The Non-Ergot Derived Dopamine Agonist Quinagolide as an Anti-Endometriotic Agent

Akyol, Alpaslan; Kavak, Ebru Çelik; Akyol, Hadice; Pala, Şehmus; Gürsu, Ferit

doi:10.1159/000452796

Cited by 10 publications

(11 citation statements)

References 30 publications

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“…Interestingly, the first line pharmacological treatment for RLS may have a role in endometriosis management. For example, dopamine agonists may regress endometriotic lesions ( 32 , 33 ) and although not yet specifically tested in clinical trials, alpha-2-delta ligands such as gabapentin and pregabalin are commonly used in clinical practice to treat endometriosis associated pelvic pain ( 34 , 35 ).…”

Section: Discussionmentioning

confidence: 99%

Premenopausal Women With a Diagnosis of Endometriosis Have a Significantly Higher Prevalence of a Diagnosis or Symptoms Suggestive of Restless Leg Syndrome: A Prospective Cross-Sectional Questionnaire Study

et al. 2021

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BackgroundEndometriosis and restless leg syndrome (RLS) are both chronic conditions that can negatively affect a woman’s quality of life. A higher prevalence of RLS is seen in women and particularly in those who are pregnant, suggesting a possible ovarian hormonal influence. Endometriosis is a common (affecting 1 in 10 women) estrogen driven gynecological condition, and the prevalence of RLS in women with symptoms or a diagnosis of endometriosis is unknown.MethodsA prospective, cross-sectional, observational self-completed questionnaire study was distributed to 650 pre-menopausal women attending the gynecological department at Liverpool Women`s Hospital over a period of 4 months. 584 questionnaires were returned and 465 completed questionnaires were included in the final dataset. Data on RLS-associated (The International Restless Leg Syndrome Study Group rating scale) and endometriosis-associated (modified-British Society of Gynaecological Endoscopists pelvic pain questionnaire) symptoms were collected.ResultsWomen who reported a prior surgical diagnosis of endometriosis had a greater risk of having a prior formal diagnosis of RLS (OR 4.82, 95% CI 1.66,14.02) and suffering RLS symptoms (OR 2.13, 95% CI 1.34-3.39) compared with those without a diagnosis. When women with either a formal surgical diagnosis or symptoms associated with endometriosis were grouped together, they also have a significantly increased risk of having either a formal diagnosis or symptoms suggestive of RLS (OR 2.49, 95% CI 1.30, 3.64). In women suffering with endometriosis-associated symptoms, the cumulative endometriosis-associated symptom scores demonstrated a modest positive correlation with RLS severity scores (r=0.42 95% CI 0.25 to 0.57).ConclusionsThis is the first study highlighting an association between the symptoms relevant to the two chronic conditions RLS and endometriosis, showing that women with a reported prior surgical diagnosis or symptoms suggestive of endometriosis have a significantly higher prevalence of a prior formal diagnosis or symptoms suggestive of RLS. This data will help in facilitating the discovery of novel therapeutic targets relevant to both conditions. The simultaneous treatment of these conditions could potentially lead to improvement in the overall quality of life for these women.

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Section: Discussionmentioning

confidence: 99%

Premenopausal Women With a Diagnosis of Endometriosis Have a Significantly Higher Prevalence of a Diagnosis or Symptoms Suggestive of Restless Leg Syndrome: A Prospective Cross-Sectional Questionnaire Study

et al. 2021

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“…When these women were treated for 18–20 weeks with orally administered quinagolide, endometriotic lesions either disappeared or showed reduced size at the preplanned second look laparoscopy 8 . These clinical findings were further supported by experiments demonstrating that quinagolide reduced lesion volume in an autologous rat endometriosis model (rats transplanted with own uterine fragments on the peritoneum) 29 and a heterologous mouse model (nude mice transplanted with human endometrial fragments on the peritoneum) 7 . Considering the translatability of the D2R agonist effects from the preclinical to the clinical situation and the large effect size of PRLR blockade in the murine endometriosis interna model, we assume that PRLR blockade may provide a new treatment opportunity for endometriosis.…”

Section: Discussionmentioning

confidence: 76%

The effects of prolactin receptor blockade in a murine endometriosis interna model

