Uterine leiomyoma Medical Services in China

Uterine leiomyoma—commonly known as uterine fibroids—is a benign monoclonal smooth muscle tumor arising from the myometrium of the uterus. These tumors are estrogen- and progesterone-sensitive, exhibiting growth during reproductive years and typically regressing after menopause. Pathogenically, leiomyomas originate from genetic alterations in myometrial stem cells, with recurrent mutations in the MED12 gene (present in ~70% of cases), HMGA2 rearrangements, and abnormalities in the TGF-β, WNT/β-catenin, and PI3K/AKT/mTOR signaling pathways. Epigenetic dysregulation, extracellular matrix remodeling, and local tissue hypoxia further contribute to tumor initiation and expansion. Epidemiologically, uterine leiomyomas affect approximately 40–80% of women by age 50, with higher prevalence among Black women (up to 80% by age 45), earlier onset, larger size, and greater symptom burden. Risk factors include early menarche (<11 years), nulliparity, obesity (BMI ≥30), hypertension, vitamin D deficiency, family history, and African ancestry. Conversely, parity, oral contraceptive use (especially long-term low-dose formulations), and smoking (though not recommended due to health risks) are associated with reduced risk. Symptomatology varies widely: up to 50% of cases are asymptomatic, while others experience heavy or prolonged menstrual bleeding (menorrhagia), pelvic pressure or pain, urinary frequency or retention, constipation, dyspareunia, and reproductive challenges—including subfertility, recurrent pregnancy loss, and obstetric complications such as placental abruption or preterm birth. Quality of life impact is substantial: chronic anemia from blood loss leads to fatigue and cognitive impairment; pelvic discomfort restricts physical activity and sexual function; and emotional distress—including anxiety, depression, and diminished body image—is prevalent, particularly among younger patients facing fertility concerns. Economic burden extends beyond direct medical costs to lost work productivity and caregiver strain. Early diagnosis via transvaginal ultrasound (TVUS) or MRI is critical for risk stratification and personalized management. Given its hormone-dependent nature and heterogeneous clinical behavior, treatment must be individualized—not solely based on size or number, but on symptom severity, reproductive goals, patient preference, and anatomical location (submucosal, intramural, subserosal, or pedunculated). Multidisciplinary care involving reproductive endocrinologists, interventional radiologists, gynecologic oncologists, and minimally invasive surgeons ensures optimal outcomes in the Department of Reproductive Medicine.

Uterine leiomyomas—commonly termed fibroids—are benign monoclonal smooth muscle tumors of the myometrium. While their precise etiology remains incompletely elucidated, current evidence supports a multifactorial pathogenesis involving hormonal, genetic, epigenetic, and environmental influences. Estrogen and progesterone are central to leiomyoma growth: these steroids stimulate proliferation of myometrial smooth muscle cells via receptor-mediated transcriptional activation (e.g., upregulation of growth factors such as TGF-β3, IGF-1, and EGF). Leiomyomas express significantly higher levels of estrogen receptor alpha (ERα) and progesterone receptor (PR-B) compared with adjacent normal myometrium, rendering them exquisitely sensitive to ovarian steroid fluctuations. Consequently, fibroids typically develop after menarche, enlarge during reproductive years—especially in pregnancy—and regress after menopause or with gonadotropin-releasing hormone (GnRH) agonist therapy. Androgen signaling may also contribute, as androgen receptors are expressed in leiomyomas and hyperandrogenic states (e.g., PCOS) correlate with increased prevalence.

