Hormone Therapy for Menopause Symptoms PDF

Hormone Therapy and Other Treatments for Symptoms of Menopause D. ASHLEY HILL, MD, and MARK CRIDER, MD, University of Central Florida College of Medicine, Orlando, Florida SUSAN R. HILL, MD, Orlando, Florida The results of large clinical trials have led physicians and patients to question the safet...

Hormone Therapy and Other Treatments for Symptoms of Menopause D. ASHLEY HILL, MD, and MARK CRIDER, MD, University of Central Florida College of Medicine, Orlando, Florida SUSAN R. HILL, MD, Orlando, Florida The results of large clinical trials have led physicians and patients to question the safety of hormone therapy for meno- pause. In the past, physicians prescribed hormone therapy to improve overall health and prevent cardiac disease, as well as for symptoms of menopause. Combined estrogen/progestogen therapy, but not estrogen alone, increases the risk of breast cancer when used for more than three to five years. Therefore, in women with a uterus, it is recommended that physicians prescribe combination therapy only to treat menopausal symptoms such as vasomotor symptoms (hot flashes) and vaginal atrophy, using the smallest effective dosage for the shortest possible duration. Although estrogen is the most effective treatment for hot flashes, nonhormonal alternatives such as low-dose paroxetine, venlafaxine, and gabapentin are effective alternatives. Women with a uterus who are using estrogen should also take a progestogen to reduce the risk of endometrial cancer. Women who cannot tolerate adverse effects of progestogens may benefit from a combined formulation of estrogen and the selective estrogen receptor modulator bazedoxifene. There is no high- quality, consistent evidence that yoga, paced respiration, acupuncture, exercise, stress reduction, relaxation therapy, and alternative therapies such as black cohosh, botanical products, omega-3 fatty acid supplements, and dietary Chi- nese herbs benefit patients more than placebo. One systematic review suggests modest improvement in hot flashes and vaginal dryness with soy products, and small studies suggest that clinical hypnosis significantly reduces hot flashes. Patients with genitourinary syndrome of menopause may benefit from vaginal estrogen, nonhormonal vaginal mois- turizers, or ospemifene (the only nonhormonal treatment approved by the U.S. Food and Drug Administration for dyspareunia due to menopausal atrophy). The decision to use hormone therapy depends on clinical presentation, a thorough evaluation of the risks and benefits, and an informed discussion with the patient. (Am Fam Physician. 2016;94(11):884-889. Copyright © 2016 American Academy of Family Physicians.) M CME This clinical content enopause is the physiologic this study, many patients took hormones to conforms to AAFP criteria for continuing medical edu- transition when the ovaries improve overall health, prevent cardiac dis- cation (CME). See CME Quiz stop releasing eggs, ovarian ease, and treat menopausal symptoms. The Questions on page 868. function decreases, and men- large study of approximately 16,000 women Author disclosure: No rel- strual periods stop. Although some women go compared a combined oral regimen con- evant financial affiliations. through the menopausal transition without sisting of conjugated equine estrogen and Patient information: symptoms, many women have hot flashes or medroxyprogesterone with placebo, and ▲ A handout on this topic, genital tract symptoms, such as vulvar or vag- found that the combined regimen increased written by the authors of inal dryness, painful intercourse, and urinary the risk of coronary artery disease, breast can- this article, is available at http://www.aafp.org/ problems. When counseling patients who are cer, stroke, and venous thromboembolism afp/2016/1101/p884-s1.html. going through menopause, clinicians should (VTE). The study also found a decreased risk understand the benefits and risks of hormone of colorectal cancer, hip fractures, and total therapy, nonhormonal prescription medi- fractures with combined hormone