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Myometrium

The myometrium is the thick, middle muscular layer of the uterine wall, composed primarily of smooth muscle cells arranged in interlacing bundles, enabling the uterus to expand significantly during pregnancy and generate powerful, coordinated contractions during labor to facilitate childbirth and postpartum uterine involution.^[1]^[2] The uterine wall comprises three distinct layers: the inner endometrium, which lines the uterine cavity; the myometrium, providing structural support and contractility; and the outer perimetrium, a serous membrane that covers the uterus.^[1]^[3] The myometrium receives its blood supply from the uterine and ovarian arteries, which branch into arcuate, radial, basal, and spiral vessels, ensuring adequate perfusion that increases markedly during pregnancy to support fetal growth.^[1] In terms of physiology, the myometrium maintains relative quiescence during most of pregnancy through hormonal regulation, primarily progesterone, which inhibits contractility by reducing intracellular calcium levels and gap junction formation, while estrogen promotes myometrial growth and hypertrophy.^[4]^[5] Toward term, progesterone withdrawal and rising estrogen levels enhance myometrial excitability, leading to the formation of gap junctions that synchronize contractions across the uterine muscle.^[4] Oxytocin, released during labor, further amplifies contractions by stimulating calcium influx through L-type channels and intracellular release, activating myosin light chain kinase to drive actin-myosin interactions.^[4]^[5] The myometrium's contractions are essential for several reproductive processes: sporadic, irregular Braxton Hicks contractions occur throughout pregnancy to maintain uterine tone without cervical change, while true labor contractions become regular, progressive, and forceful, progressing through latent and active phases to dilate the cervix from 0 to 10 cm and expel the fetus.^[4] Postpartum, continued myometrial contractions help minimize bleeding by compressing blood vessels and aiding uterine involution back to its non-pregnant size of approximately 7.5 cm long, 5 cm wide, and 3 cm thick.^[4]^[3] Dysfunctions in myometrial contractility, such as preterm contractions or uterine inertia, can lead to complications like premature birth or prolonged labor, highlighting its critical role in reproductive health.^[4]

Anatomy

Gross anatomy

The myometrium forms the middle layer of the uterine wall, positioned between the inner endometrium and the outer perimetrium (serosa). It consists primarily of smooth muscle tissue that provides structural support and enables uterine contractility. In the non-pregnant state, the myometrium accounts for the majority of the uterine wall's thickness and mass, comprising approximately 75-80% of the total uterine wall's thickness.^[6]^[1] The myometrium exhibits a layered organization visible on gross examination. It is divided into three distinct layers: an inner junctional layer adjacent to the endometrium, composed of circularly oriented smooth muscle fibers; a middle vascular layer featuring interlacing bundles of longitudinal and circular fibers that form a dense mesh interwoven with prominent blood vessels; and an outer longitudinal layer with longer fibers that blend seamlessly with the perimetrium. This arrangement facilitates coordinated contractions while accommodating vascular supply. Thickness varies regionally, being thicker in the fundus (up to 2-3 cm) and progressively thinner toward the lower uterine segment (approximately 1 cm or less), reflecting functional adaptations for support and expulsion.^[7]^[8]^[6] During pregnancy, the myometrium undergoes marked hypertrophy and hyperplasia, with thickness remaining approximately 1-2 cm at term in the upper uterus to accommodate fetal growth and facilitate labor, while the lower segment thins further to form the functional pathway for delivery.^[1]^[7]^[9] Postpartum, the myometrium involutes rapidly, returning to its pre-pregnancy dimensions within weeks.^[1]^[7]

