PDF Summary:The New Menopause, by Mary Claire Haver

Menopause brings significant changes to a woman's body, but many women lack clear information about what to expect and how to manage it. In The New Menopause, Dr. Mary Claire Haver explains the physiological changes that occur during menopause and how declining estrogen levels affect various systems in the body—from gastrointestinal health to cardiovascular risk to cognitive function.

Haver covers the stages of menopause and the health risks associated with hormonal changes, including increased visceral fat, muscle loss, heart disease, and Alzheimer's disease. She also discusses management strategies, with particular attention to menopausal hormone therapy (MHT): its benefits, risks, and considerations for different health situations. This guide provides practical information to help women understand menopause and make informed decisions about their health during this transition.

(continued)... The authors also propose an algorithm for identifying and staging sarcopenia:

• Find cases: Use the SARC-F questionnaire to identify individuals at risk.
• Assess: Measure muscle strength, muscle quantity/quality, and physical performance.
• Confirm: Diagnose sarcopenia if muscle strength and muscle quantity/quality are below the cut-off points.
• Stage: Classify sarcopenia as severe if physical performance is also below the cut-off points.)

Addressing and avoiding sarcopenia involves combining top-notch nutrition and exercise to boost muscular strength and performance. Since inflammation could contribute to the deterioration of muscle tissue, consuming lots of anti-inflammatory foods, cutting back on alcohol, avoiding smoking, sleeping well, and reducing stress will safeguard important muscle tissue. Helpful nutritional tactics include increasing consumption of vegetables and fruit, consuming a minimum of 1.2 grams of protein per kilogram of body weight daily, and having a high-protein meal or shake with 20 grams of protein shortly after exercising to aid muscle development and preservation.

(Shortform note: While the protein recommendations above are generally safe for most women, nutrition researchers warn that women with moderate or advanced chronic kidney disease (CKD) should be cautious about increasing their protein intake. In one research article, the authors explain that high-protein diets can worsen kidney function in people with CKD. They recommend that women with CKD consult their doctor before making significant changes to their diet, especially if they’re considering adding a 20-gram protein shake after workouts.)

Besides protein from your diet, ensure you have sufficient vitamin D and calcium, as they are vital for bone support. Sarcopenia and osteoporosis are linked by how they affect the health of muscles and bones, as well as overall bodily functioning. Sufficient calcium and vitamin D are essential to manage and avoid both conditions. Calcium contributes to healthy bones, and vitamin D assists with calcium uptake and supports muscle function. For those facing the risk of osteoporosis and sarcopenia, or currently experiencing these conditions, it's essential to seek advice from healthcare professionals to evaluate your unique dietary requirements and create a tailored strategy for sustaining musculoskeletal well-being and preventing fractures and muscle deterioration.

(Shortform note: While vitamin D and calcium are essential for bone health, some studies have raised concerns about the potential cardiovascular risks associated with high-dose calcium supplementation. Bolland et al. (2010) found that calcium supplements, with or without vitamin D, were associated with a modest but significant increase in the risk of myocardial infarction (heart attack) in postmenopausal women. The authors suggest that the increased risk may be due to the acute elevation of serum calcium levels following supplementation, which could promote vascular calcification and atherosclerosis.)

The best workout plan for managing sarcopenia seems to be one that includes aerobic exercise along with strength training. Regular resistance exercise is essential to avoiding sarcopenia, as it's been proven to assist in building and maintaining muscle mass and strength.

(Shortform note: To create a workout plan that combines aerobic exercise with strength training, choose two days a week to do strength training and two days a week to do aerobic exercise. Then, create a cue for each workout.)

Increased Disease Risks Linked to Menopause

Haver notes that menopause raises the likelihood of cardiovascular disease in which plaque composed of fats and cholesterol accumulates in the arteries, restricting the flow of blood rich in oxygen to the heart. It's the top cause of death for women, and the likelihood of getting it rises at about 55 years old, when most women are postmenopausal. Menopause raises the risk of coronary artery disease because it increases cholesterol, LDL, and triglycerides, which are linked to heart disease. It also causes more constriction in blood vessels, boosts the creation of proteins that cause blood to coagulate, and decreases the production of hormones that aid the relaxation of the vascular system and enable smooth blood flow. These elements together pose a significant risk to cardiovascular wellness.