therapy.1 cations, and alternative treatments, and be Critics of the study believe it is not appropri- familiar with the various delivery methods. ate to generalize results to all women going through menopause, partly because the aver- Risks and Benefits of Hormone age age of participants was 63 years. Therapy Other studies have helped refine informa- In 2002, the first Women’s Health Initiative tion about hormone therapy. The 2004 pub- (WHI) clinical trial was published, causing lication of a conjugated estrogen–only arm patients and clinicians to question the safety of the WHI trial in women without a uterus of menopausal hormone therapy.1 Before showed that those taking estrogen alone had 884 American Downloaded Family from the Physician American www.aafp.org/afp Family Physician website at www.aafp.org/afp. Volume Copyright © 2016 American Academy 94, Number of Family Physicians.11For the December 1, 2016 private, noncom- ◆ mercial use of one individual user of the website. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests.  Menopause SORT: KEY RECOMMENDATIONS FOR PRACTICE Evidence Clinical recommendation rating References Combined estrogen/progestogen therapy, but not estrogen alone, increases the risk of breast B 3 cancer after three to five years of use. Systemic estrogen, alone or in combination with a progestogen, is the most effective therapy A 9 for menopausal hot flashes, and is approved by the U.S. Food and Drug Administration for this indication. Because of the potential risks with long-term use of hormone therapy, clinicians should prescribe C 8, 12 the lowest effective dosage for the shortest duration necessary to improve symptoms. There is no high-quality, consistent evidence that black cohosh, botanical products, omega-3 B 19-21 fatty acid supplements, or lifestyle modification alleviates hot flashes. The decision to continue combined hormone therapy for more than three to five years should C 12 be made after reviewing the risks, benefits, and symptoms with the patient. Effective nonhormonal therapies for genitourinary syndrome of menopause include vaginal B 31, 32 moisturizers and oral ospemifene (Osphena). A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence; C = consensus, disease-oriented evidence, usual practice, expert opinion, or case series. For information about the SORT evidence rating system, go to http://www.aafp.org/afpsort. no significant change in risk of coronary heart disease or smoke cigarettes, or who are black.7 Treatment options breast cancer and, similar to the trial of combined estrogen include hormone therapy, nonhormonal prescription and progestogen, an increase in strokes and VTE.1,2 A 2013 medications, and clinical hypnosis. poststoppage review of findings from both WHI trials after Estrogen is the most effective therapy for hot flashes a median follow-up of 13 years revealed that women taking and is approved by the U.S. Food and Drug Administra- combined hormone therapy had a significantly increased tion (FDA) for this indication.8,9 Although some women risk of breast cancer and VTE, and a reduction in hip frac- may prefer lifestyle modification, there is no evidence tures. In contrast, women taking estrogen alone had a sig- that lowering the ambient temperature; using fans; exer- nificantly reduced risk of breast cancer.3 cising; or avoiding triggers, such as alcohol and spicy The “timing hypothesis” suggests that starting hormone foods, improves hot flashes.10 Because all systemic estro- therapy early in menopause (compared with starting it 10 gen formulations are effective, patient preference should years or more after the onset of menopause) may be car- guide the choice of therapy, unless there are contraindi- dioprotective because of estrogen’s apparent ability to slow cations such as undiagnosed vaginal bleeding or a his- the progression of atherosclerosis in younger women.3,4 tory of breast cancer, VTE, or severe liver disease. Table 1 Although the evidence suggests that beginning hormone summarizes the estrogen formulations available for the therapy near the