Algorithm and mobile app for menopausal symptom management and hormonal/non-hormonal therapy decision making

OVERVIEW The Menopause Decision-Support Algorithm (Fig. 1) and companion MenoPro iPhone/iPad app, developed in collaboration with The North American Menopause Society (NAMS), are designed to help clinicians decide which patients are candidates for pharmacologic treatment of menopausal symptoms, understand what the treatment options are, and gain experience deciding among the options. Menopausal symptoms vary dramatically among women.1,2 Some women are good candidates for hormonal treatments and others, due to their personal preferences or risk factor profiles, are not appropriate candidates and should consider non-hormonal options. One of the most complex health care decisions facing women in mid-life is whether to use prescription medications for menopausal symptom management, and the array of pharmacologic options has expanded markedly in recent years.2,3 The new MenoPro app, which can be downloaded free of charge on a mobile phone or tablet device, helps clinicians and patients work together to “personalize” treatment decisions, based on risk stratification4-9 and the patient’s personal preferences. The mobile app has two modes, one for clinicians and a companion mode for patients, to facilitate shared decision making and patient-centered care.FIG. 1: Algorithm for menopausal symptom management and hormonal/non-hormonal therapy decision making. Algorithm footnotes appear at the end of the article.The algorithm and MenoPro mobile app address options for “moderate to severe” hot flashes and/or night sweats (defined as bothersome enough to interfere with daily activities, impair quality of life, and/or interrupt sleep), as well as genitourinary symptoms (including vaginal dryness or pain with intercourse or other sexual activities). Convenient links provide information about treatment options, formulations and doses, and contraindications to therapy. The app calculates an atherosclerotic cardiovascular disease (CVD) risk score for each patient,10 which is relevant to the decision regarding initiation of systemic menopausal hormone therapy (HT). Women at high risk of, or with significant concern about, breast cancer should be informed about availability of non hormonal therapies. Once the clinician becomes familiar with the algorithm, personalized decision-making for most patients will require only 2-3 minutes, and the app provides a summary at the end that can be printed out or directly emailed to the patient. The tool can be used for women with menopausal symptoms who are ages ≥45 years old. The algorithm can also be used for women who have had removal of both ovaries, regardless of age. Women below age 45 or those who are not clearly menopausal, as well as women who have had endometrial ablation, progestin-releasing intrauterine device/system, or hysterectomy without removal of ovaries, may need additional clinical evaluation before applying this algorithm (evaluation may include hCG, FSH, TSH, prolactin, and other tests).3 The algorithm encourages all patients to try lifestyle modifications for at least 3 months before beginning HT or other pharmacologic therapies. For information on lifestyle modifications, cognitive behavioral therapy, and/or alternative remedies, clinicians may want to print out the materials for the patient at the below link (or send the link by email via the app): http://www.menopause.org/docs/for-women/mnflashes.pdf. Women at high risk of osteoporotic fracture and unable to tolerate standard preventive medications may also be candidates for HT (NAMS Hormone Therapy Position Statement: http://www.menopause.org/docs/default-document-library/psht12.pdf?sfvrsn=2).2 The algorithm also addresses considerations relevant to decisions about duration of treatment, including balancing risks of breast cancer, cardiovascular disease, and osteoporosis.1-3 Each step of the algorithm should be reassessed at least once every 12 months or if health status changes. BACKGROUND Women have an increasing number of options, both hormonal and non-hormonal, for the management of menopausal symptoms.1-3 A major deterrent to treatment, however, is the complexity of the decision-making process and the lack of information about available options. This new algorithm and mobile app for menopausal symptom management incorporate state-of-the-science evidence and research to clarify and streamline the decision-making process for both patients and clinicians. Menopausal HT continues to have an important clinical role in the management of vasomotor and other menopausal symptoms, but it has complex biological effects. The rational use of HT requires balancing the potential benefits and risks of treatment. Although findings from the Women’s Health Initiative (WHI) and other randomized clinical trials have helped to clarify the benefits and risks of HT and provided insights to improve decision making,4-7 current options include lower doses and transdermal formulations that may further minimize risks. Available research suggests that risk stratification based on clinical characteristics of the patient has utility in identifying those for whom benefits of HT are likely to outweigh the risks.4-9 Age and time since menopause are strong predictors of health outcomes on HT, and the absolute risks of adverse events are much lower in younger than older women (see Fig. 2).4 Differences by age have been particularly apparent for estrogen alone among women with hysterectomy.4,5 In addition, women at higher baseline cardiovascular risk, due to dyslipidemia, metabolic syndrome, or other cardiometabolic risk factors, have greater