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From the Townsend Letter
January 2016

Phytotherapeutic Alternatives or Adjuvants to Testosterone Replacement Therapies in Men
by Joseph J. Collins, RN, ND
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The benefits of testosterone replacement therapy (TRT) in men, the possible risks of TRT, and the contraindications of TRT are well discussed in published literature, with most authors agreeing that more research is still required.1-4 One author concluded with a call for TRT research to also take into account other variables such as diet, exercise, nutraceutical supplementation, sleep, and obesity, in that these factors influence assessments of risk and benefits associated with TRT.2
Parallel to the research being done regarding the replacement of hormones, there is a growing body of study which proposes that there are phytotherapeutic agents that may be used as an alternative to testosterone replacement therapies in men. A review of the literature shows that a number of plants are able to increase testosterone production through gonadotrophic action or by other actions. In addition, many of these herbs improve sexual function through mechanisms beyond the actions of testosterone. Some may actually improve fertility in men, which is contrary to the infertility that results from testosterone replacement therapies. The anabolic activity of the herbs is in many cases enhanced by anticatabolic activity. In contrast to the putative increased risks of prostate cancers, many of these phytotherapeutic agents have anticancer properties.
To be fully informed of the choices available, clinicians and patients may both be interested in learning more about how phytotherapeutic agents increase testosterone production, improve sexual function, improve fertility in men, increase anabolic activity, and contain anticancer properties.

Herbs Increase Testosterone Production
An alternative to testosterone replacement therapy (TRT) is the use of phytotherapeutic agents that can increase the endogenous production of testosterone. A number of herbs have been shown to increase endogenous production of testosterone, some of which actually maintain or increase the gonadotrophic hormones follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This is in contrast to TRT, which can suppress pituitary secretion of the gonadotrophic hormones, resulting in testicular atrophy and infertility.
Epimedium sagittatum
(horny goat weed extract) promotes testosterone production through the action of icariin, a flavonol that improves the condition of reproductive organs and increases the circulating levels of testosterone in animal studies.5 Mucuna pruriens (velvet bean extract) promotes testosterone production in humans by its action on the hypothalamus-pituitary-gonadal axis, and raises serum levels of both testosterone and LH.6 Tribulus terrestris (gokhru fruit extract) promotes testosterone production. A previous study showed the concentration of blood testosterone increased statistically within 10 days in athletes consuming Tribulus.7 Primates also experienced positive outcomes during studies. Tribulus terrestris increases testosterone, dihydrotestosterone (DHT) and dehydroepiandrosterone sulphate.8 In fact, chronic administration of Tribulus terrestris produced a significant increase in serum testosterone levels and sexual behavior with no significant effect on the sperm count. In addition no overt body system dysfunctions were observed in the 28-day oral toxicity animal study published in January 2012.9 Eurycoma longifolia (Tongkat Ali 100:1 extract) promotes testosterone production with a significant increase of plasma testosterone level in human studies as well as animal studies.10,11 It has been postulated that Eurycoma longifolia should be considered as a natural alternative to TRT and has been shown to restore serum testosterone levels.12 Panax ginseng (root extract) may also promote testosterone production. Male patients treated with Panax ginseng showed an increase in spermatozoa number/ml and progressive oscillating motility, an increase in plasma total and free testosterone, DHT, FSH, and LH levels, and a decrease in PRL.13 Withania somnifera (Ashwagandha root extract) promotes testosterone production and caused significant increases in serum testosterone and luteinizing hormone in men with a history of infertility.14