start of menopause decreases the risk of treatment of hot flashes. cardiac disease, further study is needed. Current guidelines Although there are no randomized trials, observa- recommend against using hormone therapy to prevent or tional studies have shown that transdermal estrogen, treat cardiac disease.5 Further, the American Academy of Family Physicians recommends against using hormone therapy for the prevention of chronic conditions.6 WHAT IS NEW ON THIS TOPIC: Counseling patients about the options for treating TREATMENTS FOR MENOPAUSAL SYMPTOMS the vasomotor symptoms of menopause is challenging. The North American Menopause Society provides a free After a median of 13 years of follow-up, women taking mobile application called MenoPro to help clinicians combined estrogen/progestogen therapy in the Women’s Health Initiative trial had a significantly increased risk assess the benefit-risk profile of hormone therapy when of breast cancer and venous thromboembolism, and a counseling patients. MenoPro is available at http://www. reduction in hip fractures. menopause.org/for-women/-i-menopro-i-mobile-app. In 2014, a consensus conference endorsed new terminology: the term genitourinary syndrome of menopause replaces Vasomotor Symptoms the terms vulvovaginal atrophy and atrophic vaginitis. This Vasomotor symptoms (hot flashes) are the most com- is partly because older terminology does not encompass the extent of genital tract symptoms that many women mon indication for hormone therapy. During meno- experience. pause, approximately 70% of women report hot flashes, There is no evidence that using low-dose vaginal estrogen which are more common in women with a higher body increases the risk of breast cancer recurrence. mass index, with lower income and education, who December 1, 2016 ◆ Volume 94, Number 11 www.aafp.org/afp American Family Physician 885 Menopause Table 1. Estrogen Medications for the Treatment of Vasomotor Symptoms Medication Available dosages (mg) Bioidentical? Cost* Oral Enjuvia (conjugated estrogen) 0.3, 0.45, 0.625, 0.9, 1.25 (per day) No $87 Estrace (estradiol) 0.5, 1.0, 2.0 (per day) Yes $131 Menest (esterified estrogen) 0.3, 0.625, 1.25, 2.5 (per day) No $48 Premarin (conjugated estrogen) 0.3, 0.45, 0.625, 0.9, 1.25 (per day) No $143 Transdermal patch (estradiol) Alora 0.025, 0.05, 0.075, 0.1 (twice per week) Yes $90 Climara 0.025, 0.0375, 0.05, 0.06, 0.075, 0.1 (once per week) Yes $50 Minivelle 0.025, 0.0375, 0.05, 0.075, 0.1 (twice per week) Yes $137 Vivelle Dot 0.025, 0.0375, 0.05, 0.075, 0.1 (twice per week) Yes $84 Transdermal gel (estradiol) Divigel 0.25, 0.5, 1.0 (per day) Yes $118 Elestrin 0.52 (per day; adjust dosage based on response) Yes $109 Estrogel 0.75 (per day) Yes $126 Transdermal spray (estradiol) Evamist 1.53 per spray (start with 1 spray per day, adjust up to Yes $118 3 sprays per day based on response) Vaginal (estradiol) Femring 0.05, 0.10 (for 90 days) Yes $355 *—Estimated retail price of one month’s treatment based on information obtained at http://www.goodrx.com (accessed June 13, 2016). which avoids the first-pass liver effect, may have a lower Despite the effectiveness of estrogen, some patients risk of VTE compared with oral estrogen.11 All estrogen may prefer nonhormonal medications or may have con- medications should be given at the lowest effective dos- traindications to using estrogen. Several antidepressants age for the shortest duration necessary to improve symp- reduce hot flashes8,18 (Table 3). Low-dose paroxetine (Bris- toms.8,12 If necessary, the dosage may be increased after delle) is the only nonhormonal medication approved by evaluating for effectiveness during the first eight weeks the FDA to treat hot flashes, although other dosages can of therapy, with reassessment annually or as needed. be used. Patients taking tamoxifen should not use parox- Because all formulations of unopposed estrogen etine because of inhibition of the hepatic enzyme cyto- increase the risk of endometrial hyperplasia and can- chrome P450 2D6, which decreases the effectiveness of cer in women with a