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Where Is Estrogen Produced In Males

Neurodegenerative Diseases And Learning

Hormones and Gender Transition

Because of its proximity to genes involved in dyslexia , CYP19A1 has been considered as a candidate gene for cognitive functions and implicated in reading, speech, and language . Furthermore, higher serum E2 concentrations at 5 mo of age are positively associated with language performance in 4-yr-old boys and girls . There is a gender-specific preponderance in the onset and predisposition to neurodegenerative and psychiatric diseases such as Alzheimer’s and Parkinson’s disease, and schizophrenia is more common in males , suggesting a possible E2 role in these diseases. In addition, E2 is being considered for therapeutic management of schizophrenia in men .

Estrogen Function In Immune Organs And Cells

Many major differences in male and female immune function involve estrogen action. Both humoral and cell-mediated immunity are typically more robust in females, but increased immune surveillance in females may predispose to autoimmunity. For example, multiple sclerosis is three times more common in women than men , and disease progression is sexually dimorphic. Despite lower MS incidence, men typically have more rapid MS progression than women following diagnosis . More rapid progression in men may result from neuroprotective E2 effects, which could reduce neurodegenerative processes in females and facilitate tissue repair. The recent study suggesting that disease progression is similar in men and women initially diagnosed at an older age is consistent with the idea of protective estrogen effects only in younger women. Despite apparent protective effects of estrogen in women versus men, it is unclear whether circulating E2 in men modulates rates of overall disease progression or neurodegenerative effects accompanying this disease.

Overall E2 effects on the immune system and its constituent cells are complex and are dependent on estrogen concentration and specific cell types involved, among other factors. In general, E2 regulates a variety of chemokines and cytokines in immune cells such as neutrophils, macrophages, and dendritic cells. For a complete descriptions of E2 effects on immune cells, see Reference .

Estrogen Actions Human Estrogen Receptors

Estrogen actions are mainly mediated through ERs, alpha , and beta , which belong to the steroid receptor superfamily and are encoded by the ESR1 and ESR2 genes, respectively . Both receptors contain six functional domains: the activation function domain that contains the N-terminal transactivation domain, a target for phosphorylation, a DNA binding domain, a hinge region, a ligand-binding domain, and a modulation region . Both receptors are highly homologous in DNA and ligand-binding domains and divergent in other regions . The ESR1 gene consists of eight exons spanning more than 140 kb. The ESR2 gene contains eight exons as well. Both the ESR1 and ESR2 genes are subject to alternative splicing with the use different start sites and although their exon and functional domain organization is similar, the splice variant isoforms identified are distinct and have been implicated in tissue-specific patterns of gene expression.

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A Estrogen Sources And Estrogen Concentrations

Table 1. Estrogen concentrations in males

1.09 nM , 52.4 nM Boar
900 ng /ml Horse
~4,500 pg/g , ~100 pg/g Avian
0.38 nM , 8.60 nM Boar
430 pg/ml , 860 pg/ml Boar

Many of these references, especially before 2010, used immunoassays to measure estrogen concentrations. It is now recommended that liquid chromatography, tandem mass spectroscopy be used when assaying for steroid hormones present in low concentrations. Unless otherwise indicated, measurements are for E2.

In males, E2 production requires aromatase , a ubiquitous NADPH cytochrome P450 reductase enzyme . The testis was known to be involved in estrogen synthesis for years , but early studies focused on various T metabolites . Despite descriptions of E2 binding in both testis and epididymis , well into the 1990s E2 was not considered a major regulator of male reproduction, at least in adults , and estrogen binding activity was considered a remnant of developmental processes influenced by estrogen action .

FIGURE 1.Aromatase expression in male mouse reproductive tract. A: testis and epididymis from an adult Cyp19RFP mouse showing RFP expression that is extensive within the testis, but lower in epididymis. B: adult testis showing immunohistochemical localization of aromatase in Leydig cells , round spermatids , and elongated spermatids . C: adult caput epididymis showing immunohistochemical localization of aromatase in the cytoplasmic droplet of sperm in the tubular lumen. E, epithelium.

16 17

Diet Lifestyle And Exercise

Thyroid and Adrenal Gland Dysfunction

Changes to your diet can also help keep your estrogen levels low.

