Heavy Menstrual Flow: Current and Future Trends in Management

Abstract

Menorrhagia accounts for a large number of secondary care referrals in the West. Women of different ages have different expectations from the treatment offered to them. Young women of reproductive age often demand treatment that simultaneously reduces bleeding, preserves fertility, and has very few side effects, whereas older women who ultimately wish to keep their reproductive organs may have reason to avoid hormonal manipulation. This article discusses possible management options and introduces a hierarchical approach to the management of menorrhagia based on the medical therapies and surgical procedures currently available. We explore the medical therapies for menorrhagia, which include hormone-modifying drug therapies and the new combined oral contraceptive pill. We also review novel fibroid surgical therapies and the latest surgical procedures, such as laparoscopic bilateral uterine artery occlusion, transvaginal Doppler-guided vascular clamp, and laparoscopic and intrauterine ultrasound-guided radiofrequency ablation.

Heavy menstrual bleeding (HMB) is a benign yet debilitating social and health condition. It is clinically defined as blood loss ≥ 80 mL per menstrual cycle. In general clinical practice, diagnosing menorrhagia is subjective and it is the woman’s perception of menstrual blood loss (MBL) and how it is interfering with her physical, social, and emotional quality of life that is the key determinant in her presentation, referral, and subsequent treatment. In the United Kingdom, HMB accounts for > 20% of gynecologic referrals and cost the National Health Service £50 million in 2010. It has an overall prevalence of 3.0% in premenopausal women but absolute risk nearly doubles to > 5% in women between 40 and 51 years.¹ Any intervention should, therefore, aim to improve the psychosocial aspect of HMB rather than just focus on MBL.

Causes of HMB

HMB can be caused by fibroids (present in 20%–30% of cases), uterine polyps (present in 5%–10% of cases), or endometriosis (present in 5% of cases). Other conditions, such as coagulation disorders and endocrine disorders, can also cause HMB. In some cases, the cause of bleeding in premenopausal women may be due to gynecologic malignancy.^1–4

In the majority of cases, however, no pathology is found in women who present with HMB. HMB in women with no endometrial, uterine, or endocrine abnormal cause remains poorly understood and this is one of the main challenges faced when developing novel and efficient nonsurgical therapies to treat menorrhagia.

Over 10 years ago, 60% of women complaining of HMB were referred for a hysterectomy. Since then, the number of hysterectomies performed has greatly reduced and current trends estimate that only one in five women will have a hysterectomy to address HMB. In fact, 30% of women who have had a hysterectomy have reportedly had normal uteri removed.

The Right Treatment

Pharmaceutical therapy has always been considered the first-line treatment for women complaining of excessive menstrual loss. Conservative and uterine-preserving treatment options are obviously preferred. Over 300,000 women were written medical prescriptions to control their menstrual flow in 2007, and this cost the UK National Health Service over £6 million. The choice to undergo surgical manipulation is dependent on the age of the woman. Women who are in their reproductive years tend to choose treatment that preserves their fertility, reduces their menstrual flow, and (if possible) also acts as a form of contraception. In women over age 45, there is often still a wish to keep the uterus, even though the need to preserve fertility is reduced.^1,5 Surgical treatment of HMB tends to follow failed or ineffective medical therapy.

The ultimate goal of any form of treatment is to reduce menstrual flow in order to improve quality of life. The current medical and surgical treatments involved in the management of HMB, as well as their associated effects on fibroid size and fertility, are compared in Table 1.

Table 1.