uterus, these patients should use tamoxifen.18 Desvenlafaxine (Khedezla) and venlafaxine estrogen plus progestogen for endometrial protection; a do not inhibit CYP2D6 and are appropriate alternatives. continuous regimen appears to be more effective than Starting at a low dose and titrating as necessary should be sequential therapy at reducing the risk of endometrial considered for antidepressants other than low-dose par- neoplasia.13 Patients can take an estrogen/progestogen oxetine. Other nonhormonal options include gabapentin combination product (Table 2) or an estrogen product (Neurontin) and pregabalin (Lyrica). These medications used in conjunction with a separate progestogen. can cause dizziness and other adverse effects, and should Progestogens can cause fatigue, dysphoria, and fluid be titrated from a lower dosage.18 Although clonidine is retention.14 Patients with a uterus who cannot tolerate somewhat more effective than placebo, adverse events, these adverse effects may benefit from Duavee, a com- such as hypotension, dizziness, and rebound hyperten- bination of 0.45-mg conjugated equine estrogen and sion, limit its usefulness for menopausal symptoms.10 the selective estrogen receptor modulator bazedoxifene, Stellate ganglion block of the C6-T2 anterior cervical which is approved by the FDA for treating hot flashes and spine has shown promise in uncontrolled studies and one preventing osteoporosis. Bazedoxifene does not stimu- small randomized trial, but larger studies are needed.10,18 late the endometrium.15,16 Like all products containing Some patients may want to use alternative therapies estrogen, Duavee is contraindicated in women who have or compounded formulations. Clinicians should coun- a history of breast cancer or VTE. The levonorgestrel- sel patients that there is no high-quality, consistent evi- releasing intrauterine system (Mirena) is an off-label dence that black cohosh, many botanical products, and option for providing local progestogen to the endome- omega-3 fatty acid supplements are effective for treat- trium for patients who cannot tolerate systemic therapy.17 ing hot flashes.19-21 One recent systematic review found a 886 American Family Physician www.aafp.org/afp Volume 94, Number 11 ◆ December 1, 2016  Menopause Table 2. Combination Estrogen/Progestogen Medications for the Treatment of Vasomotor Symptoms Available dosages (mg of estrogen/progestogen Medication unless otherwise indicated) Cost* Oral Activella (estradiol/norethindrone acetate) 0.5/0.1, 1.0/0.5 (per day) $215 Angeliq (estradiol/drospirenone) 0.5/0.25, 1.0/0.5 (per day) $133 Duavee (conjugated equine estrogen/bazedoxifene) 0.45/20.0 (per day) $153 Femhrt (estradiol/norethindrone acetate) 2.5 mcg/0.5 mg (per day) $150 Prefest (estradiol/norgestimate) 1.0/0.09 (per day; estrogen alone for 3 days followed $120 by estrogen/progestogen for three days, then repeat) Premphase (conjugated estrogen/ 0.625/5.0 (per day; estrogen alone for days 1 to 14 then $161 medroxyprogesterone) add progestogen for days 15 to 28) Prempro (conjugated estrogen/medroxyprogesterone) 0.3/1.5, 0.45/1.5, 0.625/2.5, 0.625/5.0 (per day) $161 Transdermal patch Climara Pro (estradiol/levonorgestrel) 0.45/0.015 (once per week) $149 Combipatch (estradiol/norethindrone acetate) 0.05/0.14, 0.05/0.25 (twice per week) $158 NOTE: None of these therapies are bioidentical. *—Estimated retail price of one month’s treatment based on information obtained at http://www.goodrx.com (accessed June 13, 2016). modest benefit for soy-based foods and supplements in (five 45-minute sessions weekly) has been shown to reducing hot flashes and vaginal dryness compared with reduce hot flashes by 74%, compared with a 17% placebo. Red clover and some non-Chinese herbal medi- reduction in patients who received only education and cines also variably improved symptoms.22 Overall, the encouragement.24 low quality and heterogeneity of the studies included in Celebrity endorsements and online marketing have this review do not allow definitive conclusions about the given increased attention to compounded