A diet low in fat and high in fiber is commonly recommended for estrogen level control. Some foods that might be involved in this kind of diet include:

  • cruciferous vegetables contain phytochemicals that block estrogen production
  • shiitake and portobello mushrooms naturally reduce aromatase
  • red grapes contain natural estrogen blockers resveratrol and proanthocyanidin
  • sesame seeds and flaxseed, as well as whole grains like oats, corn, and rice contain a micronutrient called polyphenol
  • green tea is another good source of polyphenol
  • pomegranates are high in estrogen-blocking phytochemicals

Some meat products contain estrogen as a result from treatment with synthetic hormones and should be avoided. Some other products to avoid that can increase your estrogen levels include:

  • wraps or containers made of plastic that can be absorbed by your food
  • hygiene products that have parabens containing estrogens, such as shampoos

Staying in shape can also keep your estrogen levels low:

  • get a physical to check your overall health

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Vii Summary And Future Directions

The past half-century has witnessed a major paradigm shift in understanding of the role of E2 and other estrogens in the male. Originally considered female hormones, estrogens play critical roles in developing and adult male reproductive organs, especially the efferent ductules where ESR1 is essential for normal fluid reabsorption physiology. In addition, many male nonreproductive tissues express estrogen receptors and are regulated by estrogen. However, many questions remain unanswered, including why the aromatase knockout phenotype does not replicate the Esr1KO male. Future studies are needed to understand how AR and ESR1/ESR2, sometimes all expressed in the same cell, work together to regulate cellular activity, as well as how emerging players such as membrane ESR1 and GPER fit into our continually evolving understanding of estrogens role in males.

Foods That Increase Estrogen In Males

A wide range of foods contain a class of substances called phytoestrogens, which are basically estrogens of plant origin.

Phytoestrogens are capable of mimicking the actions of estrogen when ingested by humans. In essence, when these foods are eaten, they increase the estrogen levels in the body.

As you probably know, estrogen is the hormone responsible for female sexual characteristics like developed breasts, curvy hips, high-pitched voice, etc.

Consequently, increased estrogen in males can result in the slowing of body and facial hair growth, fat redistribution in the female shape and boosted breast growth.

To increase estrogen in your body, include these foods in your diet:

  • Flaxseeds: These golden yellow to reddish-brown seeds of flax top the list of foods containing phytoestrogens. They contain incredibly large amounts of phytoestrogens called lignans, which boost body estrogen levels. Ground flax seeds can be used as a topping on oatmeal or breakfast cereal or added to smoothies.
  • Soybean and Edamame: Soybean is a ubiquitous legume with numerous established health benefits, while Edamame beans are green whole, immature soybeans, sometimes referred to as vegetable-type soybeans. They are both very rich in phytoestrogens known as isoflavones, which produce estrogen-like activity in the body by mimicking the effects of natural estrogen. There are numerous fun ways to consume soy, including cooked soybeans, soy milk, soy yogurt, tofu, and miso.
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    Regulation Of Erectile Response

    One of the most significant effects of estrogen in a male body is its role in regulating erectile response. First, it is useful to mention erectile function is multifaceted, where endocrine, nerve, and blood vessel actions work together to produce a strong and durable erection.

    The exact role of estrogen on erectile response in men requires further research, but it could be due to its positive effect on penile vasculature and the brain.

    Keep in mind excessive levels of estrogen in the male body could pave the way to erectile dysfunction and other problems. Therefore, ensuring you have a normal hormonal balance is vital for maintaining your sexual health.

    Role Of Estrogens In Gonadotropin And Testicular Physiology In Humans

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    Evidence suggests that in adult males, estrogens exert a negative feedback both at the hypothalamic and the pituitary level. The exogenous administration of estradiol to normal men and patients with isolated GnRH-deficiency was associated with significant decreases in serum gonadotropins as well as LH pulse amplitude suggesting a direct pituitary effect of estrogens. Additionally, lack of gonadotropin suppression was reported when a non-aromatizable androgen was used .

