It is undeniable that Testosterone Replacement Therapy (TRT), when done appropriately, results in a myriad of changes in men with low testosterone levels. Many men who have undergone TRT have reported improvement in sex drive, energy levels, and even quality of erection. Knowing the harmful effects of high estrogen in men, it is clear that TRT that is done while not managing estrogen levels can bring fatal consequences. To prevent this, the management of estrogen levels in men is necessary while they are on testosterone replacement therapy.
In this blog post, we will look at Testosterone Replacement therapy, the importance of estrogen in men, and how ample estrogen levels in men can be maintained while on Testosterone Replacement Therapy.
WHAT IS TESTOSTERONE REPLACEMENT THERAPY?
To adequately understand what Testosterone Replacement Therapy (TRT) is, one must first digest the meaning of Testosterone. Testosterone is the primary male sex hormone which regulates fertility, fat distribution, and muscle mass. It plays a crucial role in the development of male reproductive tissues such as the prostate and testes, as well as enhancing secondary sexual characteristics such as the increase in muscle, bone mass, and body hair growth. Although testosterone is often associated with males, females also have small amounts of testosterone. More broadly, testosterone is involved in the well-being, behavior, and moods of both sexes. Insufficient levels of testosterone can prompt symptoms like erectile dysfunction in males and reduced sex drive and bone mass in both females and male.
Testosterone Replacement Therapy (TRT), also referred to as androgen replacement therapy is a medical procedure generally used to treat low testosterone levels in males. Low testosterone is usually due to aging or hypogonadism. Since testosterone level generally tends to peak during adolescence and early adulthood, one’s testosterone level gradually suffers about a 1% yearly decline after the age of 30 or 40, which could lead to the need for TRT. On the other hand, hypogonadism, which is when the sex glands produce little or no sex hormone, can hamper the ability to produce an adequate amount of testosterone. Testosterone replacement therapy is administered either in the way of skin creams, gels, patches, subcutaneous pellets, or injections.
WHY IS A BALANCED LEVEL OF ESTROGEN IN MEN SO IMPORTANT?
Estrogen is a type of sex hormone that is responsible for the regulation and development of the female reproductive system and secondary sexual characteristics. While many assume that estrogen is only needed in females, the actual reality is that both males and females need to maintain certain estrogen levels because estrogen hormones are necessary for the body to perform general sexual, cardiovascular, and hormone functions. However, a high level of estrogen will lead to a decrease in the production of testosterone in men. The majority of the estrogen in males is a result of the breakdown of testosterone or production in the adrenal glands, Leydig cells in the testicles, and peripheral tissues. There are three major endogenous estrogens that have estrogenic hormonal activity: estrone (E1), estradiol (E2), and estriol (E3). Since the most prominent form of estrogen in males is E2 (Estradiol), during TRT, it is the most important form to manage.
While testosterone is important in men, one cannot overlook some of the crucial importance of a balanced level of estrogen in men.
Gonadotropin-releasing hormone (GnRH) from the hypothalamus and Luteinizing Hormone (LH) from the pituitary gland are both necessary for the production of an ample amount of testosterone. However, to control the release of these hormones, an adequate among of estrogen is required. When estrogen levels get too high when undergoing testosterone replacement therapy, the GnRH and LH can be blocked or severely limited, which will, in turn, limit the amount of testosterone being produced. Management of estrogen will keep it balanced even after the therapy.
Estrogen plays a major role in penile development, erection, and detumescence. In a study, estrogen supplementation was used to increase the sexual behavior of aromatase-deficient men. It is believed that the balance of estrogen and testosterone is what informs male sexual behavior. Due to this, the management of estrogen is very important; the goal should be to reduce the estradiol level to a therapeutic range that is not harmful to the patient.
