Tag Archive for: women’s health

By Sophia Fay, BS

Headshot of Dr. Marcia Stefanick

Marcia L. Stefanick, PhD has spent her career changing the way medicine understands both the differences and similarities in health across sex and gender. A professor of medicine at Stanford and a leading researcher in women’s health and sex differences, she has dedicated decades to advocating for the inclusion of women in clinical trials and challenging outdated medical norms. As a principal investigator in the landmark Women’s Health Initiative (WHI) and co-founder of Stanford’s Women’s Health and Sex Diversity in Medicine (WHSDM) Center, Dr. Stefanick has shaped public health policies and medical guidelines that continue to influence patient care all over the world.

“I’m interested in everything that relates to sex and gender across the life course,” says Dr. Stefanick. “My research has been very autobiographical—I first studied the menstrual cycle, then pregnancy complications, then midlife and menopause, and now aging.”

Early Life and Career Path

Born in Western Pennsylvania into a family of seven children, Dr. Stefanick developed an early curiosity about sex differences—wondering why puberty affected her brothers differently and why societal expectations varied by gender.

“I was always trying to figure out—when my brothers went through puberty, is that going to happen to me? Why do they get to do certain things, and I don’t? That made me interested in both biology and gender norms,” says Dr. Stefanick.

After spending a year in Germany as a Rotary International Exchange student, she pursued a degree in biology from the University of Pennsylvania, where she became interested in sex differences, particularly in primate behavior.

“When I graduated, I had hoped to study lowland gorillas in Africa, which led me to the Oregon Regional Primate Center. There, I became a research assistant in a sex hormone laboratory and developed a deeper interest in hormones and behavior and neuroendocrinology. This motivated me to pursue a PhD in Physiology with Julian Davidson at Stanford,” says Dr. Stefanick.

During graduate school, she realized she was not meant to be an animal researcher. Seeking a new direction, she connected with researchers at the Stanford Prevention Research Center (SPRC) who were focusing on physical activity and heart disease prevention.

Breaking Barriers in Research

At the SPRC, Dr. Stefanick’s research in the early 1990s primarily focused on body composition, weight loss, and exercise’s impact on cardiovascular risk. At the time, clinical trials were overwhelmingly conducted on men.

Her first two trials—one on exercise and HDL cholesterol and the other on diet, exercise, and weight loss—only included men because that was all that was funded. Frustrated by this, she refused to conduct another male-only study, successfully pushing for the inclusion of pre-menopausal and post-menopausal women in subsequent research.

“I told them, ‘I’m not doing another study without women. We have to include women in our research and not only study men’,” says Dr. Stefanick.

Her interest in sex and hormones led her to take on a National Institutes of Health (NIH) request for applications to study menopausal hormones and heart disease. At the time, doctors were widely prescribing menopausal hormone therapy (HT), often referred to as hormone replacement therapy (HRT), for older women despite a lack of research on its effects. Dr. Stefanick and her colleagues designed one of the first studies to examine these treatments.

This resulted in the Postmenopausal Estrogen/Progestin Interventions Trial (PEPI), published in 1995, which was the first clinical trial by the National Heart, Lung, and Blood Institute (NHLBI) conducted exclusively on women. “It was the first trial done by NHLBI that had only women in it,” says Dr. Stefanick with pride.

Women’s Health Initiative: A Landmark Study

Dr. Stefanick’s PEPI trial laid the foundation for the Women’s Health Initiative (WHI)—the largest study of women’s health ever conducted. Launched in the 1990s, WHI enrolled nearly 162,000 women at 40 clinical centers nationwide to study menopausal hormone therapy, diet and cancer risk, and calcium and vitamin D supplementation.

WHI is still ongoing, and Dr. Stefanick serves as Principal Investigator of the Western Regional Center. “It’s the biggest study of women’s health ever done—and it’s still going on,” says Dr. Stefanick.

