It's best to start with nonsteroidal anti- inflammatory drugs (NSAIDs), which effectively reduce heavy menstrual bleeding (strength of recommendation [SOR]: B, systematic review of randomized clinical trials [RCTs]). Perimenopausal women with heavy bleeding not controlled by NSAIDs, or other forms of dysfunctional uterine bleeding, can benefit from continuous, combined hormonal therapy with estrogen and progestin; hormonal therapy with estrogen and a cyclical progestin; or a cyclical progestin alone (SOR: B, RCTs and a systematic review of RCTs). Intrauterine devices (IUDs) containing levonorgestrel also effectively reduce bleeding and may avoid surgical intervention (SOR: B, systematic review of RCTs)

Chen, Edward C.

Danis, Peter G.

Tweed, Elizabeth M.

University of Missouri: MOspace

CliniCal InquIrIes Evidence Based Answers from the Family Physicians Inquiries Networkwww.jfponline.comfast trackMenstrual disturbances  in perimenopausal women: What’s best?  Evidence-based answerIt’s best to start with nonsteroidal anti-inflammatory drugs (nsAIDs), which effectively reduce heavy menstrual bleeding (strength of recommendation [sOr]: B, systematic review of randomized clinical trials [rCTs]).  Perimenopausal women with heavy bleeding not controlled by nsAIDs, or other forms of dysfunctional uterine bleeding, can benefit from continuous, combined hormonal therapy with estrogen and progestin; hormonal therapy with estrogen and a cyclical progestin; or a cyclical progestin alone (sOr: B, rCTs and a systematic review of rCTs). Intrauterine devices (IuDs) containing levonorgestrel also effectively reduce bleeding and may avoid surgical intervention (sOr: B, systematic review of rCTs).  If medical management fails, endometrial ablation offers an effective, minimally invasive alternative to hysterectomy (sOr: B, systematic review of rCTs and 1 rCT). Hysterectomy should be considered when medical management or endometrial ablation fails (sOr: B, systematic review of rCTs and 1 rCT). z Evidence summaryPerimenopause encompasses the period of irregular menstrual cycles and flow that precedes menopause (absence of menstrual bleeding for 1 year). Meno-pause 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 perimeno-pause, therapeutic approaches are based primarily on studies of women before and shortly after this stage. Once malig-nancy and other causes of abnormal uter-ine bleeding (pregnancy, bleeding disor-ders, infection, thyroid disorders, uterine fibroids, or polyps) have been excluded, treatment of perimenopausal dysfunc-tional 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 proce-dures). NSAIDs reduce heavy bleedingA Cochrane review of 16 small RCTs that examined the use of NSAIDs for menor-OnlinE ExclusivEMedical  management with NSAIDs is the first choice for initial  treatment  of abnormal  uterine bleeding.Edward C. Chen, MD,  and Peter G. Danis, MDSt. John’s Mercy Family  Medicine, St. Louis, MoElizabeth Tweed, MliS, aHiPDenver Health Sciences Library, University of Colorado, Aurora vOl 58, nO 6 / June 2009 331cfast trackCliniCal InquIrIesrhagia found NSAIDs to be superior to placebo and comparable to other medical treatments such as luteal progestin, oral contraceptive pills, and progestin-releas-ing intrauterine systems.2 Hormone therapy is also effectiveAn RCT of 132 perimenopausal wom-en compared 24 weeks of combina-tion hormonal therapy (20 mcg ethinyl estradiol/1 mg norethindrone acetate) with placebo for treating climacteric symptoms, including abnormal uter-ine 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 as-sociated with a higher incidence of in-termenstrual 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 dy-drogesterone) with cyclical progestogens alone.4 In the combined treatment group, the incidence of cyclical menstrual bleed-ing 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 pri-marily of RCTs, examined uterine bleed-ing patterns in 3000 postmenopausal women taking combined continuous hormones (various regimens of estro-gen and progestin).5 In 22 of 23 studies that included data past 6 months, 75% or more of participants became amenor-rheic 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 hyperplasiaA more recent Cochrane review of 30 RCTs examined hormone replacement therapy for irregular bleeding and endo-metrial 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 con-tinuous estrogen and progestin became amenorrheic after 1 year of therapy. It also reiterated that unopposed estrogen increased the risk of endometrial hyper-plasia, whereas continuous combined es-trogen and progestogen treatment didn’t.Continuous progestogen regimen has blood loss benefitNo randomized trials have compared oral progestogens with placebo. A Cochrane review examined the use of cyclical pro-gestogens (given from 10 to 20 days per cycle) for heavy menstrual bleeding.7 Cy-clical 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 great-er benefit in terms of blood loss. IUDs help avoid surgery,  but can have side effects A Cochrane review found that progesto-gen-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 random-ized women scheduled for hysterectomy for heavy bleeding to the levonorgestrel intrauterine device (LNG-IUD) or their existing medical therapy (not further de-scribed) found that women in the LNG-IUD group were more likely to