Aromatase Inhibitors for Men
Ronald Steriti, ND, PhD; Jonathan V. Wright, MD
The enzyme aromatase converts testosterone into estradiol and converts androstenedione into estrone. The mechanism of aromatase metabolism is shown in the Figure.
Inappropriate diet is considered the main cause of insulin resistance, which is the primary pathophysiologic feature of metabolic syndrome. Increased insulin levels stimulate aromatase activity.1,2
In obese men, increased aromatase activity results in reduced testosterone and increased estradiol and estrone concentrations, ultimately resulting in a decrease in muscle mass and an increase in total fat mass. Increased total fat mass contributes to oxidative stress, inflammation, and further increased aromatase activity (wrong diet à hyperinsulinism à hyperaromatization à excess obesity).3-5
Cohen3 proposed that aromatase inhibitors could be potential therapeutic agents for men with obesity. Leder6 recommended their use during testosterone therapy in older men to prevent adverse effects of estradiol.
Male gynecomastia is usually caused by increased estrogen activity, decreased testosterone activity, or the use of numerous medications. Excess aromatase activity is also a cause of gynecomastia.7-12
Hyperaromatization is a term used to describe excessive aromatase activity, which results in conversion of testosterone into estrogen. Although possible in both sexes, hyperaromatization is particularly found in men and often accompanies low testosterone concentration and obesity related to metabolic syndrome and insulin resistance.13
Myomin and Chrysin
Available natural formulas that help reverse hyperaromatization include myomin and chrysin. Myomin is a combination of Smilax glabra Roxb, Curcuma zedoria, Cyperus rotundus, and Aralia dasyphylla Mig.14
A fluorescent antibody study15 in animals showed that myomin significantly reduced the population of hepatic aromatase within 30 days. In another study,16 myomin significantly inhibited aromatase expression in in vivo ovary, ectopic endometrium, and in vitro–cultured primary ovarian granulosa cells of rats.
Chrysin is a naturally occurring flavone. It is chemically extracted from the blue passion flower (Passiflora caerulea).17-20
While these aromatase inhibitors of natural origin appear to be harmless, they are not known to correct hyperinsulinism. It is important for men with excess testosterone-to-estrogen transformation to undergo testing for insulin resistance21 and, if found, to follow appropriate diet, exercise, and supplementation to decrease or stop hyperinsulinism, thus reducing or eliminating the excess conversion and in many cases rendering aromatase inhibitor use of any sort less necessary or unnecessary at all.
A study22 showed that Turnera diffusa (damiana) extract and 2 isolated compounds (pinocembrin and acacetin) could significantly suppress aromatase activity. Apigenin 7-glucoside, Z-echinacin, and pinocembrin demonstrated estrogenic activity.
Aromataste Inhibitor Drugs
Aromatase inhibitor drugs (patent pharmaceuticals) are “approved” for estrogen receptor positive (ER+) early breast cancer and following Tamoxifen therapy. They include Aromasin ® (exemestane), an irreversible steroidal inhibitor; Femara ® (letrozole) and Arimidex ® (anastrozole), which are non-steroidal inhibitors. Aromatase inhibitors are generally not used to treat breast cancer in premenopausal women, since the decrease in estrogen stimulates androgen production by the ovaries, which will counteract their effect. The most common side effects of aromatase inhibitors are joint stiffness or joint pain. Regular bone density testing is recommended for those taking aromatase inhibitor drugs.23-25
Alcohol consumption increases estrogen levels and breast cancer risk.26,27 A study28 proposed that increased aromatization may be a mechanism for feminization in some male alcoholics and for plasma estrogen level increases in postmenopausal women who consumed moderate levels of alcohol.
In conclusion, metabolic syndrome presents a unique challenge because of its multiple mechanisms. Addressing glucose metabolism with diet, exercise, and natural therapies is a mainstay of naturopathic treatment. In addition, several natural aromatase inhibitors may be useful for men with metabolic syndrome accompanied by increased estrogen and decreased testosterone concentrations. They may be particularly useful as an adjunct to testosterone therapy in these patients.
Ron Steriti, ND, is researcher for Dr Jonathan V. Wright of the Tahoma Clinic and Meridian Valley Labs in Renton, Washington. He is a graduate of Southwest College of Naturopathic Medicine and has a PhD in electrical engineering from the University of Massachusetts at Lowell.
Jonathan V. Wright is medical director and founder of the Tahoma Clinic and Meridian Valley Labs. He is a pioneer in holistic medicine and bioidentical hormone therapy.
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