Boomer Patients?
Testosterone Levels Not Affected By Soy Protein, Isoflavones
Introduction
Soyfoods have been rigorously investigated for the past 20 years. However, much of the recent clinical research has specifically focused on menopausal women. In large part this is because the soybean is essentially a unique dietary source of isoflavones. Isoflavones have estrogen-like properties and have been posited to function as natural alternatives to conventional hormone therapy. This having been said, there is also interest in the role that isoflavones may have in reducing risk of prostate cancer. Prostate cancer is quite low in soyfood-consuming countries1 and many rodent studies have found that isoflavones, especially genistein, the isoflavone found in the highest concentration in the soybean, inhibit the development of prostate cancer and prostate tumor metastasis.2,3 In addition, a number of studies have found that isoflavones slow the rise in prostate specific antigen levels in prostate cancer patients who have been unsuccessfully treated for their disease.4
Occasionally questions are raised in the popular media about the possible “feminizing” effects of soyfoods and isoflavones, because of the estrogen-like effects of the latter. Concerns include a reduction in sperm count and testosterone levels. Low bioavailable testosterone in men has been associated with a number of abnormalities including a loss of energy, depressed mood, decreased libido, erectile dysfunction, decreased muscle mass and strength, increased fat mass, frailty, osteopenia, and osteoporosis5, 6 and may even increase risk for coronary heart disease.7
In fact, some clinical studies of men who consume isoflavones have reported a drop in testosterone levels; for example, a study8 published in 2003 found a modest 5% decrease whereas a small study published in 2007 found a more marked 19% decrease.9 However, many other studies have not found any effects whatsoever. Because it is necessary to consider the totality of the evidence when reaching conclusions about a possible clinical effect, a systematic review and meta-analysis of studies that evaluated the effects of isoflavone-rich products on total and free (biologically active) testosterone levels in men was undertaken.
Methods
To identify appropriate intervention trials, the PUBMED database (National Library of Medicine, Bethesda, MD) was searched through July 1, 2008 using the keywords soy, isoflavones, genistein, phytoestrogens, red clover, androgen, hormones, testosterone, free androgen index (FAI), and sex hormone binding globulin (SHBG). References within identified papers as well as papers that had come to the attention of the authors through other means were also examined for suitability. When sufficient details regarding the study design or results were not provided in the paper, the authors were contacted for additional information.
Results
The Studies at a Glance
- Eleven studies used a parallel design, 10-20 seven a crossover design 21-27 and 14 single group studies 8, 9, 27-39
- 16 of the 32 studies were limited to men with prostate cancer 10-12, 16, 17, 19, 24, 25, 29-31, 34-37, 39
- Average age of participants ranged from 21-74 years of age 35,38
- Study length ranged from 1 week to 4 years 17,38
- Isoflavone intake in aglycone equivalants ranged from 20 mg/d to 900 mg/d27,35
- Soy protein ranged from 0 g/d to 71 g/d16, 22, 24, 25, 28, 29, 31, 32, 34-36
- In soyfoods studies, control group subjects consumed similar amounts of a non-soy protein
- The reported mean baseline values for testosterone ranged from 4.8 nmol/L29 to 58nmol/L29,33
- The baseline for free testosterone ranged from 29 pmol/L to 284 pmol/L15,16
- The baseline for FAI ranged from 34 to 50 12,23
- The baseline for SHBG ranged from 21nmol/L to 100nmol/L 17,21
Although 32 papers were identified, some papers presented data to which multiple arms could be included in the meta-analysis, therefore the number of treatment groups analyzed was 37 and was greater than the number of trials reviewed.
Regardless of statistical model, there were no significant effects of soy protein or isoflavone intake on total testosterone, SHBG, free testosterone, or FAI. All 37 treatment groups were analyzed in the full statistical model and showed no significant effects on any outcomes. In addition, the 15 placebo-controlled clinical trials with baseline and ending measures were extracted and analyzed separately due to their superior study design for hormone assessment yet the analysis still showed no significant effects of isoflavone intake on total testosterone, SHBG, free testosterone, or FAI measures.10-21, 24, 26, 27
Conclusions
The results of this meta-analysis show that neither soyfoods nor isoflavone supplements derived from soy and red clover affect either free or total testosterone levels in men. It should be noted, however, that many of the studies included in the full model of the meta-analysis were of poor quality; for example, many were not placebo-controlled and many were relatively short-term, with the average study duration of about 10 wks. On the other hand, isoflavone exposure was quite high relative to typical Asian and Japanese intake. Overall, the results are very reassuring that soy does not lead to any adverse or feminizing effects such as reducing testosterone concentrations in men. These data also indicate that changes in circulating levels of testosterone are not a mechanism for the proposed role of soy in reducing prostate cancer risk.
About the Authors:
Jill Hamilton-Reeves, Ph.D., R.D. is an Assistant Professor at the College of St. Catherine and an Adjunct Assistant Professor in the Department of Food and Nutrition Science at the University of Minnesota. She currently teaches at the College of St. Catherine and collaborates on nutrition research projects at the University of Minnesota.
Mark Messina, Ph.D. is the co-owner of Nutrition Matters, Inc., a nutrition consulting company, and is an adjunct associate professor at Loma Linda University. His research focuses on the health effects of soyfoods and soybean components. He is chairperson of The Soy Connection Editorial Board.
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