Current Medical and Surgical Treatments Involved in the Management of Heavy Menstrual Bleeding

Treatment	Effect on Fibroid Size	Effect on Heavy Menstrual Bleeding	Effect on Fertility	Study
First-line treatments (all medical)
Tranexamic acid	No effect	Decrease 30%–50%	No effect	Bonnar and Sheppard,37 Philipp,38 Callender et al,39 Edlund et al,40 Preston et al41
Nonsteroidal anti-inflammatory drugs (eg, mefenamic acid)a	No effect	Decrease 20%–40%	No effect	Bonnar and Sheppard,37 Cameron et al,42 Grover et al,43 Fraser et al,44 Farquhar and Brown,45 Roy and Bhattacharya,46 Cameron47
Combined oral contraceptive	No data	Decrease 40%	Contraceptive	Fraser et al,44 Farquhar and Brown,45 Roy and Bhattacharya46
Oral progestin (high dose)	No effect	Decrease 50–60%	Contraceptive	Roy and Bhattacharya,46 Kriplani et al,48 Fraser49
Progestin levonorgestrel-releasing intrauterine systemb	Decrease 30%	Decrease 70%–100% (may also treat endometriosis and adenomyosis	Contraceptive	Kaunitz,50 McCormack,51 Guida et al52
Second-line treatments (all minimally invasive surgery)
Hysteroscopic fibroid/polyp resectionc	Excision and removal of intracavity lesion	Decrease 50%–70%	Improved if excising submucosal fibroid; no effect if excising uterine polyp	Kim et al53
Endometrial ablationc	No effect	Decrease 80% (may also treat adenomyosis)	Likely contraceptive but contraception advised following ablation	Lethaby et al,54 Lethaby et al55
Laparoscopic myomectomy	Excise subserosal and non-deeply embedded intramural fibroids	No effect or may decrease up to 30%	No effect or may increase	Sharif Al-Mahrizi and Tulandi56
Uterine fibroid embolization	Decrease 30%	Decrease 60%–80%	May decrease, no effect, or improve fertility	Razavi et al,57 Gupta et al,58 Shen et al59
Magnetic resonance imaging-guided focused ultrasound therapy	Decrease 15%–20%	Decrease 60%	May decrease, no effect, or improve fertility	Stewart et al,60 Hindley et al,61 Hanafi62
Third-line treatments (minor/major surgical procedures)
Abdominal myomectomy	Excise subserosal, intramural, and intracavity lesions	Decrease 60%–80%	Improved, particular if uterine cavity is no longer distorted	Razavi et al,57 Farquhar et al63
Hysterectomy	Complete cure	Complete cure	Irreversible contraceptive	Sowter et al64

^aNonsteroidal anti-inflammatory drugs can be combined with tranexamic acid to help treat both dysmenorrhea and heavy menstrual bleeding.

^bThe Progestin levonorgestrel-releasing intrauterine system is contraindicated in uterine cavities \s> 12 cm in length.

^cEndometrial ablation can be performed immediately following hysteroscopic fibroid/polyp resection and this combined treatment has greater treatment efficacy.

Medical Therapies

Combined Oral Contraceptive Pill

Combined oral contraceptives (COCs) contain estrogen and progestogens. They act on the hypothalamic-pituitary axis to suppress ovulation and fertility. COCs are believed to work by regulating the cycle and thinning the endometrium, which eventually leads to a lighter withdrawal bleed. The majority of COCs are monophasic; that is, they are dosed at the same strength throughout the 21-day treatment phase. COCs are generally used in 21-day treatment cycles followed by a 7-day break, during which time endometrial breakdown and loss will occur. Such withdrawal bleeding is physiologically different from the bleeding that occurs after a natural ovulatory cycle. COCs have a number of side effects, including mood changes, headaches, nausea, fluid retention, and breast tenderness. In a recent Cochrane review assessing the effectiveness of the oral contraceptive pill in the management of menorrhagia, one randomized control trial (RCT; n = 45) focused on comparing COCs with naproxen, mefenamic acid, and danazol. This study randomly allocated 45 ovulatory women to the three treatment groups before they received mefenamic acid in two cycles and a low-dose monophasic COC or low-dose danazol for two additional cycles. The menstrual blood flow was measured in two to four control cycles and during therapy. Mefenamic acid reduced measured blood loss by 20%, 38%, and 39% in the naproxen, mefenamic acid, and danazol groups, respectively. Naproxen reduced blood loss by 12%, the oral contraceptive reduced blood loss by 43%, and danazol reduced blood loss by 49%.^6,7