    The relevance of estrogen action in the hypothalamus is supported by the effect on serum gonadotropin levels with the use of the selective aromatase inhibitor anastrozole in normal men and men with idiopathic hypogonadotropic hypogonadism after long-term pulsatile GnRH therapy . Anastrozole led to an increase of mean serum LH and FSH levels in IHH and normal men. Moreover, greater increases in serum gonadotropin levels were observed in normal subjects, suggesting that an intact hypothalamus is needed for the full effect of the aromatase inhibitor.

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    Effects Of Obesity On E2

    Observational studies have consistently found a negative linear correlation between serum testosterone and body mass index in men . Insulin resistance lowers SHBG and therefore total testosterone, but as obesity increases, free testosterone also falls, and this is associated with low or inappropriately normal LH. One hypothesized mechanism is that in obesity, excess adipose tissue aromatase activity elevates E2 concentrations, which increases negative feedback on LH production. In the 1970s higher E1 and E2 serum concentrations and urinary production rates were reported in obese men compared with lean controls . However, there are little subsequent data to support the excess aromatization hypothesis. For example, a study by Dhindsa et al. employed mass spectrometry and equilibrium dialysis to accurately measure total and free E2 in obese men with type 2 diabetes with either subnormal or normal serum free T . Men with subnormal free testosterone had lower E2 concentrations than those with normal serum free testosterone. In Dhindsas study, and also in the European Male Aging Study in which men mostly did not have diabetes , testosterone and E2 concentrations were positively correlated.

    What Are The Types Of Estrogen

    There are three major forms of estrogen:

    • Estrone is the primary form of estrogen that your body makes after menopause.
    • Estradiol is the primary form of estrogen in your body during your reproductive years. Its the most potent form of estrogen.
    • Estriol is the primary form of estrogen during pregnancy.

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    Iv Abnormalities In Estrogen Production Or Er Expression In Humans

    Progress in understanding the role of estrogen in men has been made in the past two decades through identification and characterization of human patients with mutations in ESR1 or aromatase. The first man lacking functional ESR1 was reported in 1994 , although a woman and three siblings lacking ESR1 function were recently reported. Shortly thereafter, humans lacking aromatase were identified , with 13 reported cases of loss of function mutations in CYP19A1 in men now known .

    Table 5. Effects of loss of aromatase or ESR1 in men

    Original and Related Case Reports Type of Mutation, Subject Age Reproductive Effects
    Smith et al. 1994 Point mutation resulting in truncated protein, 28 yr Normal sexual and pubertal development elevated E2, LH, and FSH normal T normal testes size, sperm count, sexual behavior, and orientation reduced sperm vitality Tall stature, genu valgum, bone abnormalities, younger bone age Impaired glucose tolerance and insulin resistance, acanthosis nigricans, BMI 30.5
    Bernard et al. 2017 Point mutation in ligand binding domain with reduced transcriptional activity, 18 yr Elevated FSH, LH, and E2 low to normal serum T low serum inhibin B and AMH unilateral right cryptorchidism hypoplastic left testis normal pubertal development Low bone age BMI 23.7

    How To Increase Estrogen In Males

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    Estrogen is a sex hormone primarily responsible for the sexual characteristics and reproductive ability of females. It is equally present in males, where it plays a role in the formation of sperm and maintenance of a healthy libido.

    Males can benefit from increased levels of estrogen under certain medical conditions, including prostate cancer, breast cancer, and schizophrenia.

    More importantly, increased estrogen in males has been successfully used in male-to-female feminizing therapy for trans-women and other genderqueer persons, to tilt their physical and sexual features in the feminine direction.

    This results in the slowing of body and facial hair growth, fat redistribution in the female shape and boosted breast growth. If youre interested in learning more about estrogen, to include how to identify and treat low estrogen, how to increase estrogen levels fast in men, women, and MTF transgender during the transition, then check out our new website

    Estrogen in males can be increased in three primary ways:

    • Administration of synthetic estrogen preparations.
    • Diet Adjustments.
    • Lifestyle modifications.


    Prescription estrogen preparations are available for use in males. The most common estrogens used in transgender women includeestradiol and estradiol esters such as estradiol valerate and estradiol cypionate.