Otto

Ulbrich

Freiberg

2022

Pharmacology Res & Perspec

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Endometriosis in an estrogen‐dependent disease that is characterized by the presence of endometrial tissue outside the uterine cavity leading to pain and infertility in many affected women. Highly efficient treatment options which create a hypo‐estrogenic environment can cause side effects such as hot flushes and bone mass loss that are not favorable for premenopausal women. Previous work has demonstrated that increased local or systemic prolactin seems to be involved in the pathogenesis of endometriosis. Here we examined two prolactin receptor (PRLR) blocking antibodies in a murine endometriosis interna model which relies on the induction of systemic hyperprolactinemia in female SHN mice. The severity of the disease is determined by the degree of endometrial invasion into the myometrium. In this model, endometriosis was inhibited by clinical gold standards such as progestins and anti‐estrogenic approaches. PRLR blockade completely inhibited endometriosis in this mouse model to the same extent as the anti‐estrogen faslodex or the GnRH antagonist cetrorelix. In contrast to cetrorelix and faslodex, the PRLR antibodies did not decrease relative uterine weights and were thus devoid of anti‐estrogenic effects. We therefore hypothesize that PRLR antibodies may present a novel and highly efficient treatment option for endometriosis with a good safety and tolerability profile. Clinical studies are on the way to test this hypothesis.

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“…Compared to luteinizing hormone releasing hormone (LHRH) agonist, cabergoline (dostinex) yields better resulted in decreasing the size of endometrioma by vaginal ultrasound in endometriosis patients in a prospective randomized study [ 54 ]. Quinagolide, another non-ergot-derived dopamine agonist, reduced the levels of both IL-6 and VEGF in peritoneal fluid and was shown to be of potential use for the treatment of endometriosis-induced endometriosis in a rat model [ 55 ]. These drugs may regulate the angiogenesis process by regulating the regulation of related immune inflammatory factors and angiogenic factors.…”

Section: Resultsmentioning

confidence: 99%

Anti‐Angiogenic Alternative and Complementary Medicines for the Treatment of Endometriosis: A Review of Potential Molecular Mechanisms

Zheng

Cao²,

et al. 2018

Evidence-Based Complementary and Alternative Medicine

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Endometriosis is caused by the growth or infiltration of endometrial tissues outside of the endometrium and myometrium. Symptoms include pain and infertility. Surgery and hormonal therapy are widely used in Western medicine for the treatment of endometriosis; however, the side effects associated with this practice include disease recurrence and menopause, which can severely influence quality of life. Angiogenesis is the main biological mechanism underlying the development of endometriosis. Numerous natural products and Chinese medicines with potent anti-angiogenic effects have been investigated, and the molecular basis underlying their therapeutic effects in endometriosis has been explored. This review aims to describe natural products and compounds that suppress angiogenesis associated with endometriosis and to assess their diverse molecular mechanisms of action. Furthermore, this review provides a source of information relating to alternative and complementary therapeutic products that mediate anti-angiogenesis. An extensive review of the literature and electronic databases, such as the China National Knowledge Infrastructure, PubMed, and Embase, was conducted using the keywords ‘endometriosis,' ‘traditional Chinese medicine,' ‘Chinese herbal medicine,' ‘natural compounds,' and ‘anti-angiogenic' therapy. Anti-angiogenic therapy is an emerging strategy for the treatment of endometriosis. Natural anti-angiogenic products and Chinese medicines provide several beneficial clinical effects, including pain relief. In this review, we summarize clinical trials and experimental studies of endometriosis using natural products and Chinese medicines. In particular, we focus on anti-angiogenic products and alternative and complementary medicines for the treatment of endometriosis and additionally examine their therapeutic efficacy and mechanisms of action. Anti-angiogenic natural products and/or compounds provide a new approach for the treatment of endometriosis. Future work will require randomized trials with larger numbers of subjects, as well as long-term follow-up to confirm the findings described here.

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The Non-Ergot Derived Dopamine Agonist Quinagolide as an Anti-Endometriotic Agent

Cited by 10 publications

References 30 publications

Premenopausal Women With a Diagnosis of Endometriosis Have a Significantly Higher Prevalence of a Diagnosis or Symptoms Suggestive of Restless Leg Syndrome: A Prospective Cross-Sectional Questionnaire Study

Premenopausal Women With a Diagnosis of Endometriosis Have a Significantly Higher Prevalence of a Diagnosis or Symptoms Suggestive of Restless Leg Syndrome: A Prospective Cross-Sectional Questionnaire Study

The effects of prolactin receptor blockade in a murine endometriosis interna model

Anti‐Angiogenic Alternative and Complementary Medicines for the Treatment of Endometriosis: A Review of Potential Molecular Mechanisms

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