Oral Progesterone

Progesterone is a physiologic hormone produced during the luteal phase of the menstrual cycle. It is responsible for secretory transformation of the endometrium, and bleeding occurs when endogenous levels of estrogen and progesterone fall if fertilization does not occur. Although progesterone is not available in oral formulation in the United Kingdom, a variety of oral synthetic progestogens are in clinical use. They vary in their potency and adverse effect profiles. The mechanisms by which oral progestogens reduce MBL are not fully understood.⁸

Two systematic reviews are available addressing the use of progestogens during the luteal phase of the menstrual cycle. The first review, published in 1995 and comprising four RCTs, showed that norethisterone had no effect on MBL (MBL percentage change: 95% confidence interval [CI], −6.1% to +1.1%).⁹

The second review, undertaken in 2003, consisted of seven RCTs. It showed that norethisterone was not as effective as the nonsteroidal anti-inflammatory drugs (NSAIDs), which were associated with an MBL of −23.0 mL in favor of the NSAIDs. When compared with danazol, the latter was more effective in producing a reduction in MBL of 55.6 mL. A comparison with tranexamic acid revealed that norethisterone was not superior, as it failed to produce the 111.0-mL reduction in MBL associated with tranexamic acid. Oral progesterone versus a progesterone intrauterine system (IUS) showed a change in MBL of −51.0 mL in favor of the IUS.¹⁰

Another RCT (n = 44) examined the use of oral progestogens cyclically for 21 days versus the use of a levonorgestrel-releasing IUS (LNG-IUS). It concluded that an 83% reduction in MBL was associated with long-term use of oral progestogens, compared with a 94% reduction with the LNG-IUS. The 11% difference was not deemed to be statistically significant; however, 66% of patients were satisfied with their LNG-IUS as compared with 22% who were satisfied with norethisterone.¹¹

NSAIDs

NSAIDs are a first-line medical therapy in ovulatory menorrhagia. Recent evidence reviewed by the National Institute for Health and Clinical Excellence showed that the use of NSAIDs in the management of menorrhagia was associated with a 20% to 40% significant reduction in blood loss. Mefenamic acid was associated with a 29% reduction in menstrual flow, whereas naproxen and ibuprofen were also associated with a 26% and 16% reduction, respectively, although they are not licensed for menorrhagia.⁸

Tranexamic Acid

Tranexamic acid, a plasminogen activator inhibitor, controls menorrhagia by inhibiting the dissolution of thrombosis. A study by Lethaby and colleagues¹² reported that the use of antifibrinolytic therapy was associated with a greater reduction in HMB when compared with placebo or other medical therapies such as NSAIDS, oral luteal phase progestogens, and etamsylate. The review undertook a meta-analysis of two RCTs of tranexamic acid versus placebo and found a difference of −93.96 mL (95% CI, −151.43 mL to −36.49 mL; P = .001), in favor of treatment.¹² Two further reviews have assessed the efficacy of tranexamic acid on HMB. The second review consolidated the results of seven trials and found a reduction in MBL of 46.7% (95% CI, 47.9%–51.6%) with tranexamic acid.¹³ The last review reviewed five trials and concluded that oral tranexamic acid, 2.0 to 4.5 g daily, for 4 to 7 days per cycle reduced MBL by 34% to 59% over two to three cycles.¹⁴

Levonorgestrel-releasing Intrauterine System

The LNG-IUS is an intrauterine, long-term progestogen-only method of contraception licensed for 5 years of use. The device consists of a T-shaped plastic frame with a rate-limiting membrane on the vertical stem containing 20 µg of levonorgestrel. The levonorgestrel is released in a controlled dose over 24 hours for up to 5 years. The effects of the LNG-IUS are mostly local and hormonal; it prevents endometrial proliferation and causes thickening of cervical mucus. A minority of women will also have suppression of ovulation. The use of the LNG-IUS coil is limited to women with normal uteri because uterine cavities containing fibroids or congenital pathologies cannot retain the device appropriately.² Two recent systemic reviews demonstrated a 71% to 96% reduction in menstrual blood flow and amenorrhea in 20% to 30% of women when the LNG-IUS was used.^15,16

