Guideline sources The following summarized guidelines for the evaluation and management of menopause are prepared by our editorial team based on guidelines from the American Society of Hematology (ASH 2023), the Society of Obstetricians and Gynaecologists of Canada (SOGC 2021; 2017; 2014), the Endocrine Society (ES 2020; 2015), the American College of Obstetricians and Gynecologists (ACOG 2014), the North American Menopause Society (NAMS 2013), the U.S. Preventive Services Task Force (USPSTF 2013), the Society for Cardiovascular Angiography and Interventions (SCAI/PCNA/STS/AATS/ACP/AHA/ACC 2012), and the American Association of Clinical Endocrinologists (AACE 2011). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 Guidelines 1. Screening and diagnosis Diagnostic criteria: Consider diagnosing menopause based on the clinical criteria of the menstrual cycle C https://web.pathway.md/diseases/recrhpm93I0npbDgI 1/15 6/30/23, 1:01 AM Menopause Pathway Consider diagnosing menopause based on the clinical criteria of the menstrual cycle. C Consider making a presumptive diagnosis of menopause based on the presence of vasomotor symptoms and, when indicated, laboratory testing (FSH and serum estradiol), if establishing a diagnosis of menopause is necessary in females having undergone a hysterectomy without bilateral oophorectomy or presenting with a menstrual history inadequate to ascertain menopausal status. C 2. Diagnostic investigations Evaluation of vulvovaginal atrophy: As per SOGC 2021 guidelines, obtain comprehensive screening for genitourinary syndrome of menopause symptoms on an ongoing basis in menopausal females, as symptoms can present insidiously and become bothersome long after the menopausal transition. A As per SOGC 2014 guidelines, address vulvovaginal atrophy in all middle-aged females complaining of sexual dysfunction. A Evaluation of sexual dysfunction: As per SOGC 2021 guidelines: Elicit a sexual screening history and perform a physical examination in the initial evaluation of menopausal females. B Categorize the patient's problem as related to desire, arousal, pain, or orgasm, in order to facilitate treatment and to triage care. B As per SOGC 2014 guidelines, elicit a short sexual screening history as part of a medical history of menopausal females. Obtain interventions only if the patient is distressed about the problem. B Show 2 more Evaluation of vaginal bleeding: As per ES 2015 guidelines, obtain evaluation to rule out pelvic pathology, most importantly, endometrial hyperplasia and cancer in patients with persistent unscheduled bleeding while taking menopausal hormone therapy. B As per SOGC 2014 guidelines, evaluate all patients with postmenopausal bleeding, defines as any unexpected vaginal bleeding occurring after 12 months of amenorrhea. A As per NAMS 2013 guidelines, obtain a thorough evaluation including transvaginal ultrasound and/or endometrial biopsy in postmenopausal patients with an intact uterus presenting with spotting or bleeding. A Cardiovascular risk assessment: As per ES 2020 guidelines, assess and treat lipids and other cardiovascular risk factors in females entering menopause early (< 40-45 years old). B As per ES 2015 guidelines, consider evaluating the baseline risk of CVD and taking this risk into consideration when advising for or against menopausal hormone therapy in females < 60 years https://web.pathway.md/diseases/recrhpm93I0npbDgI 2/15 6/30/23, 1:01 AM Menopause Pathway of age or < 10 years past menopause onset considering hormone therapy for menopausal symptoms. C As per SOGC 2014 guidelines, recognize that a waist circumference 88 cm in females is associated with an increased risk of health problems such as diabetes, heart disease, and hypertension. Measure waist circumference as part of the initial assessment to identify risk. B Show 4 more As per AACE 2011 guidelines, assess smoking status, diabetes history, and family history, and obtain lipid profile to assist in the determination of individual cardiovascular risk. A Evaluation before hormone therapy: avoid obtaining thrombophilia testing to guide the use of hormone-replacement therapy in patients from the