The WHI hormone trials, published in 2002 and 2004, challenged long-held medical beliefs. Doctors were prescribing menopausal hormone therapy for older women to prevent heart disease, but the study found that HT actually increased the risk of strokes, heart attacks, breast cancer, and dementia. Within a year of publication, HT prescriptions in the US dropped from 20 million to 6 million. “Doctors became afraid to prescribe hormones for menopause management. Women now ask, ‘Why won’t anyone treat my menopause symptoms?’ There are alternative estrogen therapies that don’t carry the same risks, but they remain underutilized,” says Dr. Stefanick.

Dr. Stefanick is currently leading the largest-ever study on whether physical activity prevents heart disease—a question that, despite decades of research, has never been definitively proven.

“We’ve never actually proven that physical activity reduces heart disease. All our data is based on surrogate markers—blood pressure, cholesterol, glucose tolerance—but we haven’t studied enough men or women (or nonbinary people) to say for sure,” says Dr. Stefanick.

The WHSDM Center: Advancing Sex Differences Research

Dr. Stefanick believes that one of the biggest problems in sex differences research is the overemphasis on sex hormones while ignoring other biological factors and broader sociocultural influences. “People tend to believe it’s all about estrogen and testosterone, but the biggest biological difference is probably the X chromosome. Every cell in an XX (female) body is different from every cell in an XY (male) body and some people have other variations of X and Y combinations,” says Dr. Stefanick.

For example, women have a stronger immune response than men, yet medical studies rarely adjust for these differences. Even in vaccine development, the COVID-19 vaccine was given at the same dose to men and women, despite evidence that women may need much lower doses.

“We don’t need to treat women like men. We are not men. We need to treat women like women—XX people with estrogen between puberty and menopause and with low estrogen after menopause, which may be over a third of our lives,” says Dr. Stefanick.

To address these gaps, Dr. Stefanick co-founded the WHSDM Center at Stanford, which serves as a hub for sex and gender research in medicine. The center funds studies, ensures that departments consider sex and gender in research, and promotes the inclusion of underrepresented groups in medical studies.

“Our goal at the WHSDM Center is to encourage researchers to study sex differences at every level—cells, tissues, animals, people, and populations,” says Dr. Stefanick.

Future Research Priorities

Dr. Stefanick continues to advocate for more inclusive research in several key areas:

  • Menopause and why some women have more severe symptoms than others and how to treat these more serious cases
  • Adverse pregnancy outcomes and their link to increased risk of diabetes and premature heart attack
  • Aging in women and why women live longer than men in many parts of the world
  • LGBTQ+ health research and the need for broader representation

“Women are incredibly resilient,” says Dr. Stefanick. “Our culture doesn’t value women in the same way it values men, yet women persist. I just love women. Women are incredible.”

By Maya Shetty, BS and Felicia Song, BS

Asian woman holding glass of water in one hand and vitamins in another

Midlife marks a significant life transition, bringing hormonal shifts that can reshape a woman’s body and well-being. As women navigate this period, their bodies undergo physiological changes that can impact muscle mass, bone density, metabolism, and overall well-being. Lifestyle factors play a fundamental role in healthy aging, but strategic supplementation can further support women in optimizing their health through midlife and beyond.

Nutrition and exercise researcher at Stanford Lifestyle Medicine Rachele Pojednic, PhD shares evidence-based strategies to help women maintain strength, vitality, and resilience as they age.

Different Supplements for Different Stages of Life

As women age, there are distinct shifts in body composition, and as a result, our nutritional needs change. For example, in our thirties, the focus should be on building and maintaining muscle mass, as bone formation peaks in the late teens and 20s. This foundation is critical because it helps offset the decline in estrogen during perimenopause, which reduces the body’s ability to preserve muscle and bone.

“Research shows that women begin losing skeletal muscle around age 30, with declines ranging from three to five percent per decade, and in some cases, up to 10 percent during the first postmenopausal decade,” states Dr. Pojednic.

After menopause, estrogen and other hormones stabilize at lower levels, making it more difficult for the body to build bone and muscle. Therefore, strength training, a nutrient-dense diet, and intentional supplementation become essential tools not just to mitigate loss of bone density and muscle mass, but to support long-term health.

Also, estrogen has anti-inflammatory properties throughout the body. When estrogen levels begin to decrease during perimenopause, systemic inflammation increases, contributing to a range of health concerns including changes in cognitive function, mood, and sleep. To help counter these effects, strategic supplementation can play a key role in supporting overall health, reducing inflammation, and maintaining balance.