The first review, published in 2005, identified 10 RCTs comparing LNG-IUS with surgery or medical treatments. When comparing LNG-IUS against any pharmaceutical treatment (1 RCT, n = 35), the odds ratio (OR) for amenorrhea (> 3 mo) was calculated as 8.67 (95% CI, 1.52–49.35) in favor of LNG-IUS and the OR for the proportion of women who were satisfied with treatment (1 RCT, n = 40) was 2.13 (95% CI, 0.62–7.33).¹⁵

In the second review, five RCTs and five case series were analyzed. The MBL reductions reported in the RCTs were between 71% and 96%.¹⁶ The multicenter Effectiveness and Cost Effectiveness of Levonorgestrel-containing Intra-uterine System in Primary Care Against Standard Treatment for Menorrhagia (ECLIPSE) trial is currently underway to study the success rate and cost effectiveness of the LNG-IUS compared with other pharmaceutical therapies available in the primary care setting.¹⁷

Pharmaceutical Therapy Failure

In the event that medical therapies prove to be ineffective, the patient should be transferred to secondary care for further management. Table 2 lists the indications for secondary care referral.⁸

Table 2.

Indications for Secondary Care Referral

Persistent menorrhagia Patient’s wish for surgical intervention due to poor quality of life Failed medical treatment Age over 40 years Presence of alarming symptoms such as abnormal Papanicolaou test result, which may be suggestive of a possible malignancy

Surgical Management

The choice between surgical options and medical therapies for the management of HMB is dependent on the age of the woman, the extent to which the HMB is affecting her life, and her contraceptive needs. In the majority of cases, surgical options are only really explored once medical therapies fail. A recent systematic review assessed the long-term benefits of medical versus surgical therapies and showed that, in secondary care facilities, surgical management of HMB has a slight advantage over medical treatment, which diminishes over time (control of bleeding at 5 years [n = 140] OR, 1.99 [95% CI, 0.84–4.73]) in favor of surgery. In one RCT included in the review, women who underwent immediate surgery had statistically higher quality of life at 5 years than those who underwent surgery after failed pharmaceutical treatment.¹⁸ Although surgery has an advantage over pharmaceutical treatment with regard to outcome, the reversible nature of pharmaceutical treatment compared with surgery must be taken into account.

Endometrial Ablation

In the 1990s, if medical therapies failed to control HMB, a hysterectomy was the only definitive surgical option available. Since then, a number of surgical options have been developed. Endometrial ablation destroys and removes the endometrium along with the superficial myometrium. First-generation endometrial ablation involved distending the uterine cavity with fluid and resecting the tissue with an electrosurgical loop. Second-generation methods use thermal balloon endometrial ablation (TBEA), microwave endometrial ablation (MEA), hydrothermablation, bipolar radiofrequency (RF) endometrial ablation, and endometrial cryotherapy. In comparison with first-generation methods, the second-generation methods do not need to be carried out under direct uterine visualization and tend to be easier to learn.

A 2004 systematic review consisting of 2 reviews and 10 RCTs examined the safety and effectiveness of MEA and TBEA for HMB; the rate of amenorrhea 1 year after treatment ranged between 36% and 40% for MEA and between 10% and 40% for TBEA.¹⁹

Uterine Artery Embolization

In women in whom fibroids are the cause of the HMB, two further surgical options are available: uterine artery embolization (UAE) and myomectomy. UAE is usually performed by an interventional radiologist on a sedated patient. It involves injecting small polyvinyl particles into the uterine arteries through a catheter that is inserted via the femoral artery; this causes the eventual blockage of the feeding capillaries associated with the myoma. The eventual loss of the blood supply to the fibroids causes them to shrink, thereby allowing us to treat the cause of the HMB.