Histology

The myometrium is primarily composed of interlacing bundles of spindle-shaped smooth muscle cells, known as myocytes, embedded within a stromal connective tissue framework and an extracellular matrix. These myocytes form interconnected fasciculi that provide the structural basis for uterine contractility, surrounded by a supportive matrix that includes fibrous proteins and glycosaminoglycans.^[10] Myometrial myocytes are uninucleated cells featuring a central oval nucleus and abundant contractile apparatus, including dense arrays of actin and myosin filaments that enable phasic contractions. Unlike striated muscle, these cells lack sarcomeres but possess caveolae for calcium signaling and a notably high actin-to-myosin ratio of approximately 6:1—which supports efficient force generation during uterine activity.^[5] Intercellular communication in the myometrium occurs via gap junctions, primarily composed of connexin-43 proteins, which facilitate the propagation of electrical impulses and ions between adjacent myocytes. The expression and assembly of these connexin-43 gap junctions markedly increase toward term pregnancy, enhancing synchronized contractions essential for labor.^[11] The stromal component consists of fibroblasts that synthesize and maintain the extracellular matrix, featuring predominantly type I and type III collagen fibers that impart tensile strength, alongside elastin fibers that confer elasticity to accommodate uterine expansion. Arterioles and venules are interspersed throughout the myometrial bundles, integrating vascular elements into the tissue architecture without forming distinct layers. Additionally, interstitial Cajal-like cells, identified by KIT immunoreactivity, are present within the myometrium and may function as pacemakers by generating slow-wave electrical activity to coordinate myocyte depolarization.^[12]^[13]^[10]^[14]

Blood supply and innervation

The arterial supply to the myometrium is primarily provided by the uterine arteries, which are branches of the internal iliac arteries.^[15] These uterine arteries enter the uterus at its base and form arcuate arteries within the middle layer of the myometrium, which then branch into radial arteries that penetrate through all layers of the myometrial wall.^[1] Smaller basal arteries arise from the arcuate arteries to supply the deeper basal layer, ensuring comprehensive perfusion of the smooth muscle tissue.^[16] Venous drainage of the myometrium parallels the arterial supply, occurring through the uterine venous plexus that accompanies the uterine veins and ultimately drains into the internal iliac veins.^[15] This venous network is particularly prominent in the middle myometrial layer, where it supports the elevated metabolic demands required for uterine expansion and function during pregnancy.^[17] Lymphatic drainage from the myometrium follows the vascular pathways, directing lymph from the uterine body and fundus toward the pelvic lymph nodes, including the internal and external iliac nodes, and further to the para-aortic nodes.^[1] This segmental drainage pattern facilitates efficient clearance of interstitial fluid across the myometrial layers.^[18] Innervation of the myometrium involves both sympathetic and parasympathetic components of the autonomic nervous system, along with sensory fibers. Sympathetic innervation arises from the hypogastric plexus (T10-L2 spinal segments) and exerts vasoconstrictor effects on uterine vessels while modulating myometrial tone.^[15] Parasympathetic innervation originates from the pelvic splanchnic nerves (S2-S4) via the uterovaginal plexus and promotes myometrial motility and vasodilation.^[1] Sensory fibers, traveling alongside these autonomic nerves, transmit pain signals during myometrial contractions, such as those experienced in labor.^[19] In the non-pregnant state, adrenergic (sympathetic) dominance maintains relative uterine quiescence and vascular tone.^[20] During labor, this balance shifts toward cholinergic (parasympathetic) dominance, facilitating coordinated contractions and increased blood flow.^[21] The rich vascularity of the myometrium contributes to a heightened risk of hemorrhage during surgical procedures, such as hysterectomy or myomectomy, necessitating careful hemostatic techniques.^[22]

