madman
Super Moderator
Androgens, Endometriosis and Pain (2022)
Susan F. Evans, M. Louise Hull, Mark R. Hutchinson, and Paul E. Rolan
The intriguing relationship between androgens, endometriosis, and chronic pain continues to unfold. Determining this relationship is of crucial importance to gynecologists managing people with these conditions, as common treatments dramatically alter her hormonal profiles, with both intended and unintended consequences. Although they may be present in the same individual, there is a recognized disconnect between pain or pain-related symptoms, and the presence or extent of endometriosis lesions. Reduced androgen levels provide a potential mechanism to link the development of endometriosis lesions and the presence of chronic pain. This research paper expands the presentation of our research at the World Endometriosis Congress in 2021, subsequently published in the Journal of Pain Research which demonstrated a strong inverse relationship between androgen levels and days per month of pelvic and period pain. Here we extend and further explore the evidence for the role of androgens in the etiology and management of dysmenorrhea and pelvic pain in women, both with and without endometriosis. We explore the potential for inflammation to induce low androgen levels and consider ways in which clinicians can optimize levels of androgens when treating women with these conditions. This article prompts the question: Is it estrogens that predispose people to a life of pain, or androgens that are protective?
INTRODUCTION
Women are over-represented in chronic pain populations when compared to males (1, 2). Over recent years, there have been extensive and often conflicting outcomes from research seeking to determine the ways in which a female’s relatively higher levels of estrogen when compared to males may predispose her to chronic pain (1, 3, 4). In contrast, research to determine the effect of androgens on pain in women is sparse. In a group of healthy women, Bartley and Fillingim (1) found higher testosterone levels to be anti-nociceptive, and higher estrogen levels to be mildly nociceptive. To our knowledge, our research is the first to document an inverse correlation between levels of testosterone and the experience of pain in young women (5). This article outlines our recent research findings and how androgens can influence pain at different stages of life and when different pathologies are present. Finally, we explore the potential for androgens to provide a therapeutic benefit in women and what role they may have in future treatment pathways.
RESEARCH FINDINGS
Our work, as published in the Journal of Pain Medicine (5), investigated the relationship between serum levels of 10 steroid hormones and the subjective experience of dysmenorrhea-related pelvic pain symptoms (5). We used high-sensitivity liquid chromatography-mass spectrometry (LC-MS) assays to measure serum levels at 2 stages of a single menstrual cycle, Day 1–2 (when estrogen is baseline) and Day 7–10 (when estrogen peaks). We measured estrogen, progesterone, and androgen levels and determined their correlation with the Days per Month of Pelvic Pain (DPelvicPM), Period Pain (DPeriodPM), and Headache (DHeadachePM).
Our results showed that in non-users of the oral contraceptive (OC), there was a strong inverse correlation between a reducing Free Androgen Index (FAI) (6) and increasing DPelvicPM (p = 0.0032) and DPeriodPM (p = 0.013) on Day 1–2 (Table 1). Nonusers of the OC also demonstrated a strong inverse correlation between a reducing FAI and an increasing DPelvicPM (p = 0.058) and DPeriodPM (p = 0.029) on days 7–10. A weakly positive correlation between estradiol and DPelvicPM (p = 0.49) was found only on days 7–10 in women who used the OC.
*ANDROGENS, PAIN, AND PUBERTAL DEVELOPMENT
*TESTOSTERONE AS AN INHIBITOR OF INFLAMMATION
*ANDROGENS AND ENDOMETRIOSIS
*POTENTIAL CLINICAL USE OF ANDROGENS IN WOMEN
*COMBINED TESTOSTERONE AND AROMATASE INHIBITOR THERAPY
CONCLUSION
There has been a dearth of research into the role of androgens in the development of endometriosis lesions, the experience of pain, inflammatory disease processes, and optimizing a woman’s quality of life. Our research indicates that inflammation, pain, and androgen levels are intimately associated, with a lack of clarity regarding whether low androgen levels pre- or post-date the presence of inflammation. Optimal products for the treatment of testosterone deficiency in women are yet to be developed, and the potential pharmacological doses required to achieve therapeutic benefits using existing testosterone therapies are yet to be established. Hormonal therapy for menstrual suppression profoundly influences androgen levels and may contribute to reduced androgen effects. The development of new therapies to reduce inflammation may offer a novel approach to addressing androgen deficiency in women.