(Shortform note: Menopause was recognized as a cardiovascular disease risk factor when medical researchers noticed that women’s risk of cardiovascular disease increased after menopause. This was based on long-term studies that tracked women’s health over time. These studies showed that women’s risk of cardiovascular disease increased after menopause, even when other risk factors like age, smoking, and high blood pressure were taken into account. This led researchers to conclude that menopause itself was a risk factor for cardiovascular disease. A medical review article and an academic paper both discuss how menopause was recognized as a cardiovascular disease risk factor.)

Coronary artery disease risk factors include a family history of heart disease, elevated cholesterol, diabetes, high blood pressure, smoking or past smoking, long-term secondhand smoke exposure, prolonged exposure to air pollution or other environmental toxins, being overweight or obese, and physical inactivity. You may also have a heightened likelihood if you went through menopause before turning 45, underwent surgical menopause, or experienced severe menopause-related symptoms like night sweats and hot flashes. Coronary artery illness rarely shows symptoms until a rupture occurs or it becomes so severe that blood flow is blocked, and effective screening tests aren't available.

(Shortform note: In addition to the risk factors Haver lists, researchers have found that women who experience preeclampsia during pregnancy are at a higher risk of developing coronary artery disease. Preeclampsia is a condition that causes high blood pressure and organ damage during pregnancy. According to medical researchers, women with a history of preeclampsia have a twofold increased risk of developing coronary artery disease later in life compared to women who had normal pregnancies. This increased risk persists even after accounting for other traditional risk factors like high blood pressure and diabetes.)

Your yearly checkup will involve assessing your weight, cholesterol, and blood pressure, factors that can elevate heart disease risk if they are high. However, these tests don't offer a thorough look at the state of your arteries. A more thorough evaluation is a coronary calcium score assessment, which uses a CT scan to examine the extent of plaque or calcium accumulation that could be found in the coronary arteries. A test measuring coronary calcium can indicate the presence or likelihood of coronary heart disease.

(Shortform note: Coronary calcium scoring is not recommended for people who are at low risk for cardiovascular disease, as it rarely changes treatment decisions. For those at intermediate risk, the test can help guide decisions about starting statin therapy. However, for people at high risk, treatment is typically recommended regardless of the calcium score. The test is most useful for people who are uncertain about their risk level or who are hesitant to start medication. It’s important to discuss with your doctor whether this test is appropriate for you based on your individual risk factors and health history.)

Hormone replacement therapy can greatly decrease the likelihood of developing cardiovascular disease and overall mortality when administered to women under the age of 60 who are at or near menopause, within 10 years of the transition. But if you begin MHT more than a decade after menopause, your chances of developing cardiovascular disease might rise—and that likelihood increases even more if over two decades have passed.

(Shortform note: Despite the benefits of MHT, the U.S. Preventive Services Task Force (USPSTF) recommends against using it to prevent chronic conditions like heart disease or stroke. The Task Force argues that the potential harms of hormone therapy outweigh the benefits for this purpose. They cite increased risks of blood clots, stroke, gallbladder disease, and urinary incontinence. The Task Force also notes that hormone therapy may increase the risk of dementia in women over 65.)

Haver also points out that menopause can cause cells to lose sensitivity to insulin, resulting in elevated blood sugar levels. The initial stage of a metabolic disorder is resistance to insulin. If left unchecked, it can lead to prediabetes and type two diabetes. It can also cause a collection of conditions known as metabolic syndrome, which increases the likelihood of developing type 2 diabetes, coronary artery disease, and stroke. Metabolic syndrome might feature raised glucose levels in the blood, elevated triglycerides, reduced HDL cholesterol, and increased blood pressure. Declining estrogen during menopause makes women more likely to develop insulin resistance.

(Shortform note: Rodrigo P. Barros and Jan-Åke Gustafsson explain that estrogen helps regulate how the body uses fats and sugars. When estrogen levels drop, the body starts storing more fat in the liver and muscles. This extra fat interferes with how insulin works inside cells. Normally, insulin helps cells take in sugar from the blood, but when there’s too much fat inside the cells, it blocks insulin’s signals. This makes it harder for the body to control blood sugar levels, leading to insulin resistance.)

