials (42, 57, 58, 63, 64) and one was a randomized, double-blind, placebo-controlled crossover study (53). Moreover, making specific recommendations for certain herbs should be done cautiously until further robust research is conducted. Finally, matching treatment based on presentation may also clarify populations in whom herbal supplementation may be most beneficial. This may moderate the conclusions of the review since an herb's efficacy may only be identified with long-term use. Accordingly, men with existing prostate disease, elevated hematocrit concentrations, high CVD risk, or obstructive sleep apnea may be contraindicated for TRT (17–20). Despite TRT being the primary treatment for men with AD, its use remains controversial due to its association with an increased risk of exacerbating pre-existing medical conditions. Testosterone replacement therapy (TRT), on the other hand, was found to significantly increase survival rates of hypogonadal men (15, 16). From the 4 databases searched, there were 13 herbs identified in 32 studies, published between 2001 and 2019. Testosterone therapy has modest advantages, especially for men who have hypogonadism symptoms and low testosterone levels. It has an effect on many body systems, underscoring its importance for men's physical health and fertility.