Susan F. Evans, M. Louise Hull, Mark R. Hutchinson, and Paul E. Rolan
The intriguing relationship between androgens, endometriosis, and chronic pain continues to unfold. Determining this relationship is of crucial importance to gynecologists managing people with these conditions, as common treatments dramatically alter her hormonal profiles, with both intended and unintended consequences. Although they may be present in the same individual, there is a recognized disconnect between pain or pain-related symptoms, and the presence or extent of endometriosis lesions. Reduced androgen levels provide a potential mechanism to link the development of endometriosis lesions and the presence of chronic pain. This research paper expands the presentation of our research at the World Endometriosis Congress in 2021, subsequently published in the Journal of Pain Research which demonstrated a strong inverse relationship between androgen levels and days per month of pelvic and period pain. Here we extend and further explore the evidence for the role of androgens in the etiology and management of dysmenorrhea and pelvic pain in women, both with and without endometriosis. We explore the potential for inflammation to induce low androgen levels and consider ways in which clinicians can optimize levels of androgens when treating women with these conditions. This article prompts the question: Is it estrogens that predispose people to a life of pain, or androgens that are protective?
INTRODUCTION
Women are over-represented in chronic pain populations when compared to males (1, 2). Over recent years, there have been extensive and often conflicting outcomes from research seeking to determine the ways in which a female’s relatively higher levels of estrogen when compared to males may predispose her to chronic pain (1, 3, 4). In contrast, research to determine the effect of androgens on pain in women is sparse. In a group of healthy women, Bartley and Fillingim (1) found higher testosterone levels to be anti-nociceptive, and higher estrogen levels to be mildly nociceptive. To our knowledge, our research is the first to document an inverse correlation between levels of testosterone and the experience of pain in young women (5). This article outlines our recent research findings and how androgens can influence pain at different stages of life and when different pathologies are present. Finally, we explore the potential for androgens to provide a therapeutic benefit in women and what role they may have in future treatment pathways.
RESEARCH FINDINGS
Our work, as published in the Journal of Pain Medicine (5), investigated the relationship between serum levels of 10 steroid hormones and the subjective experience of dysmenorrhea-related pelvic pain symptoms (5). We used high-sensitivity liquid chromatography-mass spectrometry (LC-MS) assays to measure serum levels at 2 stages of a single menstrual cycle, Day 1–2 (when estrogen is baseline) and Day 7–10 (when estrogen peaks). We measured estrogen, progesterone, and androgen levels and determined their correlation with the Days per Month of Pelvic Pain (DPelvicPM), Period Pain (DPeriodPM), and Headache (DHeadachePM).
Our results showed that in non-users of the oral contraceptive (OC), there was a strong inverse correlation between a reducing Free Androgen Index (FAI) (6) and increasing DPelvicPM (p = 0.0032) and DPeriodPM (p = 0.013) on Day 1–2 (Table 1). Nonusers of the OC also demonstrated a strong inverse correlation between a reducing FAI and an increasing DPelvicPM (p = 0.058) and DPeriodPM (p = 0.029) on days 7–10. A weakly positive correlation between estradiol and DPelvicPM (p = 0.49) was found only on days 7–10 in women who used the OC.
*ANDROGENS, PAIN, AND PUBERTAL DEVELOPMENT
*TESTOSTERONE AS AN INHIBITOR OF INFLAMMATION
*ANDROGENS AND ENDOMETRIOSIS
*POTENTIAL CLINICAL USE OF ANDROGENS IN WOMEN
*COMBINED TESTOSTERONE AND AROMATASE INHIBITOR THERAPY
CONCLUSION
There has been a dearth of research into the role of androgens in the development of endometriosis lesions, the experience of pain, inflammatory disease processes, and optimizing a woman’s quality of life. Our research indicates that inflammation, pain, and androgen levels are intimately associated, with a lack of clarity regarding whether low androgen levels pre- or post-date the presence of inflammation. Optimal products for the treatment of testosterone deficiency in women are yet to be developed, and the potential pharmacological doses required to achieve therapeutic benefits using existing testosterone therapies are yet to be established. Hormonal therapy for menstrual suppression profoundly influences androgen levels and may contribute to reduced androgen effects. The development of new therapies to reduce inflammation may offer a novel approach to addressing androgen deficiency in women.
