Diagnose and manage uterine fibroids across the reproductive lifespan

In one line

Uterine fibroids are benign monoclonal smooth-muscle tumours whose symptoms — heavy menstrual bleeding, bulk effects and reproductive consequences — are predicted far better by the FIGO 0–8 location of the fibroid than by its size, so the consultant task is to match the intervention to the symptom and to the woman's fertility intent, sparing the uterus wherever that is what she values and reserving hysterectomy for the woman who has completed her family and wants the problem gone for good.

The bleeding mechanism and first-line medical control are developed in depth at heavy-menstrual-bleeding; the groundwork on pathology, basic classification and presentation is assumed from the Intermediate chapter fibroids. The focus here is the consultant decision — choosing between, and defending, the uterine-sparing and definitive options, and managing the tumour through pregnancy and the perimenopause.

Mechanism & pathophysiology

Each fibroid is an independent monoclonal proliferation: a single myometrial smooth-muscle cell acquires a driver lesion and clonally expands, which is why a woman commonly carries multiple genetically distinct tumours rather than one disease that has spread. The commonest driver, present in roughly 50–85% of leiomyomas, is a mutation in MED12 (a subunit of the Mediator transcription-regulatory complex); the next, in most MED12-wild-type tumours, is overexpression of the architectural transcription factor HMGA2, usually through a 12q14–15 rearrangement. These are largely mutually exclusive events. A clinically important minority are fumarate hydratase (FH)-deficient, the uterine manifestation of hereditary leiomyomatosis and renal cell cancer (HLRCC) — a woman with multiple early-onset, often symptomatic fibroids and cutaneous leiomyomas or a family history of aggressive renal cancer warrants genetic referral, because the renal tumours are lethal and screenable.

Whatever the driver, the tumour is steroid-hormone-dependent. Fibroid tissue overexpresses both oestrogen and progesterone receptors relative to normal myometrium, and — counter to the old teaching that they are purely oestrogen-driven — progesterone is the dominant proliferative signal: progesterone receptor activation drives mitosis and survival, oestrogen largely by upregulating that progesterone-receptor machinery. This is the rationale for every effective medical therapy. Removing the steroid drive (GnRH analogues), blocking the progesterone receptor (selective progesterone-receptor modulators), or suppressing the gonadal axis with controlled add-back (GnRH antagonist combinations) all shrink fibroids and stop bleeding; the corollary is that fibroids characteristically grow through the reproductive years, can enlarge in pregnancy, and regress after the menopause as the hormonal substrate falls away — which itself is part of the management calculus in the woman near 50.

The bulk of a fibroid is not cells but extracellular matrix — a disordered, collagen-rich, stiff matrix that the tumour cells actively deposit and remodel. This matters mechanically: the stiffness and the slow matrix turnover explain why fibroids are firm, why they outgrow their blood supply and undergo degeneration (hyaline, cystic, calcific, and the painful red/carneous degeneration of pregnancy, in which a rapidly enlarging fibroid infarcts), and why purely cytoreductive drugs shrink them only so far.

The clinical syndromes follow directly from where this matrix sits, codified in the FIGO leiomyoma subclassification (types 0–8) nested within PALM-COEIN:

• Submucosal (types 0–2) distort the endometrial cavity. Type 0 is wholly intracavitary on a stalk; type 1 has <50% intramural extension; type 2 has ≥50%. These are the fibroids that cause heavy menstrual bleeding out of proportion to their size — by increasing and distorting the endometrial surface, dysregulating local vasoactive and clotting factors, and impairing myometrial contraction — and the ones that impair implantation and raise miscarriage risk. A small submucosal fibroid can dominate the clinical picture; a large subserosal one may be silent.
• Intramural (types 3–5) sit within the myometrium. Type 3 abuts the endometrium without distorting it; type 5 abuts the serosa. They contribute to bleeding and bulk, and their effect on fertility is the contested middle ground (below).
• Subserosal (types 6–7) project outward; type 7 is pedunculated. These produce bulk and pressure symptoms — urinary frequency, retention, hydronephrosis from ureteric compression, constipation, abdominal distension, and the dragging discomfort of a heavy pelvic mass — rather than bleeding.
• Type 8 is "other" — cervical, or parasitic fibroids that have acquired an extra-uterine blood supply.
• Hybrid lesions touching both endometrium and serosa are written as two numbers (e.g. 2–5).

