Treatment of endometriosis-associated pain with linzagolix, an oral gonadotropin-releasing hormone–antagonist: a randomized clinical trial

Donnez, Jacques; Taylor, Hugh S.; Taylor, Robert N.; Akin, Mark; Tatarchuk, T.F.; Wilk, Katarzyna; Gotteland, Jean‐Pierre; Lecomte, V.; Bestel, Elke

doi:10.1016/j.fertnstert.2020.02.114

Cited by 82 publications

(81 citation statements)

References 33 publications

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“…A phase 2b, dose-ranging clinical trial evaluated linzagolix 50 to 200 mg/day in premenopausal women with endometriosis. 71 Modest, dose-dependent reductions in lumbar spine BMD (1%-3%) were observed during the 24-week treatment period in patients who received linzagolix doses of 75 mg/day or higher. Two phase 3, randomized,…”

Section: Gnrh Antagonistsmentioning

confidence: 92%

“…One publication each was identified for the GnRH antagonists ASP1707, linzagolix, and relugolix (Table 3). [69][70][71] A phase 2, dose-ranging clinical trial assessed the efficacy and safety of ASP1707 3 to 15 mg once daily compared with placebo and monthly leuprolide acetate 3.75 mg in premenopausal women with endometriosis (N = 540). 70 Decreases in BMD at week 24 were observed in all active-treatment groups; however, the magnitude of decrease in total hip and spine BMD was significantly greater with leuprolide versus ASP1707 (-1.2% to -2.3% vs. -3.9%; p < 0.001).…”

Section: Gnrh Antagonistsmentioning

confidence: 99%

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Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life

Watts

Binkley

Owens

et al. 2021

Journal of Women's Health

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Bone mineral density (BMD) changes during the life span, increasing rapidly during adolescence, plateauing in the third decade of life, and subsequently entering a phase of age-related decline. In women, menopause leads to accelerated bone loss and an increase in fracture risk. Between peak bone mass attainment and menopause, BMD is generally stable and the risk of fracture is typically low. This time period is marked by life events such as pregnancy and lactation, which transiently decrease BMD, yet their long-term effects on fracture risk are less certain. BMD may also be altered by exposure to medications that affect bone metabolism (e.g., contraceptives, glucocorticoids, antidiabetic medications, antiepileptic drugs). Although oral contraceptives are often believed to be neutral with regard to bone health, depot medroxyprogesterone acetate (DMPA) and gonadotropinreleasing hormone (GnRH) agonists have been associated with decreases in BMD. Development of newer medical therapies, principally GnRH antagonists (e.g., ASP1707, elagolix, linzagolix, relugolix), for treatment of endometriosis-associated pelvic pain and heavy menstrual bleeding due to uterine fibroids has renewed interest in the short-and long-term impacts of changes in BMD experienced by premenopausal women. It is important to understand how these drugs influence BMD and put the findings into context with regard to measurement variability and naturally occurring factors that influence bone health. This review summarizes what is known about the effects on bone health pregnancy, lactation, and use of DMPA, GnRH agonists, and GnRH antagonists in premenopausal women and potential consequences later in life. ClinicalTrials.gov identifier: NCT03213457.

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Section: Gnrh Antagonistsmentioning

confidence: 92%

Section: Gnrh Antagonistsmentioning

confidence: 99%

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life

Watts

Binkley

Owens

et al. 2021

Journal of Women's Health

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“…Relugolix and linzagolix are the two new oral GnRH antagonists, in an advanced stage of clinical development for the management of pain associated with endometriosis [180,181]. A Phase 2, multicenter, randomized, double-blind, placebo-controlled study on oral administration of relugolix for 12 weeks demonstrated efficacy in alleviating endometriosisassociated pain in a dose-response manner with some adverse events (hot flush, heavy menstrual bleeding, and irregular menstruation, and bone mineral density decrease).…”

