Understanding the Influence of Estradiol on Male Sexual Health—A Brief Introduction
The impact of estradiol on male libido, performance, testosterone production, and fertility highlight just how multifaceted the hormonal milieu is in male urological health. While many people see testosterone as the holy grail and estrogen (E2, or estradiol) as its kryptonite, the reality is far from this reductionist view. And similar to trying to put your finger on a droplet of mercury, a true understanding of the interplay is elusive. Here, a very brief introduction to the topic is provided.
What is Estradiol?
Estradiol (also known as E2 and also spelled as oestradiol) is a type of estrogen and is the primary female sex hormone. In much of the literature and within popular culture, when the word estrogen is used, the reference is to estradiol.
In men, estradiol is produced through aromatization of testosterone into estrone, and then converting the estrone through 17β-hydroxysteroid dehydrogenase into estradiol. Again, when referring to estrogen, most are referring to estradiol.
Estradiol, the Brain, and Libido
Estradiol in the brain has a profound impact on sexual desire (libido), as estrogen receptors (ER) and aromatase receptors in the brain launch the cascade of physiological changes needed for libido and arousal. Specifically, the pre-optic area and the hypothalamus have high levels of estrogen and aromatase receptors. These receptors contribute to the regulation of libido. In this way, estradiol has an important function in libido.
Low Testosterone and the Role of Estradiol
For those with low testosterone, supplementation with estradiol improves libido. A hallmark of low testosterone is low libido, and the application of exogenous (supplemental) estradiol improves this. To explore the relationship even further, researchers have evaluated the impact of supplemental estradiol on castrate men (with testosterone levels less than 50 ng/dl), and have shown that it can preserve the brain regions necessary for sexual desire (important with the treatment of prostate with androgen deprivation therapy (ADT).
Healthy Testosterone and the Role of Estradiol
At this point, estradiol appears to be beneficial in promoting healthy libido and desire in men, as it has been shown to be beneficial in men with low-to-no levels of testosterone. However, for healthy, eugonadal men, a markedly different story unfolds.
One study showed that when exogenous (supplemental) estradiol was given to men with normal, healthy levels of testosterone, and that subsequently “ sexual interest, fantasy, masturbation, and erections” all decreased (another study showed no change).
For men with secondary hypogonadism (when the testes are healthy but testosterone levels are low), the drug clomiphene citrate (Clomid) was given. Clomiphene citrate weakly binds to estrogen receptors (ER), which signals the hypothalamus to increase secretion of follicle stimulating hormone luteinizing hormone. The clomiphene citrate increased testosterone levels and increased the testosterone to estrogen ratio (T/E), effectively lowering estrogen, and the men reported increased “libido, energy, and sense of well-being.” This study seems to demonstrate an inverse relationship between estradiol and libido (when testosterone levels are within a healthy range), where low estradiol equals higher libido.
In a study of men receiving testosterone supplementation treatment, when testosterone levels were above 300 ng/dl and estradiol was below 5 ng/dl, men reported increased libido. But when testosterone levels were below 300 ng/dl, libido was reported as increased when estradiol was above 5 ng/dl.
With this, we can assume that dependent upon testosterone levels, estradiol can increase or lower libido in men. With normal levels of testosterone, estradiol inhibits libido, and with low testosterone levels, estradiol increased libido.
Estradiol and Erectile Function
Erectile function is dependent on a carefully orchestrated cascade of influences by and upon nerve, vessel, and endocrine function. Together, these result in the structural changes needed to coordinate an erection. Here, smooth muscle, the endothelium, and synaptic communication all must coalesce in exactly the right harmony to produce an erection—should just one be out of tune the result is erectile dysfunction.
With erectile function (which is a separate conversation then libido), estradiol appears to negatively affect it in several ways.
Firstly, early exposure to high levels of can cause abnormal development in the size of the “bulbospongiosus muscle, reduction of the spaces in corpus cavernosum, and an accumulation of fat cells within existing spaces,” all of which can lead to erectile dysfunction later in life. In rat models, exposure only negatively influenced development within the first 12 weeks of life.
Secondly, throughout the lifespan, estrogen (estradiol) influences the permeability of the vasculature of the penis, where estrogen can cause venous leakage leading to ED, where higher levels of estradiol were associated with higher levels of venous leakage and ED.
In the brain, estradiol inhibits the hypothalamus, pituitary, and testes axis resulting lower testosterone (by decreasing follicle stimulating hormone and luteinizing hormone). Because testosterone is necessary for healthy erectile function, through its negative effects on testosterone production, estradiol can lead to impaired erectile function and performance. In animal models, ertradiol supplementation lead to poor smooth muscle in the penis, poor condition of the corpus cavernosum, and an increase in connective tissule— all leading to lower ability to achieve and maintain an erection. This is in addition to the overall effect of estradiol lowering testosterone. In men taking estrogen, a reduction is seen in spontaneous and nocturnal erections and lowered testosterone.
With this, evidence supports that estrogen independently negatively influences erectile function outside of the testosterone lowering effects of it.
In a similar way, high estrogen inhibits the production and maturation of sperm (spermatogenesis) , but some estrogen is required for normal spermatogenesis. This happens upon multiple pathways, but similar to the effects of estrogen/estradiol upon erectile function, it is multifaceted, both negatively influencing the production of follicle stimulating hormone and testosterone, but also acting directly upon the germ, nurse, and other cells responsible for healthy development and maturation of sperm.
The point here is not to state that estrogen is bad and testosterone is good. The point is to highlight how multifaceted the topic is, and how estradiol both helps and hinders libido, performance, and fertility—all within a complex balance of influences by the endocrine system (testosterone, estradiol, and aromatase) upon estrogen receptors in the testes, penis, and the brain. Additionally, it is important to note that:
- The location of estrogen receptors and aromatase receptors within the brain show that estradiol contributes both to sexual development in childhood and in sexual behavior in adulthood.
- While estrogen can lower libido by inhibiting testosterone, estrogen can help sustain libido and that estrogen acts upon serotonin receptors in the brain.
- Estrogen exposure negatively influences early penile development which can lead to erectile dysfunction later in life.
- Estradiol can increase vascular permeability within the penis, causing erectile dysfunction.
- Estradiol can cause erectile dysfunction independently of its effects of lowering testosterone.
- Sperm production and maturation is dependent upon estradiol, but too much can impair the process.
- Depending on testosterone levels, estradiol can either inhibit or increase libido.