The fertility and obstetric mechanisms are the same anatomy applied to pregnancy, and they sort cleanly by FIGO type. Submucosal (cavity-distorting) fibroids reduce implantation and live-birth rates and increase miscarriage, and their resection improves outcomes — the one situation where the fertility benefit of treatment is reasonably secure. Subserosal fibroids do not measurably affect fertility. The genuinely contested ground is the intramural fibroid that does not distort the cavity: the meta-analytic signal is a modest reduction in implantation and live birth, but the evidence that removing such a fibroid restores fertility is weak, so myomectomy here is a judgement call, not a reflex. In an established pregnancy, fibroids raise the risks of malpresentation (a lower-segment fibroid displaces the presenting part; OR ~2.7), obstructed labour, placental abruption (OR ~2.6) and praevia (OR ~2.2), preterm birth (OR ~1.5), caesarean delivery (OR ~2.6), and postpartum haemorrhage (OR ~3) from an impaired contractile uterus. Red degeneration — acute, severe, localised pain with low-grade fever and a tender enlarging fibroid in the second trimester, occurring in roughly 1 in 12 pregnant women with fibroids — is the characteristic pregnancy event and is managed conservatively.

The diagnosis that haunts this whole field is the rare uterine leiomyosarcoma. It is not a fibroid that has "turned malignant" — the two are largely distinct from the outset, and malignant transformation of a benign fibroid is vanishingly rare. The problem is that no current imaging or clinical feature reliably distinguishes a benign fibroid from a sarcoma before histology, and a leiomyosarcoma can masquerade as a "growing fibroid". This diagnostic uncertainty is the engine of the morcellation controversy addressed below: an operation that fragments the specimen will, in the unlucky woman with an occult sarcoma, disseminate it.

Assessment

• History. Characterise the dominant symptom, because it predicts both the FIGO type and the right intervention. Bleeding — heavy, prolonged, with flooding/clots, fatigue and the symptoms of iron deficiency — points to a submucosal or large intramural lesion. Bulk/pressure — abdominal swelling, urinary frequency or incomplete emptying, constipation, dyspareunia, a palpable mass — points to subserosal or large intramural disease. Ask specifically about subfertility and adverse obstetric history, and about the woman's reproductive intent, because that single fact reorganises the whole management plan. Acute severe pain suggests degeneration or torsion of a pedunculated fibroid.
• Examination. Abdominal palpation may reveal a firm, irregular, non-tender mass arising from the pelvis and (unlike an ovarian mass) usually one you cannot get below; bimanual examination finds an enlarged, mobile, irregular uterus that moves with the cervix — the bedside discriminator from an adnexal mass, which moves independently. Quantify the size in weeks-of-gestation equivalent and look for the pallor and tachycardia of anaemia.
• Transvaginal ultrasound is the first-line investigation: it confirms fibroids, sizes and counts them, and locates them well enough to assign FIGO type in most cases. Saline-infusion sonography (sonohysterography) is the key refinement for submucosal lesions — distending the cavity defines the type 0/1/2 boundary precisely, which is exactly the information that decides whether a hysteroscopic resection is feasible.
• Assigning the FIGO type — the language that drives the plan. Imaging exists to place each fibroid in the FIGO leiomyoma subclassification, because the type, not the size, selects the procedure:

