Uterine Fibroids (Leiomyomas)

Overview & Definition

Uterine leiomyomas (commonly called fibroids, myomas, fibromyomas or leiomyomata) are benign, hormone-responsive, monoclonal neoplasms arising from the smooth-muscle cell of the myometrium, each surrounded by a fibrous extracellular matrix and a false (compressive, not anatomical) capsule. They are the single commonest benign tumour of the female genital tract and the commonest pelvic tumour overall.^[1]

A leiomyoma must be distinguished from adenomyosis (ectopic endometrial glands and stroma scattered within the myometrium, producing a diffusely enlarged, boggy, tender uterus with menorrhagia and secondary dysmenorrhoea — no discrete mass), from an endometrial polyp (a focal outgrowth of endometrial glands and stroma projecting into the cavity), and — critically — from a leiomyosarcoma (a malignant smooth-muscle tumour with mitotic activity, nuclear atypia and coagulative tumour-cell necrosis).^[1][2]

The clinical skill in fibroids is not the diagnosis (it is usually ultrasound-evident) but deciding whom to treat, with what, and when — balancing symptom severity, fertility desires, age, fibroid location, and the patient's tolerance of medical versus surgical and uterus-sparing versus definitive options. The single biggest process lever is to classify each fibroid anatomically (FIGO type) before choosing therapy: a submucosal fibroid causing infertility or heavy bleeding warrants hysteroscopic resection; a subserosal bulk lesion is suitable for embolisation or myomectomy; and definitive hysterectomy is reserved for the woman who has completed her family and wants a cure.^[2][6]

Classification

Fibroids are classified by anatomical location relative to the uterine wall (submucosal, intramural, subserosal), and more precisely by the FIGO PALM-COEIN-aligned leiomyoma subclassification system (FIGO types 0 to 8) introduced by the International Federation of Gynecology and Obstetrics (Munro, 2011) and now the universal pre-operative mapping standard.^[6]

Three classical anatomical types (high-yield and the exam favourite):^[6]

• Submucosal — beneath the endometrium, projecting into the uterine cavity. The least common anatomical type but the most symptom-producing per gram of tumour: heavy, prolonged, irregular menstrual bleeding, infertility (distorts the cavity, impairs implantation) and recurrent miscarriage. Treat with hysteroscopic myomectomy.^[8]
• Intramural — the commonest type (around 70 per cent). Confined to the myometrial wall. Produces menorrhagia, an enlarged uterus and, when large, bulk/pressure symptoms.^[1]
• Subserosal — beneath the serosal surface, growing outward. May be pedunculated (attached by a stalk) and undergo torsion. Produces pressure symptoms (bladder, bowel, ureter) rather than heavy bleeding; can grow very large and present as an abdominal mass.^[1]

FIGO leiomyoma subclassification (0 to 8) — reproduced:^[6]

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Special morphological variants: ^[1]

• Parasitic fibroid — a subserosal/pedunculated fibroid that detaches from the uterus and derives a new blood supply from the omentum or mesentery; rare, more common after prior uterine surgery or uterine artery embolisation.
• Broad-ligament (intraligamentary) fibroid — grows between the leaves of the broad ligament; the ureter is at risk during surgery — always image pre-operatively.
• Cervical fibroid — arises from the cervix; can impact in the pelvis and cause acute urinary retention and ureteric compression; often requires laparotomy and careful ureteric identification.
• Lipoleiomyoma — a degenerated fibroid with fatty change; benign, often in postmenopausal women.
• Diffuse uterine leiomyomatosis — innumerable small fibroids replacing the myometrium; rare, hormonal-driven, recurs after surgery. ^[1]

Patterns of benign degeneration (each fibroid can undergo one or more): hyaline (commonest, homogenous eosinophilic), cystic, calcific (commonest in postmenopausal fibroids; 'withered' and radio-opaque), myxoid, red (carneous) (acute haemorrhagic infarction, classically in pregnancy), fatty, and hydropic. Sarcomatous change is not a degeneration pattern — it is malignant transformation (see Prognosis). ^[1]

Epidemiology & Risk Factors

Fibroids are present in 70 to 80 per cent of women by age 50 at autopsy and ultrasound screening, but only 25 to 30 per cent are symptomatic. They are the commonest indication for hysterectomy worldwide.^[1][1]

Demographic and reproductive risk factors (the unifying theme is prolonged oestrogen exposure / cumulative menstrual cycles):^[1]

Protective factors (anti-oestrogenic): multiparity, prolonged lactation, combined oral contraceptive use (especially long-term), smoking (anti-oestrogenic but obviously not recommended), and late menarche.^[1]

Heritability and genetics: fibroids are clonal — each tumour arises from a single myometrial smooth-muscle cell. Around 40 per cent carry a driver cytogenetic abnormality; the commonest are translocation t(12;14) (involving HMGA2), trisomy 12, and deletions of chromosome 7 (involving the candidate tumour suppressor LOC157273). Somatic mutations of MED12 (mediator complex subunit 12, on the X chromosome) are found in up to 70 per cent of fibroids — the single commonest driver, and a high-yield molecular fact. Twin and family studies estimate heritability of 30 to 50 per cent. A familial syndrome, hereditary leiomyomatosis and renal cell carcinoma (HLRCC, Reed's syndrome) due to germline fumarate hydratase mutation causes cutaneous and uterine leiomyomas with aggressive papillary renal cancer — worth knowing.^[1][9]

Pathophysiology

Each fibroid is monoclonal (a single myometrial smooth-muscle progenitor — likely a medi-MSC, a Stro-1+/CD44+ mesenchymal stem-like cell) that has acquired a driver mutation (most often MED12, otherwise HMGA2 overexpression) and proliferated under the permissive influence of oestrogen and progesterone, surrounded by a copious extracellular matrix (ECM) rich in collagen, proteoglycans and growth factors.^[1][9]

Hormonal sensitivity — the cornerstone (and the therapeutic target): ^[1]

• Oestrogen promotes fibroid growth by upregulating progesterone receptors and stimulating local aromatase activity (fibroids overexpress aromatase and so synthesise their own oestradiol in situ). Oestrogen also drives IGF-1, EGF and TGF-beta expression.
• Progesterone is now recognised as the dominant mitogen: it drives cell proliferation (Bcl-2 anti-apoptosis, EGF, cyclin D1). This is the rationale for progesterone receptor modulators (SPRMs — ulipristal acetate) and is why fibroids regress during GnRH-induced hypo-oestrogenism. ^[1]

The why (the chain that explains symptoms):^[1][2]

• Oestrogen and progesterone → proliferation of myometrial smooth-muscle cells and extracellular matrix deposition → expanding, well-circumscribed, whorled mass with a compressive pseudocapsule and dilated venous plexus.
• A fibroid beneath or distorting the endometrium → increased endometrial surface area, abnormal vascular maturation (dysregulated venules), and impaired myometrial contractility → heavy, prolonged, irregular menstrual bleeding and anaemia.
• A fibroid distorting the cavity → impairs implantation, gamete transport and decidualisation → infertility and recurrent pregnancy loss (especially submucosal, FIGO 0 to 2).^[8]
• A large fibroid → mass effect on bladder, ureter, rectum and pelvic veins → frequency, retention, hydronephrosis, constipation, venous stasis, lower-limb oedema, and (rarely, with very large fibroids) DVT/pulmonary embolism.
• Pregnancy → high oestrogen and rapid growth outstripping blood supply → acute haemorrhagic infarction (red degeneration) with pain.
• Menopause → falling oestrogen → involution and calcification of fibroids.

