Heavy Menstrual Bleeding Xử trí

Nguyên tắc điều trị

The appropriate management for heavy menstrual bleeding is based on the cause/s of bleeding, comorbid conditions, related symptoms (eg pressure, pain), and the patient's preferences. Treatment options include medical management, which is divided into hormonal and non-hormonal therapy, and procedural interventions to preserve the uterus and/or hysterectomy. Uterine-preserving procedures include endometrial ablation (EA), uterine artery embolization (UAE), and surgical removal of local pathology.

Surgery (eg hysteroscopic myomectomy, hysteroscopic polypectomy) may be considered in patients with abnormal uterine bleeding with known structural etiology (eg endometrial polyp, submucosal fibroid) to correct the abnormal uterine bleeding or to make further medical therapy for abnormal uterine bleeding more effective. Surgery (eg endometrial ablation, hysterectomy) may be considered in patients with abnormal uterine bleeding without a structural etiology and who have completed childbearing and prefer to avoid medical therapy, those who failed to respond to medical therapy or had adverse effects from medical therapy, or those who desire definitive therapy. The timing of treatment initiation should be individualized.

Goals of Therapy

The goals of therapy are to correct or treat underlying primary etiology; establish a regular bleeding pattern or amenorrhea; prevent an episode of acute uterine bleeding requiring urgent assessment; prevent or treat anemia and iron deficiency; prevent or treat endometrial hyperplasia or carcinoma; and improve the quality of life.

Pharmacological therapy

Pharmacological therapy is recommended for patients with no structural or histological abnormalities or with fibroids <3 cm in diameter that did not cause deformation of the uterine cavity. This should include iron supplements if iron deficiency anemia is present secondary to heavy menstrual bleeding.

Non-Hormonal Therapies

Non-hormonal therapies are the treatment of choice for patients who desire to maintain fertility and be pregnant in the near future. These are also an alternative treatment for patients who do not desire hormonal therapy or those awaiting workup and definitive treatment. Non-hormonal therapies are used to treat heavy menstrual bleeding that is cyclic or has predictable timing. These should be taken from the start of menstruation until heavy blood loss has stopped. Discontinue non-hormonal therapies if no improvement in symptoms is seen after use for three cycles.

Hemostatic Therapy

Antifibrinolytic agents

Example drugs: Tranexamic acid

Antifibrinolytic agents competitively inhibit plasminogen activation and other factors associated with blood clotting. These decrease the breakdown of fibrin in a preformed clot and are used to treat heavy menstrual bleeding that is cyclic or has predictable timing. Antifibrinolytic agents are treatment options for women with suspected bleeding disorders, certain contraindications to hormonal therapy (eg personal history of breast cancer), or those who failed to respond or wish to avoid first-line therapy agents. Studies showed that it reduced menstrual bleeding by 26-54% through reduction of liquefaction of clotted blood from spiral endometrial arterioles. High-dose Tranexamic acid may aid in reducing or stopping acute HMB. Antifibrinolytic agents do not reduce dysmenorrhea nor regulate cycles and are not contraceptive.

Desmopressin (DDAVP)

Desmopressin stimulates release of von Willebrand’s factor (VWF) from endothelial cells. This is given to patients with type 1 and some cases of type 2 von Willebrand disease (VWD) with heavy menstrual bleeding. Desmopressin is not recommended in patients with type 2B VWD due to possible worsening of thrombocytopenia and thrombosis. This is not more effective than oral contraceptives in controlling heavy menstrual bleeding.

Coagulation Factor Replacement

Coagulation factor replacement is used in patients with VWD-related heavy menstrual bleeding where antifibrinolytics and Desmopressin are not effective. VWF/factor VIII replacement therapy can be considered definitive therapy, particularly in massive hemorrhage (eg severe von Willebrand disease).

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Example drugs: Ibuprofen, Mefenamic acid, Naproxen

Nonsteroidal anti-inflammatory drugs reduce prostaglandin synthesis, which is implicated in uterine bleeding and cramps. These cause a 10-52% decrease in menstrual blood loss, and are the preferred treatments for patients with heavy menstrual bleeding and dysmenorrhea. Nonsteroidal anti-inflammatory drugs should be started on the first day of bleeding and should be continued for 2-3 days or until menstruation stops. These are not as effective as Tranexamic acid or Danazol but have fewer side effects than Danazol. NSAIDs are not recommended for patients with heavy menstrual bleeding secondary to bleeding disorders.

Hormonal Therapies

Hormonal therapies are considered first-line therapy (combined with conservative medical management) if future fertility is desired but pregnancy is not wanted in the near future.

Levonorgestrel-Releasing Intrauterine System (LNG-IUS)

Levonorgestrel-releasing intrauterine system is the first line of treatment for patients suitable for pharmacological therapy, provided long-term use is expected. This is the most effective medical therapy for heavy menstrual bleeding. Levonorgestrel-releasing intrauterine system reduces bleeding by 71-95%, but full benefit may not be seen after at least six cycles. The bleeding patterns may vary for the first 6 months of use. A small plastic device placed in the uterus that slowly releases 20 mcg/day of Levonorgestrel. This is used for contraception, management of idiopathic heavy menstrual bleeding, and as a progestogen content of the hormone replacement therapy regimen.