• Predicting hysteroscopic resectability — the STEP-W (Lasmar) score. For a submucosal (type 0–2) fibroid the FIGO type alone underdetermines whether a single hysteroscopic resection will succeed, so the STEP-W classification grades difficulty from five parameters — Size, Topography (lower/mid/upper cavity third), Extension of the base across the wall, Penetration into the myometrium, and lateral Wall — each scored 0–2. A total ≤4 (Group I) predicts a straightforward complete resection; 5–6 (Group II) is complex and may need a two-stage procedure or pre-treatment; 7–9 (Group III) predicts that hysteroscopic surgery is inadvisable and an alternative route should be chosen. It is the tool that turns "type 2" into a concrete operative decision, and the one to cite when asked how you select a submucosal fibroid for hysteroscopic myomectomy.
• MRI is the consultant's mapping tool when ultrasound is inconclusive, the uterus is very large or has numerous fibroids, the differential includes adenomyosis, or surgery is planned and the surgeon needs an exact map of number, size, location and proximity to the cavity and serosa. MRI also informs candidacy for uterine artery embolisation and focused ultrasound. In South Africa, MRI access is uneven and concentrated at tertiary centres, so most mapping is done on a good transvaginal scan with sonohysterography, and MRI is reserved for the genuinely difficult case or pre-procedure planning.
• Distinguishing a benign fibroid from a sarcoma — and being honest about the limits. Features that should raise suspicion are rapid growth (particularly postmenopausal growth, when fibroids should be regressing), an irregular or ill-defined mass, and certain MRI signatures (high T2 signal with restricted diffusion and irregular contrast enhancement). None is reliable enough to rule a sarcoma in or out. The defensible position is to treat each feature as a risk modifier, not a test: counsel the woman with a suspicious mass that the pre-operative probability of malignancy is low but real, and let that probability shape the surgical route (toward an approach that does not fragment the specimen) rather than pretend it can be resolved before histology.
• Baseline work-up. Full blood count (iron-deficiency anaemia is common and correctable), ferritin, and renal function if there is a bulky mass that could obstruct the ureters. An HIV test is part of routine SA gynaecological assessment.

Management

The management decision is driven by the dominant symptom, the FIGO location, the woman's fertility intent, and her proximity to the menopause — in that order, ahead of fibroid size. Organise it as immediate symptom control, then ongoing/definitive treatment, then the long view.

Immediate — control the symptom while the definitive decision is made. For heavy menstrual bleeding, start with the non-hormonal/hormonal medical ladder (developed at heavy-menstrual-bleeding): tranexamic acid during menses and NSAIDs (e.g. mefenamic acid) reduce blood loss and are first-line, cheap and available throughout the SA service. The levonorgestrel-releasing intrauterine system (LNG-IUS) is highly effective for fibroid-associated heavy bleeding provided the cavity is not significantly distorted — a type 0–2 submucosal fibroid distorts the cavity, raises the expulsion rate and limits efficacy, so confirm cavity shape (sonohysterography) before relying on it. Correct iron-deficiency anaemia in parallel; in a severely anaemic woman heading for surgery this is part of preoperative optimisation, not an afterthought.

Ongoing/definitive treatment — choose by intent. Lay the options out against what the woman wants:

Medical options worth the consultant's command:

• GnRH agonists (leuprolide, goserelin) shrink fibroids and induce amenorrhoea by downregulating the pituitary–gonadal axis. Their problem is hypo-oestrogenic morbidity — vasomotor symptoms and, beyond ~6 months, bone loss — and rebound regrowth on stopping. Their settled, evidence-based role is therefore short-term and preoperative: correcting anaemia and shrinking a bulky uterus for ~3 months before myomectomy or hysterectomy to ease surgery and reduce blood loss. Add-back therapy (low-dose oestrogen/progestogen or tibolone) mitigates the menopausal symptoms and bone loss and allows somewhat longer use without losing the bleeding control.
• GnRH antagonists in fixed combination with add-back are the modern oral advance. Relugolix combined with estradiol and norethindrone acetate (and the related elagolix combinations) gives immediate, dose-controlled gonadal suppression plus built-in add-back in a single daily tablet — fast bleeding control without the flare of an agonist and with bone density largely preserved, suitable for longer-term medical management of the woman who wants to avoid surgery.
• Selective progesterone-receptor modulators (SPRMs) — ulipristal acetate — and the liver-safety restriction. Ulipristal controls bleeding rapidly, induces amenorrhoea and shrinks fibroids, and was widely used. Following cases of serious liver injury, including liver failure requiring transplantation, European regulators restricted it: the European Medicines Agency now permits ulipristal acetate 5 mg only for premenopausal women in whom surgical procedures (including uterine artery embolisation) are not appropriate or have failed, with liver-function monitoring before, during and after each course. This is not a drug to reach for routinely; it is a reserved option in a woman who has exhausted alternatives and is not a surgical candidate. (The single-dose ulipristal used for emergency contraception is a different product and is unaffected by this restriction.)