general population. D Show 3 more 3. Medical management Management of vasomotor symptoms, hormonal therapy: As per SOGC 2021 guidelines, initiate menopausal hormone therapy as the most effective treatment for menopausal symptoms. A As per ES 2015 guidelines: Consider initiating estrogen therapy (after hysterectomy) or estrogen plus progestogen therapy (without hysterectomy) in menopausal patients < 60 years of age or < 10 years past menopause with bothersome vasomotor symptoms (with or without additional climacteric symptoms) not having contraindications or excess cardiovascular or breast cancer risks and willing to take menopausal hormone therapy. C Consider initiating a combination of conjugated equine estrogens and bazedoxifene, where available and if not contraindicated, as an option for vasomotor symptoms in symptomatic postmenopausal patients with a uterus. C As per SOGC 2014 guidelines: Initiate hormone therapy, estrogen alone or combined with a progestin, as the most effective therapy for menopausal symptoms. A Consider offering progestins alone or low-dose oral contraceptives as alternatives for menopausal symptoms during the menopausal transition. B As per AACE 2011 guidelines: Consider initiating menopausal hormone therapy during the perimenopause and early menopause for menopausal symptoms. Consider initiating menopausal hormone therapy for severe menopausal symptoms in selected postmenopausal patients, on the basis of an individually determined benefit-versus-risk profile. B Administer menopausal hormone therapy in the lowest dose and for the shortest period necessary to control menopausal symptoms. A Management of vasomotor symptoms (tibolone): https://web.pathway.md/diseases/recrhpm93I0npbDgI 3/15 6/30/23, 1:01 AM Menopause Pathway Consider initiating tibolone, if available and not contraindicated, as an alternative to menopausal hormone therapy in patients with bothersome vasomotor and climacteric symptoms. C Do not add tibolone to other forms of menopausal hormone therapy. Do not use tibolone in patients with a history of breast cancer. D Management of vasomotor symptoms, non-hormonal therapy: As per ES 2015 guidelines: Offer selective serotonin-reuptake inhibitors, serotonin norepinephrine-reuptake inhibitors, gabapentin, or pregabalin in patients seeking pharmacological management for moderate-to- severe vasomotor symptoms, if hormone therapy is contraindicated. B Consider offering a trial of clonidine, if not contraindicated, for moderate-to-severe vasomotor symptoms in patients not responding to or tolerating SSRIs, serotonin norepinephrine- reuptake inhibitors, gabapentin, or pregabalin. C As per SOGC 2014 guidelines, consider offering non-hormonal therapies, including certain antidepressant agents, gabapentin, and clonidine, for hot flashes when hormone therapy is contraindicated or not desired. B As per AACE 2011 guidelines, consider offering therapeutic trials of non-hormonal prescription medications, including clonidine, antidepressants (SSRIs), and gabapentin, for menopausal symptoms in patients with no specific contraindications. C Considerations for hormone therapy: As per SOGC 2021 guidelines: Optimize modifiable risk factors, such as weight, smoking, alcohol use, and exercise, in menopausal patients considering hormone therapy. A Prescribe a menopausal hormone therapy regimen, when indicated, conferring the lowest possible breast cancer risk. B As per SOGC 2021 guidelines, initiate menopausal hormone therapy in patients < 60 years of age or less than 10 years post-menopause, if not contraindicated. A Show 5 more As per ES 2015 guidelines, consider using a shared decision-making approach when initiating hormone therapy, and discuss the choice of formulation, starting dose, the route of administration, and how to tailor treatment to each patient's individual situation, risks, and goals. C Show 5 more As per SOGC 2014 guidelines: Review the risks and benefits of prescribing hormone therapy periodically, in light of the association between duration of use and breast cancer risk. A Consider initiating hormone therapy for menopausal symptoms in patients at increased risk of