Elizabeth Tweed, MLIS, AHIP

Evidence summary

An RCT demonstrated increased prescribing rates when unannounced, standardized patients who imitated symptoms of either major depression or adjustment disorder requested a prescription. In 298 visits, 152 family physicians and internists prescribed antidepressants at significantly different rates when patients mimicking major depression requested brand-specific (53%), general (76%), or no medication (31%) (P<.001). Corresponding rates for adjustment disorder were 55%, 39%, and 10% (P<.001). The study found no difference in prescribing rates between family physicians and internists or between male and female physicians.

For patients presenting with depression, physician fidelity to minimum recommended treatment (defined as any combination of antidepressants, mental health referral, and 2-week follow-up) was 90% for patients making a brand-specific request, 98% for those making a general request, and 56% for those making no request (P<.001).¹

Patients who ask for DTCA meds are more likely to get a prescription
A cross-sectional survey compared prescribing decisions by 38 US and 40 Canadian physicians for 1431 patients. Most physicians fulfilled requests for DTCA medications (US 78%, Canadian, 72%). Patients who requested a DTCA medication were far more likely to receive a new prescription (DTCA or other) than patients who didn’t (odds ratio [OR]=16.9; 95% confidence interval [CI], 7.5-38.2). Although DTCA is illegal in Canada, market contamination seems likely, because the study was done in Vancouver, British Columbia.

US patients made more requests for DTCA medications (OR=2.2; 95% CI, 1.2-4.1) than Canadian patients. When patients made DTCA-related requests, physicians considered 50% of new prescriptions to be only “possible” or “unlikely” choices for other similar patients, compared with only 12.4% when patients didn’t make such requests (P<.001).²

DTCA drugs often trump other options
A national telephone survey of 3000 adults found that 35% of respondents were prompted by DTCA to discuss the medication or related health concern at a doctor visit. Of these, 72.9% reported receiving a new prescription, and 43% of them were for the advertised drug.³

Another survey of 643 physicians showed that 39% of visits influenced by DTCA resulted in new prescriptions for the advertised drug. Physician stated they prescribed the DTCA medication because they wanted to:

• prescribe the most effective drug (46%),
• accommodate the request despite other equally effective options (48%), or
• accommodate the request despite more effective options (5.5%).

Medications other than the advertised drug were prescribed during 22% of DTCA influenced visits.⁴

DTCA and prescriptions: Mixed results
A time-series analysis examined the relationship between advertising expenditures for several types of drugs and prescriptions written from 1992 to 1997.⁵

Advertising for antilipemic drugs was positively associated with prescriptions for both antilipemics in general (41 prescriptions for every $1000 of advertising; P=.003) and Zocor in particular (23/$1000; P<.001). Advertising for antihistamines in general and Claritin in particular were both positively associated with prescriptions for Claritin (general advertising: 24/$1000; P=.004; Claritin-specific advertising: 45/$1000; P=.005).

Advertising for acid-peptic disorder medications was inversely associated with Zantac prescriptions (-59 prescriptions/$1000, P=.004). This finding may be related to the emergence of, and advertising for, proton pump inhibitors during this time.

No relationship between advertising and prescribing was found for antihypertensives or medications for benign prostatic hypertrophy.

More frequent advertising doesn’t necessarily mean more prescriptions
Another time-series analysis examined the relationship between the frequency of local DTCA for cyclooxygenase-2 (COX-2) inhibitors and prescriptions for COX-2 inhibitors in the corresponding months. DTCA was not significantly associated with Celebrex prescriptions, but was slightly associated with Vioxx prescriptions (P=.04, 10-fold increase in DTCA associated with a 0.5% increase in prescriptions; P=.04). Practices farther than 100 miles from a media market and those that prescribed Vioxx infrequently were excluded.⁶ (In 2004, Vioxx was withdrawn from the US and worldwide markets.)

But patient questions about a specific ad get results
A survey of 2929 patients regarding the appropriateness of COX-2 inhibitors showed that 78% of patients who asked their physician about a COX-2 advertisement received a prescription for a COX-2 inhibitor (instead of a nonsteroidal anti-inflammatory drug) compared with 43% of all other patients.⁷

Recommendations

The American Medical Association (AMA) encourages physicians approached by patients about advertised medications to initiate a dialogue in order to enhance the patient’s understanding of the underlying condition. Request ed medications should be prescribed only if indicated and cost effective relative to other options.