Myomectomy, on the other hand, involves the surgical removal of fibroids and can be done by laparotomy, laparoscopy, or hysteroscopically. UAE is often preferred over myomectomy as it is a quicker procedure and is associated with a shorter hospital stay. A recent systematic review, however, favored myomectomy to UAE as the rates of re-intervention were fewer when compared with UAE.²⁰ A further cohort study analyzed the outcomes associated with myomectomy versus UAE; at 14 months, a greater reduction in menorrhagia was seen in the UAE group (92%) compared with the myomectomy group (64%).²¹

Hysterectomy

Although the most radical form of management of HMB, hysterectomy does provide a definitive cure for menorrhagia. It involves the surgical removal of the uterus. Until approximately the 1990s, hysterectomy was considered as the only viable surgical treatment for HMB. Because of the morbidities associated with a hysterectomy, the permanent repercussions of the surgery, and its cost to the National Health Service, there is a strong incentive to reduce the number of hysterectomies performed and to encourage conservative modes of treatment such as the LNG-IUS, endometrial ablation, and UAE as management options for HMB. Since the development of new pharmaceutical and less invasive surgical options, the number of hysterectomies in the United Kingdom has decreased (from 24,355 in 1993 down to 10,559 in 2002).¹ Concurrently, advances in endoscopic technologies such as diathermy, laser, and ultrasonic energy have enabled most hysterectomies to be performed with minimally invasive techniques. More conservative, effective, and medical interventions are currently being developed and should provide additional alternatives to hysterectomy.

Future Pharmaceutical Therapy

Gonadotropin-releasing Hormone Antagonists

Uterine fibroids are often the cause of HMB in women, and their growth is often dependent on ovarian steroids. Therefore, it was hypothesized that a pharmacologically induced hypoestrogenic state, similar to menopause, should decrease their growth and consequently the associated HMB. Gonadotropin-releasing hormone (GnRH) antagonists have been shown to be effective in creating this pseudomenopausal environment by competing with endogenous GnRH for binding sites in the pituitary gland, causing a reduction in gonadotropin release. The efficacy of GnRH antagonists compared with the new medical treatment for menorrhagia is shown in Table 3. In comparison with GnRH agonists, antagonists suppress pituitary gonadotropins immediately and because GnRH antagonist activity is dose dependent, it can be adjusted to obtain the desired therapeutic outcome. Discontinuation of GnRH antagonist treatment leads to a rapid and predictable recovery of the pituitary-gonadal axis.

Table 3.

Comparison of Future Medical Treatments

Fibroid Size		Heavy Menstrual Bleeding	Fertility	Study
Gonadotropin-releasing hormone antagonist: ganirelix	Decrease 30%–40%	Decrease	Contraceptive	Flierman et al,65 Gonzalez-Barcena et al66
Progesterone receptor antagonist: mifepristone	Decrease uterine size 40%	Decrease (risk of endometrial hyperplasia)	Contraceptive	Sankaran and Manyonda,26 De Leo et al,67 Eisinger et al68
Selective progesterone receptor modulators	Decrease up to 40%	Decrease	Contraceptive	Sankaran and Manyonda,26 Chwalisz et al,69 Chwalisz et al70
SERM Ormeloxifene	Decrease 10%–15%	Decrease	Contraceptive	Jirecek et al,71 Palomba et al72
Aromatase Inhibitor: Anastrozole	Decrease (70% reduction has been reported)	Decrease	Contraceptive	Kaunitz,50 Shozu et al73
Oral progestogen dienogest	Unknown	May decrease	Contraceptive	McCormack51
Combined pill: dienogest combined with estradiol valerate	Unknown	May decrease	Contraceptive	Guida et al52

