Progesterone and Endometriosis: A Sex Hormone on the Wrong Track

In endometriosis, a hormonal imbalance is a common observation, often characterized by elevated estrogen levels and insufficient progesterone. Additionally, some individuals with endometriosis may display progesterone resistance, meaning that the hormone is present in sufficient quantities but fails to exert its full effect [1]. But why is the corpus luteum hormone progesterone so crucial, and how does it relate to endometriosis? In this discussion, I will answer these intriguing questions and shed light on the vital role that synthetic luteal hormones play in treating endometriosis.

What is Progesterone?

Progesterone, often called the corpus luteum hormone, is one of the progestins and plays a pivotal role in the second half of the menstrual cycle. It is also commonly known as the ‘pregnancy hormone’ for a good reason. Its crucial functions become apparent when we examine its role in the female body. While estrogen, another essential female sex hormone, promotes the build-up of the uterine lining, progesterone comes into play in the subsequent phase to facilitate the implantation of a fertilized egg. Additionally, progesterone initiates uterine growth during pregnancy and lays the groundwork for breastfeeding. If a pregnancy does not occur, the female body registers this, and the progesterone level drops, leading to menstruation. However, the influence of progesterone extends beyond its reproductive functions, impacting other organ systems such as blood vessels, intestines, the brain, and even bone health [2].

A Closer Look at Progesterone’s Tasks:

  • Preparation of the uterine lining built up by estrogen to facilitate the implantation of a fertilized egg.
  • Induction of a rise in body temperature during the second half of the menstrual cycle.
  • Maintenance of pregnancy.
  • Promotion of mammary gland growth in preparation for breastfeeding [3].

Progesterone, the Female Hormone

Progesterone, the primary female sex hormone, is primarily produced in the ovaries. During pregnancy, the placenta takes on the responsibility of its production, and a small portion can be synthesized in the adrenal cortex [4]. It is important to note that progesterone is not exclusive to women; men also produce it. In males, progesterone is generated in the adrenal cortex and testes and plays a role in hormone metabolism, potentially influencing fertility [5]. The pituitary gland, specifically the luteinizing hormone (LH) it produces, serves as the stimulus for progesterone production. A stable menstrual cycle is not attainable without an adequate level of progesterone. Insufficient progesterone levels can lead to cycle irregularities, resulting in intermenstrual bleeding or fertility problems.

Recognizing Progesterone Deficiency: Common Symptoms

Progesterone deficiency, also known as luteal insufficiency, can manifest in various symptoms, although they may not always be discernible. As a result, individuals can experience a progesterone deficiency for an extended period without realizing it. In some cases, it is only discovered when investigating the cause of infertility.

Here are some common symptoms associated with low progesterone levels:

  • Shortened menstrual cycle, with the second half lasting 12 days or less.
  • Spotting during the latter half of the cycle.
  • Development of growths on the ovaries and uterus (e.g., fibroids).
  • Occurrence of hot flashes.
  • Mood swings and anxiety.
  • Sleep disturbances.
  • Dizziness.
  • Loss of libido.
  • Weight gain due to water retention.

Good to Know!

Progesterone yields remarkable effects in the human body, with its potency most evident during pregnancy, where its levels are notably elevated. One notable manifestation of its influence is its profound sense of tranquility in the brain, often observed as pregnancy fatigue. Additionally, progesterone’s capacity to relax smooth muscle fibers can sometimes lead to the development of varicose veins during pregnancy [2].

Endometriosis: The Hormone Cocktail is Crucial

The proper functioning of the human body is intricately tied to the action of hormones. Hormones regulate essential processes, such as maintaining the female menstrual cycle and facilitating pregnancy, and they also play a vital role in overall well-being. As previously mentioned, progesterone mainly exhibits a calming effect on the brain. The delicate interplay between the sex hormones estrogen and progesterone is of great significance in the context of endometriosis. This interplay often reveals a phenomenon known as ‘estrogen dominance,’ where estrogen levels are heightened compared to progesterone. It is a phenomenon that can be detected by medical professionals in patients with endometriosis. In essence, endometriosis can be characterized by excess estrogen and a progesterone deficiency. To fully grasp the full extent of this hormonal interplay, let us embark on a journey into the world of estrogen. Join me for an exploration of estrogen-progesterone dynamics.