Genetic factors play a pivotal role. Approximately 70% of leiomyomas harbor somatic driver mutations, most commonly in the *MED12* gene (exon 2 mutations in ~60–70% of cases), which disrupts the mediator complex and dysregulates RNA polymerase II–dependent transcription. Other recurrent alterations include *HMGA2* rearrangements (often via translocations involving 12q14–15), *FH* (fumarate hydratase) loss-of-function mutations (associated with hereditary leiomyomatosis and renal cell cancer syndrome), and less frequently *COL4A5/COL4A6* deletions. Germline predisposition is evident: first-degree relatives of affected women have a 2.5- to 3-fold increased risk; African ancestry confers the strongest known genetic susceptibility—Black women experience earlier onset, greater tumor burden, larger size, and more severe symptoms, independent of socioeconomic variables. Genome-wide association studies (GWAS) have identified multiple risk loci, including variants near *TNRC6B*, *OBFC1*, *SLK*, and *GREB1*, many involved in sex steroid signaling, extracellular matrix organization, or cell cycle regulation.

Environmental and lifestyle-related risk factors modulate disease expression. Obesity (BMI ≥30 kg/m²) increases risk by 20–40%, likely through aromatase-mediated peripheral conversion of androgens to estrogens in adipose tissue, elevated bioavailable estradiol, insulin resistance, and chronic low-grade inflammation. Hypertension is independently associated with leiomyoma development and severity, possibly via renin-angiotensin system activation and vascular remodeling. Vitamin D deficiency (<20 ng/mL serum 25(OH)D) is consistently linked to higher incidence and volume—vitamin D exerts antiproliferative, pro-differentiation, and antifibrotic effects on myometrial cells via VDR-mediated suppression of *HMGA2* and *TGFB3*. Early menarche (≤10 years) and nulliparity confer modest but significant risk elevation, whereas parity—particularly early and multiparous births—is protective, likely due to long-term downregulation of ovarian steroid receptors and structural remodeling of the myometrium. Dietary patterns matter: high red meat and ham intake correlates with increased risk, while consumption of green vegetables, fruits, and dairy (particularly calcium- and vitamin D–fortified) appears protective. Endocrine-disrupting chemicals—including phthalates, bisphenol A (BPA), and certain organochlorine pesticides—may act as xenoestrogens or interfere with steroid metabolism, with epidemiologic data suggesting associations between urinary phthalate metabolites and fibroid prevalence, especially in susceptible populations. Psychosocial stress has not been definitively established as causal but may exacerbate symptom burden via hypothalamic-pituitary-adrenal axis dysregulation and immune modulation. Importantly, no credible evidence links oral contraceptive use, IUDs, or abortion history to increased leiomyoma risk; conversely, some data suggest combined hormonal contraceptives may modestly attenuate growth. Understanding this integrated biopsychosocial framework is essential for risk stratification, personalized counseling, and emerging targeted therapies in reproductive medicine.

Uterine leiomyomas—commonly termed uterine fibroids—are benign monoclonal smooth muscle tumors of the myometrium. They affect up to 70–80% of women by age 50, with highest prevalence during the reproductive years (30–45 years). While many leiomyomas are asymptomatic and incidentally discovered on imaging or pelvic examination, clinically significant lesions produce a spectrum of symptoms that vary according to size, number, location (submucosal, intramural, subserosal, pedunculated, or cervical), and hormonal milieu. Early symptoms often reflect subtle mechanical or endocrine perturbations and may be overlooked or attributed to normal menstrual variation. These include mild, cyclical pelvic pressure or dull lower abdominal discomfort, especially premenstrually; intermittent spotting between menses (intermenstrual bleeding) due to localized endometrial distortion or vascular compromise; and slight prolongation of menses (e.g., 6–7 days instead of 4–5) without overt menorrhagia. Some patients report early satiety or urinary frequency before significant uterine enlargement occurs—suggesting paracrine signaling or microenvironmental inflammation rather than mass effect alone.