breast cancer, with appropriate counseling and surveillance. B As per NAMS 2013 guidelines: Recognize that: https://web.pathway.md/diseases/recrhpm93I0npbDgI 4/15 6/30/23, 1:01 AM Menopause Pathway estrogen therapy carries a class effect risk of VTE low-dose vaginal estrogen may carry a very low risk but there has been no report of an increased risk in the vaginal estrogen clinical trials insufficient evidence in high-risk patients. B Do not use progestogen generally when low-dose vaginal estrogen is administered for symptomatic vulvovaginal atrophy. D As per USPSTF 2013 guidelines: Do not use combined estrogen and progestogen therapy for the prevention of chronic conditions in postmenopausal patients. D Do not use estrogen therapy for the prevention of chronic conditions in postmenopausal patients after hysterectomy. D Management of vulvovaginal atrophy, lubricants and moisturizers: As per SOGC 2021 guidelines, offer vaginal lubricants and/or vaginal moisturizers as first-line therapy for genitourinary syndrome of menopause, particularly if patient concerns are limited to vaginal dryness or dyspareunia. A As per SOGC 2021 guidelines, consider offering vaginal lubricants and moisturizers for the treatment of vaginal atrophy related to menopause. B As per ES 2015 guidelines: Consider offering vaginal lubricants in patients with insufficient vaginal secretions for comfortable sexual activity. C Consider offering a trial of vaginal moisturizers at least twice weekly in postmenopausal patients with symptoms of vulvovaginal atrophy. C As per SOGC 2014 guidelines, offer vaginal dilators, lubricants, and moisturizers in patients with signs or symptoms of vulvovaginal atrophy unable to use estrogens. B As per NAMS 2013 guidelines, offer nonhormonal lubricants and long-acting vaginal moisturizers (if indicated) as first-line therapy in patients with symptomatic vulvovaginal atrophy. A Management of vulvovaginal atrophy, local estrogen therapy: As per SOGC 2021 guidelines, consider offering vaginal estrogens and DHEA for the treatment of vaginal atrophy related to menopause. B As per SOGC 2021 guidelines: Offer vaginal estrogen, administered either as a cream, tablet, or sustained-release ring as second-line therapy for genitourinary syndrome of menopause. Do not use concomitant progestogen therapy as clinically significant systemic hormone absorption does not occur with low-dose therapy. A Offer vaginal DHEA ovules as another second-line therapy option for atrophic vaginal symptoms. A As per SOGC 2021 guidelines, consider offering local vaginal estrogen, after consulting with the patient's oncologist, if local lubricants and moisturizers are ineffective in patients with breast https://web.pathway.md/diseases/recrhpm93I0npbDgI 5/15 6/30/23, 1:01 AM Menopause Pathway cancer and symptomatic genitourinary syndrome of menopause. C As per ES 2015 guidelines, offer low-dose vaginal estrogen therapy in patients without a history of hormone/estrogen-dependent cancers seeking relief from symptoms of genitourinary syndrome of menopause (including vulvovaginal atrophy) persisting despite using vaginal lubricants and moisturizers. B Show 3 more As per SOGC 2014 guidelines: Offer vaginal estrogen therapy (conjugated estrogen cream, intravaginal sustained-release estradiol ring, or low-dose estradiol vaginal tablets) in postmenopausal patients with vulvovaginal atrophy and sexual dysfunction. A Do not offer progestin co-therapy routinely for endometrial protection in patients receiving vaginal estrogen therapy in an appropriate dose. D As per NAMS 2013 guidelines: Offer low-dose vaginal estrogen therapy or systemic estrogen therapy in patients with moderate-to-severe vulvovaginal atrophy and in patients with milder vulvovaginal atrophy not responding to lubricants and moisturizers. Prefer low-dose vaginal estrogen therapy over systemic estrogen therapy if vulvovaginal atrophy is the only menopausal symptom. A Consider continuing vaginal estrogen therapy with appropriate clinical surveillance as long as bothersome symptoms are present. C As per AACE 2011 guidelines, consider offering transvaginal estrogen to provide topical effects