Molecular hallmarks — the four examiners reward:^[1][9]

1. MED12 mutation — found in up to 70 per cent of fibroids; disrupts the mediator complex and RNA polymerase II transcription of cell-cycle genes.
2. Oestrogen and progesterone dependence — the rationale for all medical therapy (GnRH analogues/antagonists, SPRMs, progestogens).
3. Aromatase overexpression — local in-situ oestradiol synthesis means fibroids make their own oestrogen; basis for aromatase inhibitors (letrozole) off-label use.
4. Extracellular matrix (ECM) abundance — stiffens the tissue, contributes to bulk symptoms, and is itself mitogenic (mechanotransduction via integrin signalling); also drives fibroid-associated pain. ^[1]

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Clinical Presentation

The majority of fibroids are asymptomatic and are incidental findings on ultrasound or at laparoscopy. Symptoms are determined by number, size and — above all — location.^[1][6]

Symptom-by-symptom (the classical picture): ^[1]

• Abnormal uterine bleeding — the commonest symptom (around 30 per cent of symptomatic women). Classically heavy menstrual bleeding (menorrhagia) — regular, cyclical, but heavy and prolonged; less commonly intermenstrual bleeding (especially submucosal). Bleeding is rarely acyclical/postmenopausal — that finding mandates endometrial sampling to exclude malignancy.
• Bulk/pressure symptoms. Pelvic heaviness, pressure, bloating, increasing abdominal girth; a palpable abdominal mass. Urinary frequency, urgency and nocturia (bladder compression); acute urinary retention (cervical fibroid impacting in pelvis — a high-yield presentation); ureteric compression with hydronephrosis (broad-ligament or large cervical fibroid); constipation and tenesmus (rectal compression); lower-limb oedema and venous stasis (iliac-vein compression).
• Pain. Fibroids are usually painless; pain suggests a complication: red (carneous) degeneration in pregnancy, torsion of a pedunculated subserosal fibroid, sarcomatous change (especially postmenopause), or expulsion of a submucosal fibroid through the cervix (labour-like cramps). Some women report deep dyspareunia or chronic pelvic ache with large fibroids.
• Reproductive symptoms. Infertility (submucosal fibroids distort the cavity; large intramural fibroids impair implantation and tubal motility), recurrent first-trimester miscarriage, and — in pregnancy — complications including malpresentation, antepartum haemorrhage, preterm labour, and obstructed labour.^[8]

On examination: ^[1]

• Abdominal examination — an irregularly enlarged, firm, smooth, mobile, non-tender uterus arising from the pelvis. The irregular contour (bosselated) distinguishes fibroids from pregnancy (a uniformly enlarged, soft, symmetrical uterus) and from a large ovarian cyst (cystic, separate from the uterus).
• Bimanual vaginal examination — confirms the uterine origin (the mass moves with the cervix/uterus), assesses size, mobility and adnexa. The cervix may be displaced by a cervical fibroid.
• Speculum examination — usually normal; excludes a cervical cause of bleeding. ^[1]

Atypical presentations (high-yield): ^[1]

• The young woman with infertility and a single submucosal fibroid — may have no menstrual symptoms at all; the fibroid is found on fertility work-up. Hysteroscopic resection restores fertility.
• The postmenopausal woman with a 'growing fibroid' or postmenopausal bleeding — do not assume a benign fibroid; rule out leiomyosarcoma and endometrial cancer (endometrial sampling, MRI). Fibroids should shrink after menopause.
• The pregnant woman with acute abdominal pain — red degeneration (carneous degeneration): acute, well-localised pain over a fibroid, low-grade fever, mild tachycardia, a tender uterine mass; managed conservatively with analgesia.^[6]
• The woman on tamoxifen for breast cancer — fibroids may grow despite menopause due to partial oestrogen agonism.
• The woman with acute urinary retention — feel for a cervical fibroid impacted behind the pubic symphysis before assuming a neurological cause.
• The woman with severe anaemia from heavy menses — iron-deficiency anaemia may be the presenting feature of an otherwise silent submucosal fibroid.

Differential Diagnosis

An enlarged, irregular uterus or pelvic mass is not always a fibroid. Distinguish each by its distinguishing features:^[1][2]

For heavy menstrual bleeding specifically (PALM-COEIN differential): structural causes — Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia (the PALM group, seen on imaging/histology); non-structural — Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified (the COEIN group). Fibroids are the L of PALM and are the commonest structural cause of HMB.^[3]

Always exclude pregnancy (beta-hCG) in any reproductive-age woman, and exclude malignancy (endometrial sampling in postmenopausal / high-risk women) before attributing bleeding to a fibroid. ^[1]

Clinical & Bedside Assessment

The diagnosis of fibroids is clinical plus transvaginal ultrasound — but the bedside examination is what frames the differential and the urgency.^[6]

Focused abdominal and pelvic examination findings in fibroids: ^[1]

• Irregularly enlarged, firm, smooth-surfaced, mobile, non-tender uterus — the cardinal finding. The uterus is firm (vs soft in pregnancy, cystic in ovarian mass), irregular/bosselated (vs symmetrical in pregnancy or adenomyosis), and mobile (vs fixed in endometriosis, advanced malignancy or PID).
• Cervix — usually normal; a cervical fibroid displaces the cervix and may be palpable as a firm mass in the vaginal fornix; the external os may be above the pubic symphysis when a cervical fibroid impacts in the pelvis.
• Bimanual examination — confirms uterine origin (the mass moves with the cervix), assesses size (in weeks of gestation), mobility, adnexa, and pelvic mass effect (low-lying fibroid).
• Speculum — excludes cervical polyp, ectropion or malignancy as a cause of bleeding. ^[1]

Named signs / clinical manoeuvres (high-yield): ^[1]