cancel surgery. Another RCT comparing hysterecto-331d vOl 58, nO 6 / June 2009  ThE JOurnal Of family PracTicEWomen using  the LNG-IUD  often canceled  scheduled  hysterectomy. fast trackwww.jfponline.commy with the LNG-IUD found that wom-en with the LNG-IUD reported greater pain. The LNG-IUD was more cost effec-tive 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, bal-loon thermal ablation, free fluid ablation, cryotherapy, microwaves) significantly reduce menstrual blood flow.9 These min-imally invasive techniques were an op-tion 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 resectionAn RCT of 187 women, average age 42 years, compared immediate transcervical resection of the endometrium to medical management for heavy menstrual bleed-ing.10 A 5-year follow-up was completed on 144 patients. The study showed tran-scervical resection of the endometrium to be superior with regard to menstrual sta-tus (less bleeding or no bleeding), patient satisfaction with outcomes, and health-related quality of life as indicated on pa-tient questionnaires.When other options fail… Patients who fail medical treatment and minimally invasive uterine ablation may require hysterectomy. An RCT of 63 pre-menopausal women (30-50 years of age) with abnormal uterine bleeding com-pared hysterectomy with medical treat-ment.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 Al-though the initial cost was higher for the hysterectomy group, the difference nar-rowed over time because of the need for retreatment in the endometrial destruc-tion group. RecommendationsThe American College of Obstetricians and Gynecologists (ACOG) recommends initial medical management (cyclic pro-gestins, low-dose oral contraceptives, or cyclic hormone replacement therapy) for anovulatory bleeding in women 40 years and older.13 The Practice Committee of the Amer-ican 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 inva-sive surgical options such as hystero-scopic endometrial ablation result in less short-term morbidity and cost less than hysterectomy.15 Results with re-sectoscopic and nonresectoscopic tech-niques are similar. Hysterectomy rates following these approaches are at least 24% at 4 years.15 nreferences 1.  seltzer vl, Benjamin F, Deutsch s. Perimenopausal bleeding patterns and pathologic findings. J Am Med Womens Assoc. 1990;45:132-134. 2.  lethaby A, Augood C, Duckitt K. nonsteroidal anti-inflammatory drugs for heavy menstrual bleeding. Cochrane Database Syst Rev. 2007;(4):CD0004000.  3.  Casper r, Dodin s, reid r, et al. The effect of 20 micrograms of ethinyl estradiol/1 mg norethindrone acetate (Minestrin), a low-dose contraceptive, on vaginal bleeding patterns, hot flashes, and qual-ity of life in symptomatic perimenopausal women. Menopause. 1997;4:139-147. 4.  De Francis P, Cobellis l, Fornaro F, et al. low-dose hormone therapy in the perimenopause. Int J Gyn-aecol Obstet. 2007;98:138-142.  5.  udoff l, langenberg P, Adashi eY. Combined con- vOl 58, nO 6 / June 2009 331eAmong patients followed for more than 5 years after endometrial  ablation,  20% to 40%  required repeat treatment or  hysterectomy.Menstrual disturbancesfast trackCliniCal InquIrIestinuous hormone replacement therapy: a critical review. Obstet Gynecol. 1995;86:306-316.  6.  suckling lA, Barlow D, Farquhar CM, et al. Hor-mone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. Cochrane Database Syst Rev. 2004;(3):CD000402.  7.  lethaby A, Irvine G, Cameron I. Cyclical progesto-gens for heavy menstrual bleeding. Cochrane Da-tabase Syst Rev. 2008;(1):CD001016.  8.  lethaby A, Cooke I, reese M. Progesterone or pro-gestogen-releasing intrauterine systems for heavy menstrual bleeding. Cochrane Database Syst Rev. 2005;(4):CD002126.  9.  Munro MG. endometrial ablation for heavy men-strual bleeding. Curr Opin Obstet Gynecol. 2005;17:381-394. 10.  Cooper KG, Jack sA, Parkin De, et al. Five-year follow-up of women randomised to medical man-agement or transcervical resection of the endome-trium for heavy menstrual loss: clinical and quality of life outcomes. BJOG. 2001;108:1222-1228.11.  Kuppermann M, varner re, summitt rl Jr, et al. effect of hysterectomy vs. medical treatment on health-related quality of life and sexual function-ing. The medicine or surgery (Ms) randomized trial. JAMA. 2004;291:1447-1455. 12.  lethaby A, shepperd s, Cooke I, et al. endome-trial resection and ablation versus hysterectomy for heavy menstrual bleeding. Cochrane Database Syst Rev. 1999;(2):CD000329. 13.  American College of Obstetricians and Gynecolo-gists Committee on Practice Bulletins—Gynecol-ogy. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. Manage-ment of anovulatory bleeding. In J Gynaecol Ob-stet. 2001;72:263-271.14.  Practice Committee of the American society for reproductive Medicine. Committee opinion: the menopausal transition. Fertil Steril. 2006;86(suppl 5):s253-s256.15.  American College of Obstetricians and Gynecolo-gists Committee on Practice Bulletins—Gynecol-ogy. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. endome-trial ablation. Obstet Gynecol. 2007;109:1233-1248.331f vOl 58, nO 6 / June 2009  ThE JOurnal Of family PracTicEACOG recommends initial medical management  for anovulatory bleeding in  women ≥ 40. 

Menstrual disturbances in perimenopausal women: What's best?

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