with less systemic absorption. C Management of vulvovaginal atrophy, systemic estrogen therapy: As per SOGC 2021 guidelines, offer oral selective estrogen receptor modulator ospemifene as second-line pharmacotherapy for atrophic vaginal symptoms. A As per SOGC 2021 guidelines, consider offering ospemifene for the treatment of vaginal atrophy related to menopause. B As per ES 2015 guidelines: Consider offering a trial of ospemifene in postmenopausal patients with moderate-to-severe dyspareunia associated with vaginal atrophy, if not contraindicated. C Do not use ospemifene in patients with a history of breast cancer presenting with dyspareunia. D As per NAMS 2013 guidelines: Offer systemic estrogen therapy in patients with moderate-to-severe vulvovaginal atrophy and in patients with milder vulvovaginal atrophy not responding to lubricants and moisturizers. Offer ospemifene for the management of dyspareunia. A Consider continuing ospemifene with appropriate clinical surveillance as long as bothersome symptoms are present. C As per AACE 2011 guidelines, consider offering menopausal hormone therapy during the perimenopause and early menopause for the treatment of vulvovaginal atrophy. B https://web.pathway.md/diseases/recrhpm93I0npbDgI 6/15 6/30/23, 1:01 AM Menopause Pathway Management of vulvovaginal atrophy (vaginal laser therapy): insufficient evidence regarding the long-term use of intravaginal laser therapy to manage genitourinary syndrome of menopause outside of a clinical trial. I Management of sexual dysfunction: As per SOGC 2021 guidelines: Offer the following as the best treatment options for hypoactive sexual desire disorder in postmenopausal patients: pain management addressing biopsychological factors counseling transdermal testosterone (off-label) or flibanserin. B Offer psychological therapies, including cognitive-behavioral therapy, mindfulness-based therapy, couples therapy, and sexual therapies, for the treatment of sexual dysfunctions. B As per SOGC 2014 guidelines: Treat vaginal atrophy, address treatable contributing factors, and provide sexual counseling for the management of decreased sexual desire. A Do not offer treatment if patients have decreased sexual desire but are not distressed. D Management of urinary incontinence: As per SOGC 2021 guidelines, insufficient evidence regarding the long-term use of intravaginal laser therapy to manage stress urinary incontinence outside of a clinical trial. I As per SOGC 2014 guidelines, consider offering vaginal estrogen for the management of urinary urge incontinence. B Show 3 more Management of recurrent UTIs: As per SOGC 2017 guidelines, offer vaginal estrogen to prevent episodes of UTI in postmenopausal patients with recurrent UTIs. A As per SOGC 2014 guidelines, consider offering vaginal estrogen therapy for the prevention of recurrent UTIs in postmenopausal females. B Management of cardiovascular risks: As per SOGC 2021 guidelines, use the lowest effective dose of estrogen, and, where indicated, estrogen-only therapy when prescribing menopausal hormone therapy to minimize the associated risk of VTE. B Show 3 more As per ES 2020 guidelines: Initiate statin therapy, rather than hormone therapy, for the treatment of dyslipidemia in postmenopausal patients. B Initiate statin therapy to reduce cardiovascular risk in postmenopausal patients on hormone therapy and with other risk factors for CVD. A Obtain lipid profile and initiate treatment for dyslipidemia and other cardiovascular risk factors in patients entering menopause early (< 40-45 years of age). B https://web.pathway.md/diseases/recrhpm93I0npbDgI 7/15 6/30/23, 1:01 AM Menopause Pathway As per ES 2015 guidelines: Use the non-oral route of estrogen therapy at the lowest effective dose in patients at increased risk of VTE requesting menopausal hormone therapy, if not contraindicated. B Choose a progestogen having neutral effects on coagulation parameters (such as progesterone or dydrogestone) in patients at increased risk of VTE with an intact uterus. B As per ES 2015 guidelines: Consider offering transdermal estradiol as first-line therapy in patients at moderate risk of CVD, because