Selective Estrogen Receptor Modulators

Ormeloxifene, a nonsteroidal selective estrogen receptor modulator (SERM), is currently undergoing clinical evaluation for the treatment of HMB. Its beneficial role in the treatment of menorrhagia was observed when it regulated dysfunctional uterine bleeding and improved endometriosis symptoms in women using it as a form of contraception.²² Because of its antiestrogenic effects as well as its antiprogestational capacity, it is also being evaluated for its use in the treatment of advanced breast cancer and the prevention of osteoporosis. A study by Kriplani and colleagues assessed its efficacy and safety in the medical management of menorrhagia and it was found that the median duration of bleeding reduced from a pretreatment length of 7 days (range 4–30) to 3 days (range 0–6) after 4 months of treatment (P < .001).²³

Progesterone Receptor Antagonist

Progesterone antagonists such as mifepristone are commonly used for the evacuation of the pregnant uterus and for the induction of labor. It has also been extensively used in research settings as a possible treatment for fibroids. A systematic review by Samuel and Clark²⁴ analyzed six studies that used mifepristone as a treatment option for women with HMB associated with uterine fibroids; uterine blood loss ranged from 27% to 49%.

A Cochrane review about the use of mifepristone in the management of symptomatic uterine fibroids concluded that even though mifepristone had no effect on the size of the fibroids, a definite reduction in menstrual flow secondary to the fibroids was noted when compared with placebo (OR, 17.84; 95% CI, 6.72–47.38; 2 RCTs, 77 women; I₂ 5 0%).²⁵

Selective Progesterone Receptor Modulators

Selective progesterone receptor modulators have been reported to induce an antiproliferative effect on the endometrium, although the exact mechanism of action is not clear. Trials assessing the effectiveness of asoprisnil in the management of HMB showed reduction in menstrual flow proportionate to the dose prescribed.²⁴

Aromatase Inhibitors

Aromatase inhibitors markedly reduce plasma estrogen levels in postmenopausal women by inhibiting the aromatase enzyme, which catalyzes the synthesis of estrogens from androgenic substances such as androstenedione. Fibroids express aromatase, and the use of aromatase inhibitors in the management of HMB due to fibroids is only confined to some case reports in which they were shown to cause a dramatic reduction in fibroid size, as well as thinning of the endometrium, leading to much lighter menstrual bleeding. A 71% reduction in fibroid size over an 8-week period has been reported by Japanese investigators.²⁶ The effects of future medical treatments on fibroid size, HMB, and fertility are shown in Table 3.

Surgical Treatment

Laparoscopic Bilateral Uterine Artery Occlusion

A 2001 study evaluating the effectiveness of laparoscopic bilateral uterine artery occlusion (LUVO) compared with UAE concluded that it was as effective as UEA, with 88.4% of patients reporting definitive symptomatic improvement and 21.2% reporting complete resolution of their symptoms.²³ LUVO essentially involves occlusion of the uterine arteries, at the level of the internal iliac artery, with an endoclip, and coagulation of the collateral arteries between the ovaries and uterus. Current studies are now looking at expanding the use of LUVO by analyzing its effectiveness when combined with procedures such as simultaneous myomectomy, either through laparoscopy or through a mini laparotomy. Early results from these trials report this combination to produce maximum symptom relief (98.1%–100% symptom resolution) in women with symptomatic uterine myomas, in addition to minimized tumor recurrence and a reduction in the number of reinterventions.²⁴

Transvaginal Doppler-guided Vascular Clamp

Even though UAE and LUVO are known to provide symptomatic relief to patients with fibroids, they do have limitations. UAE needs to be performed by an interventional radiologist, whereas LUVO is limited by the laparoscopic expertise of the surgeon and is associated with laparoscopic complications. Consequently, alternative techniques such as the transvaginal Doppler-guided vascular clamp are being explored. The Flostat™ system (Vascular Control Systems, San Juan Capistrano, CA), is presently being used in the United States; it consists of (1) a guiding cervical tenaculum, (2) a transvaginal vascular clamp with integrated Doppler ultrasound crystals, (3) a coupler that advances the clamp over the tenaculum, and (4) a battery-powered ultrasound transceiver that generates an audible Doppler signal.²⁷

