Progesterone and Endometriosis: A Sex Hormone on the Wrong Track

The functioning of the human organism relies heavily on hormonal activity, particularly in processes like maintaining the female menstrual cycle and initiating pregnancy. Hormones are pivotal contributors to overall well-being, and one hormone with notable effects is progesterone, recognized for its calming impact on the brain. Furthermore, the intricate interplay between the sex hormones estrogen and progesterone is essential concerning endometriosis. In endometriosis, there is often an observed condition known as “estrogen dominance,” characterized by excess estrogen relative to progesterone. Physicians also frequently identify a lack of progesterone in individuals with endometriosis. Endometriosis can involve an abundance of estrogen and a progesterone deficiency. To understand the comprehensive dynamics of this hormonal interplay, I invite you to delve into the world of estrogen with me.

Estrogen Progesterone Excursion

Estrogen, like progesterone, is a sex hormone vital in maintaining a healthy endometrium. The harmonious interaction of these hormones relies on specialized receptors, which act as messengers in the body. Receptors are specialized cells or cellular components that process specific stimuli and transmit them as signals [6]. However, this is precisely where endometriosis appears to encounter an issue. Research indicates that estrogen and progesterone signaling pathways are disrupted in this condition [7]. These disruptions have far-reaching consequences, potentially leading to progesterone resistance. Unlike progesterone deficiency, where there is an adequate hormone supply, progesterone resistance occurs when the receptors responsible for its effects fail to function correctly or to their full potential. This phenomenon contributes to estrogen dominance, where estrogen gains the upper hand.

Probing Progesterone Receptors

In exploring progesterone receptors, we uncover their unique role in endometriosis. Progesterone acts as an antagonist to estrogen, providing balance in a healthy menstrual cycle. It stimulates the uterine lining to prepare for potential pregnancy. After ovulation, progesterone takes the reins, maintaining the uterine lining while undergoing necessary adjustments. This relay race of hormonal action ensures a well-ordered cycle. Research has revealed that endometrial cells respond less sensitively to progesterone in endometriosis, and this altered behavior is believed to contribute to the condition [1, 8].

Progesterone Receptors Are No Longer Shoulder to Shoulder

Endometriosis tissue does not only appear different; it behaves differently as well.

Scientific have demonstrated that progesterone no longer has its usual counteractive effect on estrogen within endometriosis foci [1, 9]. This change is attributed to the endometriosis cells’ reduced sensitivity to natural progesterone. Ordinarily, progesterone helps convert estradiol into estrone through enzymes, a crucial mechanism because estrone is less potent. Progesterone’s role is to temper estrogen’s influence. However, when this transformation fails in endometriosis lesions, it intensifies estrogen dominance, triggering inflammation and pain, hallmark symptoms of endometriosis. Moreover, the density of progesterone receptors varies in endometriosis tissue. A particular progesterone receptor (PR-B) For example, one specific progesterone receptor (PR-B) mediates progesterone action is notably absent, resulting in reduced effectiveness. This condition is termed “progesterone resistance.” Additionally, fewer representatives of another progesterone receptor (PR-A) are present, and they have an opposing effect on PR-B, underscoring the intricate balance of hormonal interactions [7, 9].

Regulatory Mechanisms and Estrogen Receptors Influence Progesterone Levels

Further research reveals that an excess of steroid receptors, accompanied by distinct regulatory mechanisms, could account for the unresponsiveness of progesterone levels within endometriosis tissue [14]. Steroids, a group of hormones derived from the sterane primary substance and cholesterol, contribute to producing female sex hormones like progestin and estrogen. In this context, the density of estrogen receptors, which are also present in higher numbers in endometriosis, comes into focus. However, this variance in receptor types is notable. For example, the ERβ receptor type significantly outnumbers the ERα receptor type. This imbalance could lead to higher estradiol levels and less progesterone as ERβ suppresses ERα [15].

These shifts in hormone receptors on cells are an area of ongoing exploration, offering valuable insights into the complex interplay of hormones in the context of endometriosis.