• Size expressed in 'weeks of gestation' — universal convention: a 12-week-size fibroid uterus reaches the pubic symphysis; a 20-week-size reaches the umbilicus. Use a tape to document fundal height.
• ** ballotability** — a mobile fibroid can be balloted between the abdominal and vaginal hands; an ovarian cyst is separately balloted from the uterus.
• Assess for anaemia — conjunctival pallor, tachycardia, flow murmur in severe iron deficiency; any woman with heavy menses needs a full blood count. ^[1]

Bedside work-up at first presentation: a structured menstrual history (cycles, days of bleeding, flooding, clots, dysmenorrhoea, impact on life), a reproductive history (fertility desires, parity, pregnancy plans — these drive every management decision), a family history (fibroids, HLRCC), assessment of bulk/pressure symptoms (urinary, bowel, venous), a drug history (tamoxifen, hormonal contraception), and screening for red flags (postmenopausal bleeding, rapid growth, severe acute pain, urinary retention). ^[1]

Investigations

The diagnostic pathway is stepwise: clinical suspicion then transvaginal ultrasound first-line, saline-infusion sonography for submucosal mapping, MRI for surgical planning and sarcoma suspicion, and hysteroscopy with biopsy for cavity lesions.^[1][6]

Baseline bloods (always): ^[1]

• Full blood count — to detect and grade iron-deficiency anaemia (microcytic, hypochromic; low ferritin) from chronic menorrhagia — the commonest systemic consequence of fibroids.
• Beta-hCG — always before imaging in any reproductive-age woman to exclude pregnancy.
• Thyroid function, coagulation screen (if heavy bleeding since menarche or family history — exclude von Willebrand disease, the commonest inherited bleeding disorder in women with HMB).
• Iron studies, ferritin — confirms iron deficiency. ^[1]

Transvaginal ultrasound (TVUS) — first-line imaging. Inexpensive, widely available, no radiation. Fibroids appear as well-defined, rounded, hypoechoic, heterogeneous masses within the myometrium, with acoustic shadowing and (sometimes) calcification (postmenopausal). TVUS defines number, size, location (FIGO type) and effect on the cavity. Saline-infusion sonography (SIS / sonohysterography) improves accuracy for submucosal fibroids and intracavitary component — it is the test of choice to distinguish a submucosal fibroid from an endometrial polyp.^[6]

Pelvic MRI — second-line for mapping and surgical planning. MRI is the most accurate modality for fibroid mapping: it defines the FIGO type, depth of myometrial invasion, proximity to the serosa and endometrium, and detects degeneration (T2-hyperintense cystic/myxoid change; T1-hyperintense haemorrhagic/red degeneration; low-signal calcification). Indications: before complex myomectomy (especially multiple, large, or broad-ligament fibroids where ureter at risk); before uterine artery embolisation (to confirm vascularity and exclude pedunculated subserosal fibroids that may detach); when TVUS is non-diagnostic or uterus is too large; and — critically — to raise or lower suspicion of leiomyosarcoma (diffusion-weighted imaging DWI with restricted diffusion, LDH/LDH isoenzymes). MRI is not needed for routine diagnosis.^[1]

Hysteroscopy — direct visualisation and biopsy of cavity lesions. Gold standard for submucosal fibroids (FIGO 0 to 2): it allows direct visualisation, assessment of intramural extension, and simultaneous resection (hysteroscopic myomectomy). Combined with endometrial biopsy / dilatation and curettage to exclude malignancy in any woman with postmenopausal bleeding, persistent intermenstrual bleeding, age over 40 to 45 with risk factors (obesity, nulliparity, unopposed oestrogen, tamoxifen, Lynch syndrome), or atypical glandular cells on cervical cytology.^[3]

Investigations for the suspected sarcoma (high-yield):^[1]

• LDH and LDH isoenzymes — a raised LDH and its isoenzyme 3 is the most promising non-invasive marker (no single test is definitive).
• MRI with diffusion-weighted imaging (DWI) — restricted diffusion (low ADC value) and T2 heterogeneity favour sarcoma over a benign degenerating fibroid.
• Histology is definitive — mitoses over 10 per 10 high-power fields, diffuse moderate-to-severe nuclear atypia, and coagulative tumour-cell necrosis (the three Stanford criteria).
• NEVER transabdominal needle biopsy of a suspected fibroid if morcellation/sarcoma is a concern — risks intra-abdominal spread. ^[1]

Severity / impact scoring: there is no universally applied numeric score for fibroid severity (unlike CURB-65 in CAP). The clinically relevant 'grading' is the FIGO type plus uterine size in weeks plus symptom severity (pictorial blood-loss assessment chart, PBAC, with a score over 100 defining menorrhagia). The Uterine Fibroid Symptom and Quality-of-Life (UFS-QOL) questionnaire is the validated disease-specific instrument used in trials and clinical practice to assess symptom burden and treatment response.^[1]

Management — Resuscitation

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^{[2] [6]}

Fibroids are usually chronic, but severe acute heavy menstrual bleeding is a medical emergency.^[10]

Acute severe AUB — guidance for nonpregnant reproductive-aged women (ACOG Committee Opinion No. 557):^[10]

• Assess for hypovolaemia and haemodynamic instability first — prompt assessment and stabilization precede any specific therapy; classify the bleeding cause with the PALM-COEIN system once stabilised.^[10][12]
• Exclude pregnancy in any reproductive-age woman before treating — the acute-AUB guidance applies to nonpregnant women.^[10]
• Medical management is the initial treatment for most patients, if clinically appropriate. Options include intravenous conjugated equine estrogen, multi-dose regimens of combined oral contraceptives or oral progestins, and tranexamic acid — choose on the basis of the patient's medical history and contraindications to each therapy.^[10]
• Surgical management for patients who are not clinically stable, are not suitable for medical management, or have failed to respond to medical management; the choice of procedure depends on underlying medical conditions, underlying pathology, and desire for future fertility.^[10]
• Once the acute episode is controlled, transition to long-term maintenance therapy.^[10]

Management — Definitive & Stepwise

Treatment is goal-directed — define first the primary goal: (1) control of bleeding, (2) control of bulk/pressure symptoms, (3) fertility preservation / restoration, or (4) definitive cure. The choice then depends on fertility desires, age, fibroid FIGO type, size and number, severity of symptoms, prior treatments, and patient preference.^[1][2][6]

Principles

• Asymptomatic fibroids do NOT require treatment — observe. The exception is a fibroid that is rapidly growing, causes ureteric obstruction/hydronephrosis, or is in a postmenopausal woman (sarcoma concern).^[6]
• Fertility desires are the master variable. Myomectomy (uterus-sparing) for women wanting future fertility; hysterectomy (definitive) only for completed family.
• Location drives modality. Submucosal (FIGO 0 to 2) → hysteroscopic myomectomy; intramural/subserosal (FIGO 3 to 7) → medical, laparoscopic/abdominal myomectomy, embolisation, or hysterectomy; cervical/broad-ligament (FIGO 8) → open surgery with ureteric care.

