Menorrhagia Treatment & Management

Medical therapy for menorrhagia should be tailored to the individual. Factors taken into consideration when selecting the appropriate medical treatment include the patient's age, coexisting medical diseases, family history, and desire for fertility. Medication cost and adverse effects are also considered because they may play a direct role in patient compliance. ^[29]  Options for hormonal therapy include combined oral contraceptive pills, combined hormonal patches, vaginal rings, progestin-only pills, depot medroxyprogesterone acetate, the levonorgestrel-releasing intrauterine device, and the etonogestrel implant, according to American College of Obstetricians and Gynecologists. ^[30]

Nonsteroidal anti-inflammatory drugs

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the first-line medical therapy in ovulatory menorrhagia. Studies show an average reduction of 20-46% in menstrual blood flow. ^[31] NSAIDs reduce prostaglandin levels by inhibiting cyclooxygenase and decreasing the ratio of prostacyclin to thromboxane. NSAIDs are ingested for only 5 days of the entire cycle, limiting their most common adverse effect of stomach upset.

Oral contraceptive pills

Oral contraceptive pills (OCPs) are a popular first-line therapy for women who desire contraception. Menstrual blood loss is reduced as effectively as NSAID's secondary to endometrial atrophy. ^[32] OCPs suppress pituitary gonadotropin release, preventing ovulation.

Common adverse effects include breast tenderness, breakthrough bleeding, nausea, and, possibly, related weight gain in some individuals.

A long-term combination of oral estradiol valerate and dienogest was found to be highly effective when compared with placebo in the treatment of women with heavy menstrual bleeding. ^[33] In March 2012, dienogest/estradiol valerate (Natazia) was the first oral contraceptive approved by the FDA for heavy menstrual bleeding.

Progestin therapy

Progestin is the most frequently prescribed medicine for menorrhagia. Therapy with this drug results in a significant reduction in menstrual blood flow when used alone. Progestin works as an antiestrogen by minimizing the effects of estrogen on target cells, thereby maintaining the endometrium in a state of down-regulation. Common adverse effects include weight gain, headaches, edema, and depression.

Levonorgestrel intrauterine system

The levonorgestrel intrauterine system reduces menstrual blood loss by as much as 97% ^[34] It is comparable to transcervical resection of the endometrium for reduction of menstrual bleeding ^{[35, 36, 37]} Adverse effects include uterine bleeding or spotting, headache, ovarian cysts, vaginitis, dysmenorrhea, and breast tenderness.

A study by Kim et al indicated that the presence of a large myoma increases the likelihood of treatment failure with either thermal balloon ablation or the levonorgestrel intrauterine system. The study involved 106 women with menorrhagia and either intramural or submucosal myomas, including 67 patients who underwent thermal balloon ablation and 39 who were treated with the levonorgestrel intrauterine system; follow-up lasted more than 12 months. ^[38]

The investigators found that treatment failure (ie, hysterectomy at some time during follow-up or recurrence or persistence of menorrhagia within one year of treatment) for thermal balloon ablation for women with myomas of under 2.5 cm was 12%, compared with 28% for women with myomas that were less than 5 cm but greater than or equal to 2.5 cm, and 56% for women whose myomas were at least 5 cm in size. Those figures for women treated with the levonorgestrel intrauterine system were 14%, 29%, and 25%, respectively. ^[38]

In the ECLIPSE trial, which compared the clinical effectiveness and cost-effectiveness of the levonorgestrel-releasing intrauterine system with standard medical care (ie, tranexamic acid, mefenamic acid, combined oestrogen-progestogen or progesterone alone) for menorrhagia, investigators noted that although both treatment groups had improved scores as measured by the Menorrhagia Multi-Attribute Scale (MMAS), significantly greater improvement occurred in the levonorgestrel intrauterine system group over a 2-year period. ^[39] However, the differences between treatment groups were no longer significant at 5 years, and there was a similarly low proportion of women who required surgery in the groups. The investigators also indicated that the levonorgestrel intrauterine system was cost-effective in the short and medium term. ^[39]

Gonadotropin-releasing hormone agonists

These agents are used on a short-term basis due to high costs and severe adverse effects. GnRH agonists are effective in reducing menstrual blood flow. They inhibit pituitary release of FSH and LH, resulting in hypogonadism. A prolonged hypoestrogenic state leads to bone demineralization and reduction of high-density lipoprotein (HDL) cholesterol.

Danazol

Danazol competes with androgen and progesterone at the receptor level, causing amenorrhea in 4-6 weeks. Androgenic effects cause acne, decreasing breast size, and, rarely, lower voice.

Conjugated estrogens

These agents are given intravenously every 4 hours in patients with acute bleeding. A D&C procedure may be necessary if no response is noted in 24 hours. If menses slows, follow up with estrogen-progestin therapy for 7 days. This is followed by OCPs for 3 months.

Tranexamic acid

Tranexamic acid (Lysteda) was the first nonhormonal product approved by the FDA (in November of 2009) for the treatment of heavy menstrual bleeding. It is a synthetic derivative of lysine that uses antifibrinolytic effects by inhibiting the activation of plasminogen to plasmin.

Tranexamic acid’s mechanism of action in treating heavy menstrual bleeding is by prevention of fibrinolysis and the breakdown of clots via inhibiting endometrial plasminogen activator.

In a double-blind, placebo-controlled study, women taking 3.9 g/d of tranexamic acid showed a significant reduction in menstrual blood loss and an increase in their health-related quality of life compared with those taking placebo. ^[40] Common adverse effects include menstrual discomfort, headache, and back pain.

