Reviewed: Rao A, Steels E, Inder WJ, Abraham S, Vitetta L. Testofen, a specialized Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a double-blind randomized clinical study. Aging Male. June 2016;19(2):134-142.
Editor's note: The investigational products and study funding were provided by Gencor Pacific.
The aging male syndrome (also known as andropause, partial androgen deficiency of the aging male, and late-onset hypogonadism) is characterized by a decrease in testosterone levels in men after age 40 in response to age-related physical changes such as weight gain, increased waist circumference, and deterioration of general health associated with chronic diseases such as diabetes, liver disease, and cardiovascular disease. Symptoms include weakness, increased abdominal fat, musculoskeletal changes and joint pain, hot flashes or sweating, sleep disturbances, insomnia, fatigue, depression, and low bone mineral density. Fenugreek (Trigonella foenum-graecum, Fabaceae) seed extract is reported to have a positive effect on male sexual health and promote anabolic and androgenic activity in younger men. This double-blind, randomized trial assessed the effect of a standardized fenugreek seed extract on symptoms of possible androgen deficiency, sexual function, and serum hormone concentrations in healthy aging males.
The study was conducted between February and November 2014 in Brisbane, Australia. Healthy male subjects (N = 120), aged 43 to 75 years, were recruited through a trial recruitment database and public media. The subjects underwent a comprehensive screening after an initial health assessment that included lifestyle questions, current medications, medical history, and a physical examination. The long list of exclusion criteria included any condition which, in the opinion of the investigator, made the subject unsuitable (e.g., any urogenital dysfunction, disease, abnormality, or surgery; medications affecting any of the measured parameters; major physical or psychiatric disorders, etc.).
The active treatment was Testofen (Gencor Pacific; Hong Kong, China), a standardized fenugreek seed extract, at a dose of 600 mg daily for 12 weeks. Testofen is a fenugreek extract standardized to 50% fenuside, described by Gencor Pacific as a proprietary matrix of saponin glycosides. The placebo contained maltodextrin.
The primary outcome measure was the change in the Aging Male Symptom (AMS) questionnaire, a measure of possible androgen deficiency symptoms. The AMS questionnaire, which includes 17 questions in three domains (psychological, somatic, and sexual), was completed at baseline, week six, and week 12. Secondary outcome measures were sexual function and serum testosterone. Sexual function was assessed using the Derogatis Interview for Sexual Functioning-Self Report (DISF-SR) questionnaire at baseline and at week 12. Serum levels of total testosterone, calculated free testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulfate (DHEA-S), androstenedione, estradiol, and prolactin were measured from fasting blood draws at baseline, week six, and week 12. Serum lipids, electrolytes, and liver function were also assessed at baseline and week 12.
Of the 120 enrolled subjects, 111 completed the study (55 in the active treatment group and 56 in the placebo group). Five subjects in the placebo group discontinued treatment (two noted a lack of results and three gave no reason). In the fenugreek group, four subjects discontinued treatment (two for personal reasons and two because of adverse effects [AEs] including headache and dizziness). The remaining subjects in the treatment group ranged in age from 43 to 75 years (mean = 54.8 years); those in the placebo group were aged from 40 to 74 years (mean = 56.4 years).
No significant baseline between-group differences were seen in anthropometric measures, lifestyle factors, or lipid profiles. In both groups, the mean serum levels of total testosterone and free testosterone concentrations fell within the lower end of the healthy reference range for men in this age group. Correlations observed at baseline for all subjects were as follows: weak negative correlation between age and free testosterone, negative correlation between body mass index (BMI) and both total testosterone (P = 0.002) and free testosterone (P = 0.003), and total testosterone positively associated with high-density lipoprotein cholesterol (HDL-C) (P = 0.017) but not with total cholesterol or low-density lipoprotein cholesterol (LDL-C). No correlation between testosterone and the AMS score was observed except for the somatic subdomain (P = 0.001), and no correlations were seen between total or free testosterone levels and sexual function, sleep, or physical activity.
Fenugreek seed extract significantly improved total AMS score (P = 0.013) compared to placebo, with significant improvements in the somatic (P < 0.03) and sexual (P = 0.009) sub-scores. No treatment effect was seen for the psychological sub-score. Total score on the DISF-SR was improved significantly in the fenugreek group at week 12 compared with baseline (P = 0.006), with significant increases in the sexual arousal (P = 0.001) and sexual drive/relationship (P = 0.007) domains. No significant changes were seen in the placebo group.
At baseline, both groups reported an average of one erection weekly; this increased significantly to two to three weekly (P = 0.001) in the fenugreek group. Both groups at baseline reported sexual activity approximately one to two times monthly; by week 12, this increased significantly (P = 0.004) to almost once weekly in the fenugreek group. These results are consistent with the positive results reported in the AMS sexual function subdomain. No significant changes were seen in the placebo group. Between-group differences were not reported.
Small but significant increases were seen in total testosterone (P = 0.001) and calculated free testosterone (P = 0.002) levels from baseline to week 12 in the fenugreek group. These increases suggest a potential mechanism for the positive effects observed in somatic and sexual function. No significant changes were observed in any of the other hormones, liver function, or lipids in either group. No changes in BMI, waist-hip ratio, grip strength, sleep patterns, physical activity, or fatigue were observed in either group.
The fenugreek seed extract was well-tolerated, with no serious AEs reported. Of the five minor AEs reported, three occurred in the fenugreek group (headaches in two subjects and dizziness in one), and two occurred in the placebo group (nausea in one subject and increased asthma symptoms in another). The AEs were not attributed to the study medications.
The authors concluded that the fenugreek seed extract was safe and effective, reducing symptoms of possible androgen deficiency, improving sexual function, and increasing testosterone levels in healthy middle-aged and older men. A limitation of the study was the lack of between-group comparisons for two of the measures (number of erections and sexual frequency).