The AMA also recommends that physicians report (to the pharmaceutical company or the US Food and Drug Administration) ads that are inaccurate, incomplete, or imbalanced, and ads that don’t enhance patient education or encourage patients to have a discussion with their physician.⁸

Evidence summary

An RCT demonstrated increased prescribing rates when unannounced, standardized patients who imitated symptoms of either major depression or adjustment disorder requested a prescription. In 298 visits, 152 family physicians and internists prescribed antidepressants at significantly different rates when patients mimicking major depression requested brand-specific (53%), general (76%), or no medication (31%) (P<.001). Corresponding rates for adjustment disorder were 55%, 39%, and 10% (P<.001). The study found no difference in prescribing rates between family physicians and internists or between male and female physicians.

For patients presenting with depression, physician fidelity to minimum recommended treatment (defined as any combination of antidepressants, mental health referral, and 2-week follow-up) was 90% for patients making a brand-specific request, 98% for those making a general request, and 56% for those making no request (P<.001).¹

Patients who ask for DTCA meds are more likely to get a prescription
A cross-sectional survey compared prescribing decisions by 38 US and 40 Canadian physicians for 1431 patients. Most physicians fulfilled requests for DTCA medications (US 78%, Canadian, 72%). Patients who requested a DTCA medication were far more likely to receive a new prescription (DTCA or other) than patients who didn’t (odds ratio [OR]=16.9; 95% confidence interval [CI], 7.5-38.2). Although DTCA is illegal in Canada, market contamination seems likely, because the study was done in Vancouver, British Columbia.

US patients made more requests for DTCA medications (OR=2.2; 95% CI, 1.2-4.1) than Canadian patients. When patients made DTCA-related requests, physicians considered 50% of new prescriptions to be only “possible” or “unlikely” choices for other similar patients, compared with only 12.4% when patients didn’t make such requests (P<.001).²

DTCA drugs often trump other options
A national telephone survey of 3000 adults found that 35% of respondents were prompted by DTCA to discuss the medication or related health concern at a doctor visit. Of these, 72.9% reported receiving a new prescription, and 43% of them were for the advertised drug.³

Another survey of 643 physicians showed that 39% of visits influenced by DTCA resulted in new prescriptions for the advertised drug. Physician stated they prescribed the DTCA medication because they wanted to:

• prescribe the most effective drug (46%),
• accommodate the request despite other equally effective options (48%), or
• accommodate the request despite more effective options (5.5%).

Medications other than the advertised drug were prescribed during 22% of DTCA influenced visits.⁴

DTCA and prescriptions: Mixed results
A time-series analysis examined the relationship between advertising expenditures for several types of drugs and prescriptions written from 1992 to 1997.⁵

Advertising for antilipemic drugs was positively associated with prescriptions for both antilipemics in general (41 prescriptions for every $1000 of advertising; P=.003) and Zocor in particular (23/$1000; P<.001). Advertising for antihistamines in general and Claritin in particular were both positively associated with prescriptions for Claritin (general advertising: 24/$1000; P=.004; Claritin-specific advertising: 45/$1000; P=.005).

Advertising for acid-peptic disorder medications was inversely associated with Zantac prescriptions (-59 prescriptions/$1000, P=.004). This finding may be related to the emergence of, and advertising for, proton pump inhibitors during this time.

No relationship between advertising and prescribing was found for antihypertensives or medications for benign prostatic hypertrophy.

More frequent advertising doesn’t necessarily mean more prescriptions
Another time-series analysis examined the relationship between the frequency of local DTCA for cyclooxygenase-2 (COX-2) inhibitors and prescriptions for COX-2 inhibitors in the corresponding months. DTCA was not significantly associated with Celebrex prescriptions, but was slightly associated with Vioxx prescriptions (P=.04, 10-fold increase in DTCA associated with a 0.5% increase in prescriptions; P=.04). Practices farther than 100 miles from a media market and those that prescribed Vioxx infrequently were excluded.⁶ (In 2004, Vioxx was withdrawn from the US and worldwide markets.)

But patient questions about a specific ad get results
A survey of 2929 patients regarding the appropriateness of COX-2 inhibitors showed that 78% of patients who asked their physician about a COX-2 advertisement received a prescription for a COX-2 inhibitor (instead of a nonsteroidal anti-inflammatory drug) compared with 43% of all other patients.⁷

Recommendations

The American Medical Association (AMA) encourages physicians approached by patients about advertised medications to initiate a dialogue in order to enhance the patient’s understanding of the underlying condition. Request ed medications should be prescribed only if indicated and cost effective relative to other options.