risk of adverse vascular outcomes on HT than women at lower risk.2-7 These findings, based on proximity to menopause, underlying cardiovascular risk, and other personal risk factors, have been incorporated into the decision-making process used in this algorithm. Women who are not candidates for, or do not choose to take, HT can be evaluated for non-hormonal treatments. The use of risk stratification and personalized risk assessment offers promise for improved safety and a more favorable benefit:risk profile for both hormonal and non-hormonal treatments.FIG. 2: WHI hormone therapy trials: absolute risks (cases per 10,000 person-years) for outcomes in the intervention phases of the estrogen-progestin and estrogen-alone trials, by age group. Data are from reference 4.DECISION-MAKING PROCESS AND TREATMENT OPTIONS The key elements of the algorithm (Fig. 1) include assessment of whether the patient has moderate to severe vasomotor symptoms (the primary indication for initiating systemic HT); eliciting the patient’s personal preference regarding treatment; evaluating the patient for the presence of any contraindications to systemic HT, as well as the patient’s time since menopause onset and baseline risks of CVD and breast cancer; reviewing the benefits and risks of treatment with the patient (giving more emphasis to absolute than to relative measures of effect) (Fig. 2); and, if HT is initiated, regularly reviewing the patient’s need for continued treatment. If hormonal treatment is chosen, lower doses may be effective for many women, and the transdermal route may be preferable to oral for patients with metabolic syndrome or other significant CVD risk factors. In appropriate patients, a tissue-selective estrogen complex, such as conjugated estrogens combined with bazedoxifene (a selective estrogen receptor modulator) may be an option. A similar process is followed for non-hormonal treatments in women who are not candidates for, or who choose not to take, hormonal therapy. Paroxetine 7.5 mg/d is an FDA-approved non-hormonal medication for vasomotor symptoms; a wide range of other selective serotonin reuptake inhibitors or serotonin/norepinephrine reuptake inhibitors, as well as gabapentin, pregabalin, and clonidine, can be considered. For patients who do not have moderate or severe hot flashes but have significant genitourinary symptoms (vaginal dryness or pain with intercourse/sexual activities) without adequate response to vaginal lubricants and/or moisturizers, low-dose vaginal estrogen is an option. Ospemifene can also be considered for women without contraindications and who prefer a non-estrogen oral treatment. Clinicians should check product labeling for a comprehensive listing of contraindications and cautions for any medications prescribed. Whether or not to initiate systemic HT to prevent osteoporosis is controversial, but if done, current guidelines from NAMS recommend that treatment be limited to women at high risk of osteoporotic fracture who cannot tolerate alternate osteoporosis therapies.2 CONCLUSIONS Risk stratification can be used to identify appropriate candidates for pharmacologic treatment of menopausal symptoms and to facilitate a safer and more personalized approach to clinical decision making. Recent research has advanced our understanding of the benefits and risks of available treatment options and enhanced the ability of both clinicians and patients to make informed choices about treatment. JoAnn E. Manson, MD, DrPH, NCMP1 Jeffrey M. Ames, BS, MEng2 Marla Shapiro, MD, NCMP3 Margery L.S. Gass, MD, NCMP4 Jan L. Shifren, MD, NCMP1 Cynthia A. Stuenkel, MD, NCMP5 JoAnn V. Pinkerton, MD, NCMP6 Andrew M. Kaunitz, MD, NCMP7 Diane T. Pace, PhD, FNP-BC, NCMP8 Risa Kagan, MD, NCMP9 Peter F. Schnatz, DO, NCMP10 Sheryl A. Kingsberg, PhD4 James H. Liu, MD4 Hadine Joffe, MD, MSc1 Gloria Richard-Davis, MD11 Steven R. Goldstein, MD, NCMP12 Isaac Schiff, MD1 Wulf H. Utian, MB, Bch, PhD, DSc (Med)4 Disclaimer: This Application is intended for informational purposes only and is not intended as a substitute for professional medical judgment, diagnosis, or treatment. Users of the app are asked to read and accept an End User License Agreement, available on the app. Financial disclosure/conflicts of interest: JEM, JMA, JLS, MLSG, PFS, IS, and WHU report no disclosures. MS is a consultant/advisory board member for Amgen, Merck, Pfizer and serves on the speakers’ bureau for Amgen, Merck, Novo Nordisk, and Pfizer. CAS has served as a consultant to Pfizer. JVP is a consultant (fees to the University of Virginia) for Pfizer Inc, TherapeuticsMD, Noven, NovoNordisk, and Shionogi. AMK is a consultant/advisory board member for Actavis, Bayer, Teva, and has received grant support from Bayer, Endoceutics, Noven, Teva, and TherapeuticsMD. DTP is a consultant/advisory board member for Hologic and Pfizer. RK is a consultant for Amgen and Merck, is a consultant for and has received payment for lectures/service on speakers’ bureaus for, Pfizer, Novo Nordisk, Noven, and Shionogi, and receives research support from TherapeuticsMD (fees to Sutter Research Institution). SAK serves as a consultant/advisory board member for Apricus, Novo Nordisk, Pfizer, Shionogi, Teva, Trimel Biopharm, and Viveve. JL is on advisory board for Noven, Pfizer, and Shionogi. HJ receives grant support from Cephalon/Teva and serves as a consultant to Noven and on an advisory board for Merck. GRD is a consultant/advisory board member for Pfizer. SRG is a consultant to, and has received payment for lectures/service on speakers’ bureaus for, Shionogi, Pfizer, Noven, and JDS Therapeutics, and is a consultant and has received payment for service for Smith and Nephew.