The Possible Role of Fluoxetine in Adenomyosis: An Animal Experiment with Clinical Correlations

Sengupta, Partha Pratim

doi:10.7860/jcdr/2013/5654.3128

Cited by 9 publications

(11 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Both administration of fluoxetine, a selective serotonin reuptake inhibitor that causes an increase in prolactin secretion, and pituitary isograft can be used to induce adenomyosis, though again, neither of these rat models appears to have been used for substantial further experimentation. 106,107 Nevertheless, these reports substantiate the broader biological applicability of the mouse findings that demonstrate hormonal dysregulation leading to adenomyosis and provide nonmouse options for further study of adenomyosis using induced animal models.…”

Section: Other Animal Models Of Adenomyosismentioning

confidence: 76%

Animal Models of Adenomyosis

2020

View full text Add to dashboard Cite

Adenomyosis is a nonmalignant uterine disorder in which endometrial tissue exists within and grows into the myometrium. Animal models have generated limited insight into the still-unclear pathogenesis of adenomyosis, provided a platform for preclinical screening of many drugs and compounds with potential as therapeutics, and elucidated mechanisms underlying the pain and fertility issues that occur in many women with the disease. Spontaneous adenomyosis has been studied in nonhuman primates, primarily in the form of case reports. Adenomyosis is routinely experimentally induced in mice through methods such as neonatal tamoxifen exposure, pituitary engraftment, and human tissue xenotransplantation. Several studies have also reported hormonal or environmental toxicant exposures that give rise to murine adenomyosis, and genetically engineered models have been created that recapitulate the human-like condition, most notably involving alteration of β-catenin expression. This review describes the animal models for adenomyosis and their contributions to our understanding of the factors underpinning the development of symptoms. Animal models represent a unique opportunity for understanding the molecular basis of adenomyosis and developing efficacious treatment options for affected women. Herein, we assess their different potentials and limitations with regard to identification of new therapeutic interventions and reflect on future directions for research and drug validation.

show abstract

Section: Other Animal Models Of Adenomyosismentioning

confidence: 76%

Animal Models of Adenomyosis

2020

View full text Add to dashboard Cite

show abstract

“…107 Similar results were found in a bovine model. 108 In humans, higher levels of PRL have been reported in women with than without adenomyosis, 109 and vaginal administration of bromocriptine significantly decreased menstrual bleeding and pain and improved quality of life in women with disease. 110 Mechanisms underlying elevated PRL and PRLR in the pathogenesis of adenomyosis are still unclear.…”

Section: The Role Of Pituitary Hormonesmentioning

confidence: 99%

Adenomyosis: Mechanisms and Pathogenesis

et al. 2020

View full text Add to dashboard Cite

Adenomyosis is a common disorder of the uterus, and is associated with an enlarged uterus, heavy menstrual bleeding (HMB), pelvic pain, and infertility. It is characterized by endometrial epithelial cells and stromal fibroblasts abnormally found in the myometrium where they elicit hyperplasia and hypertrophy of surrounding smooth muscle cells. While both the mechanistic processes and the pathogenesis of adenomyosis are uncertain, several theories have been put forward addressing how this disease develops. These include intrinsic or induced (1) microtrauma of the endometrial–myometrial interface; (2) enhanced invasion of endometrium into myometrium; (3) metaplasia of stem cells in myometrium; (4) infiltration of endometrial cells in retrograde menstrual effluent into the uterine wall from the serosal side; (5) induction of adenomyotic lesions by aberrant local steroid and pituitary hormones; and (6) abnormal uterine development in response to genetic and epigenetic modifications. Dysmenorrhea, HMB, and infertility are likely results of inflammation, neurogenesis, angiogenesis, and contractile abnormalities in the endometrial and myometrial components. Elucidating mechanisms underlying the pathogenesis of adenomyosis raise possibilities to develop targeted therapies to ameliorate symptoms beyond the current agents that are largely ineffective. Herein, we address these possible etiologies and data that support underlying mechanisms.

show abstract

“…Consistently, SHN mice treated with dopamine antagonists, which resulted in increased PRL release, also developed adenomyosis [ 112 ]. Treatment of rats for 90–100 days with fluoxetine hydrochloride, a selective serotonin reuptake inhibitor (SSRI) that can increase the PRL secretion, induced adenomyosis with high incidence in rats [ 89 , 113 ]. In addition, aged female mice deficient in DRD2 developed uterine adenomyosis spontaneously in response to prolonged PRL exposure [ 90 ].…”

Section: Resultsmentioning

confidence: 99%

“…In humans, patients with adenomyosis frequently exhibit hyperprolactinemia [ 113 , 133 ], but one less appreciated result is that the elevated levels of PRL can cause increased pain by promoting nociceptor sensitization through the short isoform of PRLR (RPLR-S) [ 134 , 135 , 136 , 137 , 138 ], the expression of which is also found to be higher in the bovine uterus with adenomyosis [ 139 ] and, we can speculate, in humans as well. DRD2 agonists have been shown to suppress PRL-induced adenomyosis and also have therapeutic potential for reducing pain and treating adenomyosis, likely through the promotion of the long isoform of PRLR (PRLR-L) and the inhibition of angiogenesis by DRD2 [ 140 , 141 , 142 , 143 ].…”

Section: Resultsmentioning

confidence: 99%

Unveiling the Pathogenesis of Adenomyosis through Animal Models

Wang

Benagiano

Liu

et al. 2022

JCM

View full text Add to dashboard Cite

Background: Adenomyosis is a common gynecological disorder traditionally viewed as “elusive”. Several excellent review papers have been published fairly recently on its pathogenesis, and several theories have been proposed. However, the falsifiability, explanatory power, and predictivity of these theories are often overlooked. Since adenomyosis can occur spontaneously in rodents and many other species, the animal models may help us unveil the pathogenesis of adenomyosis. This review critically tallies experimentally induced models published so far, with a particular focus on their relevance to epidemiological findings, their possible mechanisms of action, and their explanatory and predictive power. Methods: PubMed was exhaustively searched using the phrase “adenomyosis and animal model”, “adenomyosis and experimental model”, “adenomyosis and mouse”, and “adenomyosis and rat”, and the resultant papers were retrieved, carefully read, and the resultant information distilled. All the retrieved papers were then reviewed in a narrative manner. Results: Among all published animal models of adenomyosis, the mouse model of adenomyosis induced by endometrial–myometrial interface disruption (EMID) seems to satisfy the requirements of falsifiability and has the predictive capability and also Hill’s causality criteria. Other theories only partially satisfy Hill’s criteria of causality. In particular, animal models of adenomyosis induced by hyperestrogenism, hyperprolactinemia, or long-term exposure to progestogens without much epidemiological documentation and adenomyosis is usually not the exclusive uterine pathology consequent to those induction procedures. Regardless, uterine disruption appears to be a necessary but not sufficient condition for causing adenomyosis. Conclusions: EMID is, however, unlikely the sole cause for adenomyosis. Future studies, including animal studies, are warranted to understand how and why in utero and/or prenatal exposure to elevated levels of estrogen or estrogenic compounds increases the risk of developing adenomyosis in adulthood, to elucidate whether prolactin plays any role in its pathogenesis, and to identify sufficient condition(s) that cause adenomyosis.

show abstract

The Possible Role of Fluoxetine in Adenomyosis: An Animal Experiment with Clinical Correlations

Cited by 9 publications

References 10 publications

Animal Models of Adenomyosis

Animal Models of Adenomyosis

Adenomyosis: Mechanisms and Pathogenesis

Unveiling the Pathogenesis of Adenomyosis through Animal Models

Contact Info

Product

Resources

About