Typical symptoms emerge as leiomyomas grow (>4–5 cm) or occupy critical anatomic niches. Menorrhagia—excessive menstrual blood loss—is the most prevalent symptomatic presentation, occurring in approximately 30–50% of symptomatic patients. It manifests as prolonged duration (>7 days), increased volume (soaking >1 pad/tampon hourly for several consecutive hours), passage of large clots (>2.5 cm), or iron-deficiency anemia (fatigue, pallor, tachycardia, dyspnea on exertion). Submucosal and large intramural fibroids disrupt normal endometrial architecture and vasculature, impairing decidualization and increasing prostaglandin E2 and thromboxane A2 expression, thereby promoting abnormal uterine bleeding. Pelvic pain or pressure is reported by 20–40% of symptomatic individuals: constant dull ache (often midline or bilateral), worsening with menses or prolonged standing, and occasionally radiating to the lower back or thighs. Acute, severe pain may occur with red degeneration—a hemorrhagic infarction typically in pregnancy or perimenopause—characterized by fever, leukocytosis, and localized tenderness. Bulk-related symptoms include urinary frequency, urgency, or incomplete bladder emptying due to anterior wall or fundal fibroids compressing the bladder trigone or ureters; constipation or rectal pressure from posterior or cervical lesions impinging on the rectum; and abdominal distension mimicking pregnancy, sometimes with visible contour deformity. Subfertility or recurrent pregnancy loss may be the sole presenting feature in women seeking reproductive medicine evaluation, particularly with submucosal or cavity-distorting intramural fibroids impairing implantation, altering tubal ostial patency, or disrupting endometrial receptivity via aberrant HOXA10 and integrin expression.

Accompanying symptoms frequently reflect systemic consequences or comorbidities. Chronic fatigue and reduced exercise tolerance commonly stem from iron-deficiency anemia secondary to menorrhagia. Dyspareunia—particularly deep dyspareunia—is associated with broad ligament, cervical, or retroverted uterine fibroids causing traction on uterosacral ligaments or direct vaginal fornix compression. Some patients report bloating, nausea, or low-grade malaise linked to cytokine-mediated inflammation (elevated IL-6, TNF-α) within the fibroid microenvironment. Rarely, large fibroids induce a hypercoagulable state or promote venous stasis, contributing to lower extremity edema or varicosities.

Complications arise from progressive growth, degeneration, or anatomical distortion. Acute torsion of a pedunculated subserosal fibroid causes sudden, severe unilateral pelvic pain, nausea, and possible peritoneal signs—requiring urgent surgical intervention. Red degeneration, though usually self-limited, may necessitate analgesia and supportive care; infection (rare) mandates antibiotics and possible drainage. Hydronephrosis or renal impairment can result from ureteral compression by massive or lateral fibroids, especially if unilateral and undetected over time. Severe chronic menorrhagia may lead to transf cardiac decompensation in vulnerable patients. In pregnancy, leiomyomas increase risks of spontaneous abortion, preterm labor, placental abruption, fetal malpresentation, and cesarean delivery—particularly with submucosal or large intramural lesions. Rare malignant transformation into leiomyosarcoma (<0.1%) must be considered in postmenopausal women with rapid growth, new-onset pain, or imaging features such as necrosis, irregular margins, or high signal intensity on diffusion-weighted MRI—but clinical suspicion should not override histopathologic confirmation.

Diagnosis integrates clinical assessment with multimodal imaging. Transvaginal ultrasound (TVUS) remains first-line: it identifies size, number, location, echogenicity, and vascularity (via Doppler), with sensitivity >90% for lesions ≥1 cm. Saline infusion sonohysterography (SIS) enhances delineation of submucosal and intracavitary components, differentiating polyps from pedunculated fibroids. Pelvic MRI is reserved for complex cases—e.g., indeterminate TVUS, suspected adenomyosis coexistence, preoperative mapping for myomectomy or focused ultrasound, or evaluation of atypical degeneration. MRI excels in characterizing tissue composition (T2-weighted hypointensity typical of leiomyoma vs. intermediate signal in adenomyosis), detecting degeneration (hyperintense areas on T1 for hemorrhage), and assessing vascularity (dynamic contrast enhancement). Hysteroscopy provides direct visualization and biopsy of endocavitary lesions but is invasive and less sensitive for intramural extension.