The AMA also recommends that physicians report (to the pharmaceutical company or the US Food and Drug Administration) ads that are inaccurate, incomplete, or imbalanced, and ads that don’t enhance patient education or encourage patients to have a discussion with their physician.⁸

Evidence summary

An RCT demonstrated increased prescribing rates when unannounced, standardized patients who imitated symptoms of either major depression or adjustment disorder requested a prescription. In 298 visits, 152 family physicians and internists prescribed antidepressants at significantly different rates when patients mimicking major depression requested brand-specific (53%), general (76%), or no medication (31%) (P<.001). Corresponding rates for adjustment disorder were 55%, 39%, and 10% (P<.001). The study found no difference in prescribing rates between family physicians and internists or between male and female physicians.

For patients presenting with depression, physician fidelity to minimum recommended treatment (defined as any combination of antidepressants, mental health referral, and 2-week follow-up) was 90% for patients making a brand-specific request, 98% for those making a general request, and 56% for those making no request (P<.001).¹

Patients who ask for DTCA meds are more likely to get a prescription
A cross-sectional survey compared prescribing decisions by 38 US and 40 Canadian physicians for 1431 patients. Most physicians fulfilled requests for DTCA medications (US 78%, Canadian, 72%). Patients who requested a DTCA medication were far more likely to receive a new prescription (DTCA or other) than patients who didn’t (odds ratio [OR]=16.9; 95% confidence interval [CI], 7.5-38.2). Although DTCA is illegal in Canada, market contamination seems likely, because the study was done in Vancouver, British Columbia.

US patients made more requests for DTCA medications (OR=2.2; 95% CI, 1.2-4.1) than Canadian patients. When patients made DTCA-related requests, physicians considered 50% of new prescriptions to be only “possible” or “unlikely” choices for other similar patients, compared with only 12.4% when patients didn’t make such requests (P<.001).²

DTCA drugs often trump other options
A national telephone survey of 3000 adults found that 35% of respondents were prompted by DTCA to discuss the medication or related health concern at a doctor visit. Of these, 72.9% reported receiving a new prescription, and 43% of them were for the advertised drug.³

Another survey of 643 physicians showed that 39% of visits influenced by DTCA resulted in new prescriptions for the advertised drug. Physician stated they prescribed the DTCA medication because they wanted to:

• prescribe the most effective drug (46%),
• accommodate the request despite other equally effective options (48%), or
• accommodate the request despite more effective options (5.5%).

Medications other than the advertised drug were prescribed during 22% of DTCA influenced visits.⁴

DTCA and prescriptions: Mixed results
A time-series analysis examined the relationship between advertising expenditures for several types of drugs and prescriptions written from 1992 to 1997.⁵

Advertising for antilipemic drugs was positively associated with prescriptions for both antilipemics in general (41 prescriptions for every $1000 of advertising; P=.003) and Zocor in particular (23/$1000; P<.001). Advertising for antihistamines in general and Claritin in particular were both positively associated with prescriptions for Claritin (general advertising: 24/$1000; P=.004; Claritin-specific advertising: 45/$1000; P=.005).

Advertising for acid-peptic disorder medications was inversely associated with Zantac prescriptions (-59 prescriptions/$1000, P=.004). This finding may be related to the emergence of, and advertising for, proton pump inhibitors during this time.

No relationship between advertising and prescribing was found for antihypertensives or medications for benign prostatic hypertrophy.

More frequent advertising doesn’t necessarily mean more prescriptions
Another time-series analysis examined the relationship between the frequency of local DTCA for cyclooxygenase-2 (COX-2) inhibitors and prescriptions for COX-2 inhibitors in the corresponding months. DTCA was not significantly associated with Celebrex prescriptions, but was slightly associated with Vioxx prescriptions (P=.04, 10-fold increase in DTCA associated with a 0.5% increase in prescriptions; P=.04). Practices farther than 100 miles from a media market and those that prescribed Vioxx infrequently were excluded.⁶ (In 2004, Vioxx was withdrawn from the US and worldwide markets.)