Development

Embryonic origins

The myometrium originates from the mesenchyme surrounding the paramesonephric (Müllerian) ducts during early embryonic development. These ducts form from the coelomic epithelium around the 7th week of gestation and elongate caudally alongside the Wolffian ducts.^[23] The surrounding splanchnic mesoderm differentiates into the smooth muscle precursors of the myometrium, with initial organization occurring as the ducts fuse to form the uterine primordium.^[24] Differentiation of the mesenchymal cells into smooth muscle begins around the 10th week of gestation, coinciding with the caudal fusion of the Müllerian ducts between weeks 8 and 12, which establishes the basic uterine body and fundus. The unfused cranial portions of the ducts develop into the uterine tubes by approximately week 10.^[23] Layer-specific origins are evident: the inner junctional layer derives directly from the Müllerian duct mesenchyme, while the outer myometrial layers incorporate contributions from Wolffian (mesonephric) duct mesenchyme, particularly on the mesometrial side.^[25]^[26] Genetic regulation plays a critical role in this patterning, with HOX cluster genes such as HOXA10 and HOXA11 directing the anterior-posterior specification of the uterine mesenchyme and its differentiation into myometrial tissue.^[27] These transcription factors ensure proper segmentation and myogenic commitment of the undifferentiated mesenchymal stem cell precursors, which proliferate under the influence of embryonic signaling pathways.^[28] Incomplete fusion of the Müllerian ducts during weeks 9 to 12 can result in anomalies such as uterine septa, where persistent mesenchymal septa disrupt uniform myometrial development and lead to structural weaknesses.^[23] Full myometrial maturation, including significant thickening, continues postnatally in response to hormonal changes.^[29]

Postnatal adaptations

Following birth, the myometrium undergoes maturational changes influenced by hormonal shifts, particularly during puberty. Estrogen-driven hypertrophy leads to substantial growth of the myometrial smooth muscle layer, transforming the uterus from an inverted pear shape in prepubertal girls—where the cervix dominates and the myometrial body is relatively thin—to a pear-shaped adult configuration with a prominent, thicker myometrial fundus exceeding the cervical portion in size.^[30] This hypertrophy, primarily in the later stages of puberty, reflects estrogen's role in stimulating myocyte proliferation and extracellular matrix reorganization, including a 90° reorientation of collagen fibrils around smooth muscle cells observed in rodent models.^[31] Consequently, myometrial thickness increases from roughly 0.5 cm in childhood to 1-2 cm in reproductive-age adults, enhancing the tissue's capacity for future contractile demands.^[32] In the reproductive years, the myometrium experiences cyclic influences from the menstrual cycle, characterized by modest proliferation of myocytes during the estrogen-dominant proliferative phase, followed by partial involution in the progesterone-influenced secretory phase. These changes involve estrogen-induced increases in myocyte proliferation markers and hypertrophy, balanced by progesterone-mediated suppression, resulting in no significant net growth over cycles but maintaining tissue homeostasis and responsiveness.^[10] Progesterone plays a key role in sustaining myometrial quiescence throughout these cycles by inhibiting inflammatory pathways and contractile gene expression, preventing unsynchronized activity.^[33] Concurrently, oxytocin receptor density rises with reproductive maturity, from low levels in prepuberty to heightened expression in adults, priming the myometrium for coordinated contractions without triggering premature activity.^[34] Myometrial stem and progenitor cells, including side population cells identified in human tissue, support regeneration and repair post-injury or minor trauma, contributing to the tissue's resilience without altering overall architecture.^[35] Experimental evidence from mouse models demonstrates label-retaining cells—quiescent populations that retain DNA labels—as key stem-like contributors to myometrial turnover, proliferating in response to hormonal stimuli like human chorionic gonadotropin to facilitate repair.^[36] With aging, particularly after menopause, declining estrogen levels induce gradual myometrial fibrosis, characterized by increased collagen deposition and extracellular matrix stiffening, alongside thinning of the muscle layer and reduced contractility.^[37] This leads to diminished elasticity and vascular alterations, impairing the myometrium's functional reserve, as evidenced by single-cell analyses showing shifts in fibroblast and smooth muscle populations toward a pro-fibrotic state.^[38]