Medical management — drug, dose, route, rationale, monitoring

1. Symptomatic control of heavy menstrual bleeding (non-hormonal and hormonal options):^[16][3]

• Antifibrinolytics (tranexamic acid) — the best-supported non-hormonal option: a Cochrane overview and network meta-analysis ranked antifibrinolytics the second-best first-line treatment for reducing menstrual blood loss (mean difference about 80 mL per cycle versus placebo, moderate-certainty evidence).^[16]
• NSAIDs (e.g. mefenamic acid — one of the usual medical treatments in the ECLIPSE trial) — only slightly reduce menstrual blood loss (about 41 mL per cycle, confidence interval consistent with no effect; low-certainty) and are a reasonable non-hormonal choice for bleeding with dysmenorrhoea.^[16][3]

2. Levonorgestrel-releasing intrauterine system (LNG-IUS, Mirena) — the best first-line medical treatment for heavy menstrual bleeding:^[16][3]

• LNG-IUS produces the largest reduction in menstrual blood loss of the medical options (about 106 mL per cycle versus placebo; low-certainty) and is ranked first-line in the Cochrane overview.^[16] In the ECLIPSE primary-care randomised trial, the LNG-IUS improved women's assessment of the effect of heavy bleeding on daily life more than usual medical treatment over 2 years, though the difference was no longer significant at 5 years; 5-year surgery rates were similarly low (20%) in both groups.^[3] The LNG-IUS is also FDA-approved for additional use to treat heavy menstrual bleeding in intrauterine device users.^[9]

3. Combined hormonal contraception — an option when contraception is also desired:^[3][10]

• Combined oestrogen-progestogen was one of the usual medical treatments for HMB in the ECLIPSE trial, and multi-dose regimens of combined oral contraceptives are listed among medical options for acute abnormal uterine bleeding — choose according to the woman's medical history and contraindications.^[3][10]

4. Progestogens — oral:^[16][3]

• Oral progestogens (luteal-phase or long-cycle regimens) — long-cycle progestogen reduces menstrual blood loss by about 77 mL per cycle (low-certainty), ranked third-best of the first-line medical options in the Cochrane overview; progestogen alone was also one of the usual medical treatments in ECLIPSE, and multi-dose oral progestins are an option for acute abnormal uterine bleeding.^[16][3][10]

5. Gonadotropin-releasing hormone (GnRH) agonists — short-course, often pre-operative:^[15][9]

• GnRH agonists induce a state of hypo-oestrogenism that shrinks fibroids, and are FDA-approved for reducing fibroid volume and related symptoms.^[15][9] Pre-operatively they reduce uterine volume (mean difference 175 mL), reduce fibroid volume, and increase preoperative haemoglobin (mean difference 0.88 g/dL); at hysterectomy they shorten surgery, reduce blood loss and transfusions — at the cost of more adverse events, particularly hot flushes (odds ratio 7.7).^[15] In one comparison uterine volume fell 47 per cent with a GnRH agonist versus 20 to 22 per cent with ulipristal acetate 5 to 10 mg.^[15]

6. GnRH antagonist combination — the modern oral option:^[5]

• Relugolix combination therapy — relugolix 40 mg + estradiol 1 mg + norethindrone acetate 0.5 mg, once daily. In two replicate 24-week phase 3 trials (LIBERTY 1 and LIBERTY 2) in women with fibroid-associated heavy menstrual bleeding, 73 per cent and 71 per cent of women on the combination met the primary bleeding-response endpoint (menstrual blood loss under 80 mL and at least a 50 per cent reduction from baseline) versus 19 per cent and 15 per cent on placebo (P under 0.001).^[5] Secondary endpoints improved for menstrual blood loss (including amenorrhoea), pain, distress from bleeding and pelvic discomfort, anaemia and uterine volume — but not fibroid volume. Bone mineral density was preserved with the combination but fell with relugolix monotherapy.^[5]

7. Selective progesterone receptor modulators (SPRMs):^[14][7][2]

• Ulipristal acetate 5 mg oral once daily for up to 13 weeks before surgery. In PEARL I, uterine bleeding was controlled in 91 per cent on 5 mg (92 per cent on 10 mg) versus 19 per cent on placebo, amenorrhoea occurred in 73 per cent (5 mg), and median total fibroid volume fell 21 per cent (5 mg) versus a 3 per cent rise on placebo; the most common adverse events were headache and breast tenderness.^[14] SAFETY: the European Medicines Agency has suspended ulipristal acetate for uterine fibroids and is reassessing its risk of liver injury — a worldwide FAERS disproportionality analysis found significant signals for drug-induced liver injury, autoimmune hepatitis and acute hepatic failure with ulipristal (2.9 per cent of reports were liver disorders).^[7] Long-term intermittent ulipristal efficacy has been shown in randomised trials, but verify the current licence status locally before prescribing.^[2][7]

8. Investigational and adjunct options: ^[9]

• Beyond GnRH agonists and the LNG-IUS (both FDA-approved for fibroid-related indications), mifepristone, asoprisnil, ulipristal acetate and epigallocatechin gallate have shown fibroid regression and symptomatic improvement in clinical trials, and several synthetic and natural compounds plus growth-factor inhibitors are under laboratory investigation as future options.^[9]

Surgical management

Indications for surgery:^[2][6]

• Symptomatic fibroids failing or unsuitable for medical therapy (heavy bleeding with anaemia, severe bulk/pressure symptoms, ureteric obstruction, infertility with cavity distortion).
• Submucosal fibroid (FIGO 0 to 2) causing bleeding or infertility → hysteroscopic myomectomy (first-line surgical).
• Rapid growth, postmenopausal growth, or imaging suggestive of sarcoma → hysterectomy (do not morcellate). ^[1]

Myomectomy — uterus-sparing, for women desiring fertility or uterus preservation: ^[1]

• Hysteroscopic myomectomy — for submucosal fibroids FIGO 0, 1 and 2. Resectoscope with monopolar or bipolar energy shaves the fibroid under direct vision; cold-loop (Bigatti shaver) reduces thermal injury. Limit total operative time to under 90 minutes and use hypotonic distension media (glycine) judiciously — risk of fluid overload, hyponatraemia (TURP syndrome). Pretreatment with GnRH agonist for FIGO 0 to 1 may reduce size. Recurrence around 15 to 30 per cent.
• Laparoscopic myomectomy — for intramural and subserosal fibroids (FIGO 3 to 7), especially under 10 cm and fewer than 4. Multilayer uterine closure essential; counsel on risk of uterine rupture in future pregnancy — these women should usually deliver by elective caesarean if the cavity was entered.
• Abdominal (open) myomectomy — for very large (over 10 cm), numerous, cervical or broad-ligament fibroids where laparoscopy is not feasible; minilaparotomy is an alternative. Blood loss is higher; preoperative GnRH agonist or preoperative uterine artery occlusion reduces bleeding. ^[1]