But patient questions about a specific ad get results
A survey of 2929 patients regarding the appropriateness of COX-2 inhibitors showed that 78% of patients who asked their physician about a COX-2 advertisement received a prescription for a COX-2 inhibitor (instead of a nonsteroidal anti-inflammatory drug) compared with 43% of all other patients.⁷

Recommendations

The American Medical Association (AMA) encourages physicians approached by patients about advertised medications to initiate a dialogue in order to enhance the patient’s understanding of the underlying condition. Request ed medications should be prescribed only if indicated and cost effective relative to other options.

The AMA also recommends that physicians report (to the pharmaceutical company or the US Food and Drug Administration) ads that are inaccurate, incomplete, or imbalanced, and ads that don’t enhance patient education or encourage patients to have a discussion with their physician.⁸

Evidence summary

Perimenopause encompasses the period of irregular menstrual cycles and flow that precedes menopause (absence of menstrual bleeding for 1 year). Menopause generally occurs between 45 and 55 years of age; the average is 51 years. A review of 500 perimenopausal women seen sequentially by a gynecology service found that 18% had menorrhagia (heavy bleeding), metrorrhagia (intermenstrual bleeding), or hypermenorrhea (frequent periods).¹

Because few studies have examined the treatment of abnormal menstrual bleeding specifically during perimenopause, therapeutic approaches are based primarily on studies of women before and shortly after this stage. Once malignancy and other causes of abnormal uterine bleeding (pregnancy, bleeding disorders, infection, thyroid disorders, uterine fibroids, or polyps) have been excluded, treatment of perimenopausal dysfunctional uterine bleeding should address the goals of:

• stopping acute bleeding
• avoiding future irregular or heavy bleeding
• considering future family planning needs
• preventing complications (anemia, unnecessary therapeutic procedures).

NSAIDs reduce heavy bleeding

A Cochrane review of 16 small RCTs that examined the use of NSAIDs for menorrhagia found NSAIDs to be superior to placebo and comparable to other medical treatments such as luteal progestin, oral contraceptive pills, and progestin-releasing intrauterine systems.²

Hormone therapy is also effective

An RCT of 132 perimenopausal women compared 24 weeks of combination hormonal therapy (20 mcg ethinyl estradiol/1 mg norethindrone acetate) with placebo for treating climacteric symptoms, including abnormal uterine bleeding.³ The combination therapy shortened the menstrual cycle (27.7 vs 30.4 days), decreased its variability (17.5-46.7 days vs 22.4-66 days), and lowered bleeding severity scores (6.9 vs 10.2).

Hormonal therapy didn’t shorten bleeding episodes, however, and was associated with a higher incidence of intermenstrual bleeding during the first 3 months of treatment.

Continuous, combined estrogen/progestogen therapy

An RCT of 120 perimenopausal women with irregular menstrual cycles compared low-dose (1 mg) continuous estradiol and cyclical progestogens (10 mg dydrogesterone) with cyclical progestogens alone.⁴ In the combined treatment group, the incidence of cyclical menstrual bleeding was 86%, and 76% of all cycles were rated normal in amount and duration of bleeding. In the cyclical progestogen group, the incidence of cyclical menstrual bleeding during treatment was 76%, and 70% of all cycles were rated normal.

A systematic review, comprised primarily of RCTs, examined uterine bleeding patterns in 3000 postmenopausal women taking combined continuous hormones (various regimens of estrogen and progestin).⁵ In 22 of 23 studies that included data past 6 months, 75% or more of participants became amenorrheic while on therapy. Irregular uterine bleeding before 6 months of therapy was common, however, and was presumed to lower patient compliance.

Combined therapy avoids risk of endometrial hyperplasia

A more recent Cochrane review of 30 RCTs examined hormone replacement therapy for irregular bleeding and endometrial hyperplasia in postmenopausal women who had been amenorrheic for at least 6 months (a more liberal criterion for inclusion).⁶ The review concluded that many of the women treated with continuous estrogen and progestin became amenorrheic after 1 year of therapy. It also reiterated that unopposed estrogen increased the risk of endometrial hyperplasia, whereas continuous combined estrogen and progestogen treatment didn’t.

Continuous progestogen regimen has blood loss benefit

No randomized trials have compared oral progestogens with placebo. A Cochrane review examined the use of cyclical progestogens (given from 10 to 20 days per cycle) for heavy menstrual bleeding.⁷ Cyclical progestogens appeared comparable in efficacy to NSAIDs for their effect on duration of menstruation; no statistically significant difference in menstrual blood loss was noted. Progestogens given in more continuous regimens offered greater benefit in terms of blood loss.