Estrogen is vital for processing glucose, and when it's lacking, it may cause issues with metabolism. The likelihood of insulin resistance related to decreasing estrogen doesn't depend on age, so even younger women who enter menopause early might face a risk of developing it. Carrying excess weight around your midsection and lacking physical activity are major contributors to insulin resistance. Additional risks include PCOS, obstructive sleep disorder, liver disease from fat buildup, and certain medications. Hypothyroidism or Cushing's syndrome can raise your risk. Early signs of insulin resistance may not be obvious.

(Shortform note: Cushing's syndrome is a hormonal disorder that occurs when your body is exposed to high levels of the stress hormone cortisol for a long time. Cortisol is produced by the adrenal glands, which sit on top of your kidneys. Normally, cortisol helps your body respond to stress, maintain blood pressure, and regulate metabolism. But when you have too much cortisol, it can cause a range of symptoms and health problems.)

However, if your pancreas needs to increase insulin production to counteract insulin resistance, and your insulin levels stay elevated, you might have increased triglycerides and blood pressure. If you have low HDL cholesterol along with either condition, you possess at least one component of metabolic syndrome and likely have elevated insulin levels. It's important to closely monitor your glucose levels in this situation. Haver explains that in her practice, she evaluates the hemoglobin A1C and fasting glucose levels of every patient, and if particular risk factors exist, she tests fasting insulin and determines a HOMA-IR score. The HOMA-IR measurement, which assesses resistance to insulin, is determined using fasting levels of insulin and blood sugar. If you think you might be susceptible to insulin resistance, she recommends that you speak up and request that your doctor perform this test.

Is the HOMA-IR Test Necessary?

While Haver recommends that you request a HOMA-IR test if you’re concerned about insulin resistance, medical researchers suggest that this test isn’t always necessary. In a medical research article, researchers explain that the HOMA-IR test was developed for research purposes, not for clinical use. They argue that the test is most useful for studying groups of people, not for diagnosing or treating individual patients. They also point out that the test can be misleading if not used correctly, and that it doesn’t provide much additional information beyond what standard diabetes tests already show. Therefore, they recommend that doctors use the HOMA-IR test only in specific cases where it might provide unique insights, rather than as a routine screening tool.

Finally, Haver says that menopause may increase the likelihood of getting Alzheimer's disease. Neuroinflammation refers to the swelling that happens in the central nervous system, which can harm neurons crucial for cognitive processes. Alzheimer’s risk for women is twice that for men, a disparity traditionally explained by women’s longer life expectancy and the heightened Alzheimer’s risk that aging brings. However, new studies have identified an additional factor: the significant hormonal shifts that occur throughout menopause. These changes, particularly estrogen depletion, may raise neuroinflammation and speed up brain aging in women. The aging process during menopause may raise the likelihood of Alzheimer's disease in women.

The APOE ε2 Gene Variant and Alzheimer’s Disease

While menopause may increase the likelihood of developing Alzheimer’s disease for most women, this may not be the case for women with certain genetic variations. According to Liu et al., the APOE ε2 gene variant is associated with a significantly reduced risk of late-onset Alzheimer’s disease. Individuals with one or two copies of the ε2 allele have a much lower incidence of Alzheimer’s and a delayed onset compared to those with the more common ε3 allele or the high-risk ε4 allele. The protective effect of ε2 is dose-dependent, meaning that having two copies of the allele provides even greater protection than having just one. This strong genetic resistance to Alzheimer’s may counteract the increased risk associated with menopause, suggesting that women with the ε2 variant might not experience the same heightened likelihood of developing Alzheimer’s disease during menopause as those without this genetic protection.

Coping With and Managing Menopause

We’ll start by discussing MHT, or hormonal therapy for menopause.

Evaluating Hormone Therapy for Menopause

Haver explains that the advantages and disadvantages of MHT should be assessed for each individual. The benefits are greatest for people within 10 years of menopause, while the risks are highest for individuals who have a history of hormone-sensitive cancers, unexplained vaginal bleeding, blood clotting disorders, severe liver disease, or allergies to MHT components.

