Estradiol: The “Other” Male Hormone

Estradiol in Men: The Stigma

In the 2014 film The Other Woman, Cameron Diaz, Leslie Mann, and Kate Upton, portray three jilted females who discover they are being wronged by the same man. (1) Seeking vengeance, they concoct a plan that in part calls for lacing the man’s smoothie drinks with ground up estrogen pills. After an undisclosed amount of time, the man begins to complain to his wife (Leslie Mann) that he seems to be growing breasts (a condition called gynecomastia). Hilarity ensues among the women as they revel in the prospect that this womanizer will be publically shamed. If we delve into the meaning behind what this scene says socially about American culture, there is something stigmatizing for a man who is supposed to be masculine that in turn possesses such a female physical form as breasts. The truth is that this is no laughing matter. Stereotypical images abound when one mentions the threat of a male being emasculated. More importantly, this particular issue, not the guy cheating by the way, but rather the levels of estrogen versus testosterone in a male’s system is one that leads to an important discussion about the role of what is called estradiol. Defining what it does exactly, how it affects men in the long-term, and what this can mean for medical conditions like heart health, bone density, and decreases in sex drive are all lines of inquiry that should push one to tune in.

To begin, estradiol is a steroid, an estrogen, and the primary female sex hormone. It is vital for women because it aids reproductive health and helps to facilitate sexual development over time. Also essential for its important effects on tissues such as bone, fat, skin, liver, and even, the brain, estradiol also impacts females in these areas as they advance in age. However, estradiol’s story is fascinating because for decades it was only associated with female sex. As recently as the 1990s, when doctors started offering comprehensive blood test panels, men did not understand why they were checking estrogen levels. This stemmed, like the stereotypes associated with men having breasts, as something only for females. Several early studies of estradiol began to change this perception. (2) What they uncovered spread like wildfire in medical circles and in the popular press. They confirmed that men with even slightly elevated estrogen levels doubled their risk of stroke and had far higher incidences of coronary artery disease. Early observations also revealed that men possessing prostate cancer had higher estrogen levels and often low testosterone (Low T).

Role of Estradiol in Men: A Long Path to Understanding

After 2012, as doctors and clinical specialists debated the effects of such studies, it seemed that Low T and low levels of estradiol could be linked to several degenerative diseases. Newspapers, like the New York Times, covered the story by declaring that as men aged, they were not only susceptible to the effects of Low T, but complaints at midlife including declining muscle structure, hair loss, sex drive, and a host of other maladies were also connected to the hormone that no one believed men really needed. (3) The New England Journal of Medicine (NEJM), the benchmark publication of our age, declared that “conclusive evidence is rendered to prove that both hormones are needed for libido.” (4) Dr. Joel Finkelstein of Harvard and Dr. Peter Snyder at the University of Pennsylvania, just to name a few, were some of the specialists who conducted the first stage of testosterone studies. Their work has provided a new road map of the function of each hormone. What they found essentially was that fat accumulation kicks in at higher testosterone levels, say 300 to 350 nanograms, thus pushing estrogen levels to sink low enough that bodily breakdowns ensue. As for the lowering of sexual desires, they pronounced that both hormones are needed to maintain a “healthy level,” especially after the age of 65. Despite these breakthrough findings, Dr. Finkelstein did offer a caveat, a warning if you will, and it pertains to that “healthy level” comment. There is no consensus or even common ground on what constitutes a proper dosage of each hormone. (5) The “Testosterone Trial” as it became known has created buzz yet loads of misnomers. Choosing to focus more on Low T funneled knowledge into preconceived notions. In the process, estradiol remained a misunderstood topic among the public. Once new hormone gels and supposed advanced tests hit the market, a billion-dollar industry was created.

Other teams of medical personnel and scientists though continued to probe estradiol’s secrets. A group led by Dr. Ravi Kacker at Harvard under the auspices of the Laboratory for Sexual Medicine Research produced some findings that were more tempered than the work of their colleague Dr. Finkelstein. In an influential article they outlined the role of estrogens in male sexual function and stated, “the pathogenesis of testosterone deficiency remains controversial and poorly understood.” (6) Their aim was to review the distribution of estrogens in both normal and deficient men, with an eye on the clinical implications of elevated estrogen levels. With a broad brush, they swept through the literature on this subject and with pinpoint accuracy what they found was intriguing. Estrogens it turns out elicit a variety of responses in men and can contribute to changes in sexual function. In the absence of testosterone deficiency, elevations do not appear to be harmful and it appears that even in castrated men, sexual functions can be maintained. Estrogen supplements can suppress testosterone levels, but naturally occurring rises in estrogens, like estradiol for instance, do not appear to cause Low T. Nor does, and this is major, elevated levels of estrogen during testosterone replacement benefit male sexuality. This revelation by an accredited team of specialists speaks to the need for more research, more studies, and more time in the laboratory for data to be accrued. As they concluded, “current evidence does not support a role of naturally occurring estrogen elevations or the treatment during testosterone therapy.”