IUDs help avoid surgery, but can have side effects

A Cochrane review found that progestogen-releasing IUDs significantly reduce heavy menstrual bleeding and are more effective than cyclical norethisterone (21 days). Patients did, however, report greater progestogenic side effects (breast tenderness and intermenstrual bleeding) than cyclical therapy.⁸

One unblinded RCT that randomized women scheduled for hysterectomy for heavy bleeding to the levonorgestrel intrauterine device (LNG-IUD) or their existing medical therapy (not further described) found that women in the LNG-IUD group were more likely to cancel surgery.

Another RCT comparing hysterectomy with the LNG-IUD found that women with the LNG-IUD reported greater pain. The LNG-IUD was more cost effective at 1 and 5 years, primarily because of reduced surgical expenses. Some patients or physicians may have ethical issues with the device’s mechanism of action.

Uterine ablation when preserving fertility doesn’t matter

A review article of currently available evidence on endometrial ablation for heavy menstrual bleeding concluded that both resectoscopic endometrial ablation (via hysteroscopy) and nonresectoscopic endometrial ablative technologies (radio-frequency electrosurgical ablation, balloon thermal ablation, free fluid ablation, cryotherapy, microwaves) significantly reduce menstrual blood flow.⁹ These minimally invasive techniques were an option for women who weren’t concerned about preserving fertility. However, 20% to 40% of patients who were followed for more than 5 years required repeat treatment or hysterectomy.

Heavy bleeding and transcervical endometrial resection

An RCT of 187 women, average age 42 years, compared immediate transcervical resection of the endometrium to medical management for heavy menstrual bleeding.¹⁰ A 5-year follow-up was completed on 144 patients. The study showed transcervical resection of the endometrium to be superior with regard to menstrual status (less bleeding or no bleeding), patient satisfaction with outcomes, and health-related quality of life as indicated on patient questionnaires.

When other options fail…

Patients who fail medical treatment and minimally invasive uterine ablation may require hysterectomy. An RCT of 63 premenopausal women (30-50 years of age) with abnormal uterine bleeding compared hysterectomy with medical treatment.¹¹ Hysterectomy was superior with regard to symptom resolution and health-related quality of life after 6 months.

A Cochrane review of 5 RCTs that compared endometrial resection and ablation with hysterectomy for heavy menstrual bleeding reported a significant advantage for hysterectomy in symptom resolution and patient satisfaction.¹² Although the initial cost was higher for the hysterectomy group, the difference narrowed over time because of the need for retreatment in the endometrial destruction group.

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) recommends initial medical management (cyclic progestins, low-dose oral contraceptives, or cyclic hormone replacement therapy) for anovulatory bleeding in women 40 years and older.¹³

The Practice Committee of the American Society for Reproductive Medicine lists low-dose combination hormonal pills, progestin, progestin-containing IUDs, and hormone replacement therapy as medical treatment options.¹⁴

ACOG notes that minimally invasive surgical options such as hysteroscopic endometrial ablation result in less short-term morbidity and cost less than hysterectomy.¹⁵ Results with resectoscopic and nonresectoscopic techniques are similar. Hysterectomy rates following these approaches are at least 24% at 4 years.¹⁵

Evidence summary

Perimenopause encompasses the period of irregular menstrual cycles and flow that precedes menopause (absence of menstrual bleeding for 1 year). Menopause generally occurs between 45 and 55 years of age; the average is 51 years. A review of 500 perimenopausal women seen sequentially by a gynecology service found that 18% had menorrhagia (heavy bleeding), metrorrhagia (intermenstrual bleeding), or hypermenorrhea (frequent periods).¹

Because few studies have examined the treatment of abnormal menstrual bleeding specifically during perimenopause, therapeutic approaches are based primarily on studies of women before and shortly after this stage. Once malignancy and other causes of abnormal uterine bleeding (pregnancy, bleeding disorders, infection, thyroid disorders, uterine fibroids, or polyps) have been excluded, treatment of perimenopausal dysfunctional uterine bleeding should address the goals of:

• stopping acute bleeding
• avoiding future irregular or heavy bleeding
• considering future family planning needs
• preventing complications (anemia, unnecessary therapeutic procedures).