(Shortform note: When considering whether to start MHT, it may be helpful to think of it as a shared decision-making process with your clinician. This means that you and your clinician work together to weigh the benefits and risks of MHT, taking into account your individual health history, preferences, and values. The key question to ask yourself is: How much risk are you willing to accept in exchange for relief from your menopausal symptoms?)

She also notes that progesterone must be used alongside estrogen for those with a uterus to prevent uterine lining overgrowth. It counteracts estrogen's impact on the endometrium. Estrogen makes the uterine lining thicker, and without the balance of progesterone, it may develop abnormally. Progesterone is also helpful for sleep and can relieve night sweats, headaches, vaginal dryness, mood swings, and hot flashes.

(Shortform note: The rule that you must use progesterone with estrogen if you have a uterus doesn’t apply to all forms of estrogen therapy. According to Stephanie S. Faubion, JoAnn V. Pinkerton, and the North American Menopause Society Position Statement Advisory Panel, low-dose vaginal estrogen preparations used for the treatment of genitourinary syndrome of menopause have minimal systemic absorption, and therefore the addition of a progestogen for endometrial protection is not recommended for women with an intact uterus.)

Let’s examine the effects of MHT, including its benefits and risks, and the safety and considerations for implementing it.

MHT: Advantages and Dangers

According to Haver, MHT can offer benefits like reducing the chance of cardiovascular problems and easing menopausal symptoms, but it also carries potential risks, especially if started late. MHT can help with symptoms like vasomotor symptoms, sleep issues, bone density reduction, genitourinary symptoms, decreased muscle mass, cognitive decline, joint pain, depression, and skin and hair thinning. It can also aid glycemic control in women with type 2 diabetes. Haver says that MHT can help lower cholesterol and decrease the likelihood of heart disease.

(Shortform note: If you have type 2 diabetes, glycemic control refers to how well your blood sugar stays within a healthy range over time. It’s not just about a single reading, but about your overall blood sugar patterns. Good glycemic control means your blood sugar doesn’t swing too high or too low, which helps prevent complications. Doctors use tests like A1C to see your average blood sugar over a few months, giving a clearer picture than just a single finger-prick test.)

However, if you already have high triglycerides, oral estrogen can increase them, so you might need to use a lower dose or a different form of MHT. If you possess a uterus, you ought to combine estrogen with a progestogen to safeguard the endometrial lining. Beginning MHT over a decade following menopause can raise your chances of cardiovascular issues and dementia. If you already have coronary artery disease, MHT can make it worse. If MHT is suitable for you, it’s best to start it during the decade following menopause. If you're over 60 or more than a decade past menopause and have never used MHT, Haver suggests undergoing a test for coronary calcium before beginning any type of MHT with estrogen.

(Shortform note: This test exposes you to a small amount of ionizing radiation, which can damage your DNA and increase your risk of cancer. While the risk from a single scan is low, it’s still a potential harm that should be weighed against the benefits of the test.)

Implementing Hormone Therapy for Menopause: Safety and Considerations

Haver explains that MHT is not dangerous for the majority of females who are up to a decade past menopause. It’s the most effective way to reduce menopause-related health risks and symptoms, and it can cut the likelihood of cardiovascular disease in half. However, it's unsafe for everyone. You shouldn't use MHT if you have breast cancer, had it previously, or have other cancers sensitive to estrogen or progestogen, unexplained vaginal bleeding, arterial or venous thromboembolic disease, significant liver impairment, or an allergy to any of the components of MHT. It’s also not safe to use MHT during pregnancy.

How to Decide Whether to Take MHT

If you’re not sure whether to take MHT, you might benefit from a shared decision-making process. This involves your doctor providing you with numerical estimates of your personal risk of developing certain conditions, such as breast cancer, and your risk of experiencing certain symptoms, such as hot flashes. You then consider these numbers in light of your personal preferences. For example, if you have a high risk of developing breast cancer, you might decide that you don’t want to take MHT. On the other hand, if you have a high risk of developing osteoporosis, you might decide that you do want to take MHT. This process can help you make a more informed decision about whether to take MHT.