Hysterectomy — the definitive cure, for women who have completed their family:^[6]

• Total hysterectomy (with conservation or removal of tubes and ovaries depending on age and ovarian-cancer risk) cures the disease — no recurrence. Routes: vaginal, laparoscopic, robotic, abdominal. Choose the least invasive route feasible. Consider concurrent BSO in postmenopausal women or those at high ovarian-cancer risk; counsel on surgical menopause.
• Never perform hysterectomy in a woman desiring future fertility without exhaustive counselling. ^[1]

Uterus-sparing radiological / minimally invasive options

Uterine artery embolisation (UAE):^[4]

• Interventional radiology — bilateral uterine artery catheterisation via femoral artery with injection of polyvinyl alcohol (PVA) particles (500 to 700 micrometres) or gelatin-coated tris-acryl microspheres to embolise the fibroid's arterial supply → ischaemic infarction and shrinkage (around 40 to 60 per cent volume reduction at 6 months). Symptom relief in 85 to 90 per cent of women. In REST (NEJM 2007) UAE gave a shorter median hospital stay (1 day versus 5 days) and faster return to work, but at 1 year symptom scores were better in the surgical group (P=0.03) and 9 per cent of the embolisation group needed repeat embolisation or hysterectomy; the Cochrane review found satisfaction inconclusive, more minor complications within a year with UAE, and possibly less favourable fertility outcomes than myomectomy.^[4][17] Not suitable for pedunculated subserosal fibroids (FIGO 7) (risk of detachment/torsion) or where infection is present. Post-embolisation syndrome (pain, low-grade fever, nausea) common for a few days. Pregnancy after UAE is possible but associated with higher rates of preterm delivery, miscarriage, malpresentation and postpartum haemorrhage — counsel women wanting future fertility.

MRI-guided focused ultrasound surgery (MRgFUS / HIFU): ^[1]

• High-intensity focused ultrasound under real-time MRI thermometry ablates fibroid tissue non-invasively through intact skin — no incision, day-case. Suitable for non-calcified, accessible fibroids (typically FIGO 2 to 6, not submucosal-pedunculated). Symptom relief around 70 per cent; lower reintervention risk if well-selected. Limited by depth, bowel interposition, and scar tissue. ^[1]

Radiofrequency ablation (Acessa, Sonata): ^[1]

• Laparoscopic or transvaginal ultrasound-guided radiofrequency ablation of fibroid tissue (laparoscopic Acessa; transcervical Sonata). Minimally invasive; suitable for intramural and subserosal fibroids; preserves uterus. Symptom relief around 70 to 80 per cent. ^[1]

Endometrial ablation — only for small submucosal fibroids with completed family and no fertility desire; must be combined with sterilisation or reliable contraception as future pregnancy is high-risk. ^[1]

Specific Subtypes & Scenarios

Per-subtype notes:^[1][2][6]

• Submucosal fibroid (the high-yield subtype): the most symptom-producing per gram. Causes heavy bleeding, infertility and recurrent miscarriage. Hysteroscopic resection (FIGO 0 to 2) restores fertility and controls bleeding. Pretreat with GnRH agonist for 2 to 3 months for FIGO 0 to 1 to reduce size and bleeding. Stepwise enucleation (cold or thermal); respect the 90-minute fluid-window to avoid TURP syndrome.
• Pedunculated subserosal fibroid (FIGO 7): can torsion (acute pain, mimics ovarian torsion) — emergency laparoscopic myomectomy. Not suitable for UAE (risk of detachment and parasitic migration).
• Red (carneous) degeneration in pregnancy: the fibroid outgrows its blood supply under high pregnancy oestrogen, undergoes acute haemorrhagic infarction. Presents with acute focal pain over a fibroid, low-grade fever, mild tachycardia, nausea, a tender uterine mass in pregnancy. Diagnosed clinically (after excluding ectopic, abruption, appendicitis); ultrasound may show a heterogeneous fibroid. Management is conservative — rest, paracetamol, NSAIDs (short course, avoid after 30 weeks), opiate if severe. Surgery is reserved for torsion or rupture. Usually self-limiting; fibroid may calcify afterwards. Leiomyoma in pregnancy rarely interferes with delivery unless low-lying/cervical.
• Cervical fibroid: a true surgical challenge — acute urinary retention from impaction behind the symphysis, ureteric compression, and displacement of the cervix making vaginal hysterectomy impossible. Open surgery, identify and protect ureters, may need ureteric stents.
• Parasitic fibroid: a detached fibroid surviving on omental/mesenteric blood supply; more common after prior uterine surgery or UAE. Surgical resection; recurrence common.
• The infertile woman with fibroids: submucosal fibroids (FIGO 0 to 2) and large intramural fibroids distorting the cavity clearly impair fertility and warrant myomectomy before IVF. The role of removing non-cavity-distorting intramural fibroids to improve IVF success is debated. Cavity evaluation by SIS or hysteroscopy is part of the fertility work-up.^[8]

Complications & Pitfalls

Disease-related:^[1][8]

• Iron-deficiency anaemia from chronic menorrhagia — the commonest systemic complication; can be severe and require transfusion or IV iron.
• Infertility and recurrent miscarriage — predominantly from submucosal and cavity-distorting intramural fibroids.
• Urinary complications — frequency, urgency, acute urinary retention (cervical fibroid), hydronephrosis and renal impairment (ureteric compression by large cervical or broad-ligament fibroid).
• Bowel complications — constipation, tenesmus.
• Venous stasis — lower-limb oedema; DVT/pulmonary embolism rarely with very large fibroids (over 20 weeks size).
• Pregnancy complications — red degeneration (acute pain), malpresentation (fibroid occupying the lower segment), antepartum haemorrhage (low-lying placenta more common), preterm labour, obstructed labour (cervical or lower-segment fibroid), postpartum haemorrhage (poor uterine retraction), and retained placenta.
• Torsion of a pedunculated subserosal fibroid — acute abdomen.
• Sarcomatous transformation — see Prognosis. ^[1]

Treatment-related complications:^[1][4]

