FSH stimulates aromatization

[Jucaro]

I've been on HCG monotherapy for a while now, and my response has been much better lately than it was years ago. E2 has always been an issue with HCG. In a recent lab, my TT was over 1000 ng/dL, while my E2 was around 65 pg/ml. I tried to control my E2 by alternating 780/500 IU of HCG EOD (previously 780 IU M-W-F), but I doubled my FSH from 75 to 150 IU. I then repeated the labs the morning of the day I was supposed to take the higher dose of HCG (before I took it). Results: TT: 710 ng/dL; E2: 115 pg/ml.

I did some research and found this:

- FSH upregulates CYP19A1 (aromatase) within Sertoli cells, increasing intratesticular conversion of testosterone to estradiol.
Simoni M, Weinbauer GF, Gromoll J, Nieschlag E.
Title: Role of FSH in male gonadal function.
Source: Ann Endocrinol (Paris). 1999 Jul;60(2):102‑106.
PMID: 10456180

- By enhancing Sertoli cell–Leydig cell interactions and spermatogenesis, FSH indirectly increases available testosterone, thus providing more substrate for aromatization—particularly when combined with HCG.
Hayes FJ, Seminara SB, Decruz S, Boepple PA, Crowley WF Jr.
Title: Aromatization mediates testosterone’s short‑term feedback restraint of 24‑hour endogenously driven and acute exogenous gonadotropin‑releasing hormone‑stimulated luteinizing hormone and follicle‑stimulating hormone secretion in young men.
Source: J Clin Endocrinol Metab. 2001 Jun;86(6):2600‑6.
PMID: 11397860

FSH binds to FSH receptors on Sertoli cells, inducing expression of the CYP19A1 gene, which codes for aromatase.

By improving Sertoli cell function and spermatogenesis, FSH amplifies testosterone utilization.

When HCG is also present, Leydig cells produce high levels of testosterone → more substrate for aromatase → more estradiol.

The combination of FSH + HCG creates an optimal hormonal environment for increased E2 production.


Estradiol often rises proportionally to FSH dose and testosterone levels, which seems to be what happened to me this time.

 

[Nelson Vergel]

Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis.

The role of estradiol in male reproductive function - PubMed

Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and...

pubmed.ncbi.nlm.nih.gov

 

[Jucaro]

Estradiol in men is essential for modulating libido, erectile function, and spermatogenesis.

The role of estradiol in male reproductive function - PubMed

Traditionally, testosterone and estrogen have been considered to be male and female sex hormones, respectively. However, estradiol, the predominant form of estrogen, also plays a critical role in male sexual function. Estradiol in men is essential for modulating libido, erectile function, and...

pubmed.ncbi.nlm.nih.gov

Sure! But... any amount? Does it matter how you feel, or should you be happy just for a high estradiol level, regardless of how you feel? Is it equivalent the (disruptive) amount of exogenous hormones you inject into your body, to the natural physiological and hemostatic adjustment?
Fine tuning is essential.

 

[Jucaro]

Effects of Elevated β-Estradiol Levels on the Functional Morphology of the Testis - New Insights​

• Myles Leavy,
• Matthias Trottmann,
• Bernhard Liedl,
• Sven Reese,
• Christian Stief,
• Benjamin Freitag,
• John Baugh,
• Giulio Spagnoli &
• Sabine Kölle

Scientific Reports volume 7, Article number: 39931 (2017) Cite this article

• 16k Accesses
• 91 Citations
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Abstract​

Elevated estradiol levels are correlated with male infertility. Causes of hyperestrogenism include diseases of the adrenal cortex, testis or medications affecting the hypothalamus-pituitary-gonadal axis. The aim of our study was to elucidate the effects of estradiol treatment on testicular cellular morphology and function, with reference to the treatment regimen received. Testes samples (n = 9) were obtained post-orchiectomy from male-to-female transsexuals within the age range of 26–52 years. Each patient had a minimum of 1–6 years estradiol treatment. For comparison, additional samples were obtained from microscopically unaltered testicular tissue surrounding tumors (n = 7). The tissues obtained were investigated by stereomicroscopy, histochemistry, scanning electron microscopy (SEM) and immunohistochemistry. Our studies revealed that estradiol treatment significantly decreased the diameter of the seminiferous tubules (p < 0.05) and induced fatty degeneration in the surrounding connective tissue. An increase in collagen fiber synthesis in the extracellular matrix (ECM) surrounding the seminiferous tubules was also induced. Spermatogenesis was impaired resulting in mainly spermatogonia being present. Sertoli cells revealed diminished expression of estrogen receptor alpha (ERα). Both Sertoli and Leydig cells showed morphological alterations and glycoprotein accumulations. These results demonstrate that increased estradiol levels drastically impact the human testis.

