Estrogen and Endometriosis: Exciting Correlations

The female sex hormone estrogen plays a crucial role in regulating the menstrual cycle and creating optimal conditions for pregnancy. However, this hormone has a darker side, acting as a catalyst for endometriosis. Today, we will delve into the fascinating world of estrogens, exploring why it makes sense to reduce estrogen levels in the context of endometriosis and how this can be achieved.

What is Estrogen?

Estrogen is not a single hormone but a group of hormones, with the most notable members being estradiol, estriol, and estrone. These natural estrogens serve various functions in the body. Estradiol, the most potent hormone in the group, plays a pivotal role in maintaining the female reproductive system. Estriol is essential for pregnancy maintenance and positively affects the skin and mucous membranes. Estrone becomes more prominent with age, emerging as the primary representative following menopause [1].

Roles of Estrogen in a Nutshell  [2,3]:

  • Maintains primary and secondary sex organs.
  • Participates in bone metabolism, blood clotting, and liver function.
  • Regulates the menstrual cycle in the female body.
  • Enables and sustains pregnancy.
  • Positively affects the skin and mucous membranes.
  • Contributes to reducing cholesterol levels.
  • Strengthens the immune system.

Good to Know!

Estrogens are not just a domain of the female body; men, too, depend on these hormones. They play vital roles in the liver, skin, bones, blood vessels, and more. Their influence extends far beyond the realm of sexual organs [2].

Estrogens: Production in the Female and Male Body

In women, the ovaries are the primary site of estrogen production, although the placenta, adrenal cortex, and adipose tissue also make a significant contribution. Notably, the sex hormone estrone has a unique role, with approximately 50% produced in adipose tissue. In men, estrogen production occurs partially in the testes, where androgens, hormones responsible for male sexual characteristics, are involved. These androgens serve as precursor hormones and are transformed into essential female sex hormones in adipose tissue, providing a clever mechanism that ensures estrogen production in both genders [2,6].

The 5-Step Estrogen Synthesis Process [4,5]:

  • Cholesterol transforms into
  • Pregnenolone, leading to
  • Androstenedione, which transitions into
  • Testosterone, ultimately becoming
  • Estrogen.

Once estrogens have fulfilled their bodily functions, the liver deactivates them, and a significant portion is excreted in the urine [2].

Natural Fluctuations: Programmed by Nature

Nature is inherently adaptive to ever-changing circumstances, and this adaptability is evident in the fluctuations of estrogen levels. The primary driver of these changes is the passage of time, or one’s age, which prompts the body to secrete the appropriate amount of estrogen for each stage in life.

  • Childhood and Post-Menopause: Reduced Estrogen Production
  • Childbearing Age: Increased Estrogen Production
  • Menopause: Decreased Estrogen Production

By tailoring estrogen levels to the specific life situation, fertility is ensured. In practical terms, estrogen is released more abundantly in the first half of the menstrual cycle to support the growth of the uterine lining and facilitate crucial preparations for ovulation. If pregnancy does not occur, estrogen production, among other factors, diminishes significantly, leading to menstruation. Thus, a new cycle begins, continually renewing itself until menopause arrives. At this stage, estrogen deficiency becomes prominent, giving rise to classic symptoms such as hot flashes, sleep disturbances, bladder issues, and irritability [2,7].

Good to Know!

Researchers have discovered that the sex hormone estradiol plays a role in maintaining memory and brain network health during midlife [11].

Understanding the Connection Between Estrogen and Endometriosis

In light of our discussion on estrogen, exploring its pivotal role in endometriosis is essential. Extensive research has revealed that estrogen is a significant contributor to the condition’s development and maintenance. It is believed that this female sex hormone acts as a growth stimulus, fostering the enlargement of endometriosis tissue [8]. This intricate relationship has been scrutinized in various studies, leading to improved insights and treatment strategies for the condition.

A Key Revelation: The Importance of Estrogen-Progesterone Balance

Recently and for decades, researchers have diligently examined the factors promoting the abnormal growth of tissue outside the uterine cavity in endometriosis. The common denominator they have identified is estrogen. However, the focus here is not solely on estrogen but its interaction with progesterone, another sex hormone belonging to the group of progestins. Estrogen and progesterone collaborate to regulate the menstrual cycle, sustain pregnancy, and support embryo development. These hormones, called corpus luteum hormones, are intricately interconnected. In a healthy endometrium (the uterine lining), a dynamic interplay exists in which estrogen and progesterone receptors play crucial roles. Receptors are like cellular sensors that respond to specific signals, and when a hormone binds to a receptor, it triggers a signaling pathway. Recent research findings indicate that the essential estrogen and progesterone signaling pathways are disrupted in endometriosis [10].