• Hysterectomy: bleeding, infection, visceral injury (bladder, ureter, bowel), vault haematoma, premature ovarian failure if BSO, VTE.
• Myomectomy: blood loss (often requiring transfusion), post-operative adhesions (especially open), uterine rupture in future pregnancy (after laparoscopic/abdominal myomectomy that entered the cavity — these women should deliver by elective caesarean), recurrence (15 to 30 per cent), Asherman syndrome (after hysteroscopic resection with over-aggressive resection of intramural component), TURP syndrome (hyponatraemia from glycine absorption during hysteroscopic resection).
• UAE: post-embolisation syndrome (pain, fever, nausea, leucocytosis for up to a week), infection (occasionally requiring emergency hysterectomy), premature ovarian failure (especially over age 45 — embolisation of ovarian branches), passage of fibroid tissue (submucosal), future pregnancy risks (preterm delivery, miscarriage, malpresentation, PPH).
• GnRH agonists: bone density loss, menopausal symptoms (limit to 6 months without add-back), initial flare (transient worsening in first 1 to 2 weeks).
• Ulipristal acetate: drug-induced liver injury, including liver failure requiring transplant (EMA 2018/2020) — LFT monitoring mandatory; contraindicated in hepatic impairment.^[7]
• Power morcellation of an unsuspected leiomyosarcoma at hysterectomy/myomectomy spreads tumour intra-abdominally, dramatically worsening prognosis — the FDA warned against power morcellation in 2014; use contained (in-bag) morcellation where morcellation is unavoidable.^[6]

Classic pitfalls:^[1][6]

• Failing to exclude pregnancy in a reproductive-age woman with a pelvic mass or AUB.
• Assuming postmenopausal bleeding or a growing postmenopausal fibroid is benign — always exclude leiomyosarcoma and endometrial cancer.
• Treating asymptomatic fibroids — observe; do not subject women to surgical risk for incidental findings.
• Placing an LNG-IUS in a severely distorted cavity without first resecting the submucosal fibroid — high expulsion rate.
• Morcellating a suspected fibroid without excluding sarcoma.
• Not counselling on uterine rupture risk after myomectomy, and on delivery mode.
• Missing TURP syndrome during prolonged hysteroscopic resection.
• Prescribing ulipristal acetate without LFT monitoring or in hepatic impairment.
• Dismissing severe anaemia as 'just heavy periods' without investigating the cause. ^[1]

Prognosis & Disposition

Fibroids are benign and most are asymptomatic; symptomatic disease significantly impairs quality of life, work and fertility. The natural history is governed by hormonal status.^[1][6]

Natural history by hormonal status: ^[1]

• Reproductive years — fibroids grow slowly (around 1 to 2 cm per year in symptomatic women), accelerated by pregnancy.
• Pregnancy — growth and risk of red degeneration; usually no obstruction unless low-lying/cervical.
• Menopause — fibroids shrink (volume reduction of 20 to 50 per cent) as oestrogen falls; symptoms typically resolve. Growth after menopause is a red flag for sarcoma. Postmenopausal fibroids often calcify.
• Combined HRT with systemic oestrogen may prevent involution or cause growth — use combined (oestrogen + progestogen) and the lowest effective dose; LNG-IUS provides endometrial protection and is a good choice. ^[1]

Recurrence: ^[1]

• After myomectomy, recurrence is 15 to 30 per cent at 5 years; higher in younger women, multiple fibroids, and incomplete resection. Hysterectomy is the only treatment with zero recurrence.
• After UAE, recurrent symptoms requiring reintervention occur in around 20 to 30 per cent at 5 years (higher than hysterectomy). ^[1]

Leiomyosarcoma and malignant transformation:^[1][6]

• The risk of a presumed fibroid being a leiomyosarcoma is around 1 in 200 to 1 in 400 hysterectomies or myomectomies performed for presumed fibroids (older literature cited 0.1 to 0.5 per cent). The risk is higher in postmenopausal women and those with rapid growth.
• Definite malignant transformation of a benign fibroid is debated — many leiomyosarcomas may arise de novo rather than from a pre-existing fibroid. The exam answer remains 'under 0.5 per cent'.
• Poor prognostic features: advanced stage, mitotic count over 10 per 10 HPF, tumour size over 10 cm, coagulative tumour-cell necrosis. Five-year survival for stage I leiomyosarcoma is around 50 to 60 per cent; metastatic disease has a poor prognosis. ^[1]

Disposition: most women with fibroids are managed ambulatory / outpatient by gynaecology with a multidisciplinary team (radiology, fertility, anaesthesia). Admit only for acute severe bleeding, urinary retention, torsion, sarcoma suspicion requiring urgent surgery, or for elective surgery. Referral to a specialist fibroid / minimally invasive centre is appropriate for complex, large, or fertility-sparing cases. ^[1]

Special Populations

Adolescents:^[6]

• Fibroids are rare before menarche. In adolescents, suspect an associated syndrome — HLRCC (Reed's syndrome, fumarate hydratase mutation) with cutaneous leiomyomas, or diethylstilboestrol-exposure history (older generation). Fertility-sparing management preferred; medical first-line. ^[1]

Women desiring fertility:^[8]

• Submucosal fibroids (FIGO 0 to 2) and cavity-distorting intramural fibroids should be resected before fertility treatment — they impair implantation and increase miscarriage.
• Laparoscopic/abdominal myomectomy for large intramural/subserosal fibroids in infertile women; counsel on uterine rupture risk and delivery by elective caesarean if the cavity was entered.
• Avoid UAE as first-line in women who want future pregnancy (higher pregnancy complications); if used, counsel carefully.
• Medical therapy does NOT improve natural fertility (it suppresses ovulation); it is symptomatic only, except as a bridge before surgery. ^[1]

Pregnancy:^[6]

• Fibroids grow under high oestrogen; red degeneration (acute focal pain) managed conservatively.
• Pregnancy complications: malpresentation (especially lower-segment fibroids), antepartum haemorrhage (placenta praevia and abruption more common), preterm labour, obstructed labour (cervical or low-segment fibroid), postpartum haemorrhage (poor retraction), retained placenta.
• Caesarean myomectomy is generally avoided at the time of caesarean section (high blood loss) unless the fibroid is in the incision line or pedunculated; myomectomies can be done postpartum once involution completes.
• Discontinue medical therapy (GnRH, SPRMs, combined OCP) before conception. ^[1]

Perimenopausal and menopausal:^[1]

• Fibroids shrink after menopause; symptoms usually resolve. Growth or new symptoms postmenopause mandate exclusion of sarcoma and endometrial cancer.
• GnRH agonists as a bridge to natural menopause can avoid surgery entirely in perimenopausal women.
• HRT may prevent involution — use combined, lowest dose, or LNG-IUS for the progestogen component. ^[1]

Women on tamoxifen (breast cancer):^[6]

• Tamoxifen's partial oestrogen agonism can stimulate fibroid growth despite menopause. Monitor; consider switching to an aromatase inhibitor in postmenopausal women if symptomatic. LNG-IUS provides both endometrial protection and bleeding control. ^[1]

Immunocompromised / on anticoagulation: no specific change in fibroid behaviour, but heavy bleeding risk is compounded by anticoagulation — tranexamic acid (avoid with active VTE) and LNG-IUS are particularly useful; plan surgery carefully with anticoagulation bridging. ^[1]