A Cochrane study reviewed data from a non-randomized study that found value in combining desmopressin and tranexamic acid, however, these results need further study. ^[41]

Surgical management has been the standard of treatment in menorrhagia due to organic causes (eg, fibroids) or when medical therapy fails to alleviate symptoms. ^[42] Surgical treatment ranges from a simple D&C to a full hysterectomy.

Dilatation and curettage

A D&C should be used for diagnostic purposes. It is not used for treatment because it provides only short-term relief, typically 1-2 months.

This procedure is used best in conjunction with hysteroscopy to evaluate the endometrial cavity for pathology.

It is contraindicated in patients with known or suspected pelvic infection. Risks include uterine perforation, infection, and Asherman syndrome.

Resectoscopic endometrial ablation techniques

Transcervical resection of the endometrium ^[3]

Transcervical resection of the endometrium (TCRE) has been considered the criterion standard cure for menorrhagia for many years.

This procedure requires the use of a resectoscope (ie, hysteroscope with a heated wire loop), and it requires time and skill.

The primary risk is uterine perforation.

Roller-ball endometrial ablation ^[4]

Roller-ball endometrial ablation essentially is the same as TCRE, except that a heated roller ball is used to destroy the endometrium (instead of the wire loop).

It has the same requirements, risks, and outcome success as TCRE.

Satisfaction rates are equal to those of TCRE.

Endometrial laser ablation

Endometrial laser ablation requires Nd:YAG equipment and optical fiber delivery system.

The laser is inserted into the uterus through the hysteroscope while transmitting energy through the distending media to warm and eventually coagulate the endometrial tissue.

Disadvantages include the expense of the equipment (high), the time required for the procedure (long), and the risk of excessive fluid uptake from the distending media infusion and irrigating fluid.

This technique has largely been replaced by the nonresectoscopic systems (discussed below).

Nonresectoscopic endometrial ablation techniques

Thermal balloon therapy ^{[5, 6]}

A balloon catheter filled with isotonic sodium chloride solution is inserted into the endometrial cavity, inflated, and heated to 87°C for 8 minutes.

Uterine balloon therapy cannot be used in irregular uterine cavities because the balloon will not conform to the cavity.

Studies report a 90% satisfaction rate and a 25% amenorrhea rate. Long-term studies are ongoing.

Heated free fluid ^[7]

HydroThermAblator (HTA) is an office procedure in which normal saline is infused into the uterus via the hysteroscope.

The solution is heated to 194°F (90°C) for 10 minutes under direct visualization.

This procedure requires only local anesthesia.

HTA may be used in patients with irregularly shaped endometrial cavities and/or fibroids.

Vaginal and skin burns are the most reported complications.

Cryoablation ^[8]

Cryoablation is the use of liquid nitrogen to freeze the endometrium. The procedure is performed in approximately 10 minutes under ultrasonographic guidance.

Patients usually experience 1 week of watery vaginal discharge postprocedure.

Risks include perforation and suboptimal ablation of the entire uterine cavity.

Microwave endometrial ablation alternative ^[9]

Microwave endometrial ablation (MEA) was developed and has been used in Europe since 1996. It uses high-frequency microwave energy to cause rapid but shallow heating of the endometrium. Microwaves are selected so that they do not destroy beyond 6 mm in depth.

MEA requires 3 minutes of time and only local anesthetic. It is proving to be as effective as TCRE. ^[43]

In a Japanese study, investigators found that multiple MEAs in the same region in women with adenomyosis and menorrhagia was more effective than conventional single ablation treatment, as well as resulted in higher patient satisfaction rates. ^[44]

Radiofrequency electricity ^[8]

NovaSure system is a detailed microprocessor-based unit with a bipolar gold mesh electrode array. It contains a system for determining uterine integrity based upon the injection of CO₂. The device is placed transcervically, the array is opened and electrical energy is applied for 80-90 seconds, desiccating the endometrium.

Endometrial ablation or resection preparation

A trial of medical therapy should have failed in patients considered for this therapy. The endometrium should be properly sampled and evaluated before surgery.

Patients should be pretreated with danazol or a GnRH analogue for 4-12 weeks before surgery to atrophy the endometrium, reducing surgical difficulty and time.

Success rates are similar to laser ablation techniques.

A 2005 Cochrane Review (updated in 2009) concluded that "overall the existing evidence suggests that success rates and complication profiles of newer techniques of ablation compare favorably with TCRE, although technical difficulties with new equipment need to be ironed out." ^{[9, 45]}

In an observational study (2010-2012) of 235 German women aged 18 years and older with menorrhagia and high or low surgical risk of complications who underwent radiofrequency endometrial ablation (RFEA), RFEA appeared to improve quality of life as well as resulted in high satisfaction among both groups of women. ^[46] High-risk factors included anemia, coagulopathy, anticoagulation, thromboembolism, obesity, transplantation, malignancy, and severe cardiovascular/pulmonary disease. ^[46]

Surgical techniques

Myomectomy ^[10]

Myomectomy can be useful in women who wish to retain their uterus and/or fertility.

Since myomectomy can be associated with large blood loss, this procedure is often reserved for cases of a single or few myomas.

Risks include large blood loss or recurrence.

Hysterectomy ^{[11, 12]}

Hysterectomy provides definitive cure for menorrhagia.

This procedure is more expensive and results in greater morbidity than ablative procedures.

The mortality rate ranges from 0.1-1.1 cases per 1000 procedures.

The morbidity rate is usually 40%.

Risks include those usually associated with major surgery.

A study by Roberts et al reviewed the cost effectiveness of first-generation and second-generation endometrial ablative techniques, hysterectomy, and the levonorgestrel-releasing intrauterine system (Mirena) for the treatment of heavy menstrual bleeding. ^[47] Although the authors did not define "heavy menstrual bleeding," their analysis concluded that the most cost-effective initial treatment for menorrhagia that yielded the best quality of life was hysterectomy.