Levonorgestrel-releasing intrauterine system prevents proliferation of the endometrium and thickening of cervical mucus and suppresses ovulation in some women. This is approved for 5 years of use and is the preferred treatment option for long-term use or when the patient opts for long-term reversible contraception. LNG-IUS is a treatment option for women with an increased risk of thrombosis (eg personal history of a thrombotic event with selected thrombogenic mutations). This may be considered as a treatment option for obese women. Levonorgestrel-releasing intrauterine system is comparable with endometrial ablation in reducing menstrual blood loss up to 24 months. This may be considered an option before surgery. LNG-IUS is the most cost-effective approach in treating patients with heavy menstrual bleeding after 1 year of combined oral contraceptive (COC) use or when COC therapy has failed.

Combined Oral Contraceptives (COCs)

Combined oral contraceptives contain estrogen and progestogen that inhibit ovulation and fertility through action on the hypothalamo-pituitary axis. These prevent proliferation of the endometrium. Combined oral contraceptives are used in a 21-day treatment cycle followed by 7 days’ rest, where breakdown and loss of endometrium occur. These regulate and reduce bleeding and also decrease breast pain and dysmenorrhea. Trials showed that COCs (Ethinyl estradiol and Levonorgestrel) reduced menstrual bleeding by 35-69%. These are the most cost-effective approaches in the first year of treatment for women with heavy menstrual bleeding with no pathological cause. High-dose estrogen may be used initially to treat heavy menstrual bleeding and then transitioned within a few days to standard estrogen-progestin contraceptive pills. Estrogen-progestin preparations may be given continuously for prevention of recurrent heavy menstrual bleeding.

Combined oral contraceptives are not suitable for smoking women >35 years old, women with risk factors for cardiovascular (CV) disease (eg hypertension, ischemic heart disease, complicated valvular heart disease, older age, diabetes), history of stroke, migraine with aura at any age, and selected women with systemic lupus erythematosus (SLE).

Oral Progestogens

Example drugs: Norethisterone, Medroxyprogesterone

Oral progestogens prevent proliferation of the endometrium. Use oral progestogens for 7-10 days during the luteal phase of the menstrual cycle, which showed no effect on menstrual bleeding. These may reduce menstrual bleeding for up to 83% after long-term use. A progestin (eg Megestrol acetate) can be given to prevent recurrent heavy menstrual bleeding. A case series showed premenopausal women with symptomatic uterine fibroids had an improvement in abnormal uterine bleeding with 6 months of depot Medroxyprogesterone acetate therapy. Oral progestogens are an option for women who cannot tolerate estrogen-containing therapy or if estrogen is contraindicated.

Gonadotropin-Releasing Hormone Analogue (GnRH-a)

Gonadotropin-releasing hormone analogue induces reversible hypogonadism secondary to deficient production of follicle-stimulating hormone (FSH) or luteinizing hormone (LH) that causes poor follicular development and estrogen production, anovulation, lack of progesterone production, and amenorrhea. This reduces menstrual blood loss in the form of amenorrhea. When the treatment is discontinued, effects are not maintained. Gonadotropin-releasing hormone analogues may be given to patients with uterine fibroids prior to undergoing surgery or when surgery or uterine artery embolization (UAE) is contraindicated. This causes a reduction in fibroids’ size, making surgery easier. This may be given to patients with an enlarged or distorted uterus secondary to uterine fibroids 3-4 months prior to hysterectomy or myomectomy. Gonadotropin-releasing hormone analogues are associated with significant adverse effects (eg perimenopausal symptoms, headache, nausea), which prevent long-term use. Hormone replacement add-back therapy may be given to prevent undesirable effects if GnRH use is >6 months.

Ulipristal Acetate

Ulipristal acetate is used for preoperative management of women with moderate to severe symptoms of uterine fibroids. This has established efficacy in the management of heavy menstrual bleeding due to fibroids with reduction of fibroid size prior to surgery. Ulipristal acetate is an intermittent treatment option in premenopausal women with moderate to severe symptoms of uterine fibroids when surgery and uterine artery embolization for fibroids are not appropriate (eg when risks outweigh the benefits); surgery and uterine artery embolization for fibroids have failed; and the woman refuses surgery and uterine artery embolization for fibroids.

Patients with heavy menstrual bleeding may be offered up to 4 courses (20 months) of Ulipristal acetate if they have fibroids of ≥3 cm in diameter and a hemoglobin level of ≤102 g/L. Benign and reversible changes occur in the endometrial tissue with use of Ulipristal acetate. Data showed Ulipristal acetate is non-inferior to GnRH agonists with less menopausal side effects. Monitor liver function tests (LFTs) before and during treatment. Discontinue if with signs and symptoms of liver failure.

Danazol

Danazol is a synthetic androgenic steroid with anti-estrogen and antiprogestogen activity. This has an antiproliferative effect on the endometrium and an inhibitory effect on the production of gonadotropins by the pituitary gland, causing anovulation. Danazol reduces menstrual bleeding by 50% and is associated with significant androgenic adverse effects. This is not routinely given for the treatment of heavy menstrual bleeding.

¹Emergency contraceptive

Phẫu thuật

Endometrial Ablation (EA)

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Heavy Menstrual Bleeding_Management 2