Gonadotrophin-releasing hormone analogues for endometriosis

Veth, Veerle B; Kar, Majorie van de; Duffy, James M.N.; Wely, Madelon van; Mijatovic, Velja; Maas, Jacques W.M.

doi:10.1002/14651858.cd014788

Cited by 5 publications

(4 citation statements)

References 30 publications

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“…At the same time, a retrospective analysis of studies found no signi cant difference in calcium levels between case and control groups of women with endometriosis [32]. Recent studies on endometriosis and extracellular calcium homeostasis have focused on the effects of therapeutic measures (e.g., gonadotropin-releasing hormone agonists) on bone mineral density and calcium levels in endometriosis [33,34], and observational studies on the causal relationship between calcium levels and endometriosis have not yielded uniform results, leaving much room for exploration and research in this eld.…”

Section: Discussionmentioning

confidence: 99%

The role of calcium homeostasis in endometriosis: a comprehensive study of multiple types of Mendelian randomization

Deng,

Dai,

Wang

et al. 2023

Preprint

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Background: Endometriosis is considered to be a complex gynecological disorder that affects the health and quality of life of affected women. The etiology and pathogenesis of endometriosis remain unclear, and few modifiable risk factors have been identified. It is generally believed that endometriosis is a chronic inflammatory disease, which can cause local immune disorders. And calcium homeostasis of the body is closely related to inflammation and immunity. Although observational studies have assessed the association between calcium homeostasis regulatory factor levels and endometriosis risk, the conclusions have been inconsistent. Therefore, the aim of this study was to explore the causal relationship between calcium homeostasis regulators and endometriosis risk using publicly available genome-wide association studies (GWAS) aggregated statistics. Methods: The Mendelian randomization (MR) analysis was performed using GWAS data, including calcium (N = 315,153), serum 25-Hydroxyvitamin D (25(OH)D) (N = 496,946), parathyroid hormone (PTH) (N = 3,301), endometriosis (N = 77,257), endometriosis of ovary (N = 72,200), endometriosis of rectovaginal septum and vagina (N = 70,329), endometriosis of intestine (N = 69,146), endometriosis of fallopian tube (N = 69,085), endometriosis of pelvic peritoneum (N = 71,922), endometriosis of uterus (N = 71,341), and Unspecified/other endometriosis (N = 70,404). Four levels of MR analysis were undertaken, starting with single univariate MR and multivariate MR to test the correlation between calcium homeostasis regulatory factors and endometriosis, followed by inverse MR to explore the effect of endometriosis on body calcium homeostasis. And further two-sample MR to probe the relationship between calcium levels and endometriosis subtypes. Cochran's Q test, MR-Egger intercept test, leave-one-out analysis and funnel plot were utilized for sensitivity analysis. Results: The two-sample MR analysis revealed a strong positive causal relationship between genetically predicted calcium levels and endometriosis risk (IVW: OR = 1.15, 95% CI: 1.02-1.29, p = 0.018). Notably, the results of MVMR analysis demonstrated that the positive correlation of calcium levels on endometriosis still held even after correction for 25(OH)D and PTH (OR = 1.14, 95% CI: 1.02-1.28, p = 0.026). After removing outliers using MR-PRESSO to ensure that horizontal pleiotropy was eliminated, MVMR analysis was performed again, and the causal association between calcium levels and endometriosis remained significant (OR = 1.13, 95% CI: 1.01-1.27, p = 0.033). The inverse MR analysis discovered a causal association between endometriosis and 25(OH)D (β = 0.01, 95% CI: 0.00-0.02, p = 0.007) and calcium (β = 0.02, 95% CI: 0.00-0.04, p = 0.035). The two-sample MR analysis we employed to further investigate that calcium levels were positively and causally associated only with endometriosis of uterus (IVW: OR = 1.23, 95% CI: 1.01-1.49, p= 0.038), with no suggestion of a causal relationship with the risk of other types of endometriosis subtypes. Conclusion：The comprehensive study of multiple types of MR provides genetic evidence for a causal relationship between calcium homeostasis and endometriosis risk, demonstrating that calcium levels are a risk factor for endometriosis. It also emphasizes the importance of monitoring calcium levels in patients suffering from endometriosis, which may provide dietary guidance for patients with endometriosis.

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Section: Discussionmentioning

confidence: 99%

The role of calcium homeostasis in endometriosis: a comprehensive study of multiple types of Mendelian randomization

Deng,

Dai,

Wang

et al. 2023

Preprint

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“…According to Pandya (2018), "to ignore health care costs implies society would pay any amount of money for services that improve the health of patients even if those services result in patients achieving only marginal improvement in health outcomes". For example, GnRH agonists and antagonists are probably the most effective hormones for relieving endometriosis-associated pain and can be safely used for long periods when combined with add-back therapy (Veth et al, 2023;Xin et al, 2023;Yan et al, 2022). However, their cost may limit adherence or even prevent their use if individual patients have to pay for the medication.…”

Section: The Perspective Of Public Health Authorities: the Concept Of...mentioning

confidence: 99%

Towards comprehensive management of symptomatic endometriosis: beyond the dichotomy of medical versus surgical treatment