Haver adds that a contraindication refers to a particular situation or justification for avoiding a drug or procedure due to potential harm to the person. For instance, MHT can promote the development of hormone-sensitive cancers, so it's not suggested for people who have a history of them. MHT may be dangerous for those with severe liver damage, as they might have difficulty properly metabolizing hormones.

Why Are Hormone-Sensitive Cancers and Severe Liver Damage Contraindications for MHT?

The reason that hormone-sensitive cancers and severe liver damage are contraindications for MHT is that clinical trials have shown that women with these conditions who take MHT experience more adverse events than those who don’t. For example, a 2022 review of clinical trials found that women with a history of hormone-sensitive cancers who took MHT had a higher risk of cancer recurrence than those who didn’t. Similarly, a 2021 review of clinical trials found that women with severe liver damage who took MHT had a higher risk of liver failure than those who didn’t.

Haver says that MHT is not automatically unsafe for women whose families have certain diseases in their history. Having relatives with cardiac, hepatic, or breast cancer issues doesn’t automatically disqualify you from MHT. The latest research and expert consensus challenge the notion that family history alone should disqualify a woman from MHT candidacy.

(Shortform note: This shift in thinking reflects a broader move away from rigid “no-MHT” rules based on single risk factors toward a more nuanced, shared decision-making approach. Instead of automatically denying MHT to women with a family history of certain diseases, doctors now weigh the overall risk profile against the severity of menopausal symptoms. This patient-centered model recognizes that for many women, the benefits of MHT in improving quality of life may outweigh potential risks, even in the presence of certain family histories.)

Haver explains that MHT could be suitable for some cancer survivors, but it necessitates careful thought. Recent research suggests that MHT doesn't heighten the chance of a recurrence in those with early stages of endometrial cancer, cervical cancer, cancer of the vagina or vulva, or epithelial ovarian cancer. However, it should not be used by people who have previously had breast cancer.

(Shortform note: The idea that some cancer survivors can use MHT while breast cancer survivors generally should not is a relatively recent development in medicine. In a medical review article, gynecologic oncologists explain that the field of cancer survivorship medicine has emerged in the past 20 years as more people survive cancer and live longer after treatment. This new field has led to a re-evaluation of MHT for gynecologic cancer survivors, balancing the risk of cancer recurrence against the long-term health effects of untreated menopause.)

A 2022 study of more than 8,000 Danish survivors of postmenopausal breast cancer found that vaginal estrogen and MHT didn't raise the likelihood of cancer coming back or dying from it. However, it did find a heightened chance of recurrence for those who used vaginal estrogen while taking aromatase inhibitors.

(Shortform note: Years before the Danish study, medical researchers had already warned that vaginal estrogen could be risky for women taking aromatase inhibitors. In 2006, oncology researchers published a research article showing that vaginal estradiol tablets raised blood estradiol levels in postmenopausal women with breast cancer who were on aromatase inhibitors.)

Carrying BRCA1 and BRCA2 mutations heightens the likelihood of getting breast and ovarian cancer, and you may have received conflicting information about MHT. The research here categorizes BRCA carriers into two sets: those who underwent preventive surgery to remove the ovaries—called a bilateral salpingo-oophorectomy (BSO) to lower risk—and people who didn't. Studies indicate that MHT use doesn't raise breast cancer risk for people who've undergone an RRBSO. Because RRBSOs might be suggested for young women, it's especially important to undergo hormone therapy to help lower the likelihood of developing chronic conditions like osteoporosis and heart problems, which can arise from low estrogen levels. If you haven't undergone an RRBSO, consult your physician regarding your choices.

How to Decide on an RRBSO and MHT

If you carry a BRCA mutation and haven’t had an RRBSO, you might find it helpful to weigh your personal risk factors against your life plans and values. For example, you might want to consider the likelihood of developing cancer at different ages and how that aligns with your family planning, career goals, and quality of life. You might also want to consider how MHT could help manage symptoms and reduce long-term health risks after surgery. By discussing these factors with a specialist, you can make a more informed decision about whether and when to proceed with an RRBSO and MHT.