Physiology

Non-pregnant state

In the non-pregnant state, the myometrium exhibits low-amplitude, uncoordinated phasic contractions that vary in intensity and occur sporadically throughout the menstrual cycle, with a tendency for greater activity at the fundus compared to the lower uterine segments.^[39] These contractions are primarily wave-like and peristaltic in nature, facilitating essential physiological functions without generating sustained tone.^[5] The resting membrane potential of myometrial smooth muscle cells is typically maintained between -50 and -65 mV through potassium (K⁺) efflux via leak channels and the sodium-potassium pump, creating a relatively depolarized state compared to other smooth muscles.^[39] Slow-wave electrical activity, originating from interstitial cells of Cajal-like cells within the myometrium, contributes to the initiation and propagation of these phasic events, though coordination remains limited due to sparse gap junctions.^[40] Contractile activity is tightly regulated by hormonal fluctuations during the menstrual cycle. In the proliferative phase, rising estrogen levels promote myometrial excitability by upregulating contractile proteins such as actin and myosin, as well as enhancing ion transport mechanisms like ATPase activity, leading to increased frequency and amplitude of contractions.^[39] Conversely, in the secretory phase, progesterone induces quiescence by hyperpolarizing the membrane, downregulating estrogen receptors, and suppressing gap junction formation, thereby reducing overall motility.^[41] During menstruation, these dynamics shift as progesterone withdrawal allows estrogen dominance, resulting in mild contractions that aid endometrial shedding by compressing spiral arterioles and limiting blood loss.^[42] Prostaglandins, particularly PGF2α synthesized in the endometrium and myometrium, further enhance this motility by sensitizing voltage-gated calcium channels and promoting vasoconstriction.^[42] Contraction in the non-pregnant myometrium is triggered by calcium (Ca²⁺) influx through L-type voltage-gated channels, which depolarize the membrane in response to slow waves or hormonal stimuli, leading to brief actin-myosin interactions without prolonged elevation of intracellular Ca²⁺.^[5] These low-intensity contractions serve critical functional roles, including supporting sperm transport toward the fallopian tubes via directed peristalsis during the periovulatory period and aiding the expulsion of menstrual debris to minimize retrograde flow into the peritoneal cavity.^[43] By compressing vessels and promoting anterograde expulsion, the myometrium helps prevent excessive retrograde menstruation, which could otherwise contribute to conditions like endometriosis.^[44]

Pregnancy adaptations

During pregnancy, the myometrium undergoes substantial growth through both hyperplasia, involving an increase in cell number primarily mediated by uterine stem cells, and hypertrophy, characterized by enlargement of smooth muscle cells, resulting in a 500- to 1,000-fold increase in uterine volume and a marked rise in myometrial mass to support fetal development.^[35]^[45] This adaptive expansion ensures the uterine wall can accommodate the growing fetus while maintaining structural integrity. Hormonally, progesterone plays a key role in preserving myometrial quiescence by suppressing the formation of gap junctions, which reduces synchronized contractions, and by decreasing calcium sensitivity in smooth muscle cells, thereby limiting excitability.^[46]^[47] Complementing this, relaxin inhibits myometrial contractility by decreasing the amplitude of spontaneous contractions and promoting relaxation of uterine smooth muscle.^[48] Vascular remodeling in the myometrium involves extensive angiogenesis, driven by factors such as vascular endothelial growth factor, which expands the vascular network and increases uterine blood flow approximately 10-fold by term to meet the heightened oxygen and nutrient demands of the placenta and fetus.^[49]^[50] Contractile adaptations include the emergence of irregular, painless Braxton Hicks contractions in the second and third trimesters, arising from localized calcium release within myometrial cells that does not propagate widely, alongside an overall reduction in myometrial tone to facilitate uterine expansion.^[51]^[5] Mechanical stretch from fetal growth induces adaptive changes in the myometrium, upregulating the expression of contractile proteins such as oxytocin receptors and connexins, which prepare the tissue for coordinated labor contractions later in gestation.^[52]^[53] Following delivery, the myometrium initiates involution, shrinking back toward its pre-pregnancy state through programmed cell death mechanisms, including apoptosis of excess smooth muscle cells and autophagy for cellular remodeling and clearance of hypertrophic components.^[54]^[55]