Earlier reports of the effectiveness of the transvaginal Doppler-guided vascular clamp include reports by Vilos and colleagues²⁷ and Lichtinger and colleagues,²⁸ in which they applied a transvaginal Doppler-guided clamp over the lateral aspect of the cervix in 10 women and laparoscopically observed bilateral occlusion of the uterine arteries. A recent study assessed the effectiveness of Doppler-guided vascular clamps to treat menorrhagia. In all 30 patients, after pelvic examination, a weighted speculum was placed in the vagina, and a tenaculum was placed on the anterior lip of the cervix.²⁹ The bladder was drained and an ultrasound of the uterus was performed. The cervix was reportedly dilated to 6 mm, and any intrauterine pathology was ruled out through a hysteroscopy. The cervix was further dilated to 10 mm, and sharp uterine curettage was performed to initiate the clotting cascade. The tenaculum was then removed, and a uterine stabilizer was placed on the posterior lip of the cervix. The Doppler-guided clamp was then attached to a stabilizer and advanced to the sides of the cervix using the coupler. The Doppler ultrasound sensors on the clamp were attached to the Doppler transceiver, and the sound of flow through the uterine arteries was detected through intact vaginal mucosa.²⁹ The clamp was advanced until the ultrasound audio changed to a “whipping” sound, thereby indicating bending of the uterine arteries over the tip of the clamp. The clamp was closed, and Doppler was used to confirm occlusion of the uterine arteries, indicated by loss of audible Doppler signal. All patients in the study were then placed in the supine position and transferred to the recovery room, where they remained supine and immobile with the clamp in place. Follow-up in the study reported a 24% average decrease in the fibroid size as well as an average reduction of 12% in uterine mass and a mean reduction of 42% in menorrhagia-associated symptoms by 6 months.^29,30

In addition to being a more cost-effective alternative, the transvaginal Doppler-guided vascular clamp procedure causes less tissue trauma, less adhesion formation, and less pain, and requires shorter hospitalization and recovery times for women. Another advantage of Doppler-guided uterine artery occlusion is the fact that its success rate is not affected by the surgeon’s level of laparoscopic expertise.²⁹

Intrauterine Ultrasound-guided RF Ablation of Uterine Fibroids

The VizAblate System® (Gynesonics; Redwood City, CA) is a transcervical device consisting of an intrauterine ultrasound probe and a single-use, disposable articulating hand piece. Through intrauterine sonography, fibroids can be accurately localized, and simultaneously ablated via high RF energy delivery.³¹ The amount of therapeutic energy delivered to the fibroid relies on a fixed treatment cycle based on fibroid size. A study trial looking at the efficiency of transvaginal RF thermal ablation in treating symptomatic uterine myomas reported a 91% reduction in symptoms and a 46% improvement in overall quality of life; a 73% mean reduction in fibroid volume was also reported.³²

Laparoscopic RF Ablation of Symptomatic Uterine Fibroids

Providing a less invasive alternative to abdominal hysterectomy in the management of symptomatic fibroids, laparoscopic RF ablation involves fibroids being precisely localized via ultrasound and targeted to high RF energy through monopolar and bipolar single electrocautery needles with multiple hooked arrays. Multiprobe array RF ablation has been associated with high satisfaction rates in the management of liver, lung, and kidney tumors; spherical regions of coagulation necrosis measuring 3.5 cm have been achieved and local tumor control of up to 95% has been reported.³³ RF volumetric thermal ablation (RFVTA) is usually performed in the outpatient setting using the Tulip™ RFVTA system (Halt Medical; Brentwood, CA) supplemented by standard laparoscopic instrumentations. The Halt Medical system consists of three components: a dual-mode, monopolar RF generator, two dispersive electrode pads, and a sterile electrosurgical probe with a deployable needle electrode array with a probe tip that enables coagulation of the needle tract.³⁴