Differential diagnosis is essential given overlapping symptomatology. Endometrial polyps present with intermenstrual or postcoital bleeding but rarely cause bulk symptoms; hysteroscopy or SIS confirms diagnosis. Adenomyosis commonly coexists with leiomyomas and shares menorrhagia and dysmenorrhea, but features diffuse uterine enlargement, globular shape, and 'venetian blind' striations on MRI—lacking discrete borders. Endometrial hyperplasia or malignancy must be excluded in perimenopausal or postmenopausal women with abnormal bleeding via endometrial biopsy or dilation and curettage. Ovarian neoplasms (e.g., fibromas, Brenner tumors) may mimic pelvic masses but lack cyclic bleeding patterns and often demonstrate distinct ultrasound morphology (e.g., calcifications, solid components). Pelvic congestion syndrome presents with chronic pelvic pain and varicosities but lacks uterine enlargement or bleeding. Finally, irritable bowel syndrome or interstitial cystitis may simulate gastrointestinal or urinary symptoms but lack objective pelvic findings or imaging correlates. Accurate differentiation guides management—from expectant monitoring and medical therapy (GnRH agonists, tranexamic acid, progestins, or selective progesterone receptor modulators) to minimally invasive procedures (uterine artery embolization, MRI-guided focused ultrasound) or definitive surgery (myomectomy, hysterectomy)—with reproductive goals central to decision-making in the Reproductive Medicine Department.

Uterine leiomyomas—commonly termed fibroids—are benign monoclonal smooth muscle tumors of the myometrium, affecting up to 70–80% of women by age 50. While often asymptomatic, they may cause menorrhagia, pelvic pressure or pain, urinary frequency, constipation, subfertility, or recurrent pregnancy loss. Management in the Department of Reproductive Medicine prioritizes fertility preservation, symptom control, and individualized risk-benefit assessment. Treatment strategies are stratified according to symptom severity, tumor size and location (submucosal, intramural, subserosal), reproductive goals, age, comorbidities, and patient preference.

Conservative management is first-line for asymptomatic or minimally symptomatic patients, particularly those approaching menopause or with small, stable fibroids (<5 cm). This entails clinical surveillance with pelvic ultrasound every 6–12 months, hemoglobin monitoring for anemia, and lifestyle counseling—including iron-rich nutrition, regular physical activity, and avoidance of exogenous estrogen sources (e.g., unopposed hormone therapy). In reproductive-age patients desiring conception, conservative observation remains appropriate if fibroids do not distort the endometrial cavity or exceed 4 cm in diameter, as evidence suggests submucosal and large intramural (>5 cm) lesions most adversely impact implantation and live birth rates.

Pharmacotherapy serves both diagnostic and therapeutic roles. Gonadotropin-releasing hormone (GnRH) agonists (e.g., leuprolide) induce temporary hypoestrogenic states, reducing fibroid volume by 30–60% over 3–6 months; however, rebound growth occurs post-discontinuation, limiting long-term use. GnRH antagonists (e.g., elagolix, relugolix) offer more rapid onset and improved tolerability, with combination regimens (e.g., relugolix + estradiol/norethindrone acetate) approved for extended use up to 24 months to control bleeding and anemia while preserving bone mineral density. Selective progesterone receptor modulators (SPRMs), notably ulipristal acetate (though currently restricted in some regions due to hepatic safety concerns) and newer agents like vilaprisan (under investigation), demonstrate potent antiproliferative effects on leiomyoma tissue with minimal systemic hormonal disruption. Tranexamic acid (1.0 g orally three times daily during menses) significantly reduces menstrual blood loss without hormonal effects and is ideal for perimenopausal or contraindicated patients. Combined oral contraceptives or progestin-only methods (e.g., levonorgestrel-releasing intrauterine system [LNG-IUS]) provide effective cycle control and endometrial suppression, though they do not shrink fibroids. Iron supplementation is mandatory for iron-deficiency anemia, with intravenous ferric carboxymaltose preferred for severe deficiency or malabsorption.