these preparations have a less untoward effect on BP, triglycerides, and carbohydrate metabolism. Offer transdermal estradiol alone in patients without a uterus. Combine this agent with micronized progesterone or another progestogen (not adversely modifying metabolic parameters) in patients with an intact uterus. C Consider initiating non-hormona therapies, rather than hormone therapy, as first-line treatment for bothersome vasomotor symptoms in patients at high risk of CVD. C As per SOGC 2014 guidelines, initiate evidence-based therapies and interventions to effectively reduce the risk of CVD events in patients with or without vascular disease. A Show 7 more As per AHA 2012 guidelines, do not use estrogen therapy in postmenopausal patients with stable ischemic heart disease with the intent of reducing cardiovascular risk or improving clinical outcomes. D As per AACE 2011 guidelines, do not initiate menopausal hormone therapy for primary or secondary prevention of CVD. D Show 2 more Management of osteoporosis: As per ES 2015 guidelines, consider initiating a combination of conjugated equine estrogens and bazedoxifene, where available and if not contraindicated, for the prevention of bone loss in symptomatic postmenopausal patients with a uterus. C As per AACE 2011 guidelines, initiate menopausal hormone therapy for the prevention and treatment of osteoporosis within the context of the overall benefit-versus-risk analysis of each patient. A Management of cognitive symptoms: As per SOGC 2021 guidelines: Offer the following to decrease the risk of cognitive decline in patients with cognitive complaints: increasing aerobic exercise increasing vegetables in the diet management of hypertension, diabetes, and atherosclerotic disease. A Do not offer menopausal hormone therapy to improve measures of cognitive function. D As per AACE 2011 guidelines, do not use hormone therapy for the prevention or treatment (or both) of dementia. D https://web.pathway.md/diseases/recrhpm93I0npbDgI 8/15 6/30/23, 1:01 AM Menopause Pathway Management of depression: take into account both adverse effects (such as sexual dysfunction, weight changes) and drug-drug interactions (such as between specific SSRIs and tamoxifen) in patients experiencing new-onset depression. B Show 4 more Management of sleep disorders: rule out primary sleep disorders and provide education about sleep hygiene as the initial management of poor sleep during the menopausal transition. A Show 2 more 4. Nonpharmacologic interventions Lifestyle modifications: As per ES 2015 guidelines, consider advising the following nonpharmacologic measures in postmenopausal patients with mild or less bothersome hot flashes: turning down the thermostat dressing in layers avoiding alcohol and spicy foods reducing obesity and stress. C As per SOGC 2014 guidelines, consider advising the following lifestyle modifications to reduce mild vasomotor symptoms: reducing core body temperature regular exercise weight management smoking cessation avoidance of known triggers, such as hot drinks and alcohol. B Show 5 more Smoking cessation: As per SOGC 2014 guidelines: Update tobacco use status on a regular basis. A Advise smoking cessation, assess the willingness of patients to begin treatment to achieve abstinence, and assist every tobacco user who expresses the willingness to quit. B As per AACE 2011 guidelines, counsel patients regarding the increased risk of cardiovascular and venous thromboembolic disease with smoking when taking estrogens. Offer aggressive smoking cessation programs. A Alternative medicine: As per ES 2015 guidelines, consider counseling females seeking relief of vasomotor symptoms with OTC or complementary medicine therapies regarding the lack of consistent evidence for benefit of botanicals, black cohosh, omega-3 fatty acids, red clover, vitamin E, and mind/body alternatives including anxiety control, acupuncture, paced breathing, and hypnosis. C https://web.pathway.md/diseases/recrhpm93I0npbDgI 9/15 6/30/23, 1:01 AM Menopause Pathway As per SOGC 2014 guidelines, consider offering complementary and alternative medicine interventions with demonstrated efficacy in the