When the Signalling Pathways are Disrupted

When the essential signaling pathways are disrupted, it can lead to significant consequences, such as progesterone resistance. In contrast to progesterone deficiency, the body has an adequate supply of corpus luteum hormone in this scenario. Still, the associated receptors fail to respond effectively, or the effect diminishes. Furthermore, in numerous instances, progesterone resistance often coincides with estrogen dominance. This is because progesterone is considered the antagonist of estrogen. But what transpires when the hormonal balance is disturbed? This disruption can trigger increased inflammation and often exacerbate the classic pelvic pain associated with the condition. Fertility may also be adversely affected [9,10]

Good to Know!

Given the critical role of progesterone in endometriosis, we have prepared an article on the subject for you.

Scientific Tidbit

Let us delve deeper into understanding the connection between estrogen and the growth of endometriosis foci. When tissue grows in places it should not, medical professionals refer to them as ectopic lesions. In the context of endometriosis, the role of aromatase has come to the forefront. This means that endometriosis tissue exhibits heightened activity in producing estrogen, thanks to the pivotal enzyme aromatase P450. This is a phenomenon not observed in healthy tissue. Simultaneously, 17ß-hydroxyroid dehydrogenase type II enzyme becomes less active, increasing local estradiol concentration. When you add to this the lack of response from the progesterone receptor, the imbalance becomes even more pronounced. The seamless alternation of phases in the female cycle (the proliferative and secretory phase) no longer occurs with the same precision, further fueling the development of endometriosis lesions [12,13,14].

Why Birth Control Pills Are a Viable Option for Managing Endometriosis

In addition to conventional painkillers and anti-inflammatory medications, hormonal treatments are often considered effective. The primary objectives in managing endometriosis include reducing the size of endometriosis lesions, alleviating pain, and preventing the formation of new lesions. Given the central role of estrogen in this condition, birth control pills and other hormonal treatments become valuable options, as they share the common feature of reducing estrogen levels.

Several alternatives are available:

  • Progestin-Only Preparations: As the name suggests, these preparations contain only luteal hormones, specifically progestins. Examples include medroxyprogesterone acetate, dydrogesterone, and dienogest, which are explicitly approved for endometriosis treatment. Progestogens can be administered through various methods, including pills, implants, injections, or intrauterine devices [8,17].
  • Single-Phase Estrogen-Progestin Combination Preparations: In the form of traditional birth control pills, combination preparations can regress the endometrial tissue and significantly contribute to pain relief. Notably, these preparations have substantially reduced pelvic pain, as highlighted in a review paper [8,18].

Good to Know!

Beyond hormonal treatments, there is another option for managing endometriosis, which involves using GnRH analogs. These compounds work by blocking the hypothalamic-pituitary axis, resulting in a significant reduction in estrogen levels. The estrogen levels during this treatment can be likened to those experienced during menopause since the usual ovarian-stimulating hormones are no longer present in their typical concentration. However, this drop in estrogen can lead to side effects like hot flashes, bone loss, and vaginal dryness [8]. To mitigate these symptoms, add-back therapy is frequently employed. This entails the administration of a small supplemental dose of estrogen and progestin to alleviate the hormonal withdrawal symptoms. According to the endometriosis guideline established by the German Gynecological Society, GnRH analogs are typically considered second-line therapy, with the first-line choice being the oral administration of progestogens [22].

Zero Hormones, Zero Problems? Not Exactly.

While it is true that lowering estrogen levels significantly in the body can be beneficial, studies have shown that even with a marked reduction in estrogen, endometriosis can persist. For instance, not all patients could bid farewell to endometriosis after entering menopause. This could be attributed to the fact that endometriosis lesions produce estrogen to a limited extent, allowing them to sustain their existence. Additionally, fatty tissue continues to produce estrogen even after menopause. It is estimated that about 2-5% of individuals continue to grapple with endometriosis post-menopause, although the exact number remains unknown. This underscores the enduring significance of estrogen in endometriosis, even beyond menopause. Therefore, theories suggesting that lesions regress entirely in every case are not accurate.

Crucially, it is essential to understand that hormone therapy cannot permanently eradicate endometriosis lesions. Therapy should ideally be tailored to the individual. Therefore, open and informed discussions with your healthcare provider are essential. Such conversations facilitate effectively managing any potential side effects [19-21].

Good to Know!

With our Endo-App, you can easily document your symptoms and treatment progress. This is the modern way to take charge of your health.