Labor and postpartum

The onset of labor, or parturition, involves a transition from myometrial quiescence to coordinated contractions, primarily driven by functional progesterone withdrawal, which allows increased estradiol effects, alongside surges in oxytocin and prostaglandin release. Progesterone withdrawal enables the expression of oxytocin receptors in the myometrium, facilitating oxytocin-induced contractions, while prostaglandins, such as PGF2α, enhance myometrial sensitivity and contractility. The Ferguson reflex further amplifies this process, as cervical and vaginal distension by the descending fetus stimulates oxytocin release from the posterior pituitary, creating a positive feedback loop that intensifies contractions. Fetal signals, including rising cortisol levels from the fetal adrenal gland, contribute to initiating this cascade by upregulating placental and membrane prostaglandin production via cyclooxygenase-2 induction, thereby promoting myometrial activation. Excitation-contraction coupling in the myometrium during labor begins with membrane depolarization to approximately -40 mV, triggered by influx of Ca²⁺ through L-type voltage-gated calcium channels, which raises intracellular Ca²⁺ levels and activates myosin light chain kinase for phosphorylation of myosin light chain, leading to cross-bridge formation and contraction. Gap junctions, upregulated at term, allow synchronous propagation of action potentials across myometrial cells, ensuring coordinated force generation. Inward Na⁺ flux via voltage-gated sodium channels contributes to initial depolarization, while Ca²⁺-activated Cl⁻ currents sustain the plateau phase of action potentials, prolonging Ca²⁺ influx and contraction duration. Restoration of the resting membrane potential occurs through Ca²⁺ extrusion via plasma membrane Ca²⁺-ATPase pumps and Na⁺/Ca²⁺ exchangers, coupled with K⁺ efflux through voltage-gated and Ca²⁺-activated K⁺ channels. Myometrial contractions during labor exhibit a characteristic pattern of propagating waves from the fundus to the cervix, with increasing frequency and intensity as labor progresses; at term, in active labor, contractions typically occur every 2 to 5 minutes, lasting 40 to 90 seconds, and generating pressures up to 50 mm Hg to facilitate cervical dilation and fetal expulsion. In the postpartum period, sustained myometrial contractions continue to expel the placenta by compressing uterine vessels and shearing the placental site, thereby reducing blood loss and preventing postpartum hemorrhage. Uterine involution follows, with the myometrium undergoing autophagy and remodeling, resulting in approximately 50% reduction in uterine mass by day 7 postpartum (to about 500 g) and full return to non-pregnant size within 6 weeks.