management of patients with mild menopausal symptoms. B As per AACE 2011 guidelines: Be cautious when using OTC supplements because they are not regulated by the U.S. FDA and have the potential to interact with drugs and cause harm. B Insufficient evidence to support the use of phytoestrogens including soy-derived isoflavonoids. Do not offer soy-based therapies in patients with a personal or strong family history of hormone-dependent cancers (breast, uterine, or ovarian), thromboembolic events, or cardiovascular events because these compounds may have estrogenic effects. I 5. Specific circumstances Patients with early menopause: As per SOGC 2021 guidelines, consider initiating HRT in patients with loss of ovarian function or with decreased ovarian function before the age of 45 years, continued until the average age of menopause. B As per ES 2015 guidelines, consider continuing hormone therapy in young patients with primary ovarian insufficiency, premature or early menopause, without contraindications, until the time of anticipated natural menopause, when the advisability of continuing menstrual hormone therapy can be reassessed. C As per SOGC 2014 guidelines, initiate hormone therapy in patients with premature ovarian failure or early menopause A , and continue until the natural age of menopause. B Show 3 more Patients with breast cancer: As per SOGC 2021 guidelines, offer paced breathing, acupuncture, and cognitive-behavioral therapy as nonpharmacological options for the management of vasomotor symptoms in patients with breast cancer. B Show 5 more As per ES 2015 guidelines: Consider using a shared decision-making approach to include the treating oncologist in discussing the use of low-dose vaginal estrogen in patients with a history of breast cancer presenting with symptomatic genitourinary syndrome of menopause (including vulvovaginal atrophy) and not responding to non-hormonal therapies. C Insufficient evidence to recommend vaginal estrogens in patients with breast cancer receiving aromatase inhibitors (where the goal of adjuvant therapy is a complete absence of estrogen at the tissue level). Its use in this circumstance needs to be dictated by quality-of-life concerns after discussion of possible risks. I As per SOGC 2014 guidelines, counsel patients with breast cancer using aromatase inhibitors that these medications may have sexual effects. B https://web.pathway.md/diseases/recrhpm93I0npbDgI 10/15 6/30/23, 1:01 AM Menopause Pathway Show 2 more As per NAMS 2013 guidelines, manage patients with a history of breast cancer depending on the patient's preference, need, understanding of potential risks, and consultation with her oncologist. B Patients with endometrial cancer: As per ES 2015 guidelines, consider using a shared decision-making approach to include the treating oncologist in discussing the use of low-dose vaginal estrogen in patients with a history of endometrial cancer presenting with symptomatic genitourinary syndrome of menopause (including vulvovaginal atrophy) and not responding to non-hormonal therapies. C As per NAMS 2013 guidelines: Consider obtaining surveillance transvaginal ultrasound or initiating intermittent progestogen therapy in patients at high risk of endometrial cancer or using a higher dose of vaginal estrogen therapy. Insufficient evidence to recommend routine annual endometrial surveillance in asymptomatic females using vaginal estrogen therapy. C Manage patients with a history of endometrial cancer depending on the patient's preference, need, understanding of potential risks, and consultation with her oncologist. B Patients with hormone-independent cancer: manage vulvovaginal atrophy in patients treated for non-hormone-dependent cancer similar to that for patients without a cancer history. B 6. Patient education General counseling: As per SOGC 2021 guidelines, educate females entering menopause about the progressive impact of estrogen deficiency on urogenital health and the many options available for symptom relief. A As per ES 2015 guidelines: Consider counseling females presenting during the menopausal transition regarding bone health, smoking cessation, alcohol