NSAIDs reduce heavy bleeding

A Cochrane review of 16 small RCTs that examined the use of NSAIDs for menorrhagia found NSAIDs to be superior to placebo and comparable to other medical treatments such as luteal progestin, oral contraceptive pills, and progestin-releasing intrauterine systems.²

Hormone therapy is also effective

An RCT of 132 perimenopausal women compared 24 weeks of combination hormonal therapy (20 mcg ethinyl estradiol/1 mg norethindrone acetate) with placebo for treating climacteric symptoms, including abnormal uterine bleeding.³ The combination therapy shortened the menstrual cycle (27.7 vs 30.4 days), decreased its variability (17.5-46.7 days vs 22.4-66 days), and lowered bleeding severity scores (6.9 vs 10.2).

Hormonal therapy didn’t shorten bleeding episodes, however, and was associated with a higher incidence of intermenstrual bleeding during the first 3 months of treatment.

Continuous, combined estrogen/progestogen therapy

An RCT of 120 perimenopausal women with irregular menstrual cycles compared low-dose (1 mg) continuous estradiol and cyclical progestogens (10 mg dydrogesterone) with cyclical progestogens alone.⁴ In the combined treatment group, the incidence of cyclical menstrual bleeding was 86%, and 76% of all cycles were rated normal in amount and duration of bleeding. In the cyclical progestogen group, the incidence of cyclical menstrual bleeding during treatment was 76%, and 70% of all cycles were rated normal.

A systematic review, comprised primarily of RCTs, examined uterine bleeding patterns in 3000 postmenopausal women taking combined continuous hormones (various regimens of estrogen and progestin).⁵ In 22 of 23 studies that included data past 6 months, 75% or more of participants became amenorrheic while on therapy. Irregular uterine bleeding before 6 months of therapy was common, however, and was presumed to lower patient compliance.

Combined therapy avoids risk of endometrial hyperplasia

A more recent Cochrane review of 30 RCTs examined hormone replacement therapy for irregular bleeding and endometrial hyperplasia in postmenopausal women who had been amenorrheic for at least 6 months (a more liberal criterion for inclusion).⁶ The review concluded that many of the women treated with continuous estrogen and progestin became amenorrheic after 1 year of therapy. It also reiterated that unopposed estrogen increased the risk of endometrial hyperplasia, whereas continuous combined estrogen and progestogen treatment didn’t.

Continuous progestogen regimen has blood loss benefit

No randomized trials have compared oral progestogens with placebo. A Cochrane review examined the use of cyclical progestogens (given from 10 to 20 days per cycle) for heavy menstrual bleeding.⁷ Cyclical progestogens appeared comparable in efficacy to NSAIDs for their effect on duration of menstruation; no statistically significant difference in menstrual blood loss was noted. Progestogens given in more continuous regimens offered greater benefit in terms of blood loss.

IUDs help avoid surgery, but can have side effects

A Cochrane review found that progestogen-releasing IUDs significantly reduce heavy menstrual bleeding and are more effective than cyclical norethisterone (21 days). Patients did, however, report greater progestogenic side effects (breast tenderness and intermenstrual bleeding) than cyclical therapy.⁸

One unblinded RCT that randomized women scheduled for hysterectomy for heavy bleeding to the levonorgestrel intrauterine device (LNG-IUD) or their existing medical therapy (not further described) found that women in the LNG-IUD group were more likely to cancel surgery.

Another RCT comparing hysterectomy with the LNG-IUD found that women with the LNG-IUD reported greater pain. The LNG-IUD was more cost effective at 1 and 5 years, primarily because of reduced surgical expenses. Some patients or physicians may have ethical issues with the device’s mechanism of action.

Uterine ablation when preserving fertility doesn’t matter

A review article of currently available evidence on endometrial ablation for heavy menstrual bleeding concluded that both resectoscopic endometrial ablation (via hysteroscopy) and nonresectoscopic endometrial ablative technologies (radio-frequency electrosurgical ablation, balloon thermal ablation, free fluid ablation, cryotherapy, microwaves) significantly reduce menstrual blood flow.⁹ These minimally invasive techniques were an option for women who weren’t concerned about preserving fertility. However, 20% to 40% of patients who were followed for more than 5 years required repeat treatment or hysterectomy.