Estrogen and Progesterone: Partners in the Menstrual Cycle

Estrogen is another vital sex hormone, and its harmonious coexistence with progesterone is crucial for a healthy endometrium. This collaboration relies on specialized receptors, cells, or cell components that process specific signals [6]. Unfortunately, it is at this very juncture that endometriosis appears to encounter difficulties. Studies have indicated that the signaling pathways for estrogen and progesterone become disrupted in this condition  [7]. You may wonder why malfunctioning signaling pathways are problematic. It carries significant consequences as it can lead to progesterone resistance. Unlike progesterone deficiency, where the hormone is insufficiently produced, progesterone resistance implies that adequate progesterone is present, but the responsible receptors fail to allow its effects to manifest fully. This, in turn, provides an advantage to estrogen. 

Examining Progesterone Receptors

Let us keep in mind that evidence suggests that endometriosis disrupts the signaling pathways for estrogen and progesterone. This disruption can elevate estrogen levels while concurrently reducing progesterone levels. A closer examination of progesterone receptors is particularly intriguing, as they appear to have a distinct role in endometriosis. As you may be aware, progesterone functions as an antagonist to estrogen, balancing the activities within a healthy cycle. This balancing act is crucial, especially in preparing the uterine lining for potential pregnancy. Progesterone takes over post-ovulation, maintaining the integrity of the uterine lining while orchestrating necessary remodeling. It resembles a relay race where smoothly passing the baton is imperative for an orderly cycle. Researchers have delved into how endometrial cells behave throughout these phases, discovering that endometriosis cells exhibit diminished sensitivity to progesterone. This reduced sensitivity may contribute to the condition’s emergence [1, 8].

Alterations in Progesterone Receptors

Endometriosis manifests morphological differences and exhibits altered behavior in comparison to healthy tissue. Now, let us delve into this modified behavior.

Scientific research has demonstrated that progesterone no longer elicits its typical response to estrogen within the localized foci [1, 9]. This mechanism results from endometriosis cells displaying reduced sensitivity to natural progesterone. Usually, the corpus luteum hormone supports the conversion of estradiol to estrone through the actions of enzymes. This conversion is pivotal as estrone is notably less potent. Therefore, progesterone typically mitigates estrogen’s influence. When endometriosis lesions disrupt this crucial conversion, it contributes to estrogen dominance. This hormonal imbalance, in turn, leads to inflammation and pain, a classic hallmark of endometriosis. But the impact extends further. Endometriosis tissue also displays differences in the density of progesterone receptors, particularly the absence of one crucial receptor, PR-B. This receptor is responsible for mediating progesterone’s effect on the endometrium. In normal circumstances, progesterone binds to this receptor, initiating a cascade of events known as progesterone action. Without the receptor or with a diminished number of receptors, the cell’s awareness of progesterone’s presence is significantly reduced. This results in a less pronounced effect of the available progesterone, a phenomenon referred to as progesterone resistance. Moreover, there are fewer representatives of another type of progesterone receptor, PR-A, which can exert an opposing influence on PR-B. Thus, these progesterone receptors have an intricate and delicate interplay, aiming for a balance [7, 9].

Regulatory Mechanisms and the Influence of Estrogen Receptors on Progesterone Levels

Further investigations have uncovered crucial findings; they attribute the lack of progesterone level response to the increased presence of steroid receptors in endometriosis tissue and alternative regulatory mechanisms [14]. Steroids constitute a group of hormones produced through the use of the basic substance sterane, which incorporates the intermediary cholesterol to facilitate the generation of female sex hormones like progestins and estrogen. Additionally, the more significant number of estrogen receptors, found in heightened quantities in endometriosis, plays a vital role in this context. However, it is essential to note that this does not apply uniformly to every receptor type. For instance, the ERβ receptor type significantly outweighs the ERα receptor type. This discrepancy is attributed to the capacity of ERβ to suppress ERα. Experts suggest this imbalanced ratio could result in higher estradiol levels and lower progesterone levels [15].

These discoveries reveal changes in hormone receptor binding sites within cells and offer a more profound understanding of this intricate interplay.

How is a Progesterone Imbalance Treated?

Many studies confirm what experts have long suspected: the quantity and effectiveness of progesterone, primarily through the receptor, play a pivotal role in both the development and treatment of endometriosis. Reduced progesterone and progesterone resistance levels, characterized by impaired cell signaling, can lead to diminished efficacy.

But how is an imbalance in the corpus luteum hormone and estrogen treated? The solution lies in the use of synthetic progestins. These synthetic corpus luteum hormones are engineered to replicate the body’s natural progesterone effects. Synthetic progestins can activate progesterone receptors, inducing an anti-estrogenic response.