use, cardiovascular risk assessment and management, and cancer screening and prevention. C Inform patients about the possible increased risk of breast cancer during and after discontinuing estrogen-progestin therapy and emphasize the importance of adhering to age- appropriate breast cancer screening. B As per SOGC 2014 guidelines, recognize that aging women are sexual and have sexual needs but may be unwilling to initiate a discussion about problems. B Show 4 more As per NAMS 2013 guidelines, provide proactive education on vaginal health in postmenopausal females. B As per AACE 2011 guidelines, inform patients that cerebrovascular accidents occur with increased frequency in patients taking estrogen alone or a combination of estrogen and progestational agent in an age-dependent manner. A https://web.pathway.md/diseases/recrhpm93I0npbDgI 11/15 6/30/23, 1:01 AM Menopause Pathway Show 2 more Clinical findings Patient demographics Symptoms Age 50 Amenorrhea Anxiety Past medical history Change in menstrual flow Chills Dementia Decreased libido Depression Dyspareunia Dyslipidemia Dysuria Exposure to chemotherapy Heat intolerance Exposure to radiation therapy Hirsutism Hip fracture Hot flashes Osteoporosis Irregular periods Recurrent UTIs Loss of breast fullness Vulvovaginal atrophy Menstrual irregularity Gynecologic exam Mood changes Night sweats Vaginal dryness Palpitations Patient thinks she is perimenopausal Integument exam Clammy skin Sexual dysfunction Skin dryness Sleeping disorder Sweating Imaging findings Thinning hair Urinary incontinence Vertebral fracture Vaginal itching Weight gain Past surgical history Hysterectomy Oophorectomy Breast exam Breast atrophy Lab findings serum FSH serum estrogen serum inhibin https://web.pathway.md/diseases/recrhpm93I0npbDgI 12/15 6/30/23, 1:01 AM Menopause Pathway Likelihood Ratios Pertinent positives The following findings increase the probability of menopause in adults. 16 Finding LR+ Value History of amenorrhea 20 Presence of age 50 17.5 Increased serum FSH (> 20-24 mIU/mL) 4.9 History of menstrual irregularity 3.5 Show 6 more Pertinent negatives The following findings decrease the probability of menopause in adults. 16 Finding LR- Value No history of patient thinks she is perimenopausal 0.3 No history of menstrual irregularity 0.4 serum FSH not increased ( 20-24 mIU/mL) 0.4 No history of change in menstrual flow 0.6 Show 6 more Studies 2023 FRAN In perimenopausal or postmenopausal women reporting 7 hot flashes per day, nitroglycerin was not superior to placebo with respect to reduction in hot flash frequency per day at week 5. Alison J Huang et al. JAMA Intern Med. 2023 Jun 5. 2002 WHI In healthy postmenopausal women aged 50-79 years with an intact uterus at baseline, estrogen plus progestin was inferior to placebo with respect to nonfatal myocardial infarction or cardiovascular death. Rossouw JE et al. JAMA. 2002 Jul 17. References 1. Stuenkel CA, Davis SR, Gompel A et al. Treatment of Symptoms of the Menopause: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2015 Nov;100 11 3975 4011. Open https://web.pathway.md/diseases/recrhpm93I0npbDgI 13/15 6/30/23, 1:01 AM Menopause Pathway 2. Saskia Middeldorp, Robby Nieuwlaat, Lisa Baumann Kreuziger et al. American Society of Hematology 2023 Guidelines for Management of Venous Thromboembolism: Thrombophilia Testing. Blood Adv. 2023 May 17;bloodadvances.2023010177. Open 3. Reid R, Abramson BL, Blake J et al. Managing Menopause. J Obstet Gynaecol Can. 2014 Sep;36 9 830 833. Open 4. Wendy Wolfman, Yonah Krakowsky, Michel Fortier. Guideline No. 422d: Menopause and Sexuality. J Obstet Gynaecol Can. 2021 Nov;43 11 1334 1341.e1. Open 5. Shawna Johnston, C line Bouchard, Michel Fortier et al. Guideline No. 422b: Menopause and Genitourinary Health. J Obstet Gynaecol Can. 2021 Nov;43 11 1301 1307.e1. Open 6. Nese Yuksel, Debra Evaniuk, Lina Huang et al. Guideline No. 422a: Menopause: Vasomotor Symptoms, Prescription Therapeutic Agents, Complementary and Alternative Medicine, Nutrition, and Lifestyle. J Obstet Gynaecol Can. 2021 Oct;43 10 1188 1204.e1. Open 7. North American Menopause Society. Management of symptomatic vulvovaginal atrophy: 2013 position statement of The North American Menopause Society. Menopause. 