Improved Sexual Function
Of the aforementioned herbs, many but not all of them have been reported to improve sexual function. Some of these properties are independent of testosterone, such as PDE5 inhibition, prolactin inhibition, or nitric oxide upregulation independent of PDE5 inhibition. Epimedium sagittatum contains icariin, which has phosphodiesterase-5 (PDE5) inhibitor action affecting all three PDE5 isoforms.15 The long history of use for treating erectile dysfunction in Traditional Chinese Medicine (TCM) may be attributed to the PDE5 inhibitor actions.16,17 PDE5 inhibitors can potentiate the sexual response in both men and women.18 The sexual potentiation effect and improved quality of life due to Epimedium sagittatum use was even seen in patients with chronic disease.19 Mucuna pruriens causes a significant improvement in sexual behavior, libido and potency, sperm parameters, and testosterone and LH levels, as well as reproductive organs in females, based on various animal studies.20-23 Mucuna also decreases prolactin levels in men, which is significant because hyperprolactinemia is a major neuroendocrine-related cause of reproductive disturbances in both men and women.24,25 Significant increase of sexual behavior through enhanced libido has been attributed to L-dopa, the constituent in Mucuna that suppresses excessive prolactin.26,27 Tribulus terrestris may improve erectile dysfunction, based on in vivo and in vitro animal studies on relaxation of the smooth muscle of the corpus cavernosum.28 Tribulus terrestris may also help with desire disorder in women experiencing female sexual dysfunction.29 The ability of Tribulus terrestris to increase the release of nitric oxide from the endothelium and nitrergic nerve endings may account for its claims as an aphrodisiac in both sexes.30
Eurycoma longifolia
improved testosterone levels and symptoms of hypogonadism in men suffering from late-onset hypogonadism, and significantly improving sexual health.31,32 Panax ginseng can mimic actions of testosterone associated with the increase in both sexual desire and sexual function.33 Various human studies demonstrate that Panax ginseng is effective for treating male erectile dysfunction.34,35 Panax ginseng also improved sexual arousal in menopausal women and caused significant improvement in the Kupperman index and the Menopause Rating Scale, indicating that Panax ginseng might be used in menopausal women to improve their sexual lives.37,36 Panax ginseng can increase in plasma total and free testosterone, DHT, FSH, and LH levels, and a decrease in PRL.38
Even though Withania somnifera can increase testosterone production and decrease prolactin levels, it has not been demonstrated as having any direct effect on libido or sexual function.39
Herbs that support sexual function, but do not actually raise serum testosterone, appear to have direct effect on sexual function beyond the properties and action of testosterone. Lepidium meyenii improves sexual desire in both genders independent of testosterone or estrogen activity.40,41 Turnera diffusa acts as a sexual stimulant, by enhancing engorgement of erectile tissue due to its vasodilatory abilities, though it does not raise testosterone levels.42,43 Ptychopetalum olacoides can enhance erectile function and orgasm in aging men suffering the effects of fatigue or age-related complaints.44 Eleutherococcus senticosus can increase endothelial nitric oxide, which can contribute to improved sexual function in both sexes.45

Improved Fertility in Men
In contrast to TRT, which can cause infertility by decreasing spermatogenesis as a consequence of suppression of FSH, a number of herbs can enhance or preserve spermatogenesis and reproductive ability. Mucuna pruriens improved semen quality and sperm concentrations in infertile men.46-48 Lepidium meyenii improved sperm production and sperm motility by mechanisms in men, via mechanisms not related to LH, FSH, PRL, T, or E2.49 Eleutherococcus senticosus can also improve sperm motility in men.50 Rats that were treated with Eurycoma longifolia exhibited significantly higher sperm counts and sperm motility when compared with the control group.51 In patients with oligoastenospermia, Panax ginseng showed an increase in spermatozoa number/ml and progressive oscillating motility.52 Men treated with Withania somnifera had improved sperm count and motility.53

Increased Anabolic Activity
The aging process is accompanied by hormonal changes characterized by an imbalance between catabolic hormones such as cortisol, which remains relatively stable with aging, and anabolic hormones such as testosterone, which decreases with aging.54 In fact, decrease in muscular mass and strength is one of the principle signs of hypogonadism in males.4 This decreased anabolic/catabolic relationship can be remediated with TRT, which decreases fat mass and increases muscle mass.55 However, a number of herbs may be used to improve the anabolic/catabolic relationship by not only increasing endogenous testosterone production, as noted, but also controlling excessive cortisol activity.
Epimedium sagittatum
has glucocorticoid antagonist properties, which may contribute to a relative increase in anabolic function.56-58 Mucuna pruriens returned elevated cortisol levels to normal and improved sperm count and motility in infertile men.59 Tribulus terrestris also decreased the stress induced rise of cortisol in animal studies.60 Lepidium meyenii also caused a substantial decrease in stress induced in blood cortisol levels in animal studies.61 Ptychopetalum olacoides prevents stress induced increase of corticosterone in animal studies, indicating that glucocorticoid antagonist properties may contribute to a relative increase in anabolic function.62 Eleutherococcus sentico­sus produced a protective effect during experimental steroid-induced osteoporosis, revealing some anticatabolic property.63 Eurycoma longifolia decreased cortisol levels and increased testosterone levels in both men and women.64 Panax ginseng has been shown to decrease catabolic activity by decreasing the cortisol to DHEA-s ratio in women.65 Withania somnifera improves an individual's resistance towards stress and substantially reduced serum cortisol levels in adults taking it for 60 days.66