Heavy bleeding and transcervical endometrial resection

An RCT of 187 women, average age 42 years, compared immediate transcervical resection of the endometrium to medical management for heavy menstrual bleeding.¹⁰ A 5-year follow-up was completed on 144 patients. The study showed transcervical resection of the endometrium to be superior with regard to menstrual status (less bleeding or no bleeding), patient satisfaction with outcomes, and health-related quality of life as indicated on patient questionnaires.

When other options fail…

Patients who fail medical treatment and minimally invasive uterine ablation may require hysterectomy. An RCT of 63 premenopausal women (30-50 years of age) with abnormal uterine bleeding compared hysterectomy with medical treatment.¹¹ Hysterectomy was superior with regard to symptom resolution and health-related quality of life after 6 months.

A Cochrane review of 5 RCTs that compared endometrial resection and ablation with hysterectomy for heavy menstrual bleeding reported a significant advantage for hysterectomy in symptom resolution and patient satisfaction.¹² Although the initial cost was higher for the hysterectomy group, the difference narrowed over time because of the need for retreatment in the endometrial destruction group.

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) recommends initial medical management (cyclic progestins, low-dose oral contraceptives, or cyclic hormone replacement therapy) for anovulatory bleeding in women 40 years and older.¹³

The Practice Committee of the American Society for Reproductive Medicine lists low-dose combination hormonal pills, progestin, progestin-containing IUDs, and hormone replacement therapy as medical treatment options.¹⁴

ACOG notes that minimally invasive surgical options such as hysteroscopic endometrial ablation result in less short-term morbidity and cost less than hysterectomy.¹⁵ Results with resectoscopic and nonresectoscopic techniques are similar. Hysterectomy rates following these approaches are at least 24% at 4 years.¹⁵

Evidence summary

Perimenopause encompasses the period of irregular menstrual cycles and flow that precedes menopause (absence of menstrual bleeding for 1 year). Menopause generally occurs between 45 and 55 years of age; the average is 51 years. A review of 500 perimenopausal women seen sequentially by a gynecology service found that 18% had menorrhagia (heavy bleeding), metrorrhagia (intermenstrual bleeding), or hypermenorrhea (frequent periods).¹

Because few studies have examined the treatment of abnormal menstrual bleeding specifically during perimenopause, therapeutic approaches are based primarily on studies of women before and shortly after this stage. Once malignancy and other causes of abnormal uterine bleeding (pregnancy, bleeding disorders, infection, thyroid disorders, uterine fibroids, or polyps) have been excluded, treatment of perimenopausal dysfunctional uterine bleeding should address the goals of:

• stopping acute bleeding
• avoiding future irregular or heavy bleeding
• considering future family planning needs
• preventing complications (anemia, unnecessary therapeutic procedures).

NSAIDs reduce heavy bleeding

A Cochrane review of 16 small RCTs that examined the use of NSAIDs for menorrhagia found NSAIDs to be superior to placebo and comparable to other medical treatments such as luteal progestin, oral contraceptive pills, and progestin-releasing intrauterine systems.²

Hormone therapy is also effective

An RCT of 132 perimenopausal women compared 24 weeks of combination hormonal therapy (20 mcg ethinyl estradiol/1 mg norethindrone acetate) with placebo for treating climacteric symptoms, including abnormal uterine bleeding.³ The combination therapy shortened the menstrual cycle (27.7 vs 30.4 days), decreased its variability (17.5-46.7 days vs 22.4-66 days), and lowered bleeding severity scores (6.9 vs 10.2).

Hormonal therapy didn’t shorten bleeding episodes, however, and was associated with a higher incidence of intermenstrual bleeding during the first 3 months of treatment.

Continuous, combined estrogen/progestogen therapy

An RCT of 120 perimenopausal women with irregular menstrual cycles compared low-dose (1 mg) continuous estradiol and cyclical progestogens (10 mg dydrogesterone) with cyclical progestogens alone.⁴ In the combined treatment group, the incidence of cyclical menstrual bleeding was 86%, and 76% of all cycles were rated normal in amount and duration of bleeding. In the cyclical progestogen group, the incidence of cyclical menstrual bleeding during treatment was 76%, and 70% of all cycles were rated normal.

A systematic review, comprised primarily of RCTs, examined uterine bleeding patterns in 3000 postmenopausal women taking combined continuous hormones (various regimens of estrogen and progestin).⁵ In 22 of 23 studies that included data past 6 months, 75% or more of participants became amenorrheic while on therapy. Irregular uterine bleeding before 6 months of therapy was common, however, and was presumed to lower patient compliance.