 

[Jucaro]

Estrogen and Spermatogenesis​

Liza O’Donnell , Kirsten M. Robertson , Margaret E. Jones , Evan R. Simpson
Endocrine Reviews, Volume 22, Issue 3, 1 June 2001, Pages 289–318, https://doi.org/10.1210/edrv.22.3.0431
Published:

01 June 2001

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Abstract​

Although it has been known for many years that estrogen administration has deleterious effects on male fertility, data from transgenic mice deficient in estrogen receptors or aromatase point to an essential physiological role for estrogen in male fertility. This review summarizes the current knowledge on the localization of estrogen receptors and aromatase in the testis in an effort to understand the likely sites of estrogen action. The review also discusses the many studies that have used models employing the administration of estrogenic substances to show that male fertility is responsive to estrogen, thus providing a mechanism by which inappropriate exposure to estrogenic substances may cause adverse effects on spermatogenesis and male fertility. The reproductive phenotypes of mice deficient in estrogen receptors α and/or β and aromatase are also compared to evaluate the physiological role of estrogen in male fertility. The review focuses on the effects of estrogen administration or deprivation, primarily in rodents, on the hypothalamo-pituitary-testis axis, testicular function (including Leydig cell, Sertoli cell, and germ cell development and function), and in the development and function of the efferent ductules and epididymis. The requirement for estrogen in normal male sexual behavior is also reviewed, along with the somewhat limited data on the fertility of men who lack either the capacity to produce or respond to estrogen. This review highlights the ability of exogenous estrogen exposure to perturb spermatogenesis and male fertility, as well as the emerging physiological role of estrogens in male fertility, suggesting that, in this local context, estrogenic substances should also be considered “male hormones.”

 

[Jucaro]

• Significant association between elevated circulating estradiol and larger prostate volume in adult men
• Implication: Hormonal imbalance can drive prostate enlargement

Estrogen and Prostate Cancer

Scientists and medical experts no longer point to high levels of testosterone as resulting in prostate cancer, since recent studies suggest a stronger link between estrodial hormones and prostate cancer diagnoses.

www.healthline.com

 

[Jucaro]

I've been on HCG monotherapy for a while now, and my response has been much better lately than it was years ago. E2 has always been an issue with HCG. In a recent lab, my TT was over 1000 ng/dL, while my E2 was around 65 pg/ml. I tried to control my E2 by alternating 780/500 IU of HCG EOD (previously 780 IU M-W-F), but I doubled my FSH from 75 to 150 IU. I then repeated the labs the morning of the day I was supposed to take the higher dose of HCG (before I took it). Results: TT: 710 ng/dL; E2: 115 pg/ml.

I did some research and found this:

- FSH upregulates CYP19A1 (aromatase) within Sertoli cells, increasing intratesticular conversion of testosterone to estradiol.
Simoni M, Weinbauer GF, Gromoll J, Nieschlag E.
Title: Role of FSH in male gonadal function.
Source: Ann Endocrinol (Paris). 1999 Jul;60(2):102‑106.
PMID: 10456180

- By enhancing Sertoli cell–Leydig cell interactions and spermatogenesis, FSH indirectly increases available testosterone, thus providing more substrate for aromatization—particularly when combined with HCG.
Hayes FJ, Seminara SB, Decruz S, Boepple PA, Crowley WF Jr.
Title: Aromatization mediates testosterone’s short‑term feedback restraint of 24‑hour endogenously driven and acute exogenous gonadotropin‑releasing hormone‑stimulated luteinizing hormone and follicle‑stimulating hormone secretion in young men.
Source: J Clin Endocrinol Metab. 2001 Jun;86(6):2600‑6.
PMID: 11397860

FSH binds to FSH receptors on Sertoli cells, inducing expression of the CYP19A1 gene, which codes for aromatase.

By improving Sertoli cell function and spermatogenesis, FSH amplifies testosterone utilization.

When HCG is also present, Leydig cells produce high levels of testosterone → more substrate for aromatase → more estradiol.

The combination of FSH + HCG creates an optimal hormonal environment for increased E2 production.


Estradiol often rises proportionally to FSH dose and testosterone levels, which seems to be what happened to me this time.

My Conclusion: If you are undergoing fertility treatment with HCG (Monotherapy), AND with the addition of exogenous FSH, the latter makes testicular use of testosterone more effective, therefore you need less HCG to obtain the same or better result, while higher doses of HCG (or FSH) produces an imbalance leading to hyperestrinism, which is undesirable.