Evidence, Guidelines & Regional Differences

NICE NG88 (Heavy menstrual bleeding: assessment and management, 2018, updated 2024) — key recommendations (anchored in the ECLIPSE primary-care RCT of LNG-IUS vs standard medical therapy):^[3]

• LNG-IUS (Mirena) is first-line pharmacological treatment for HMB in women with no pathology, small fibroids (under 3 cm), or no cavity distortion; consider hysteroscopic resection of submucosal fibroids first if cavity distortion.
• If LNG-IUS fails or is unsuitable: non-hormonal (tranexamic acid and/or NSAIDs) OR hormonal (combined OCP, oral or injectable long-acting progestogen).
• Investigations: FBC, TFTs, coagulation screen if HMB since menarche or family history; TVUS first-line for structural pathology; hysteroscopy + biopsy if persistent intermenstrual/postmenopausal bleeding or non-diagnostic ultrasound.
• Second-line / refractory: GnRH agonist (with add-back) for short-term symptom control before definitive surgery.
• Surgical: endometrial ablation (small fibroids, completed family), myomectomy (fertility-sparing), hysterectomy (definitive). Choose the least invasive feasible route. ^[1]

ACOG Practice Bulletin 228 (Uterine Leiomyomas, 2021) — key recommendations:^[6]

• Asymptomatic fibroids do not require treatment.
• Diagnosis by TVUS; MRI for surgical mapping and equivocal cases.
• Hysteroscopic myomectomy for FIGO 0 to 2; laparoscopic or abdominal myomectomy for FIGO 3 to 7; hysterectomy definitive.
• UAE and MRgFUS are uterus-sparing alternatives in well-selected women.
• Counsel on uterine rupture risk after myomectomy and on delivery mode; contained (in-bag) morcellation where morcellation is unavoidable. ^[1]

Key randomised trials and systematic reviews: ^[17]

• REST (Edwards et al., NEJM 2007): randomised trial of UAE versus surgery for symptomatic fibroids — UAE gave a shorter median hospital stay (1 day versus 5 days) and a faster return to work, but at 1 year symptom scores were better in the surgical group (P=0.03); 9 per cent of the embolisation group needed repeat embolisation or hysterectomy for inadequate symptom control within the first year.^[4]
• Cochrane review of UAE (Gupta et al., 2014; 7 RCTs, 793 women): patient satisfaction after UAE versus surgery was inconclusive (odds ratio 0.94); minor complications within one year were more frequent with UAE (odds ratio 1.99); very-low-quality evidence suggested less favourable fertility outcomes than myomectomy.^[17]
• PEARL I (Donnez et al., NEJM 2012): ulipristal acetate 5 mg or 10 mg daily for 13 weeks before surgery controlled bleeding in 91 to 92 per cent versus 19 per cent on placebo and reduced fibroid volume — the basis for SPRM therapy; subsequently complicated by the EMA suspension over liver-injury risk.^[14][7]
• LIBERTY 1 and 2 (Al-Hendy et al., NEJM 2021): relugolix combination (relugolix 40 mg + estradiol 1 mg + norethindrone acetate 0.5 mg once daily) for 24 weeks — 73 and 71 per cent met the bleeding-response endpoint versus 19 and 15 per cent on placebo, with preserved bone mineral density.^[5]

^[1]

Controversies:^[1][7]

• Ulipristal acetate and liver injury — the EMA PRAC restricted use in 2018 and again in 2020; some countries have withdrawn it; LFT monitoring is mandatory where still licensed.
• Power morcellation and occult sarcoma — FDA 2014 warning against uncontained power morcellation in hysterectomy/myomectomy for presumed fibroids due to the risk of intra-abdominal spread of an unsuspected leiomyosarcoma; contained in-bag morcellation is the modern standard where morcellation is needed.
• UAE in women wanting future pregnancy — possible but associated with higher pregnancy complication rates; not first-line.
• Myomectomy for non-cavity-distorting intramural fibroids to improve IVF outcomes — evidence debated; individualise. ^[1]

Regional differences: ^[1]

• Access to interventional radiology (UAE, MRgFUS) varies — urban tertiary centres versus rural; many low- and middle-income countries rely on open surgery.
• Ulipristal acetate availability varies — suspended in some EU countries, restricted in others, available with LFT monitoring in some, never licensed in others.
• Hysterectomy rates are higher in the United States and many developing countries than in Western Europe — reflecting fertility, cultural, and access differences. ^[1]

Exam Pearls

• Fibroids (leiomyomas) are the COMMONEST benign uterine tumour. Cumulative incidence by age 50 was nearly 70 per cent in white women and over 80 per cent in black women in an ultrasound-screened cohort; about a third of women with fibroids seek treatment for symptoms.^[11][2]
• Fibroid growth is stimulated by oestrogen, and fibroids are two- to three-fold commoner in black women (odds ratio 2.9 in a screened cohort).^[15][11]
• Submucosal fibroids are the bleeding-relevant location: hysteroscopically diagnosed submucosal fibroids were associated with lower haemoglobin and higher anaemia risk (odds ratio 1.46).^[8]
• Commonest symptoms are heavy or abnormal uterine bleeding, pelvic pain or pressure, infertility and recurrent pregnancy loss; management of acute AUB applies to nonpregnant women — exclude pregnancy first.^[9][10]
• Hysteroscopy detects submucosal fibroids better than ultrasound — hysteroscopically diagnosed submucosal fibroids carried lower haemoglobin and more anaemia than ultrasound-diagnosed ones.^[8]
• Treatment ladder — observe if asymptomatic; medical therapy first-line (LNG-IUS best for reducing menstrual blood loss, then antifibrinolytics, then long-cycle progestogen); surgery (hysteroscopic, laparoscopic or abdominal myomectomy; hysterectomy definitive) and uterus-sparing procedures (uterine artery embolisation, image-guided thermal ablation).^[16][9][2]
• Hysterectomy is definitive and fibroids are the leading indication for it, but many women seek uterus-sparing options for future childbearing.^[6]
• Leiomyosarcoma is rare in presumed fibroids — about 1 in 460 operations in one retrospective series of 921 surgeries for presumed myomas (4 malignant neoplasms, 0.43 per cent).^[18]
• Acute severe AUB — medical therapy first for most: IV conjugated equine estrogen, multi-dose combined oral contraceptives or oral progestins, or tranexamic acid; surgery for the unstable or non-responsive.^[10]
• GnRH agonists shrink uterine and fibroid volume and raise preoperative haemoglobin (mean difference 0.88 g/dL) before surgery, with more hot flushes.^[15][9]
• Relugolix combination (relugolix 40 mg + estradiol 1 mg + norethindrone acetate 0.5 mg once daily) — 73 and 71 per cent bleeding response versus 19 and 15 per cent placebo at 24 weeks, with preserved bone mineral density (LIBERTY 1 and 2).^[5]
• Ulipristal acetate 5 mg daily for 13 weeks controlled bleeding in 91 per cent (PEARL I) — but the EMA has suspended it for fibroids while reassessing liver-injury risk; verify licence status locally.^[14][7]
• MED12 is mutated in about 70 per cent of uterine leiomyomas (159 of 225 tumours, all mutations in exon 2).^[13]
• PALM-COEIN — fibroids (leiomyoma) are the L, the structural cause category of the FIGO classification of abnormal uterine bleeding in nongravid women of reproductive age.^[12]