Anticancer Properties of Androgenic Herbs
The association of TRT with increased risk of prostate cancer has been debated by authors, with one researcher noting no increase in the incidence of prostate cancer in a cohort of 2247 men treated with various forms of TRT.67-69 Nonetheless, prostate cancer as well as male breast cancer are still considered both risks of TRT and contraindications for TRT by those researchers and others.70 With the putative risks and contraindications in mind, it may be valuable to review the anticancer properties of androgenic herbs. While many of the herbs mentioned have anticancer activity against prostate cancer or other hormone sensitive cancer such as breast or ovarian cancer, some of those herbs only have generalized anticancer properties recognized at this time. At the time of this writing, no anticancer properties have been attributed to Ptychopetalum olacoides.
is purported to have antitumor activity, which may be due to icariin, which exhibits an anticancer curative effect on ovarian cancer cells.71,72 The action may also be due to icaritin, an intestinal metabolite of epimedium-derived flavonoids that has an anticancer effect that is mediated by induction of cell cycle arrest which is not associated with estrogen receptors in human prostate carcinoma PC-3 cells.73,74 A Mucuna pruriens compound shows activity against human hepatic carcinoma cell line and may be useful for future hepatic cancer treatment.75 Terrestrosin D from Tribulus terrestris strongly suppressed the growth of prostate cancer cells in a dose-dependent manner.76 Tribulus terrestris affects the processes of apoptosis and metastasizing cancer cells in breast carcinoma cell lines.77 Lepidium meyenii can induce apoptosis in the human breast cancer cell line MCF-7, and has anticancer activity against other human cancer cell lines.78,79 Turnera diffusa has a cytotoxic effect on MDA-MB-231 breast cancer cells.80 Eleutherococcussenticosus may inhibit cell growth in a number of human cancer cell lines and may boost the suppressed immunity in ovarian cancer patients who are subject to chemotherapy.81-83
Eurycoma longifolia
has anticancer activity against LNCaP human prostate cancer cells and is believed to have anticancer properties due to antiproliferative actions and growth inhibition on MCF-7 breast cells through apoptosis induction.84-86 It also has moderate cytotoxicity toward numerous cancer cell lines.87-93 Panax ginseng WKRG inhibited testosterone-induced cell proliferation, arrested cell cycle by inducing p21 and p27, and induced apoptosis in human prostate cells.94,95
Specific ginseng fractions showed proliferation inhibition on androgen-dependent and -independent prostate cancer cells; effectively inhibited prostate cancer cell proliferation, growth, and proliferation; induced apoptosis; and led to arrest in the G1 phase of the cell cycle.96-98 Withania somnifera has compounds that are cytotoxic toward human prostate cancer cells lines as well as pancreatic and breast cancer cells.99 Withania somnifera compounds possess strong cytotoxic activity against liver and breast cancer with moderate activity against colon and prostate cancer cells.100 Other studies showed that Withania somnifera induced apoptosis in prostate cancer cell lines and inhibited survival of both androgen-responsive and androgen-refractory prostate cancer cells, making it an effective chemopreventive agent relevant to prostate cancer progression.101-103

Adjuvant Therapy
Androgenic herbs may be considered an alternative to TRT in men due to their collective ability to increase testosterone production through gonadotrophic action, improve sexual function, improve fertility in men, and increase anabolic activity, and their anticancer properties. In addition, these androgenic herbs may be used as an adjuvants to improve the functions of TRT in patients who still have symptoms of poor testosterone function even after TRT has been given adequate time to work.

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