Mijatovic,

Vercellini

2024

Human Reproduction

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Except when surgery is the only option because of organ damage, the presence of suspicious lesions, or the desire to conceive, women with endometriosis-associated pain often face a choice between medical and surgical treatment. In theory, the description of the potential benefits and potential harms of the two alternatives should be standardized, unbiased, and based on strong evidence, enabling the patient to make an informed decision. However, doctor’s opinion, intellectual competing interests, local availability of specific services and (mis)information obtained from social media, and online support groups can influence the type of advice given and affect patients’ choices. This is compounded by the paucity of robust data from randomized controlled trials, and the anxiety of distressed women who are eager to do anything to alleviate their disabling symptoms. Vulnerable patients are more likely to accept the suggestions of their healthcare provider, which can lead to unbalanced and physician-centred decisions, whether in favour of either medical or surgical treatment. In general, treatments should be symptom-orientated rather than lesion-orientated. Medical and surgical modalities appear to be similarly effective in reducing pain symptoms, with medications generally more successful for severe dysmenorrhoea and surgery more successful for severe deep dyspareunia caused by fibrotic lesions infiltrating the posterior compartment. Oestrogen–progestogen combinations and progestogen monotherapies are generally safe and well tolerated, provided there are no major contraindications. About three-quarters of patients with superficial peritoneal and ovarian endometriosis and two-thirds of those with infiltrating fibrotic lesions are ultimately satisfied with their medical treatment although the remainder may experience side effects, which may result in non-compliance. Surgery for superficial and ovarian endometriosis is usually safe. When fibrotic infiltrating lesions are present, morbidity varies greatly depending on the skill of the individual surgeon, the need for advanced procedures, such as bowel resection and ureteral reimplantation, and the availability of expert colorectal surgeons and urologists working together in a multidisciplinary approach. The generalizability of published results is adequate for medical treatment but very limited for surgery. Moreover, on the one hand, hormonal drugs induce disease remission but do not cure endometriosis, and symptom relapse is expected when the drugs are discontinued; on the other hand, the same drugs should be used after lesion excision, which also does not cure endometriosis, to prevent an overall cumulative symptom and lesion recurrence rate of 10% per postoperative year. Therefore, the real choice may not be between medical treatment and surgery, but between medical treatment alone and surgery plus postoperative medical treatment. The experience of pain in women with endometriosis is a complex phenomenon that is not exclusively based on nociception, although the role of peripheral and central sensitization is not fully understood. In addition, trauma, and especially sexual trauma, and pelvic floor disorders can cause or contribute to symptoms in many individuals with chronic pelvic pain, and healthcare providers should never take for granted that diagnosed or suspected endometriosis is always the real, or the sole, origin of the referred complaints. Alternative treatment modalities are available that can help address most of the additional causes contributing to symptoms. Pain management in women with endometriosis may be more than a choice between medical and surgical treatment and may require comprehensive care by a multidisciplinary team including psychologists, sexologists, physiotherapists, dieticians, and pain therapists. An often missing factor in successful treatment is empathy on the part of healthcare providers. Being heard and understood, receiving simple and clear explanations and honest communication about uncertainties, being invited to share medical decisions after receiving detailed and impartial information, and being reassured that a team member will be available should a major problem arise, can greatly increase trust in doctors and transform a lonely and frustrating experience into a guided and supported journey, during which coping with this chronic disease is gradually learned and eventually accepted. Within this broader scenario, patient-centred medicine is the priority, and whether or when to resort to surgery or choose the medical option remains the prerogative of each individual woman.

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“…The ineffectiveness of gonadotropin-releasing hormone (GnRH) agonists or antagonists in postmenopausal women can be attributed to the fundamental physiological changes that occur during menopause. 84 Menopause is characterized by a significant decrease in the production of estrogen and progesterone by the ovaries. GnRH agonists and antagonists work by suppressing the release of these hormones from the ovaries.…”

Section: Ineffective Approaches To Therapiesmentioning

confidence: 99%

Postmenopausal endometriosis: a challenging condition beyond menopause

Vallée,

Carbonnel,

Ceccaldi

et al. 2024

Menopause

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Importance and Objective Postmenopausal endometriosis is a complex condition that challenges the conventional belief that endometriosis resolves with menopause. Despite the cessation of menstruation, a subset of women continues to experience or develop endometriosis-related symptoms during the postmenopausal period. Thus, this review aimed to shed light on postmenopausal endometriosis, exploring its clinical features, diagnostic considerations, management approaches, and the potential impact on women's health. Methods PubMed/Medline, Scopus, and Web of Science databases were used for the research, with only articles in English language, using the following terms: “postmenopausal endometriosis,” “menopause,” “management,” “treatment,” and “quality of life,” from inception to 2023. Discussion and Conclusion The clinical features of postmenopausal endometriosis include persistent or recurrent pelvic pain, dyspareunia, bowel, or urinary symptoms and, occasionally, abnormal vaginal bleeding. The absence of menstrual cycles presents a diagnostic challenge, as the traditional diagnostic criteria for endometriosis rely on menstrual patterns. Visual cues may be less evident, and the symptoms often overlap with other gynecological conditions, necessitating a thorough evaluation to differentiate postmenopausal endometriosis from other potential causes. Management approaches for postmenopausal endometriosis encompass surgical intervention, hormonal therapies, pain management, and individualized care. Postmenopausal endometriosis significantly impacts the quality of life, sexual health, and long-term well-being of women. Understanding the clinical features, diagnostic challenges, and management approaches of postmenopausal endometriosis is crucial for healthcare professionals to provide effective care and to improve the quality of life of women affected by this condition.

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Gonadotrophin-releasing hormone analogues for endometriosis

Cited by 5 publications

References 30 publications

The role of calcium homeostasis in endometriosis: a comprehensive study of multiple types of Mendelian randomization

The role of calcium homeostasis in endometriosis: a comprehensive study of multiple types of Mendelian randomization

Towards comprehensive management of symptomatic endometriosis: beyond the dichotomy of medical versus surgical treatment

Postmenopausal endometriosis: a challenging condition beyond menopause

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