An array of synthetic progestins is available for consideration, including:

  • Dienogest
  • Chlormadinone
  • Cyproterone
  • Desogestrel
  • Drospirenone
  • Dydrogesterone
  • Etonogestrel
  • Gestodene
  • Levonorgestrel
  • Medrogestone
  • Medroxyprogesterone
  • Megestrol
  • Nomegestrol
  • Norethisterone
  • Norgestimate
  • Norelgestromin
  • Tibolone
  • Trimegestone

However, it is essential to note that not all synthetic progestins are equally suitable for treating endometriosis. The German Society for Gynecology and Obstetrics guideline program recommends using progestin as the first-line therapy in symptomatic drug therapy. Dienogest, for instance, is a suitable choice for this purpose. While synthetic progestins can help positively influence the size of endometriosis lesions and reduce the risk of recurrence after surgical removal, their effectiveness depends on factors like the extent and location of the lesions. Dienogest, in particular, shows promise as it has been demonstrated in studies to diminish the size of endometriosis lesions. However, it is essential to recognize that not every progestin is equally suitable for every case of endometriosis. The evaluation of progesterone and estrogen receptors may vary depending on the type of endometriosis present [1, 12].

What about the side effects of progesterone treatment?

If your doctor has recommended a progesterone-based medication, it will help alleviate your symptoms, including pain. However, like most medications, it is essential to acknowledge that there may be potential side effects associated with progesterone treatment. These can include occasional episodes of bleeding, mood swings, and a decrease in libido are possible. We strongly recommend contacting your healthcare provider if you encounter unwanted side effects. They can evaluate your situation and explore alternative treatment options that may be better suited to your needs [13].

Good to Know!

An effective endometriosis treatment should always be conducted with your healthcare provider. It is crucial to consider all the individual factors specific to your situation. These factors encompass the severity of your endometriosis, its location, and the symptoms you are experiencing. Ideally, your treatment progress is monitored regularly and adjusted as needed. For instance, progesterone treatment may not be suitable if your goal is to conceive. This is because progestins and progesterone derivatives are critical components of birth control pills, which are contraindicated for those trying to become pregnant.

In a Nutshell

The hormonal milieu significantly influences the presence and progression of endometriosis in your body. Alongside estrogen, progesterone is considered to have a vital role in this context. Progesterone, the hormone associated with the corpus luteum, is the counterbalance to estrogen and triggers a quiescent phase in the endometriosis cells. Research has uncovered the potential existence of hormonal imbalance in endometriosis. Typically, there is an excess of estrogen and a deficiency of progesterone. Studies have also provided compelling evidence that progesterone receptors exhibit different behavior in individuals with endometriosis. Firstly, these receptors may not be as abundant as in healthy individuals, diminishing the effectiveness of the available progesterone. Secondly, these receptors may not efficiently convert estradiol into estrone. Additionally, modified regulatory mechanisms in steroid receptors and an imbalance in estradiol receptors have been observed in endometriosis. These notable alterations contribute to hormonal imbalances, where an excess of estrogen can promote inflammation and the onset of pain. In an attempt to restore this hormonal equilibrium, synthetic progestins are employed. However, it is essential to collaborate with your healthcare provider to determine if hormone therapy suits your circumstances. An appropriate medication should be selected in consultation with your doctor.


  1. Endometriosis, current drug therapy recommendations with emphasis on hormonal therapy with progestins
  2. Progesterone – more than a pregnancy hormone – TRIAS Verlag – Gesundheit (
  3. Progesterone – hormones – women’s cycle | Health Portal
  4. Progesteron – DocCheck Flexikon
  5. Progesterone formation in men (
  6. receptors |
  7. 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.
  8. Female hormones ” About estrogen, progesterone & co. |
  9. Bulun SE. Endometriosis. N Engl J Med. 2009 Jan 15;360(3):268-79. doi: 10.1056/NEJMra0804690. PMID: 19144942.
  10. 015/045 – Diagnosis and treatment of endometriosis (
  11. Angioni S, Pontis A, Malune ME, Cela V, Luisi S, Litta P, Vignali M, Nappi L. Is dienogest the best medical treatment for ovarian endometriomas? Results of a multicentric case control study. Gynecol Endocrinol. 2020 Jan;36(1):84-86. doi: 10.1080/09513590.2019.1640674. epub 2019 Jul 16. PMID: 31311360.
  12. Götze F (2014) Endometriosis and pelvic pain. St. Gallen Pelvic Floor Symposium.
  13. Treatment options for endometriosis (
Benachrichtige mich bei
Inline Feedbacks
Zeige alle
Dipl.-Ges.oec. Jennifer Ann Steinort