bioidentical benefits of plant-based complementary therapies. Yoga, hormone formulations. Bioidentical hormones, such as paced respiration, acupuncture, exercise, stress reduc- estrone, 17-beta estradiol, and estriol, are identical to tion, and relaxation therapy also have not been proven human hormones. Data are limited about the safety and to alleviate hot flashes.23 However, clinical hypnosis effectiveness of compounded bioidentical formulations. There is concern that these unregulated formulations may have similar adverse effects as estrogen medica- Table 3. Antidepressants for Nonhormonal tions, such as endometrial hyperplasia. If a patient pre- Treatment of Vasomotor Symptoms fers a bioidentical hormone, FDA-approved medications containing the bioidentical hormone estradiol can be Dosage considered; for women with a uterus, micronized pro- Antidepressant (mg per day) Cost* gestogen (100 mg or 200 mg per day) should be added. Citalopram (Celexa) 10 to 20 $10 ($231) Clonidine (Catapres) 0.1 $9 ($79) Deciding When to Discontinue Hormone Therapy Desvenlafaxine 100 to 150 $257 ($384) Because of the potential increased risk of breast cancer in (Khedezla) women taking combined estrogen/progestogen therapy, Escitalopram (Lexapro) 10 to 20 $13 ($256) some clinicians advise that patients discontinue therapy Gabapentin (Neurontin) 900 to 2,400 $14 ($340) after three to five years. An analysis of women in the Paroxetine salt 7.5 NA ($190) WHI combined hormone trial who had hot flashes when (Brisdelle) starting therapy showed that after discontinuation, 56% Paroxetine (Paxil) 10 to 25 $10 ($178) had moderate to severe hot flashes compared with 21% of Pregabalin (Lyrica) 150 to 300 NA ($185) women who took placebo.25 Venlafaxine (Effexor XR) 37.5 to 100 $17 ($300) Clinicians should inform patients that some women NA = not available. will have a difficult time stopping hormone therapy.25 *—Estimated retail price of one month’s treatment based on informa- There are limited data to inform patients and clinicians tion obtained at http://www.goodrx.com (accessed June 13, 2016). about the best way to discontinue hormone therapy. Generic price listed first; brand price listed in parentheses. Some patients will be successful with abrupt discon- tinuation, whereas others may benefit from weaning. December 1, 2016 ◆ Volume 94, Number 11 www.aafp.org/afp American Family Physician 887 Menopause Table 4. Treatment Options for Genitourinary Syndrome of Menopause Treatment Dosages The American College of Obstetricians and Estrace vaginal cream Usual dosage: 2 to 4 g applied daily for one Gynecologists recommends against routine (estradiol) 0.01% to two weeks, then 1 g applied one to three discontinuation based on age or treatment times per week for maintenance therapy duration, and advises that the decision to Estring (estradiol) vaginal 2 mg released at 7.5 mcg per day over three continue or stop hormone therapy should be ring months individualized based on the patient’s symp- Osphena (ospemifene) 60 mg per day taken orally with food toms and medical history.12 Premarin (conjugated 0.625 mg of conjugated equine estrogen estrogen) vaginal cream per g; usual dosage: 0.5 to 2 g applied Transitioning from Contraception daily for 21 days then off for seven days, to Hormone Therapy or more commonly one to three times per week for maintenance therapy Transitioning from contraception to hor- Replens vaginal moisturizer Applied three times per week mone therapy may be challenging because Vagifem (estradiol) 10 mcg applied once daily for two weeks, oral contraceptives have higher dosages than vaginal tablet then twice weekly typical hormone therapy regimens. Also, measuring follicle-stimulating hormone lev- els after stopping oral contraceptives can be inaccurate moisturizers, such as Replens, are an effective treat- during perimenopause.26 One small study found that ment for mild vaginal dryness and related dyspareunia.31 a rise in follicle-stimulating hormone level without a Ospemifene is the only FDA-approved nonhormonal change in estradiol levels two