Halt Medical’s Acessa feasibility study assessed the safety and efficacy of this technique in the management of symptoms secondary to uterine myomas in women; 135 premenopausal women with heavy uterine bleeding due to myomas were recruited.³⁵ The largest uterine myoma measured 14 weeks of gestation and no single myoma exceeded 7 cm in size. Postlaparoscopic ultrasoundguided RFVTA, the bleeding outcomes were measured by alkaline hematin analysis at baseline and subsequently 3, 6, and 12 months postprocedure (P < .001, paired t test). A higher quality of life was seen in 94% of the women, with a mean transformed score of 37.3 at baseline that improved gradually to 19.5 at 12 months (P < .001, paired t test). This was also associated with a mean myoma volume reduction of 45.1% by 12 months. One serious adverse event was reported: one patient required readmission and a second surgical procedure for persistent bleeding.³⁵

A subsequent study by Robles and colleagues³⁴ further assessed the efficacy of laparoscopic RFVTA; overall improvement in symptoms and quality of life was also reported. Among the 114 women initially screened, 36 were enrolled and 35 followed for 12 months. All women were premenopausal and were between 33 and 55 years of age. None desired any further children but every woman wished to preserve her uterus. The 36 women recruited had a maximum of six uterine myomas and the largest one measured 6 cm. At laparoscopy, two trocars were inserted (one infraumbilical and one at the level of the uterine fundus) to accommodate the laparoscope and the ultrasound transducer. Once the pelvis was assessed intra-abdominally, the laparoscopic ultrasound enabled mapping of the myoma. Under laparoscopic guidance, an RF probe was inserted percutaneously into the uterus and the myomas were targeted via ultrasound guidance and the probe was positioned 1 cm into the fibroid. Dual monitors were used to provide simultaneous laparoscopic and ultrasound imaging. Once the target temperature of 100°;C was achieved, it was maintained for the duration of the ablation. As in the Acessa trial, the patients were followed up at 3-month intervals for 1 year. Symptom severity scores reduced gradually and significantly (P < .05): baseline (63.3), 3 months (23.1), 6 months (15.4), and 12 months (9.6). Quality of life scores also improved (P < .05): baseline (37.3), 3 months (79.9), 6 months (85.1), and 12 months (87.7).³⁶

Conclusions

Menorrhagia affects a large proportion of women and accounts for a substantial percentage of gynecologic referrals to secondary care. Even though multiple medical and surgical options exist to control HMB, they are all associated with side effects and implications, thereby limiting their use and therapeutic abilities. Guidelines issued by the Royal College of Obstetricians and Gynecologists acknowledge that menorrhagia is often inappropriately managed and there is a need for further research in order to develop efficient, patient-friendly, and cost-effective drugs. With the development of new medical and surgical options, which have proven to be effective and associated with a greater patient satisfaction rate, further alternatives to invasive surgeries will become available.

Main Points.

• Heavy menstrual bleeding (HMB) is a benign yet debilitating social and health condition. It is clinically defined as blood loss ≥ 80 mL per menstrual cycle. In the United Kingdom, HMB accounts for > 20% of gynecologic referrals and cost the National Health Service £50 million in 2010.

• HMB can be caused by fibroids, uterine polyps, or endometriosis. Other conditions, such as coagulation disorders and endocrine disorders, can also cause HMB. In some cases, the cause of bleeding in premenopausal women may be due to gynecologic malignancy.

• The ultimate goal of any form of treatment is to reduce menstrual flow in order to improve quality of life. Pharmaceutical therapy has always been considered the first-line treatment. Conservative and uterinepreserving treatment options are obviously preferred.

• Medical therapies include the combined oral contraceptive pill, oral progesterone, nonsteroidal anti-inflammatory drugs, tranexamic acid, and the levonorgestrel-releasing intrauterine system. Surgical management options include endometrial ablation, uterine artery embolization, uterine artery occlusion, and hysterectomy.

• Future treatment options include gonadotropin-releasing hormone antagonists, selective estrogen receptor modulators, and progesterone receptor antagonists, among others.