Clinical significance

Pathological conditions

Uterine fibroids, also known as leiomyomas, are benign tumors originating from the smooth muscle cells of the myometrium and are the most common gynecologic neoplasms in women of reproductive age.^[56] These hormone-dependent tumors, primarily influenced by estrogen and progesterone, develop as monoclonal growths and can vary in size, number, and location within the myometrium.^[57] They are classified into types based on their position: submucosal (protruding into the uterine cavity), intramural (within the myometrial wall), and subserosal (extending outward from the serosa).^[56] The lifetime prevalence of uterine fibroids is estimated at 70% to 80% in women by age 50, with higher rates among women of African descent.^[58] Adenomyosis is characterized by the ectopic invasion of endometrial glands and stroma into the myometrium, leading to diffuse myometrial thickening, hypertrophy, and chronic inflammation.^[59] This condition results in an enlarged, globular uterus and is associated with debilitating symptoms such as dysmenorrhea, menorrhagia, and chronic pelvic pain.^[60] The pathogenesis involves disrupted myometrial architecture and increased local estrogen production, though the exact etiology remains multifactorial, potentially linked to trauma or hyperestrogenism.^[59] Prevalence varies widely, affecting 10% to 80% of premenopausal women, with higher rates observed in those with infertility or undergoing hysterectomy.^[60] Preterm labor represents a pathological premature activation of myometrial contraction pathways, occurring before 37 weeks of gestation and complicating approximately 10% of pregnancies worldwide.^[61] It arises from disrupted quiescence in the myometrium, often triggered by intrauterine infection, inflammation, oxidative stress, or decidual hemorrhage, leading to coordinated contractions and cervical changes.^[62] This dysfunction can stem from abnormal prostaglandin signaling or matrix metalloproteinase activity, which degrade the extracellular matrix and promote labor onset.^[63] Postpartum hemorrhage frequently results from myometrial atony, a failure of the uterine smooth muscle to contract effectively after delivery, accounting for about 70% of cases.^[64] This condition is often due to uterine overdistension from multiple gestation or polyhydramnios, prolonged labor, or pharmacological inhibition such as from magnesium sulfate or halogenated anesthetics.^[65] The resultant hypotonic myometrium leads to inadequate compression of uterine vessels, causing significant blood loss.^[66] Rare pathological conditions affecting the myometrium include leiomyosarcoma, a malignant transformation of smooth muscle cells with an incidence of less than 1% among uterine tumors, representing 2% to 5% of all uterine malignancies.^[67] These aggressive sarcomas often arise de novo rather than from benign fibroid degeneration and are associated with rapid growth and metastasis.^[68] Cesarean scar defects, also known as isthmocele, involve thinning or pouch-like disruptions in the myometrial layer at the site of prior cesarean incision, potentially leading to abnormal uterine bleeding or infertility due to impaired contractility.^[69] Risk factors for myometrial pathologies, particularly uterine fibroids, include prolonged estrogen exposure from early menarche, nulliparity, or obesity, as well as genetic predispositions such as MED12 gene mutations found in approximately 70% of cases.^[58] These mutations disrupt Wnt/β-catenin signaling, promoting aberrant myometrial cell proliferation.^[57]