weeks after stopping oral therapy for dyspareunia caused by menopausal atrophy. contraceptives is evidence that it is safe to transition to Short-term studies of ospemifene showed improvement hormone therapy.26 Others suggest discontinuation of in vaginal dryness.32 This medication is taken with food contraception when women are in their mid-50s because once per day, and should not be used by women with a spontaneous conception is rare at this age.27 history of breast cancer or thromboembolic disease. Hot flashes are the most bothersome adverse effect. Genitourinary Syndrome of Menopause Patients who have genitourinary syndrome of meno- Genitourinary syndrome of menopause refers to both- pause that does not respond to nonhormonal medi- ersome genital symptoms from changes in the vulva, cations or who have a narrow introitus or vagina may vagina, and lower genital tract that are caused by dimin- benefit from low-dose vaginal estrogen. All estrogen ished estrogen. This condition affects up to one-half of formulations for genital atrophy appear to have simi- women during menopause.28 In 2014, a consensus con- lar effectiveness regardless of administration method.33 ference endorsed the new term genitourinary syndrome Patient preference should guide the choice of formula- of menopause to replace the terms vulvovaginal atrophy tion. Creams have the advantage of both intravaginal and atrophic vaginitis, partly because the older terminol- and vulvar application, but they can be messy to apply. ogy does not encompass the extent of genital tract symp- Some patients may prefer the convenience of vaginal toms many women experience.29 Decreased estrogen estradiol tablets (Vagifem) or the vaginal low-dose estra- can cause several changes to genital anatomy that lead diol ring (Estring), which provides three months of con- to patient discomfort. Thinning of the vulvar mucosa tinuous therapy. Femring, another vaginal ring, provides may cause vulvar burning, irritation, or constriction of a systemic dosage of estrogen for treating hot flashes. the introitus, resulting in entry dyspareunia. Narrowing Women using low-dose vaginal estrogen for less than of the vagina and decreased lubrication can cause pain- one year should not require a progestogen to decrease ful intercourse or coital bleeding.30 Diminished estrogen the risk of endometrial cancer, but there are no long- may also lead to recurrent urinary tract infections and term data.28 Clinicians should consider an endometrial urinary urgency.29 Genitourinary syndrome of meno- biopsy and/or transvaginal ultrasonography if spotting pause is often progressive without treatment.28 or bleeding occurs while using low-dose vaginal estro- Treatment options (Table 4) include vaginal estro- gen.28 The decision to use vaginal estrogen formulations gen, nonhormonal vaginal moisturizers, and the newer for women with a history of hormone-dependent can- oral systemic estrogen agonist-antagonist ospemi- cers should be based on the woman’s preference after fene (Osphena). It is reasonable to try nonhormonal consultation with a clinician experienced with hormone therapy as a first-line option to alleviate vulvovaginal therapy. Clinicians can inform patients that there is no symptoms caused by genitourinary syndrome of meno- evidence that using low-dose local estrogen increases the pause. Although not as effective as estrogen, vaginal risk of breast cancer recurrence.34 888 American Family Physician www.aafp.org/afp Volume 94, Number 11 ◆ December 1, 2016  Menopause This review updates previous articles on this topic by Hill and Hill,35 by 13. Jaakkola S, Lyytinen H, Pukkala E, Ylikorkala O. Endometrial cancer Carroll,36 by Morelli and Naquin,37 and by Cutson and Meuleman.38 in postmenopausal women using estradiol-progestin therapy. Obstet Gynecol. 2009;114(6):1197-1204. Data Sources: An evidence-based search included PubMed, Essential 14. Goletiani NV, Keith DR, Gorsky SJ. Progesterone: review of safety for Evidence Plus, Cochrane Database of Systematic Reviews, U.S. Food and clinical studies. Exp Clin Psychopharmacol. 