Side effects of high estradiol levels in men could include gynecomastia (breast development and enlargement in men) and edema (fluid retention in the extremities)
WHAT HAPPENS TO ESTROGEN DURING TESTOSTERONE REPLACEMENT THERAPY (TRT)
Although the research by Garringer, Julie A et al. posits that aromatase genes may induce the increase in the production of estrogen, presenting a possibility that some men naturally produce a higher rate of estrogen than others, various other studies have shown that testosterone replacement therapy can lead to increased estrogen levels in men. A study by Tan et al. suggests that TRT can lead to high levels of estrogen in men, especially when taken via injectables. This is because particular injections such as testosterone cypionate or testosterone enanthate will contribute to higher levels of estradiol when compared to other formulations. More so, Amory, J.K. et al., during their research on whether exogenous testosterone or testosterone with finasteride increases bone mineral density in older men with low serum testosterone, concluded that men undergoing a combined Testosterone enanthate and Finasteride had a greater increase in estrogen levels than men on Testosterone enanthate alone. Worst still, if a man is obese, his body may convert the extra testosterone from the TRT into estrogen.
When estrogen levels become too high, the body regulates by reducing luteinizing hormone (LH) and follicle-stimulating hormone (FSH) production. The FSH and LH hormones are created in the pituitary gland and are important for stimulating one’s body’s production of testosterone and sperm. As a result, too much estrogen can actually reduce your testosterone leading to symptoms like infertility, gynecomastia, erectile dysfunction, etc. Hence the management of estrogen levels during testosterone replacement therapy is crucial.
MOST EFFICIENT WAYS TO MANAGE ESTROGEN LEVELS WHILE ON TESTOSTERONE REPLACEMENT THERAPY (TRT)
Since it has been established that it is crucial to maintain a balanced estrogen level while undergoing testosterone replacement therapy, it is pertinent to take a look at some of the most efficient ways of managing estrogen levels.
Arimidex is the brand name of one of the most popular estrogen blockers that do a very good job of decreasing the amount of estrogen hormone in a man’s body. It belongs to a class of drugs called aromatase inhibitors which comes in the form of a pill that is taken orally. Since aromatase acts upon testosterone by breaking it down by a process called aromatization into estradiol, inhibiting this production of estradiol is needed. The aromatase enzyme has been found to be present in the testicles, brain, fat tissue, muscle, hair, and vascular tissues. Because anastrozole is a third-generation aromatase inhibitor, it does not completely inhibit the aromatase enzyme, which is perfect for managing estrogen levels in men since the goal is not to completely get rid of the estrogen
Although The Endocrine Society’s Clinical Practice Guidelines for Testosterone Therapy in Adult Men does not prescribe any particular drug for increasing testosterone levels, some physicians do treat men on TRT with high estradiol levels by co-administering anastrozole (brand name Arimidex) with TRT at 0.25 mg per day or 0.5 mg every other day. This is well supported by the study in 2004 by Leder et al. that revealed that anastrozole was able to raise testosterone levels in men with low testosterone by inhibiting the aromatase enzyme.
SELECTIVE ESTROGEN RECEPTOR MODULATORS (SERMS)
These are groups of chemical compounds that are distinct from estrogen. These chemical compounds interact with estrogen receptors and possess estrogen-specific antagonist and agonist properties which will help to curb the rapid increase in estrogen levels. These estrogen antagonists help to block estrogen receptors in the hypothalamus and pituitary glands from interfering with signaling hormones that help in testosterone production. While doing this, it also prevents some of the issues that come with an increased estrogen level, such as Gynecomastia – which is the enlargement of breast tissues in males. Tamoxifen and Clomid are good examples of SERMs used in this regard.
This is an off-label medication used to treat enlargement of breast tissues in males (Gynecomastia). Like any other selective estrogen receptor modulator, it binds to estradiol (E2) receptors in estrogen-sensitive tissues, in this case male breast, and prevents estrogen from exerting an effect. The guideline released by the American Urologic Association dosed at Tamoxifen at 20mg daily, administered orally.
Clomid is the popular brand name for generic clomiphene citrate. Although it was approved for use in women who are unable to become pregnant, it is often prescribed off-label as an infertility treatment in men. Clomid blocks estrogen from interacting with the pituitary gland so that more luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are produced. Because of blockage, Clomid increases the level of testosterone.