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    Role Of Esr2 In Adipose Tissue

    Although ESR2 mRNA is expressed in human and rodent WAT , Esr2KO mice lack the obesity/insulin resistance of Esr1KO and Cyp19KO mice . Thus ESR1 is most critical for adipose and metabolic effects of E2 in males and females. In addition, mice lacking both ESR1 and ESR2 mimicked adipose/metabolic changes of Esr1KO mice, further suggesting ESR1 as the major regulator of E2 effects on WAT.

    Despite evidence that ESR2 is not the major regulator of E2 effects on WAT, some work suggests ESR2 can affect glucose tolerance and insulin resistance . Similarly, recent work indicated that in the absence of ESR1, ESR2 plays a protective role in suppressing inflammation in adipocytes.

    How To Raise Estrogen Levels

    A male who is experiencing symptoms of low estrogen should speak to their doctor about treatment options.

    Hormone replacement therapy can help treat low estrogen levels in males caused by hypogonadism. A doctor may administer testosterone using a patch, an injection, a gel, or a product absorbed by the gums.

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    What Role Does Estrogen Play In Reproductive Health For Men Or Amab

    Estrogen affects the reproductive health of people who are assigned male at birth , too. In cisgender men, transgender women and nonbinary people with penises, estrogen impacts sex drive and the ability to get an erection and make sperm.

    Too little estrogen can lead to a low sex drive. Too much of it can cause infertility and erectile dysfunction. Excessive estrogen can cause gynecomastia, or enlarged breasts.

    If youre assigned male at birth and concerned about your estrogen levels, speak with an endocrinologist or a functional medicine specialist for help.

    Estrogen Receptor Signaling Pathways And Efferent Ductule Structure And Function

    How do your hormones work? – Emma Bryce

    Cloning of the human ER and development of an ER antibody , as well as the recognition that efferent ductules were a major target for estrogen in the male were historical landmarks leading up to the discovery of an essential role for ESR1 in the ductule physiology . However, it was the generation of the first steroid receptor knockout model , the Esr1 knockout mouse , that directly led to discovery of this unique function for the estrogen signaling pathway in males . Although initial descriptions of Esr1KO males indicated that their testes were atrophic at maturity , our first experience with these males revealed that during early adulthood the testes showed a transient increase in weight, prior to regression of the seminiferous tubules . Therefore, based on prior experience with fungicides that targeted efferent ductules and also produced a transient increase in weight , it was hypothesized that loss of ESR1 could be producing an occlusion of the ductules, causing fluid back up into the testis and dilating the rete testis lumen. However, contrary to this assumption, initial histological slides from Esr1KO males revealed no occlusion, but instead extreme ductal dilation, with large open lumens filled with excessive fluid and a greatly reduced epithelial height. Additionally, seminiferous tubules were dilated and testes showed a transient increase in weight followed by atrophy, a pattern previously observed with ductal occlusions after fungicide exposures .

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    Symptoms Of High Estrogen In Men

    Symptoms to watch for include:

    • Erectile dysfunction, loss of libido, infertility, and other types of sexual dysfunction
    • Enlargement of, or development of, breasts
    • Persistent fatigue or lack of energy
    • Mood swings, anxiety, and/or depression
    • Water retention

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    C Expression Of Er In The Prostate Gland

    In adult rodents, periductal stromal cells express ESR1 , enabling estrogen-induced paracrine effects on prostate epithelium. Studies with Esr1KO mice demonstrated that developmental estrogen programming of epithelial dysplasia as well as E2-driven squamous metaplasia in adult prostates is mediated through ESR1 . While investigations on ESR1 in prostate cancer have produced variable results, possibly a function of disease heterogeneity, ESR1 has been identified in cancerous epithelial cells as well as in cancer-associated fibroblasts . Importantly, ample evidence in humans and rodent models identifies a role for estrogens acting through ESR1 to promote prostate cancer growth via stromally mediated factors and recruitment of inflammatory cells, as well as direct actions on tumor cells . Of note, ESR1 drives expression of the TMPRSS2-ERG fusion gene in prostate cancer cells, which promotes progression, as well as NEAT1, the most overexpressed lncRNA in human prostate cancer, which in turn epigenetically alters oncogenic target genes .

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