Top 6 Supplements for Perimenopause and Menopause

1) Creatine

Creatine is a tripeptide that is naturally produced by the body and found in animal products. It plays a critical role in energy production and is crucial for maintaining muscle, bone, and brain health. In the body, creatine is stored in the muscles as phosphocreatine, which acts as a fast-acting energy reserve by donating a phosphate group to regenerate ATP, the primary energy currency of cells. This makes muscles more efficient, allowing for improved muscle function and greater overall strength.

“Creatine is one of the most extensively studied supplements in the world, and for good reason,” states Dr. Pojednic. “Recent research has shown considerable benefits in muscle, bone, and brain health.”

Why Creatine Matters for Women 40+

As women age, creatine levels naturally decline. In fact, women tend to have 70 to 80 percent lower creatine stores than men, and this difference becomes even more pronounced with age. This decline can contribute to age-related muscle loss, bone density reduction, and changes in cognitive and emotional health.

Benefits of Creatine Supplementation

  • Muscle and Bone Health

    Research suggests that creatine supplementation can help improve muscle function, increase muscle size, and enhance bone density in peri- and postmenopausal women, particularly when combined with resistance training.

    “By enhancing ATP regeneration, creatine allows women to push their muscles a little harder during exercise, promoting more robust muscle mass and bone strength,” states Dr. Pojednic.

  • Cognitive Health

    The brain relies heavily on phosphocreatine for energy, and low levels can contribute to brain fog and mood changes. Studies have shown that creatine may enhance short-term memory and overall cognitive performance in adults aged 45 to 64.

  • Mood Stability

    Emerging research suggests that creatine supplementation may help offset mood changes associated with perimenopause, including anxiety, depression, and sympathetic overdrive. A recent study found that adding creatine to therapy for depression led to greater symptom improvement compared to therapy alone, highlighting its potential role in brain health as women age.

“Topping off creatine stores may help reduce brain fog, moodiness, and other cognitive side effects often experienced during perimenopause,” states Dr. Pojednic.

How to Supplement with Creatine

Dr. Pojednic recommends that women supplement with three-to-five grams of creatine per day. Timing doesn’t matter, so it can be taken at any time of the day that’s convenient. When choosing a supplement, look for one that uses a water-based wash rather than an acid-based wash, as the latter may cause gastrointestinal side effects.

2) Protein

Protein is a vital macronutrient made up of 20 amino acids, nine of which are essential, meaning they must come from food since the body cannot produce them. These essential amino acids—histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine—are crucial for muscle growth, maintenance, recovery, and overall health.

Why Protein Matters for Women 40+

  • Increased Protein Needs

As women age, their ability to absorb and utilize protein efficiently declines, making adequate protein intake even more critical. Aging leads to anabolic resistance, meaning the body requires more protein and a greater resistance training stimulus to maintain and build muscle. Without sufficient protein, women may struggle to preserve lean mass, recover from exercise, and maintain metabolic health.

“Most women at all stages of life are not consuming enough protein, and this becomes more of a problem with age. While many women consume only 40 to 60 grams per day, research suggests that a more optimal range is 80 to 100 grams per day for muscle maintenance and growth,” states Dr. Pojednic.

  • Muscle and Metabolic Health

Protein is necessary for preserving lean mass, which helps maintain strength, independence, and metabolic function. It also supports post-exercise recovery and reduces the risk of sarcopenia (age-related muscle loss).

How to Get Enough Protein

High-quality animal proteins like meat, dairy, and eggs naturally provide all nine essential amino acids needed for muscle maintenance. Plant-based options such as soy and pea protein can also be effective, but it’s important to ensure they offer a complete amino acid profile. Consuming protein after workouts is particularly beneficial for muscle recovery and growth. Dr. Pojednic recommends women aim for 1.2 to 1.6 grams of protein per kilogram of body weight per day, which translates to a more practical target of 80 to 100 grams.