Section: Gnrh Antagonistsmentioning

confidence: 99%

Hormonal treatments for endometriosis: The endocrine background

Vannuccini

Clemenza

Rossi

et al. 2021

Rev Endocr Metab Disord

133

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Endometriosis is a benign uterine disorder characterized by menstrual pain and infertility, deeply affecting women’s health. It is a chronic disease and requires a long term management. Hormonal drugs are currently the most used for the medical treatment and are based on the endocrine pathogenetic aspects. Estrogen-dependency and progesterone-resistance are the key events which cause the ectopic implantation of endometrial cells, decreasing apoptosis and increasing oxidative stress, inflammation and neuroangiogenesis. Endometriotic cells express AMH, TGF-related growth factors (inhibin, activin, follistatin) CRH and stress related peptides. Endocrine and inflammatory changes explain pain and infertility, and the systemic comorbidities described in these patients, such as autoimmune (thyroiditis, arthritis, allergies), inflammatory (gastrointestinal/urinary diseases) and mental health disorders.The hormonal treatment of endometriosis aims to block of menstruation through an inhibition of hypothalamus-pituitary-ovary axis or by causing a pseudodecidualization with consequent amenorrhea, impairing the progression of endometriotic implants. GnRH agonists and antagonists are effective on endometriosis by acting on pituitary-ovarian function. Progestins are mostly used for long term treatments (dienogest, NETA, MPA) and act on multiple sites of action. Combined oral contraceptives are also used for reducing endometriosis symptoms by inhibiting ovarian function. Clinical trials are currently going on selective progesterone receptor modulators, selective estrogen receptor modulators and aromatase inhibitors. Nowadays, all these hormonal drugs are considered the first-line treatment for women with endometriosis to improve their symptoms, to postpone surgery or to prevent post-surgical disease recurrence. This review aims to provide a comprehensive state-of-the-art on the current and future hormonal treatments for endometriosis, exploring the endocrine background of the disease.

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“…До ефектів метаболітів прогестерону також відносять пригнічення зворотного захоплення серотоніну і вплив на моноаміни, що в умовах недостатності гормону пояснює депресивні розлади на фоні ендометріозу. В цілому сучасні схеми лікування шляхом індукції гіпоестрогенного стану та пригнічення трофічних ефектів естрадіолу на еутопічний і ектопічний ендометрій дозволяють значною мірою контролювати перебіг захворювання та досягти атрофії ендометріоїдних вогнищ [15]. Проте позаматкові вогнища ендометріозу характеризуються меншою кількістю рецепторів до естрогенів і прогестерону в порівнянні з матковим ендометрієм.…”

Section: вступunclassified

“…Проте позаматкові вогнища ендометріозу характеризуються меншою кількістю рецепторів до естрогенів і прогестерону в порівнянні з матковим ендометрієм. Вираженість експресії таких рецепторів обернено пропорційна віддаленості ділянки ураження від матки, що передбачає її меншу гормонозалежність та знижену відповідь на гормональну терапію [15,16]. За таких умов доречним буде спрямувати терапевтичні зусилля також на неендокринні ланки патогенезу ендометріозу, як-от хронічне запалення, прооксидантний стан, порушення апоптозу, неоангіогенезу, проліферації, стромоутворення і психогенний компонент хвороби.…”

Section: вступunclassified

Anti-relapse therapy of endometriosis: possible variations

Захаренко

Регеда²,

Manoliak

et al. 2021

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Research aim: to determine the clinical efficacy and safety of bioavailable curcumin Longimin® in the complex anti-relapse therapy of patients with extragenital endometriosis after surgery.Materials and methods. Study involved 45 women with a mean age of 29.3 ± 3.6 years with a diagnosis of extragenital endometriosis. After surgical treatment of this disease all patients were prescribed dienogest 2 mg/day for 6 months with anti-relapse purpose. After that, 22 patients did not receive drug treatment (group 1) and other 23 women started a six-month course of 400 mg bioavailable curcumin (group 2).Results. After 12 months of observation 3 cases (13.6%) of newly formed foci of endometriosis were found among patients of group 1, two of which were multi-endometriomas, and the third was retrocervical heterotopia. There were no signs of recurrence in the group of sequential use of dienogest and bioavailable curcumin. In addition, 6 months after completion of hormonal treatment the number of women with chronic pelvic pain in group 1 was increased and average score on a visual analogue scale (VAS) was increased by 80% (p ≤0.05). It was accompanied by a stable moderately high level of anxiety throughout the observation period. At the same time the number of women who complained of intermenstrual pain in group 2 decreased from 15 to 13, and the average VAS score decreased by 13% (p ≥0.05) during the treatment period. Patients in group 2 noted an improvement in emotional control during treatment, which resulted in the average score decrease on the scale of personal and situational anxiety of the Spielberg-Hanin's questionnaire (25% and 30% respectively, p ≤0.05).Conclusions. The nature of the endometriosis development and progression is multipathogenetic. Blocking only its hormonal link, especially in cases of extragenital forms, may not be sufficient to stop the pathological process and prevent recurrence in the long term. Оbtained results of sequential course of dienogest and bioavailable curcumin Longimin® with anti-relapse purpose showed the wider clinical effectiveness of this therapy, which is probably based on additional inhibition of systemic inflammation, proliferation, stroma and psychogenic component of disease.

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Treatment of endometriosis-associated pain with linzagolix, an oral gonadotropin-releasing hormone–antagonist: a randomized clinical trial

Cited by 82 publications

References 33 publications

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life

Bone Mineral Density Changes Associated With Pregnancy, Lactation, and Medical Treatments in Premenopausal Women and Effects Later in Life

Hormonal treatments for endometriosis: The endocrine background

Anti-relapse therapy of endometriosis: possible variations

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