Weight gain is one of the most frequently seen complaints during perimenopause and menopause. In this blog we will explore why that is and how the female body changes during this magical and yet confusing life stage.
Menopause and perimenopause typically begin for women around the age of 45 – 55 years. We start to notice changes in our bodies prior to the loss of our cycle including hot flashes or night sweats, change in frequency and how heavy our periods can be, and changes in mood. Perhaps the most unsettling for females is the change in weight and body mass distribution: clothes fit differently, your body feels different, your capacity at the gym and with physical activity feels futile! And this usually happens with little change to your current nutrition or activity routine.
Menopause is often called our second puberty due to the change in hormone signaling. Progesterone relies on estrogen for ovulation in cycling (i.e. menstruating) females. Estrogen output in pre-menopause results in a progesterone surge, whereas during the peri/menopause transition, we see progesterone levels drop first, which are then followed by a drop in estrogen levels. We can see this change portrayed below:
Menopause and weight gain – why does our body betray us?
It’s not all your fault! Menopausal women are three times more likely to develop obesity and metabolic syndrome abnormalities than pre-menopausal women. We find multiple studies that show loss of estrogen is to blame for these shifts in our metabolic patterns. Estradiol levels for a cycling female average between 100-250 pg/mL and then drop to 10 pg/mL in post-menopause. Given this difference, we end up spending a third to half of our lives in estrogen deficiency.
It is well known that disease states in females become more apparent at the onset of menopause, therefore suggesting sex hormone changes as the culprit. We also tend to see women with increased visceral fat (abdominal fat, and fat around the organs) with similar or less subcutaneous fat (fat on the arms and legs) alongside the menopause transition. Visceral fat is the problematic type of fat; the one that increases risk for cardiovascular disease, immune compromise, and metabolic syndrome (precursor to diabetes), to name a few.
To understand the burden of obesity and metabolic syndrome associated with menopause, we need to dig further into the data on estrogen and metabolism. Part of this discussion includes cholesterol. Cholesterol is the backbone from which all sex hormones are made. We rely on cholesterol to make estrogens, progesterone, testosterone, DHEA, and more. Cholesterol-containing lipoproteins consist of LDL (low-density lipoproteins), HDL (high density lipoproteins), and triglycerides (fatty acids).
Estradiol influences the liver’s ability to control and excrete cholesterol. When estradiol levels decline in menopause, less cholesterol is converted to sex hormones and is not detoxed as efficiently by the liver. This leads to high levels of cholesterol which can be inflammatory and increase the risk for cardiovascular disease.
Estradiol also promotes insulin sensitivity in the liver and throughout the body. When estradiol declines, insulin resistance develops, putting women at greater risk for diabetes and fatty liver disease. With these changes we see increased correlation with central obesity, insulin resistance, dyslipidemia, hypertension, and cardiovascular disease – and this is all due to ongoing increases of circulating LDL levels.
We also know that bone density loss is a factor in the increase of fat cell accumulation. Usually, our bone marrow is busy with cells making more bone. Once we lose estrogen, our bone marrow prioritizes production of fat over bone – meaning, the marrow becomes more laden with fat cells (adipocytes) than bone cells, and our bone marrow releases these fat cells into circulation, which then migrate to certain types of adipose tissue and increase the body’s fat mass.
Fat cells – there is more than one way to trim the fat
There are several different types of fats in the human body, including:
White Adipose Tissue (WAT)
White Adipose Tissue is what we think of when we think of fat cells. These cells are located subcutaneously as well as viscerally and are used for energy. Our subcutaneous fats break into free fatty acids for consistent energy support. Visceral fats are less predictable as they break down in response to a signal versus energy demand. WAT makes up for about 10-20% of body weight in lean humans and will expand through cell size increase as well as cell size quantity when there is excess. We also see that visceral fat is correlated with menopause whereas subcutaneous fat is correlated with nutrition and activity levels. Some WAT cells come from bone marrow, as described above.
Brown Adipose Tissue (BAT)
Brown Adipose Tissue is responsible for thermogenesis. We have the highest volume of this as babies and tend to lose much of it on the way to adulthood. BAT also “appears to have an important role in regulating insulin resistance, protecting against obesity and diabetes; and is inversely correlated with body mass index.”
Bone Marrow Adipose Tissue (BMAT)
BMAT ends up competing in the marrow for growth. When bones are exposed to a mechanical force (running, strength training), or hormone signaling, the marrow favors osteoblast (bone building) cell production. When the marrow is exposed to oxidative stress, glucocorticoid signaling, and immobilization, adipocyte (fat cell) growth increases.
In this study, mice with removed ovaries had increased visceral and subcutaneous fat due to increased bone marrow fat cell production because of loss of estrogen. On average, women gain 12 pounds within 8 years of the onset of menopause. This same study found that increased body fat was associated with high blood pressure, and that post-menopausal females had gained 36% trunk fat, 49% increase in greater intra-abdominal fat area, and 22% greater subcutaneous abdominal fat
As we get older, we tend to see loss of muscle mass (lean body mass) as well as increased visceral and subcutaneous fat. Because estradiol acts on mitochondria (the part of the cell that fires up our metabolism), when we lose estradiol, we also lose the capacity to optimally signal the mitochondria for cellular energy. Skeletal muscle mass and strength peak in the mid 20s and 30s, and degenerative loss of skeletal muscle occurs at a rate of 3-8% every 10 years after the age of 30 and accelerates with age!