2013 Sep;20 9 888 902. Open 8. Neil F Goodman, Rhoda H Cobin, Samara Beth Ginzburg et al. American Association of Clinical Endocrinologists Medical Guidelines for Clinical Practice for the diagnosis and treatment of menopause. Endocr Pract. Nov-Dec 2011;17 Suppl 6 1 25. Open 9. Michelle Jacobson, Kelsey Mills, Gillian Graves et al. Guideline No. 422f: Menopause and Breast Cancer. J Obstet Gynaecol Can. 2021 Dec;43 12 1450 1456.e1. Open 10. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 141 management of menopausal symptoms. Obstet Gynecol. 2014 Jan;123 1 202 16. Open 11. Alison K Shea, Wendy Wolfman, Michel Fortier et al. Guideline No. 422c: Menopause: Mood, Sleep, and Cognition. J Obstet Gynaecol Can. 2021 Nov;43 11 1316 1323.e1. Open 12. Fihn SD, Gardin JM, Abrams J et al. 2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guideline for the diagnosis and management of patients with stable ischemic heart disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association task force on practice guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. Circulation. 2012 Dec 18;126 25 3097 137. Open 13. Connie B Newman, Michael J Blaha, Jeffrey B Boord et al. Lipid Management in Patients with Endocrine Disorders: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2020 Dec 1;105 12):dgaa674. Open 14. Annette Epp, Annick Larochelle. No. 250 Recurrent Urinary Tract Infection. J Obstet Gynaecol Can. 2017 Oct;39 10):e422-e431. Open 15. Moyer VA, U.S. Preventive Services Task Force. Menopausal hormone therapy for the primary prevention of chronic conditions: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2013 Jan 1;158 1 47 54. Open 16. Beth L Abramson, Denise R Black, Marie K Christakis et al. Guideline No. 422e: Menopause and Cardiovascular Disease. J Obstet Gynaecol Can. 2021 Dec;43 12 1438 1443.e1. Open https://web.pathway.md/diseases/recrhpm93I0npbDgI 14/15 6/30/23, 1:01 AM Menopause Pathway 17. Kahwati LC, Haigler L, Rideout S et al. What is the best way to diagnose menopause?. J Fam Pract. 2005 Nov;54 11 1000 2. Open 18. US Preventive Services Task Force, Grossman DC, Curry SJ et al. Hormone Therapy for the Primary Prevention of Chronic Conditions in Postmenopausal Women: US Preventive Services Task Force Recommendation Statement. JAMA. 2017 Dec 12;318 22 2224 2233. Open 19. Seung Ah Choe, Joohon Sung. Trends of Premature and Early Menopause: a Comparative Study of the US National Health and Nutrition Examination Survey and the Korea National Health and Nutrition Examination Survey. J Korean Med Sci. 2020 Apr 13;35 14):e97. Open 20. Ellen B Gold. The timing of the age at which natural menopause occurs. Obstet Gynecol Clin North Am. 2011 Sep;38 3 425 40. Open 21. Bjarne K Jacobsen, Ivar Heuch, Gunnar Kv le. Age at natural menopause and all-cause mortality: a 37- year follow-up of 19,731 Norwegian women. Am J Epidemiol. 2003 May 15;157 10 923 9. Open 22. Matthew Sussman, Jeffrey Trocio, Craig Best et al. Prevalence of menopausal symptoms among mid- life women: findings from electronic medical records. BMC Womens Health. 2015; 15 58. Open 23. Michelle Jacobson, Marcus Bernardini, Mara L Sobel et al. No. 366 Gynaecologic Management of Hereditary Breast and Ovarian Cancer. J Obstet Gynaecol Can. 2018 Nov;40 11 1497 1510. Open 24. Monika Sarkar, Carla W Brady, Jaquelyn Fleckenstein et al. Reproductive Health and Liver Disease: Practice Guidance by the American Association for the Study of Liver Diseases. Hepatology. 2021 Jan;73 1 318 365. Open 25. Samuel Lederman, Faith D Ottery, Antonio Cano et al. Fezolinetant for treatment of moderate-to- severe vasomotor symptoms associated with menopause SKYLIGHT 1 a phase 3 randomised controlled study. Lancet. 2023 Mar 13;S0140 6736 23 00085 5. Open 26. Alison J Huang, Steven R Cummings, Peter Ganz et al. Efficacy of Continuous Transdermal Nitroglycerin for Treating Hot Flashes by Inducing Nitrate Cross-tolerance in Perimenopausal and Postmenopausal Women: A Randomized Clinical Trial. JAMA Intern Med. 2023 Jun 5;e231977. Open https://web.pathway.md/diseases/recrhpm93I0npbDgI 15/15