Uterine-sparing procedures:

• Hysteroscopic myomectomy is the definitive treatment for symptomatic submucosal (type 0–1, selected type 2) fibroids causing heavy bleeding or subfertility — a day-case, fertility-preserving resection. Type 2 with deep intramural extension may need a staged or alternative approach.
• Uterine artery embolisation (UAE) occludes the fibroid blood supply via the radial/femoral route, infarcting fibroids while sparing the uterus. It is an excellent option for the woman with symptomatic fibroids who wants to keep her uterus but is not primarily seeking pregnancy. Counsel on post-embolisation syndrome (pain, low-grade fever, malaise), a re-intervention rate higher than surgery over time, and the small risk of premature ovarian insufficiency from off-target embolisation. Fertility intent is the key caveat: pregnancy is possible after UAE, but myomectomy is preferred where future fertility is the priority.
• Myomectomy (laparoscopic or open) removes the fibroids and conserves the uterus — the procedure of choice when fertility is actively desired and a hysteroscopic approach is not applicable (intramural/subserosal disease). Counsel on bleeding (hence preoperative GnRH-analogue shrinkage in selected bulky cases), the small risk of needing hysterectomy if haemorrhage is uncontrollable, recurrence (new fibroids arise; ~1 in 4 need further treatment over years), and the uterine-scar implication for future delivery — a myomectomy that breaches the cavity is, like a classical caesarean, a relative indication for elective caesarean and a contraindication to unsupervised labour.
• High-intensity focused ultrasound (HIFU) thermally ablates fibroids non-invasively under image guidance — either MRI thermometry (MRgFUS) or the more accessible ultrasound-guided form (USgHIFU); radiofrequency ablation (laparoscopic, as in the HALT trial, or transcervical, as in SONATA) coagulates them. Both are uterine-sparing, reduce symptoms with rapid recovery, and suit selected patients; both are limited by access (MRgFUS is scarce in SA and requires an MRI suite for treatment, not just diagnosis), by candidacy (fibroid number, size, location and the need for a clear acoustic window for MRgFUS), and by less long-term and fertility data than myomectomy or UAE. Randomised comparison of MRgFUS with UAE (the FIRSTT trial) found re-intervention to be the practical discriminator — a reminder that the ablative techniques trade lower up-front invasiveness for a higher chance of needing further treatment, which is precisely the counselling point for the woman choosing between them.

Hysterectomy is the definitive, recurrence-proof treatment for the woman who has completed her family and wants the problem ended. The route — vaginal, laparoscopic, or abdominal — follows the uterine size, fibroid position and surgeon expertise, with the minimal-access route preferred where feasible; a very large fibroid uterus may mandate laparotomy. The morcellation caution (below) governs how any contained, fragmented specimen is handled.

The SA context as part of the plan. Fibroids in the South African population are not the textbook's indolent perimenopausal nodule: women of African ancestry develop fibroids earlier, larger and more symptomatically, often presenting with profound iron-deficiency anaemia from years of unmanaged heavy bleeding and with a uterus already at hysterectomy size. The service reality compounds this — the uterine-sparing technologies that broaden choice elsewhere (MRgFUS, often UAE, the newer ablation systems and the GnRH-antagonist combination tablets) are concentrated in the private sector and a few tertiary units, so the realistic public-sector menu is frequently medical control (tranexamic acid, NSAIDs, LNG-IUS where the cavity allows, GnRH analogue to optimise for surgery) and then myomectomy or hysterectomy. The consultant move is to name the evidence-based option and the deliverable one, optimise the anaemia before any surgery, and refer early for the fertility-preserving procedure when the woman wants it and the index hospital cannot provide it — rather than defaulting a young woman who wants children straight to hysterectomy because that is what the local theatre list offers.

Fibroids in pregnancy. Most are managed expectantly. Red degeneration is treated with analgesia (paracetamol, judicious NSAIDs before the third trimester, opioids if needed), hydration and reassurance; it settles over days and surgery in pregnancy is avoided wherever possible. Anticipate malpresentation, obstructed labour and PPH, and plan delivery accordingly — a lower-segment fibroid obstructing the pelvis is a caesarean indication. Caesarean myomectomy is generally avoided because of the haemorrhage risk into a vascular gravid uterus; remove fibroids only in defined circumstances (e.g. a pedunculated fibroid preventing closure) by an experienced surgeon prepared for major blood loss.