2007;15(5):427-444. Drug Administration, UpToDate, and a professional search by our institu- 15. Pickar JH, Yeh IT, Bachmann G, Speroff L. Endometrial effects of a tissue tional library team. Search dates: January and May 2016. selective estrogen complex containing bazedoxifene/conjugated estro- gens as a menopausal therapy. Fertil Steril. 2009;92(3):1018-1024. 16. Johnson K, Hauck F. Conjugated estrogens/bazedoxifene (Duavee) for The Authors menopausal symptoms. Am Fam Physician. 2016;93(4):307-314. D. ASHLEY HILL, MD, is chair of the Department of Obstetrics and Gyne- 17. Depypere H, Inki P. The levonorgestrel-releasing intrauterine system for cology at the Florida Hospital Graduate Medical Education Program in endometrial protection during estrogen replacement therapy: a clinical Orlando, and is professor of obstetrics and gynecology at the University of review. Climacteric. 2015;18(4):470-482. Central Florida College of Medicine in Orlando. 18. Sideras K, Loprinzi CL. Nonhormonal management of hot flashes for women on risk reduction therapy. J Natl Compr Canc Netw. 2010; MARK CRIDER, MD, is assistant professor of obstetrics and gynecology at 8(10):1171-1179. the University of Central Florida College of Medicine, and is medical director 19. Newton KM, et al. Treatment of vasomotor symptoms of menopause of the Labor and Delivery Unit at the Florida Hospital for Women in Orlando. with black cohosh, multibotanicals, soy, hormone therapy, or placebo: a randomized trial. Ann Intern Med. 2006;145(12):869-879. SUSAN R. HILL, MD, is an internal medicine physician in private practice 20. Lethaby A, et al. Phytoestrogens for menopausal vasomotor symptoms. in Orlando. Cochrane Database Syst Rev. 2013;(12):CD001395. Address correspondence to D. Ashley Hill, MD, Florida Hospital Gradu- 21. Cohen LS, Joffe H, Guthrie KA, et al. Efficacy of omega-3 for vasomotor ate Medical Education, 235 East Princeton St., #200, Orlando, FL 32804 symptoms treatment. Menopause. 2014;21(4):347-354. (e-mail: [email protected]). Reprints are not available from 22. Franco OH, Chowdhury R, Troup J, et al. Use of plant-based therapies the authors. and menopausal symptoms. JAMA. 2016;315(23):2554-2563. 23. Kaunitz AM, Manson JE. Management of menopausal symptoms. Obstet Gynecol. 2015;126(4):859-876. REFERENCES 24. Elkins GR, Fisher WI, Johnson AK, et al. Clinical hypnosis in the treat- 1. Rossouw JE, Anderson GL, Prentice RL, et al.; Writing Group for the ment of postmenopausal hot flashes. Menopause. 2013;20(3):291-298. 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Menopause. 2012;19(3):257-271. 34. Farrell R; American College of Obstetricians and Gynecologists’ Com- 9. Maclennan AH, Broadbent JL, Lester S, Moore V. Oral oestrogen and mittee on Gynecologic Practice. ACOG committee opinion no. 659. The combined oestrogen/progestogen therapy versus placebo for hot use of vaginal estrogen in women with a history of estrogen-dependent flushes. Cochrane Database Syst Rev. 2004;(4):CD002978. breast cancer. Obstet Gynecol. 2016;127(3):e93-e96. 10. Nonhormonal management of menopause-associated vasomotor 35. Hill DA, Hill SR. Counseling patients about hormone therapy and alterna- symptoms: 2015 position statement of The North American Menopause tives for menopausal symptoms. Am Fam Physician. 2010;82(7):801-807. Society. Menopause. 2015;22(11):1155-1172. 36. Carroll DG. Nonhormonal therapies for hot flashes in menopause. Am 11. Mohammed K, Abu Dabrh AM, Benkhadra K, et al. Oral vs transdermal Fam Physician. 2006;73(3):457-464. estrogen therapy and vascular events: a systematic review and meta- 37. Morelli V, Naquin C. Alternative therapies for traditional disease states: analysis. J Clin Endocrinol Metab. 2015;100(11):4012-4020. menopause. Am Fam Physician. 2002;66(1):129-134. 12. ACOG practice bulletin no. 141. Management of menopausal symp- 38. Cutson TM, Meuleman E. Managing menopause. Am Fam Physician. toms. Obstet Gynecol. 2014;123(1):202-216. 2000;61(5):1391-1400. December 1, 2016 ◆ Volume 94, Number 11 www.aafp.org/afp American Family Physician 889