Diagnostic and therapeutic aspects

Diagnostic evaluation of the myometrium primarily relies on imaging modalities to assess structural abnormalities such as fibroids and adenomyosis. Transvaginal ultrasound serves as the initial noninvasive tool for detecting uterine fibroids, particularly submucosal ones, by visualizing their location, size, and impact on the endometrial cavity, while also measuring myometrial thickness to identify hypertrophy or thinning.^[70] For adenomyosis, transvaginal ultrasound can reveal myometrial heterogeneity, ill-defined endometrial borders, and cystic spaces, though its sensitivity varies.^[71] Magnetic resonance imaging (MRI) provides superior soft-tissue contrast for confirming adenomyosis, with a junctional zone thickness exceeding 12 mm being a key diagnostic criterion indicative of myometrial invasion by endometrial tissue.^[72] MRI also differentiates adenomyosis from fibroids by highlighting high-signal-intensity myometrial foci and is highly accurate in preoperative planning.^[73] Histological assessment through endometrial biopsy is essential for evaluating myometrial involvement in malignancies, such as endometrial carcinoma, where sampling assesses the depth of myometrial invasion to guide staging and treatment.^[74] Endometrial sampling via dilation and curettage or pipelle biopsy provides tissue for histopathological examination, revealing invasion patterns and tumor grade, with discrepancies between biopsy and final hysterectomy pathology occurring in up to 20-30% of cases due to sampling limitations.^[75] Immunohistochemistry on biopsy specimens further characterizes malignancy by identifying markers like p53 or mismatch repair proteins, aiding in distinguishing endometrioid from serous subtypes and predicting myometrial spread.^[76] Intraoperative frozen sections during surgery can rapidly confirm myometrial invasion and cervical involvement for real-time decision-making.^[77] Functional assessment of myometrial contractility during labor employs tocodynamometry, a noninvasive method using external transducers to monitor uterine contraction frequency, duration, and relative intensity.^[78] External tocodynamometry is widely used in clinical settings for preterm labor evaluation and labor progress tracking, though it may underestimate contraction strength compared to internal methods like intrauterine pressure catheters.^[79] This monitoring helps assess myometrial responsiveness and guides interventions, with limitations in obese patients prompting alternatives like electrohysterography.^[80] Therapeutic interventions targeting the myometrium focus on symptom relief and preservation of fertility where possible. Myomectomy surgically removes fibroids while preserving the uterus, with hysteroscopic approaches ideal for submucosal fibroids accessed via the endometrial cavity using resectoscopic tools to excise tissue without abdominal incisions.^[81] Laparoscopic myomectomy employs minimally invasive techniques for intramural or subserosal fibroids, involving morcellation for extraction and myometrial repair to minimize adhesion formation and restore uterine integrity.^[82] For preterm labor, tocolytics like nifedipine, a calcium channel blocker, inhibit myometrial contractions by blocking calcium influx, effectively delaying delivery by 48 hours or more in up to 80% of cases when administered orally.^[83] Nifedipine outperforms beta-agonists in reducing adverse maternal effects while achieving similar tocolytic efficacy.^[84] Oxytocin, administered intravenously, is the standard agent for labor induction and augmentation by binding to myometrial receptors, enhancing calcium signaling to promote coordinated contractions.^[85] It increases contraction frequency and amplitude, with dosing titrated to achieve 3-5 contractions per 10 minutes, though hyperstimulation risks necessitate fetal monitoring.^[86] In severe cases, hysterectomy remains definitive for myometrial pathologies like refractory fibroids or adenomyosis, removing the uterus to eliminate symptoms, though it ends fertility.^[87] Uterine artery embolization (UAE) offers a uterus-sparing alternative for fibroids, injecting embolic particles to occlude arterial supply, inducing ischemic necrosis and volume reduction of 30-60% within months, with comparable symptom relief to hysterectomy but faster recovery.^[88] UAE preserves myometrial function better than surgery in select patients.^[89] Emerging therapies include high-intensity focused ultrasound (HIFU) ablation, a noninvasive method using MRI-guided ultrasound waves to thermally ablate fibroid tissue within the myometrium, achieving 40-70% volume reduction and symptom improvement without incisions.^[90] HIFU targets fibroids selectively, minimizing damage to surrounding myometrium, and is suitable for patients desiring fertility preservation.^[91] Hormonal therapies with gonadotropin-releasing hormone (GnRH) agonists, such as leuprolide, suppress ovarian estrogen production, reducing myometrial proliferation in fibroids and adenomyosis by 25-50% in uterine volume after 3-6 months.^[92] These agents induce a hypoestrogenic state to shrink lesions preoperatively or manage symptoms, though side effects like bone density loss limit long-term use.^[93]

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Apparently, high progesterone levels down-regulate the ER in both fibroids and myometrium, whereas estrogen mediates the up-regulation of the PR during the ...
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Inside the Endometrial Cell Signaling Subway: Mind the Gap(s) - PMC
PGF2α induces myometrial contractions and vasoconstriction of the spiral arteries both of which are critical events in the menstruation process. However, ROS- ...
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Cyclic processes in the uterine tubes, endometrium, myometrium ...
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Review the etiology of adenomyosis. ... Data demonstrating a higher prevalence of adenomyosis following dilation and curettage and cesarean section support this ...
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External tocodynamometry is the most widely used technique. It is easy to apply and provides reasonably accurate information about the frequency and duration of ...
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Uterine-Artery Embolization or Myomectomy for Uterine Fibroids
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Uterine Adenomyosis: From Disease Pathogenesis to a New ... - NIH
Sep 22, 2021 · GnRH agonists were therefore proposed to both tackle adenomyosis-related hyperestrogenism and decrease proliferative activity in ectopic ...