In a study by Vermeulen A et Comhaire F, it was concluded that the administration of tamoxifen, 20 mg/day for 10 days, to normal males produced a moderate increase in luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and estradiol levels, comparable to the effect of 150 mg of clomiphene citrate (Clomid). However, it went on to posit that while Clomid produced a decrease in the LH response to LH-releasing hormone (LHRH), no such effect was seen after the administration of tamoxifen.
NATURAL ESTROGEN BLOCKERS
There are some natural products that have been put forward as being natural estrogen blockers. Some of these natural estrogen blockers include Wild nettle root, Chrysin, Maca, and Grape seed extract. Most of these natural blockers contain aromatase, an enzyme that catalyzes a major aromatization step in the synthesis of estrogen. While there is still a debate on the efficacy of these natural estrogen blockers, the proponents always argue that it blocks estrogen and increases the testosterone level in men.
Precisely, the management of estrogen levels is very important when undergoing Testosterone Replacement Therapy because a high estrogen level can block the important hormones necessary for the production of testosterone. This high level of estrogen present side effects including gynecomastia (breast development and enlargement in men) and edema (fluid retention in the extremities). To manage estrogen level, either Arimidex, Selective Estrogen Receptor Modulators (SERMS) such as Clomid or Tamoxifen, or any natural estrogen blockers can be taken.
If you have concerns about your hormonal balance or need additional information, don’t hesitate to reach out to HRT Doctors Group. Our team of board-certified doctors is dedicated to providing expert advice and personalized treatment options to help you achieve optimal health and wellness. Whether you have questions about managing estrogen levels on TRT or need guidance on other hormonal issues, our team is here to help you. Contact us today and take the first step toward achieving optimal hormonal balance!
Mooradian AD, Morley JE, Korenman SG (February 1987). “Biological actions of androgens”. Endocrine Reviews. 8 (1): 1–28. doi:10.1210/edrv-8-1-1. PMID 3549275
Tan RS, Cook KR, Reilly WG. High estrogen in men after injectable testosterone therapy: the low T experience. Am J Mens Health. 2015 May;9(3):229-34. doi: 10.1177/1557988314539000. Epub 2014 Jun 13. PMID: 24928451.
Tan et. al. Clinical use of Aromatase Inhibitors in Adult Males. Journal of Sexual Medicine. April 2014. Vol. 2. Iss. 2. Pages 79-90.
Amory, J.K., et al. (2004) Exogenous Testosterone or Testosterone with Finasteride Increases Bone Mineral Density in Older Men with Low Serum Testosterone. The Journal of Clinical Endocrinology & Metabolism, 89, 503-510.
Garringer, Julie A et al. “Impact of aromatase genetic variation on hormone levels and global outcome after severe TBI.” Journal of neurotrauma vol. 30,16 (2013): 1415-25. doi:10.1089/neu.2012.2565
Vermeulen A, Comhaire F. Hormonal effects of an antiestrogen, tamoxifen, in normal and oligospermic men. Fertil Steril. 1978 Mar;29(3):320-7. doi: 10.1016/s0015-0282(16)43160-2. PMID: 640052.
Tamoxifen for Low Testosterone in Males – Jeffrey Dach MD. http://truemedmd.com/2015/07/tamoxifen-for-low-testosterone-in-males/
Benjamin Z. Leder, Karen M. LeBlanc, David A. Schoenfeld, Richard Eastell, Joel S. Finkelstein, Differential Effects of Androgens and Estrogens on Bone Turnover in Normal Men, The Journal of Clinical Endocrinology & Metabolism, Volume 88, Issue 1, 1 January 2003, Pages 204–210, https://doi.org/10.1210/jc.2002-021036
Dr. Jenell Ruth Decker
Dr. Decker graduated from the Marshall University Joan C Edwards School of Medicine at Marshall University in 1996. She works in Pullman, WA and 3 other locations and specializes in Family Medicine. Dr. Decker is affiliated with Pullman Regional Hospital.
Education & Training
- Vidant Medical Center/East Carolina University Vidant Medical Center/East Carolina University – Internship, Family Medicine, 1997 – 1999
- Marshall University School of Medicine Marshall University School of Medicine – Internship, Transitional Year, 1996 – 1997
- Marshall University Joan C. Edwards School of Medicine – Class of 1996