Loss of muscle strength is called sarcopenia. Osteopenia is loss of bone density. It is not uncommon to see these together, termed “osteosarcopenia,” which can lead to increased risk of weakness, hospitalization, and death. When evaluating osteoporosis alone, the frailty risk was much less when compared to sarcopenia alone. Loss of muscle mass and muscle strength are a higher risk to our health than bone density loss. And though we are still at great risk for fractures and bone pain with loss of bone density, osteosarcopenia is the most serious risk given the health consequences.
In addition, skeletal muscle burns up to three times more energy than fat cells! Skeletal muscle, therefore, supports optimal metabolism.
Without estradiol, we don’t have the same signaling to mitochondria to enhance oxygen consumption, regulate insulin signaling, support energy expenditure, and cellular redox, resulting in less energy overall. This makes it difficult to maintain our basal metabolic rate (BMR), which allows us to maintain essential functions for life (breathing, sitting). In summary:
- We have less capacity to burn energy due to lowered lean body mass and less skeletal muscle.
- The energy we do expend is less than what it was before due to reduced mitochondrial function and reduced skeletal muscle.
- We rely on estrogen to begin the signaling of important enzymes in the Krebs cycle – the cycle that produces ATP for our cells that help us burn fat and energy.
Essentially, once we lose estrogen, we are unable to signal our powerhouses (mitochondria) to begin the process of fatty acid oxidation (breakdown), and lipid breakdown. Both processes utilize the LDL derived fatty acids for energy.
There are studies suggesting that follicle-stimulating hormone (FSH) is also a key hormone in metabolic management for menopausal females. The higher we see FSH, the more weight gain and bone loss is seen. More research needs to be done to fully understand this effect, however it is worth noting in this discussion (since FSH is usually the diagnostic marker for menopause).
Another group of hormones that may also impact estrogen deficiency are androgens, namely, testosterone. When estrogen drops in menopause, we begin to see a shift in the ratio of estrogen to androgens in our body, with androgens such as testosterone becoming more dominant. To be clear, this does not mean that testosterone is bad! It means we need to evaluate and test the levels to understand how best to approach the situation. In a state that is more androgen dominant, we may see some additional shifting toward central adiposity and insulin dysregulation.
Leaning into Estrogen Replacement Therapy (ERT) as an opportunity to improve metabolism and quality of life
Research shows mice that had their ovaries removed mirrored truncal obesity and metabolic changes, similar to humans. Upon estradiol (E2) replacement, these mice went back to their normal weight and muscle mass.
We also see in another study that estrogen replacement lowers LDL levels, therefore lowering circulating levels of LDL. Given our discussion, the less LDL present, the less risk for visceral fat in the abdomen, and more improved insulin signaling. Previously, Dr. Doreen Saltiel walked us through the best practices of menopausal hormone therapy in which she offers great insights to current guidelines for hormone replacement. We can see and deduce from this information that estradiol is a powerful cog in the wheel of metabolism and needed to ensure a healthy quality of life in post-menopause.
Estradiol supplementation is not the only helpful option. Ko,S. and Jung, Y. (2021) encourage sufficient protein, vitamin D, calcium, creatine, and strength training to complement any hormone support that may be considered.
In conclusion, the best way to understand your hormone levels, especially in relation to one another, is to test. When testing, it is necessary to understand the difference between sufficient levels of estrogen and deficient levels of estrogen. There needs to be a differentiation between pre-menopausal and post-menopausal ranges of estrogen. This can be appropriately evaluated by either LC/MS-MS serum (blood) testing, or a DUTCH Test. Here we can see more validated research on why LC/MS-MS and/or DUTCH testing is necessary for appropriate differentiation of estradiol levels.
Mind the Gap in Ranges
When looking at lab test results, the gap on the report reference ranges which represents the space between the post-menopausal range and the pre-menopausal ranges should be clear – and these two ranges should not overlap. There should be a distinct difference between these ranges. This is pictured below where we can see a marked difference between the post-menopausal range (purple box), and the luteal (cycling/pre-menopausal) ranges in green between the stars.
DUTCH Test is an easy, at home collection test that allows a comprehensive review of sex hormone levels and metabolites, as well as adrenal function. A DUTCH Complete or DUTCH Plus is a great way to begin the journey of testing to understand baseline as well as supplemented hormone levels.
Dr. Debbie Rice, ND, MPH
Director of Clinical Education
Dr. Rice is the Director of Clinical Education for Precision Analytical and practices part-time as a naturopathic doctor where she focuses care on pediatric, hormone, thyroid, and adrenal health. She has had experience working with communities in need, both in the United States and internationally. Her training is primarily in women’s health, pediatric care, hormone therapy and hormone function, as well as complimentary adjunct care. Dr. Rice uses diet and lifestyle, botanical medicine, and conventional approaches to maximize care for her patients.