Role of Estrogen in Hormonal Balance

Estrogen, the breakdown product of testosterone, controls testosterone production in males. Proper signaling to hypothalamus for the release of gonadotropin-releasing hormone (GnRH) and to pituitary gland for the release of Luteinizing hormone (LH) is essential for testosterone production by Leydig cells in the testicle. High level of estrogen, in negative feedback back mechanism, hinders the release of GnRH and LH, thus affecting testosterone production (1). High estrogen also enhances the production of sex hormone-binding globulin (SHBG) hormone which binds to and inactivates testosterone (2). This causes a disbalance in physiological testosterone and estrogen levels. ​

Need for Estrogen Regulation in TRT

Estrogen is synthesized from testosterone by the enzyme aromatase or estrogen synthetase. In TRT, the introduction of exogenous testosterone is increasingly converted to estrogen elevating its level (3). Obese men on TRT have a higher conversion to estrogen than a normal man as fat cells express high levels of aromatase enzyme. This minimizes the effect of exogenous testosterone and the overall beneficial effect of TRT (4, 5). Hence, monitoring the estrogen level frequently in men on TRT is advisable. Using estrogen blockers along with TRT alleviates the side effects of high estrogen. ​

Health Benefits of Estrogen Regulation in TRT

Men undergoing TRT (in any form: injection, patch, pellet, topical cream, or gel) usually have high levels of estradiol (E2) in their blood. Injectable testosterone, such as testosterone cypionate or testosterone enanthate, will have a higher rise in estradiol levels compared to other formulations. Additionally, older and obese men on TRT will have high levels of serum estradiol due to the increased activity of aromatase enzyme (6). High estrogen levels in males on TRT is commonly associated with many health issues. They include:

1. Decrease testosterone production
2. Erectile dysfunction
3. Gynaecomastia
4. Water retention (edema)
5. Fat deposition around the abdomen
6. Fatigue
7. Decreased testicle size
8. Mood swings
9. Decreased libido
10. Benign prostatic hyperplasia (BPH)

Therefore, lowering estrogen levels to adequate amount by using aromatase inhibitors along with testosterone is extremely crucial for the beneficial outcome of TRT. Anastrozole and letrozole are favourable in treating male infertility. They work by decreasing estrogen levels, subsequently increasing testosterone production and improving sperm count and motility (7). In obese males where aromatase enzyme is present at high levels yielding very high levels of estradiol, using Aromasin (exemestane) would be more effective as it potently inhibits aromatase enzyme (8).

Potential Risks and Side Effects of Estrogen Blockers

The side effects of estrogen blockers in males are listed below (9).

Aromatase Inhibitors (Arimidex, Anastrozole) use may cause:

1. Nausea,
2. Elevated liver enzymes,
3. Headaches,
4. Reduced bone mineral density leading to osteoporosis with increased fracture risk, Joint/Muscular pain and stiffness,
5. Cholesterol imbalance: Increased bad cholesterol (LDL) and decreased good cholesterol (HDL),
6. Increase in haemoglobin and haematocrit levels,
7. Decreases sexual drive (libido),
8. Erectile dysfunction,
9. Shortness of breath (dyspnea),
10. Fatigue, and
11. Hot flashes

Selective Estrogen Receptor Modulators (SERM): Clomiphene citrate (Clomid) usage is rarely associated with

1. Headaches,
2. Vision changes, and
3. Gynecomastia (enlargement of male breasts). 

Tamoxifen (Nolvadex) use is known to cause a few serious side effects including:

1. gastrointestinal upset,
2. risk of blood clots, and
3. cardiovascular problems.

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One of the reasons TRT patients are monitored diligently at Science&Humans via blood work and quarterly check ups is also to monitor estrogen levels. Means not eliminating estrogen from the body, but making sure the proper proportions of hormones are maintained for optimum health. ​

Testosterone is the most significant hormone for male sexual development and function. Naturally in males, testosterone levels decline with age, and estrogen levels increase. When large fluctuations of testosterone production occur, such as when anabolic steroids are injected, this creates an imbalance of hormones in the body. The body then corrects such an imbalance by aromatization or converting testosterone into estradiol, a form of estrogen. ​

Higher the levels of anabolic steroids imbibed, higher amounts of estrogen synthesized. Bodybuilders inject high doses of anabolic steroids, hence the aromatization of testosterone into estrogen is also very high. ​

Estrogen is synthesized from testosterone. TRT over a period increases testosterone which can lead to excess estrogen in men which is not a good thing. ​

Aromatization is the biochemical process in which an aromatase enzyme catalyzes or speeds up the conversion of testosterone into estradiol, the fundamental pathway for the synthesis of estrogens. ​

Why is it a necessary hormone for men?

Estradiol is crucial to male sexuality. If estradiol is not in balance with testosterone, problems will start to be noticed with sex drive, the ability to have an erection, and the production of sperm. High estrogen levels in males also increase risk of other conditions such as diabetes and cancer.

Estrogen is also crucial for executive functioning, impulse control, intelligence, controlling anti-social behavior as well as bone health. In fact, it is produced in skin, brain and penis in a man’s body which shows that it plays an important role in man’s health as well. But over-production of estrogen is counter-productive to TRT.

Why does estrogen spike affect testosterone replacement therapy?

Obesity - Obese men may convert the testosterone from TRT into estrogen, which will actually reduce the benefits of testosterone replacement.

High levels of E in the body is corrected by reducing Luteinizing Hormone(LH) and Follicle Stimulating Hormone(FSH) secretion. These two are crucial for natural synthesizing of testosterone and sperm generation. Means high E will actually reduce natural testosterone production in the body.

And then there is this aromatase gene which naturally produces excess E in some men. TRT has to be administered with estrogen blockers for such cases.

Estrogen blockers are also known as Aromatase inhibitors. Usual meds prescribed are:

• Arimidex (chemical name: anastrozole)
• Aromasin (chemical name: exemestane)
• Femara (chemical name: letrozole)

While excess E needs to be controlled, abusing estrogen blockers by taking OTC dubious preparations, supplements, herbs is counter-productive to one’s health since estrogen has an important role in men’s health. A trained clinician is best left on deciding medication.