In a Nutshell

Estrogen is a vital female sex hormone primarily produced in the ovaries. It plays a crucial role in regulating the menstrual cycle and supporting pregnancy in the reproductive years. Additionally, its representatives, estradiol, estriol, and estrone, contribute to bone health, blood clotting, and liver function. Studies suggest that estrogen can fuel endometriosis through a complex interplay of factors. Researchers propose that disruptions in estrogen and progesterone signaling pathways, leading to estrogen dominance, may be a key contributor. Excessive estrogen and insufficient progesterone can foster inflammation and the growth of new lesions. Therapeutic options aim to reduce estrogen levels, often employing hormone treatments like birth control pills. Even during menopause, when estrogen levels naturally decrease, endometriosis lesions may persist.

Referenzen

  1. Sexualhormone – AMBOSS
  2. Östrogene – »unbeschreiblich weiblich« – TRIAS Verlag – Gesundheit (thieme.de)
  3. Östrogen Definition | weibliches Hormon | CTL-Labor
  4. Östrogen – DocCheck Flexikon
  5. Steroidhormone: Synthese – via medici: leichter lernen – mehr verstehen (thieme.de)
  6. Androgene – auch für Frauen wichtig – TRIAS Verlag – Gesundheit (thieme.de)
  7. Zyklus & Hormone » Körper & Sexualität » Frauenärzte im Netz – Ihr Portal für Frauengesundheit und Frauenheilkunde » (frauenaerzte-im-netz.de)
  8. Endometriose » Therapie » (frauenaerzte-im-netz.de)
  9. Weibliche Hormone » Über Östrogen, Progesteron & Co. | minimed.at
  10. Marquardt RM, Kim TH, Shin JH, Jeong JW. Progesterone and Estrogen Signaling in the Endometrium: What Goes Wrong in Endometriosis? Int J Mol Sci. 2019 Aug 5;20(15):3822. doi: 10.3390/ijms20153822. PMID: 31387263; PMCID: PMC6695957.
  11. Sexualhormon Östradiol schützt weibliches Gehirn in der Lebensmitte | Max-Planck-Gesellschaft (mpg.de)
  12. pdf (aerztezeitung.at)
  13. Fachinformation Gynäkologie | Endometriose – ein Hormon-Prostaglandin-Teufelskreis? | GFI Der Medizin Verlag (gyn-depesche.de)
  14. Aromataseinhibitoren zur Therapie der Endometriose? | SpringerLink
  15. Vercellini P, Buggio L, Berlanda N, Barbara G, Somigliana E, Bosari S. Estrogen-progestins and progestins for the management of endometriosis. Fertil Steril. 2016 Dec;106(7):1552-1571.e2. doi: 10.1016/j.fertnstert.2016.10.022. Epub 2016 Nov 4. PMID: 27817837.
  16. Kobayashi H, Kimura M, Maruyama S, Nagayasu M, Imanaka S. Revisiting estrogen-dependent signaling pathways in endometriosis: Potential targets for non-hormonal therapeutics. Eur J Obstet Gynecol Reprod Biol. 2021 Mar;258:103-110. doi: 10.1016/j.ejogrb.2020.12.044. Epub 2020 Dec 29. PMID: 33421806.
  17. Angioni S, Cofelice V, Pontis A, Tinelli R, Socolov R. New trends of progestins treatment of endometriosis. Gynecol Endocrinol. 2014 Nov;30(11):769-73. doi: 10.3109/09513590.2014.950646. Epub 2014 Aug 21. PMID: 25144122.
  18. Jensen JT, Schlaff W, Gordon K. Use of combined hormonal contraceptives for the treatment of endometriosis-related pain: a systematic review of the evidence. Fertil Steril. 2018 Jul 1;110(1):137-152.e1. doi: 10.1016/j.fertnstert.2018.03.012. Epub 2018 Jun 21. PMID: 29937152.
  19. Marie-Scemama L, Even M, De La Joliniere JB, Ayoubi JM. Endometriosis and the menopause: why the question merits our full attention. Horm Mol Biol Clin Investig. 2019 Mar 26;37(2). doi: 10.1515/hmbci-2018-0071. PMID: 30913034.
  20. Inceboz U. Endometriosis after menopause. Womens Health (Lond). 2015 Aug;11(5):711-5. doi: 10.2217/whe.15.59. Epub 2015 Sep 7. PMID: 26343168.
  21. Streuli, H. Gaitzsch, J-M. Wenger & P. Petignat (2017) Endometriosis after menopause: physiopathology and management of an uncommon condition, Climacteric, 20:2, 138-143, DOI: 10.1080/13697137.2017.1284781
  22. 015/045 – Diagnostik und Therapie der Endometriose (awmf.org)

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Dipl.-Ges.oec. Jennifer Ann Steinort
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