Since testosterone is the precursor hormone for estradiol it is an essential part for men because when the HTP hormonal axis senses that hormones (like testosterone or estradiol) are high, it decreases production; that we do know, and this is undisputed. However, what should also be recognized are the implications of estradiol levels on other portions of the body, including the brain, the heart, and for bone density. First, the brain is impact by levels testosterone and estrogen. Professor Mohamed Kabbaj of the Biomedical Science Pepartment at Florida State University (FSU) discovered that the two hormones actually work in concert to combat Low T in patients and to ward off the effects of anxiety and depression. (7) Since women are more likely to experience depression during their lifetime it could be surmised that depression in men tends to be overlooked, just as estradiol levels were during those early blood tests in the 1990s. The purpose of the FSU Study is so that in the future antidepressants can specifically target some of the mechanisms by which testosterone acts. Since these hormones affect different pathways to the brain the issue is to find pharmacological avenues that will not inhibit other growth potential elsewhere. The other point that becomes apparent is the connectivity between what happens in the brain to what dominos to the heart. According to several studies, the heart is particularly susceptible to lower levels of estradiol because the regulation of body fat becomes strained due to accumulation of cells. (8) Serum concentrations of estradiol were directly linked to mortality in men, especially those that possessed chronic heart failure and reduced left ventricular ejection fraction. One study conducted by the JAMA found that overall increases in estradiol levels were quite effective in reducing the systolic heart failure rates in patients. These types of studies also pushed medical testing facilities to examine the rate of bone loss in their patients. (9) The results were of interest there as well because lower levels, say under 11pg/ml, were associated with increased bone loss. Young men were certainly susceptible to the effects of low estradiol as much as older men over 65 years old, but it is those elder males that are most in need of tests and preventative therapy to stem the tide of bone loss due to their age.

Sensitive Estradiol Test in Men

The tests that can drive preventative therapy and flesh out the problems of low and high estrogen levels are a delicate matter as well. Some controversy fueled discussions among clinics and online defenders of the faith that the wrong estradiol tests may be overestimating the levels in men. Calls for ultrasensitive estradiol tests in are order by most assessments (E2 test), which are more accurate per se. Yet, the issue becomes one of economics due to the higher price of such an advanced test. (10) Even more concerning for males desiring to pursue the anti-aging race is that many clinics when administering testosterone treatments are now prescribing a blocker for estradiol production called anastrozole. The professional medical opinion behind this choice is that higher estradiol levels will form gynecomastia and edema, as well as erectile dysfunction. Some groups of clinicians have even speculated that low hormone testosterone-to-estradiol ratios may be more closely correlated to these types of issues than estradiol alone. (11)

The Future of Estradiol Research in Men

The key word that demands caution when discussing estradiol levels in men is speculation. Once again, tests and data are designed with flaws built in. After only a couple of decades of research, we are still reactionary when it comes to concern with sexual drives, receding hair lines, and such. At times, this overt concern tends to push us to operate like the drunk under the streetlamp that refuses to look for his keys anywhere outside the light. More studies, the incorporation of algorithmic designs, and good old-fashioned time, might lead us down a new avenue of discovery. Trusting androgen researchers may well be our other best bet, as they work on developing the pathway specific wonder drugs through nanotechnology and time release that could hinder the guesswork that is rampant when discussing the proper balance between testosterone and estrogen levels in men. Stay tuned.  

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References:

1. The Other Woman (2014) Twentieth Century Fox Film Corporation

2. Muller M, van der Schouw YT, Thijssen JH, Grobbee DE (2003) Endogenous sex hormones and cardiovascular disease in men. J Clin Endocrinal Metab 88 (11): 5076-5086

3. Kolata G (2013) Middle-aged men, too can blame estrogen for that waistline. NY Times

4. Finklestein J, et.al. (2013) Gonaldal steroids and Body Composition, Strength, and Sexual function in men. NE J Med 369:1011-1022

5. Kolata G (2013) Middle-aged men, too can blame estrogen for that waistline. NY Times

6. Kacker R, et.al. (2012) Estrogens in men: clinical implications for sexual function and the treatment of testosterone deficiency. Intl Soc Sex Med 9(6): 1681-96

7. Kabbaj M, et.al. (2015) The anxiolytic and antidepressant-like effects of testosterone and estrogen in gonadectomized male rats. Bio Psy 78(4): 259-69

8. Jankowska EA, et.al. (2009) Circulating estradiol and mortality in men with systolic chronic heart failure. J Am Med Assoc 301(18):1892-901

9. Khosla S, et.al. (2001) Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J Clin Endocrinal Metab 86(8): 3555-61; Vandenput L, et.al. (2014) Serum estradiol levels are inversely associated with cortical porosity in older men. J Clin Endocrinal Metab 99(7): E1322-E1326

10. Kushnir M, et.al. (2008) High-sensitivity tandem mass spectrometry assay for serum estrone and estradiol. Am J Clin Pathol 129: 530-539; Rosner W, et.al. (2013) Challenges to the measurement of estradiol: an endocrine society position statement. J Clin Endocrinal Metab 98(4): 1376-1387

11. Braunstein GD (2007) Clinical practice, gynecomastia. NE J Med 357(12): 1229-1237; Kacker R, et.al. (2012) Estrogens in men: clinical implications for sexual function and the treatment of testosterone deficiency. Intl Soc Sex Med 9(6): 1681-96