While a food-first approach is ideal, strategic use of protein powders can help women meet their daily protein needs to support strength, metabolism, and longevity. When choosing a protein powder, look for one that contains all nine essential amino acids and has minimal additives, which can cause bloating or gut irritation. “I opt for unsweetened protein powders to limit additives and sweeten them with ingredients I prefer,” states Dr. Pojednic.

What About Collagen Protein?

While collagen supplements are often marketed for skin, hair, and nail health, collagen is an incomplete protein and does not contain all essential amino acids. It should not be relied upon as a primary protein source over complete protein supplements or whole foods.

3) Vitamin D3

Vitamin D3, in conjunction with calcium (next section), plays a critical role in maintaining bone density, muscle function, and overall health. While commonly associated with osteoporosis and osteopenia prevention, vitamin D is essential for many tissues beyond bone, including the muscles, immune system, cardiovascular health, and cognitive function.

“As women age, they experience a decline in skeletal muscle starting around age 30 and bone mass loss after 40, with both reducing at an accelerated rate during and after menopause,” states Dr. Pojednic. “Supplementation with Vitamin D3 can offer support with both muscle and bone health.”

Why Vitamin D3 Matters for Women 40+

Vitamin D3 is vital for calcium and phosphate regulation, ensuring that bones stay strong and muscles function properly. Additionally, estrogen and vitamin D interact to affect bone health, as estrogen regulates vitamin D metabolism. During perimenopause, declining estrogen levels reduce vitamin D’s effectiveness, making adequate intake even more important.

Key Benefits of Vitamin D3

  • Bone and Muscle Health

Vitamin D plays a critical role in skeletal muscle function and bone maintenance. Deficiency in vitamin D (<50 nmol/L) is strongly associated with age-related muscle weakness and muscle mass loss. Inadequate vitamin D levels (<29 ng/ml) have been linked to poor lower body function, particularly in women, increasing the risk of falls and fractures. Studies have shown that supplementation with vitamin D3 improves muscle strength and function, particularly in postmenopausal women with insufficient levels.

  • Iron Absorption and Recovery

Vitamin D plays a key role in iron regulation by reducing hepcidin levels, which helps improve iron absorption—particularly important for post-exercise recovery. Since training increases hepcidin, which inhibits iron absorption, taking vitamin D after exercise may counteract this effect, reducing the risk of low iron and anemia in active women.

How to Supplement with Vitamin D3

Vitamin D is difficult to obtain from diet alone, as it is naturally found in few foods, including fatty fish, liver, beef, and fortified foods like cereals, dairy, and juice. The body’s main source of vitamin D comes from sun exposure, but in many regions, the sun’s UVB rays are not strong enough to support vitamin D synthesis between October and April.

To ensure adequate levels, supplementation is often necessary. The recommended dose ranges from 800 to 4,000 IU per day, though higher doses can be detrimental to bone health.

“Finding the ‘sweet spot’ is key, as excessive intake of vitamin D offers diminishing returns. Blood testing can help determine individual needs, ensuring levels are sufficient without exceeding optimal ranges,” states Dr. Pojednic.

For best absorption, look for Vitamin D3 (cholecalciferol), the most bioavailable form. Additionally, taking a Vitamin D3 supplement with fat, such as an omega-3 supplement (keep reading for more on this) will enhance its absorption.

4) Calcium

Calcium is a key mineral required for bone rigidity, stability, and muscle contraction, yet many people—especially women—fail to consume enough from their diets. While green leafy vegetables and dairy are excellent sources, many people don’t eat enough of them, and dairy alternatives are often not fortified with calcium. Without sufficient intake, the body pulls calcium from bones, increasing the risk of osteopenia and osteoporosis with age.

“While calcium is crucial for bones, it also plays a role in nerve function, blood clotting, and muscle contractions—making it essential for heart health and overall mobility,” says Dr. Pojednic.

How Much Calcium Do You Need?

The recommended daily intake for women in their 40s is 1,000 mg of calcium per day. “However, balance is key—too little calcium weakens bones, but excessive calcium without proper nutrient pairing may lead to arterial calcification instead of proper bone mineralization,” warns Dr. Pojednic.