Surgical intervention is indicated for refractory symptoms, rapid growth suspicious for malignancy (though <0.1% risk), infertility attributable to cavity distortion, or compressive sequelae. Myomectomy—gold standard for fertility preservation—is performed via hysteroscopic (for submucosal types ≤4 cm), laparoscopic (for intramural/subserosal ≤8–10 cm), or abdominal (for multiple, large, or deeply infiltrating fibroids) approaches. Robotic-assisted laparoscopy enhances dexterity in complex cases, improving suture precision and reducing conversion rates. All modalities require meticulous myometrial repair to minimize uterine rupture risk in subsequent pregnancy. Uterine artery embolization (UAE) offers a minimally invasive alternative with ~85% symptom improvement at 2 years; however, it carries higher risks of ovarian dysfunction, post-embolization syndrome, and reduced ovarian reserve—making it less favorable in young, fertility-seeking patients. Magnetic resonance-guided focused ultrasound surgery (MRgFUS) provides non-invasive ablation under real-time imaging but has limited efficacy for large, posterior, or pedunculated fibroids and is contraindicated with intrauterine devices or extensive calcification.

China’s Reproductive Medicine Departments offer distinct advantages in leiomyoma management. First, integration of traditional Chinese medicine (TCM) with evidence-based Western protocols is routine: standardized herbal formulas (e.g., Guizhi Fuling Wan) are prescribed adjunctively to reduce pelvic congestion and modulate angiogenesis, supported by randomized trials demonstrating synergistic reduction in bleeding and fibroid volume when combined with SPRMs. Second, China leads globally in robotic surgical adoption—over 90% of tier-3 hospitals deploy da Vinci Xi systems, enabling high-volume, low-complication myomectomies with median operative times <120 minutes and hospital stays of 2–3 days. Third, centralized national registries (e.g., China Fibroid Registry) facilitate longitudinal outcome tracking, informing personalized recurrence prediction models incorporating genomic profiling (MED12 mutation status) and MRI texture analysis. Fourth, cost-effectiveness is exceptional: comprehensive myomectomy with advanced imaging and pathology costs <USD 4,500—approximately 40% lower than comparable care in North America or Western Europe—without compromising quality metrics (98% 30-day readmission-free survival, >95% patient satisfaction in national surveys).

Post-treatment recovery emphasizes structured rehabilitation. Patients undergoing hysteroscopic myomectomy resume normal activity within 3–5 days but avoid tampons, intercourse, and swimming for 2 weeks to prevent infection. Laparoscopic/abdominal myomectomy requires 2–4 weeks off work and 6–8 weeks before resuming heavy lifting (>10 kg) or vigorous exercise. All surgical patients receive thromboprophylaxis (enoxaparin 40 mg SC daily × 7 days) and early ambulation protocols. For pharmacologic therapy, monthly liver enzyme and hemoglobin monitoring is mandated during SPRM or GnRH antagonist use. Nutritional guidance includes daily intake of ≥18 mg elemental iron (if anemic), omega-3 fatty acids (to modulate inflammation), and avoidance of ultra-processed foods linked to elevated IGF-1 levels. Fertility counseling begins immediately post-recovery: hysterosalpingography or saline-infusion sonohysterography is recommended 3 months after myomectomy to confirm cavity integrity; embryo transfer is typically deferred until 6 months post-surgery to allow optimal myometrial healing. Long-term surveillance includes annual transvaginal ultrasound and symptom diaries to detect recurrence—occurring in ~15–30% at 5 years—prompting timely re-stratification. Ultimately, successful management hinges on shared decision-making, multidisciplinary coordination (gynecologic oncology, reproductive endocrinology, interventional radiology), and culturally attuned support systems that recognize psychosocial impacts of chronic gynecologic conditions.