Reference
Rao A, Steels E, Inder WJ, Abraham S, Vitetta L. Testofen, a specialised 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 randomised clinical study. Aging Male. 2016;19(2):134-142.
Design
Double-blind, randomized, placebo-controlled trial conducted between February and November 2014 in Brisbane, Australia
Intervention
The active treatment was standardized fenugreek (Trigonella foenum-graecum) seed extract at a dose of 600 mg/day.
Primary Outcome Measures
Primary outcome measure was the change in the Aging Male Symptom questionnaire (AMS), a measure of possible androgen deficiency symptoms. Secondary outcome measures were sexual function and serum testosterone.
Participants
Healthy middle age men (N=120). Subjects were excluded from the study if they
- were diagnosed with erectile dysfunction or any physical disability that may limit sexual function,
- had received any treatment/therapy (including testosterone or anabolic steroids) for any sexual disorder during last 6 months,
- were being prescribed anticoagulation therapy,
- were receiving levodopa for Parkinson’s disease or calcipotriene for psoriasis,
- were diagnosed with severe renal and/or hepatic insufficiency,
- were diagnosed with genital anatomical deformities or had any abnormal secondary sexual characteristics,
- had uncontrolled diabetes mellitus,
- had a history of spinal cord injury or major psychiatric disorder,
- were diagnosed with prostate cancer or benign prostatic hypertrophy,
- had an acute genitourinary disorder or history of genital surgery,
- had a current or past history of chronic alcohol and/or drug abuse,
- had a suspected or diagnosed chickpea allergy, or
- were currently participating in another trial or had been in any other clinical trial during the last 30 days.
Key Findings
Both total testosterone (P<0.001) and free testosterone (P=0.002) increased in the men who consumed fenugreek seed extract compared to the control group at week 12.
Additionally, fenugreek seed extract use was associated with favorable overall sexual function in the treatment group when compared to placebo when using the Derogatis Interview for Sexual Functioning-Self Report (P=0.006).
When numerous sexual sub-domains were analyzed further improvements were observed in the treatment group, especially sexual arousal (P=0.001), sexual drive/relationship (P=0.007), number of weekly erections from 1 per week to 2 to 3 per week (P=0.001), and sexual activity from 1 to 2 times per month to close to once a week (P=0.004). No changes were observed in the sub-domains of sexual cognition, sexual behavior, or orgasm.
Lastly, the AMS showed a significant difference across time (P<0.001), and a significant difference between groups (P=0.013), for total AMS Score
There were no changes observed in BMI, waist/hip ratios, grip strength, DHEA-S, androstenedione, estradiol, or liver function after treatment with fenugreek seed extract. The herbal medicine was well tolerated, although it was associated with headache in <5% of subjects.
Practice Implications
Close to 5% of all men—and 20% of men over the age of 70—have low serum testosterone (T) (ie, male hypogonadism).1 Furthermore, up to one-third of men with a diagnosis of type 2 diabetes and obesity have hypogonadism defined by a low serum free testosterone level.2
Male hypogonadism is associated with a number of health problems, including increased risk of metabolic syndrome, reduced cognition, and osteoporosis. Some data suggest low serum T levels may be paradoxically associated with an increased risk of prostate cancer.3
In adult men, hypogonadal symptoms can range from decreased libido and sexual performance to muscle loss and reduction in bone mineral density. Infertility, loss of body hair, and incomplete sexual development may also be clinical presentations. Less-specific but still commonly described symptoms may include depressed mood, difficulty sleeping, mild anemia, fatigue, or weight gain.4
If clinical symptoms are present, the goal of the integrative practitioner is to look for the potential causes of the patient’s inability to produce adequate levels of T. Total T level should be the first measurement taken to determine hypogonadic state. A blood draw should be taken between the hours of 8 am and 11 am to ensure that a peak level is captured, as diurnal fluctuations occur in T production. Free T levels and sex hormone–binding globulin (SHBG) should also be assessed to determine available T levels.
Many factors can cause alterations in SHBG concentrations. (Table)5
Table: Factors that Influence SHBG Concentrations
| INCREASE | DECREASE | |
| Aging | ✔ | |
| Hepatic cirrhosis | ✔ | |
| Anticonvulsants | ✔ | |
| Estrogen use | ✔ | |
| Hyperthyroidism | ✔ | |
| HIV | ✔ | |
| Malnutrition/malabsorption | ✔ | |
| Hypothyroid | ✔ | |
| Obesity/metabolic syndrome | ✔ | |
| Type 2 diabetes | ✔ | |
| Nephrotic syndrome | ✔ | |
| Glucocorticoids | ✔ | |
| Progestins | ✔ | |
| Anabolic steroids | ✔ |
If testosterone levels return low, other laboratory measurements should be completed, including for luteinizing hormone and follicle-stimulating. These stimulatory hormones help clinicians determine whether the identified hypogonadism is of primary or secondary nature.
Certain pharmaceuticals can also suppress T production. These include opioids,6 glucocorticoids,7 and statin drugs.8
What if low serum T levels persist after addressing the root of the problem?
Treating low T with exogenous hormones is popular these days as many men seek to “remain young” as the calendar years pile up. Exogenous hormones (also known as bioidentical hormones) are a reasonable approach for some men only after other natural and lifestyle treatment options have been exhausted.
A prudent approach in treating hypogonadal men with naturopathic and lifestyle medicine includes the proper use of botanicals. Unfortunately, natural medicine practitioners are typically at a loss with the use of botanicals since well-designed studies on androgenic herbs are scarce.
The current paper by Rao et al supports the clinical use of fenugreek seed extract (Testofen) at 600 mg a day as a reasonable option for hypogonadal men, either by itself or in combination with natural SHBG inhibitors, before turning to exogenous hormones.