Exam application bank (NEET-PG / INICET)

One-line answer

Uterine fibroids (leiomyomas) are benign, monoclonal, oestrogen- and progesterone-responsive smooth-muscle tumours of the myometrium — the commonest benign tumour of women (up to 70 to 80 per cent by age 50). Most are asymptomatic; when symptomatic the leading complaint is abnormal uterine bleeding (heavy/prolonged menses), followed by bulk/pressure symptoms (pelvic heaviness, urinary frequency, constipation) and infertility (predominantly submucosal). Classified by location (FIGO 0 to 8): submucosal cause bleeding and subfertility, intramural are commonest, subserosal cause pressure. Diagnosis is clinical plus transvaginal ultrasound; MRI maps submucosal extent and excludes sarcoma. Management is goal- and fertility-directed: observe if asymptomatic; medical (tranexamic acid, NSAIDs, LNG-IUS, GnRH agonist with add-back, GnRH antagonist); surgery (myomectomy for uterus/fertility preserva

Worked stems (answer without another resource)

Stem 1 — Classic presentation. Map symptoms to mechanism; name the first investigation and first treatment step with dose/route if drug therapy is standard. ^[1]

Stem 2 — Unstable / complicated. List red flags that force immediate resuscitation, theatre, ICU, antidote, or reperfusion — and what you do in the first 15 minutes. ^[1]

Stem 3 — Atypical group. Elderly, pregnancy, child, or immunocompromised: how presentation and thresholds change. ^[1]

Stem 4 — Differential trap. Name the three closest mimics and one discriminator for each. ^[1]

Stem 5 — Disposition. Who goes home with safety-netting, who is admitted, who needs HDU/ICU/theatre, and what follow-up is mandatory. ^[1]

Rapid viva checklist

1. Definition + classification
2. Pathophysiology chain
3. Bedside signs / criteria
4. Score with exact components (if any)
5. Emergency bundle
6. Definitive therapy with doses
7. Complications of disease and of treatment
8. Special populations
9. Guideline/trial name if classic
10. Three exam traps

Coverage self-check

If you cannot answer any stem above from this page alone, re-read the matching section — the page is intended to be self-sufficient for final-prof and NEET-PG/INICET questions on Uterine Fibroids.

References18ShowHide

1. [1]Stewart EA, Cookson CL, Gandolfo RA, Schulze-Rath R. Epidemiology of uterine fibroids: a systematic review BJOG, 2017.PMID 28296146
2. [2]Donnez J, Dolmans MM. Uterine fibroid management: from the present to the future Hum Reprod Update, 2016.PMID 27466209
3. [3]Gupta JK, Daniels JP, Middleton LJ, et al. A randomised controlled trial of the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system in primary care against standard treatment for menorrhagia: the ECLIPSE trial Health Technol Assess, 2015.PMID 26507206
4. [4]Edwards RD, Moss JG, Lumsden MA, et al. Uterine-artery embolization versus surgery for symptomatic uterine fibroids N Engl J Med, 2007.PMID 17251532
5. [5]Al-Hendy A, Lukes AS, Stewart EA, et al. Treatment of Uterine Fibroid Symptoms with Relugolix Combination Therapy N Engl J Med, 2021.PMID 33596357
6. [6]American College of Obstetricians and Gynecologists (ACOG) Management of Symptomatic Uterine Leiomyomas: ACOG Practice Bulletin, Number 228 Obstet Gynecol, 2021.PMID 34011888
7. [7]Liver Injury with Ulipristal Acetate: Exploring the Underlying Pharmacological Basis Drug Saf, 2020.PMID 32748236
8. [8]Puri K, Famuyide AO, Erwin PJ, Stewart EA, Laughlin-Tommaso SK. Submucosal fibroids and the relation to heavy menstrual bleeding and anemia Am J Obstet Gynecol, 2014.PMID 24080304
9. [9]Islam MS, Protic O, Giannubilo SR, et al. Uterine leiomyoma: available medical treatments and new possible therapeutic options J Clin Endocrinol Metab, 2013.PMID 23393173
10. [10]American College of Obstetricians and Gynecologists (ACOG) ACOG committee opinion no. 557: Management of acute abnormal uterine bleeding in nonpregnant reproductive-aged women Obstet Gynecol, 2013.PMID 23635706
11. [11]Baird DD, Dunson DB, Hill MC, Cousins D, Schectman JM. High cumulative incidence of uterine leiomyoma in black and white women: ultrasound evidence Am J Obstet Gynecol, 2003.PMID 12548202
12. [12]Munro MG, Critchley HO, Broder MS, Fraser IS; FIGO Working Group on Menstrual Disorders. FIGO classification system (PALM-COEIN) for causes of abnormal uterine bleeding in nongravid women of reproductive age Int J Gynaecol Obstet, 2011.PMID 21345435
13. [13]Mäkinen N, Mehine M, Tolvanen J, et al. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas Science, 2011.PMID 21868628
14. [14]Donnez J, Tatarchuk TF, Bouchard P, et al. Ulipristal acetate versus placebo for fibroid treatment before surgery N Engl J Med, 2012.PMID 22296075
15. [15]Lethaby A, Puscasiu L, Vollenhoven B. Preoperative medical therapy before surgery for uterine fibroids Cochrane Database Syst Rev, 2017.PMID 29139105
16. [16]Bofill Rodriguez M, Dias S, Jordan V, et al. Interventions for heavy menstrual bleeding; overview of Cochrane reviews and network meta-analysis Cochrane Database Syst Rev, 2022.PMID 35638592
17. [17]Gupta JK, Sinha A, Lumsden MA, Hickey M. Uterine artery embolization for symptomatic uterine fibroids Cochrane Database Syst Rev, 2014.PMID 25541260
18. [18]Mühlenbrock MV, Navarrete-Rey P, Kovoor E, et al. Incidence of occult uterine sarcoma and other unexpected pathologies in patients having surgery for presumed myomas: A retrospective observational study J Gynecol Obstet Hum Reprod, 2021.PMID 33217603