Combined therapy avoids risk of endometrial hyperplasia

A more recent Cochrane review of 30 RCTs examined hormone replacement therapy for irregular bleeding and endometrial hyperplasia in postmenopausal women who had been amenorrheic for at least 6 months (a more liberal criterion for inclusion).⁶ The review concluded that many of the women treated with continuous estrogen and progestin became amenorrheic after 1 year of therapy. It also reiterated that unopposed estrogen increased the risk of endometrial hyperplasia, whereas continuous combined estrogen and progestogen treatment didn’t.

Continuous progestogen regimen has blood loss benefit

No randomized trials have compared oral progestogens with placebo. A Cochrane review examined the use of cyclical progestogens (given from 10 to 20 days per cycle) for heavy menstrual bleeding.⁷ Cyclical progestogens appeared comparable in efficacy to NSAIDs for their effect on duration of menstruation; no statistically significant difference in menstrual blood loss was noted. Progestogens given in more continuous regimens offered greater benefit in terms of blood loss.

IUDs help avoid surgery, but can have side effects

A Cochrane review found that progestogen-releasing IUDs significantly reduce heavy menstrual bleeding and are more effective than cyclical norethisterone (21 days). Patients did, however, report greater progestogenic side effects (breast tenderness and intermenstrual bleeding) than cyclical therapy.⁸

One unblinded RCT that randomized women scheduled for hysterectomy for heavy bleeding to the levonorgestrel intrauterine device (LNG-IUD) or their existing medical therapy (not further described) found that women in the LNG-IUD group were more likely to cancel surgery.

Another RCT comparing hysterectomy with the LNG-IUD found that women with the LNG-IUD reported greater pain. The LNG-IUD was more cost effective at 1 and 5 years, primarily because of reduced surgical expenses. Some patients or physicians may have ethical issues with the device’s mechanism of action.

Uterine ablation when preserving fertility doesn’t matter

A review article of currently available evidence on endometrial ablation for heavy menstrual bleeding concluded that both resectoscopic endometrial ablation (via hysteroscopy) and nonresectoscopic endometrial ablative technologies (radio-frequency electrosurgical ablation, balloon thermal ablation, free fluid ablation, cryotherapy, microwaves) significantly reduce menstrual blood flow.⁹ These minimally invasive techniques were an option for women who weren’t concerned about preserving fertility. However, 20% to 40% of patients who were followed for more than 5 years required repeat treatment or hysterectomy.

Heavy bleeding and transcervical endometrial resection

An RCT of 187 women, average age 42 years, compared immediate transcervical resection of the endometrium to medical management for heavy menstrual bleeding.¹⁰ A 5-year follow-up was completed on 144 patients. The study showed transcervical resection of the endometrium to be superior with regard to menstrual status (less bleeding or no bleeding), patient satisfaction with outcomes, and health-related quality of life as indicated on patient questionnaires.

When other options fail…

Patients who fail medical treatment and minimally invasive uterine ablation may require hysterectomy. An RCT of 63 premenopausal women (30-50 years of age) with abnormal uterine bleeding compared hysterectomy with medical treatment.¹¹ Hysterectomy was superior with regard to symptom resolution and health-related quality of life after 6 months.

A Cochrane review of 5 RCTs that compared endometrial resection and ablation with hysterectomy for heavy menstrual bleeding reported a significant advantage for hysterectomy in symptom resolution and patient satisfaction.¹² Although the initial cost was higher for the hysterectomy group, the difference narrowed over time because of the need for retreatment in the endometrial destruction group.

Recommendations

The American College of Obstetricians and Gynecologists (ACOG) recommends initial medical management (cyclic progestins, low-dose oral contraceptives, or cyclic hormone replacement therapy) for anovulatory bleeding in women 40 years and older.¹³

The Practice Committee of the American Society for Reproductive Medicine lists low-dose combination hormonal pills, progestin, progestin-containing IUDs, and hormone replacement therapy as medical treatment options.¹⁴

ACOG notes that minimally invasive surgical options such as hysteroscopic endometrial ablation result in less short-term morbidity and cost less than hysterectomy.¹⁵ Results with resectoscopic and nonresectoscopic techniques are similar. Hysterectomy rates following these approaches are at least 24% at 4 years.¹⁵