Guidelines compared

There is broad international convergence on fibroid management, with the disagreements lying at the edges rather than the core. The major reference points a SA candidate should hold are NICE NG88, ACOG Practice Bulletin 228 (2021), the FIGO leiomyoma subclassification, and SA NDoH/EML practice; there is no single dedicated ESHRE fibroid guideline (ESHRE's relevant guidance is on endometriosis), so attributing a fibroid recommendation to ESHRE overreaches.

The genuinely recent change to flag is the ulipristal restriction (2020–2021): a drug that several guidelines previously positioned as a pre-surgical and even medium-term option is now a reserved, last-line agent for non-surgical candidates with mandatory liver monitoring — and where guidelines were written before 2020 they will read as out of date on this point.

The evidence & the controversy

The morcellation controversy is the defining safety debate in benign gynaecology of the last decade, and a fair consultant answer holds both halves. Laparoscopic power morcellation — fragmenting a fibroid or uterus to extract it through small ports — enabled minimal-access surgery for large specimens. In 2014 the FDA issued a Safety Communication discouraging power morcellation for hysterectomy/myomectomy, and in late 2014 required a boxed warning and contraindications, because an occult uterine sarcoma (estimated at roughly 1 in 350 women operated on for presumed fibroids; later FDA analysis put uterine sarcoma at ~1 in 305–360 and leiomyosarcoma at ~1 in 570–750) would be disseminated through the peritoneal cavity by morcellation, upstaging a potentially curable cancer and worsening survival. The counter-argument is that banning morcellation outright pushes women back toward laparotomy, which carries its own real and common morbidity and mortality — so the harm of avoiding a rare disaster is spread across many women. The resolved position, reflected in ACOG Committee Opinion 822, is neither a ban nor business-as-usual: avoid uncontained power morcellation, counsel every woman explicitly about the small-but-real occult-malignancy risk, screen for risk factors (postmenopausal status, rapid growth, prior pelvic radiation, tamoxifen, certain hereditary syndromes), and where morcellation is used, do it within a containment system. For the SA candidate, the practical translation is honesty about the limits — no imaging reliably excludes sarcoma — and a default toward contained extraction or an extraction route that does not fragment the specimen.

Which uterine-sparing procedure, and the FEMME lesson. The randomised evidence comparing UAE and myomectomy (FEMME) is more nuanced than the headlines. Myomectomy gave a better quality-of-life score at two years, but by four years that advantage had narrowed and was no longer statistically significant, while UAE carried a roughly double re-intervention rate (≈24% vs ≈13%) over the same window. The defensible synthesis is that both work, the choice is genuinely preference-sensitive, and the decisive discriminators are fertility intent (favour myomectomy) and the woman's tolerance of a higher chance of needing a further procedure (against UAE). Presenting either as simply "superior" misreads the trial.

Medical therapy is being reorganised by the GnRH-antagonist combinations. The arrival of oral GnRH-antagonist-plus-add-back regimens (relugolix combination, elagolix combinations) gives, for the first time, an effective longer-term medical option that controls bleeding without the agonist flare or the bone loss of unopposed suppression — genuinely shifting some women off the surgical pathway. Against that, the ulipristal/SPRM story is a cautionary tale in pharmacovigilance: a highly effective drug curtailed by rare but catastrophic idiosyncratic liver injury, a reminder that efficacy does not settle a benefit–risk question and that post-marketing safety signals can and should rewrite practice.

A live topical thread worth weighing honestly is the public anxiety about endocrine-disrupting chemicals and fibroid risk — early-life and ongoing exposures (some phthalates, certain personal-care and possibly sanitary-product chemicals) are biologically plausible promoters of an oestrogen/progesterone-responsive tumour and are an active research area, but the human evidence is associational and contested. The defensible stance is to acknowledge the plausibility, not overstate the data, and avoid alarming women with claims the literature does not yet support. The robust, actionable epidemiology remains that fibroids are commoner and more severe in women of African ancestry, presenting younger, larger and more symptomatic — directly relevant to the SA population and a reason for a low threshold to investigate.