5) Omega-3 Fatty Acids (Fish Oil)

Omega-3 fatty acids are essential nutrients because the body cannot produce them, meaning they must come from food or supplements. These powerful antioxidants help scavenge free radicals, reducing tissue damage and supporting cell membrane integrity in every organ. Omega-3s are particularly important for vascular health, keeping blood vessels flexible and reducing the risk of cardiovascular disease and dementia. They also play a key role in brain function, supporting neurons, maintaining myelin, and helping to keep chronic inflammation low.

Why Omega-3s Matter for Women 40+

Estrogen has natural anti-inflammatory properties, offering protection against chronic inflammation throughout life. However, perimenopausal women lose some of this protective effect, increasing the need for anti-inflammatory support through other mechanisms.

Key Benefits of Omega-3s

  • Cognitive Health

Omega-3s may help reduce the risk of Alzheimer’s disease by lowering brain inflammation and supporting nitric oxide production, which promotes blood flow to the brain.

  • Muscle Health

Research shows that omega-3s enhance muscle protein synthesis and mitochondrial function, helping to counteract sarcopenia. Their anti-inflammatory properties may also aid recovery and improve performance in athletes.

  • Inflammation Reduction

Omega-3s help regulate inflammatory cytokines like IL-1 and IL-6, which may support joint health and post-exercise recovery.

How to Supplement with Omega-3s

For optimal benefits, choose high-quality, purified fish oil supplements to avoid contaminants. If possible, prioritize whole food sources such as fatty fish (salmon, sardines, mackerel), which provide a naturally balanced omega-3 profile. While omega-3s have well-documented benefits, most research has been conducted in men, so more studies are needed to fully understand their effects in female athletes and aging women.

6) Fiber

Rather than a supplement, fiber should primarily be consumed in our diet. The current dietary guideline for fiber is 25 grams daily through fruits, vegetables, whole grains, legumes, beans, nuts, and seeds. Fiber is crucial for our gut health, helps to maintain our blood glucose levels and improve insulin sensitivity, and helps to lower LDL (the bad) cholesterol.

“If fiber is not sufficient through diet, I recommend a fiber supplement, such as psyllium husk, inulin, or methylcellulose daily to help you meet the fiber requirements,” says Gray Shimko, RD, leading dietician at the Stanford Menopause and Healthy Aging program.

 

The Importance of Exercise When Taking Supplements

While supplements like creatine, protein, vitamin D3, calcium, omega-3s, and fiber provide the body with essential nutrients for muscle, bone, and brain health, they cannot replace the need for exercise. Strength training serves as the necessary trigger for muscle growth and adaptation. While protein and creatine supply the raw materials for muscle repair, it is the physical act of contracting muscles through exercise that signals the body to build and strengthen them.

“To effectively build and maintain muscle as we age, women must actively engage in resistance training, as muscle follows a ‘use it or lose it’ principle,” states Dr. Pojednic. “Engaging in resistance training at least two-to-three times per week—whether through weightlifting, resistance bands, or bodyweight exercises—helps maintain muscle mass, improve bone density, and support metabolic health.”

Exercise also improves how the body absorbs and utilizes nutrients, making supplementation more effective. For example, creatine supplementation enhances strength and performance, but its full benefits are only realized when paired with resistance training. Similarly, omega-3s can reduce inflammation and support muscle recovery, but their impact is greatest when muscles are actively engaged in movement.

By combining strategic supplementation with regular strength training, women 40 plus can maximize muscle retention, protect bone health, and maintain cognitive function, ensuring long-term strength, mobility, and independence as they age.

Foundational Nutrition Before Supplementation

Lastly, when choosing supplements, quality and transparency are key. Look for third-party tested products to ensure two critical factors: first, that the ingredients listed on the bottle are actually present and in the correct doses. Second, third-party testing verifies that there are no undisclosed or harmful substances, such as heavy metals or adulterants. While supplements should complement–not replace–a nutrient-rich diet, the 40s decade is a pivotal transition, making it especially important to identify and address any dietary gaps.

“Think of supplementation as the icing on the cake—helpful for optimizing health, but most effective when approached with prudence and balance,” says Dr. Pojednic. “Supplements should be viewed as tools for marginal gains, not miracle solutions. Foundational nutrition—getting enough protein, fiber, and healthy fats from our food—remains crucial.”