Landmark trials & key evidence

The decision arithmetic the FEMME numbers force: at two years myomectomy looks clearly better, but project to four years and the quality-of-life gap is gone while the re-intervention gap (≈24% vs ≈13%, an absolute difference of ~11 percentage points — about one extra woman in nine needing a further procedure with UAE) persists. That single comparison is the spine of a balanced answer: choose myomectomy when fertility matters or when avoiding a repeat procedure is the priority, choose UAE when uterine preservation with a less invasive index procedure is what the woman wants and she accepts the higher chance of a top-up.

Exam traps & red flags

• Sizing the treatment to the fibroid instead of the symptom. A 2 cm submucosal type-0 fibroid causing flooding deserves resection; an 8 cm silent subserosal fibroid may need nothing. Location and symptom, not diameter, drive the plan.
• Relying on an LNG-IUS in a distorted cavity. A submucosal fibroid distorting the cavity raises expulsion and limits efficacy — confirm cavity shape (sonohysterography) before promising the coil will work.
• Offering UAE as first-line to a woman who wants to conceive. Fertility intent favours myomectomy; UAE is reasonable for symptom control when pregnancy is not the priority, and the woman must be counselled on the small risk to ovarian reserve.
• Forgetting the post-myomectomy delivery implication. A myomectomy breaching the cavity is a relative indication for elective caesarean and a contraindication to unsupervised labour, like a classical scar — and carries a uterine-rupture risk that must be planned for.
• Power-morcellating without containment or counselling. No imaging excludes an occult sarcoma; uncontained power morcellation of a presumed fibroid can disseminate a curable cancer. Avoid it, counsel explicitly, and use containment.
• Treating a postmenopausal "growing fibroid" as benign by default. Fibroids regress after menopause; new growth is leiomyosarcoma until proven otherwise and mandates urgent investigation — never reassurance.
• Reaching for ulipristal routinely. It is restricted to premenopausal non-surgical candidates with mandatory liver monitoring after the serious-liver-injury signal; it is not a first-line drug.
• Missing ureteric obstruction from a bulky uterus. Hydronephrosis from a large fibroid uterus threatens renal function and changes urgency — check renal function and image the tracts when the uterus is bulky.
• Operating on a degenerating fibroid in pregnancy. Red degeneration is managed conservatively; surgery in the gravid uterus risks catastrophic haemorrhage and is reserved for defined indications.
• Missing the FH-deficient (HLRCC) phenotype. Multiple early, symptomatic fibroids with cutaneous leiomyomas or a family history of aggressive renal cancer warrants genetic referral — the renal tumours are lethal and screenable.

Evidence anchors

• FEMME trial — Manyonda et al., N Engl J Med 2020
• FEMME 4-year follow-up — Daniels et al., Eur J Obstet Gynecol Reprod Biol 2021
• PEARL I — Donnez et al., ulipristal vs placebo, N Engl J Med 2012
• PEARL II — Donnez et al., ulipristal vs leuprolide, N Engl J Med 2012
• LIBERTY 1 & 2 — Al-Hendy et al., relugolix combination, N Engl J Med 2021
• HALT trial — Guido et al., laparoscopic RF ablation, Health Qual Life Outcomes 2013
• SONATA — Chudnoff et al., transcervical RF ablation, Obstet Gynecol 2019
• FIGO PALM-COEIN leiomyoma subclassification — Munro et al., Int J Gynecol Obstet 2011
• STEP-W (Lasmar) submucous-myoma classification — Lasmar et al., J Minim Invasive Gynecol 2005; Brazilian multicentre validation, 2012
• NICE NG88 — Heavy menstrual bleeding: assessment and management
• ACOG Practice Bulletin 228 — Management of Symptomatic Uterine Leiomyomas, 2021
• ACOG Committee Opinion 822 — Uterine Morcellation for Presumed Leiomyomas, 2021
• FDA — Laparoscopic Power Morcellators (Safety Communications, boxed warning)
• EMA — ulipristal acetate 5 mg restriction (serious liver injury), 2020
• South Africa NDoH Standard Treatment Guidelines & Essential Medicines List (Adult Hospital Level) — tranexamic acid, NSAIDs and the LNG-IUS are accessible first-line; GnRH analogues are specialist/restricted and UAE/MRgFUS are tertiary-concentrated.