Lately we’ve been thinking about the connection between hormones and aging. This is a fairly complex topic, so as a first step we decided to share an overview of the endocrine system, the group of glands that regulates the production of hormones.
You can think of the endocrine system as a messenger network that uses hormones to convey signals to different target organs in the body. These signals are responsible for controlling and regulating a variety of bodily functions, including:
- Heart rate
- Body temperature
- Cell production and growth
- Blood pressure
- Sleep/wake cycles
- Sexual function and reproduction
- Mood regulation
The endocrine system is largely controlled by the hypothalamus, a small area of the brain located just below the thalamus. The hypothalamus is part of the limbic system and is considered a neuroendocrine organ. It has both homeostatic functions (e.g., regulating thirst, hunger, body temperature) and coordinating roles between the nervous system and the glands that comprise the endocrine system.
Source: Brain Made Simple
There are eight major endocrine glands that help us function:
- Pituitary (the “master” gland)
Source: Endocrine System
There are four key hormones whose levels change significantly with time with important implications for healthspan.
Estrogen & Progesterone
Alterations in a woman’s sex hormones occur as a result of age. The ovaries decrease in size and weight. They also decrease their sensitivity to gonadotropins like follicle-stimulating hormone (FSH) and luteinizing hormone (LH), reducing their overall function. Estrogen and progesterone fall precipitously in response to the decrease in ovarian function and menopause begins (cessation of menstrual periods for at least 12 months). Estrogen has many functions in the female body, including restricting bone resorption, regulating cholesterol and fat deposits, regulating fluid balance, and producing female secondary sex charactics. Progesterone primarily functions in helping a woman conceive and sustain a pregnancy, but also has other functions like promoting collagen production, helping maintain blood levels of copper and zinc, and supporting normal thyroid function. As a result of the drop in female sex hormones, women undergo physical, psychological, and emotional changes as they age. Menopausal and post-menopausal women are at an increased risk for osteoporosis, atherosclerosis, and high cholesterol, as well as sarcopenia, depression and a variety of other age-related conditions.
This short article from the Cleveland Clinic provides a good overivew of menopause and changes in sex hormones in women over 50, including symptoms to watch out for.
Check out this recent study on age of menopause and life expectancy for a deeper-dive into the health effects of fluctuations in sex hormones.
Age also alters a man’s sex hormones, albeit to a less dramatic extent than occurs in women. Testosterone decreases with age initiating a gradual change, referred to in the scientific literature as andropause. Testosterone has various functions in the male body including development of muscle mass and strength, maintaining bone density, and producing male reproductive tissues. While sperm production isn’t affected by andropause, the quality and quantity of sperm suffers as a result. In addition to alterations to reproductive function, men in andropause are at an increased risk for age-related chronic disease just like menopausal women. According to this article from the Journal of Geriatric Cardiology, low levels of testosterone are associated with an increased risk of heart disease.
Learn how to optimize estrogen and testosterone in this very detailed podcast episode from the Andrew Huberman Lab.
Melatonin is produced by the pineal gland and helps regulate our sleep/wake cycle. Levels of circulating melatonin decrease in the morning and increase as the day progresses to get us ready for sleep. As we age, the pineal gland undergoes changes (e.g., calcification, reduction in size) that affect its structure and function. The result is a decrease in melatonin production and gradual loss of a healthy sleep/wake cycle. Some scientists suggest that age-related changes to the pineal gland account for the loss of sleep that occurs with age, independent of life factors such as stress. Furthermore, according to this article, some research suggests that melatonin’s functions extend beyond sleep. Melatonin is a powerful antioxidant and may play a neuroprotective role against age-related cognitive decline and ailments such as Alzheimer’s.
Image: Variations of blood melatonin concentrations in various age categories. Source: Melatonin and aging: prospects for human treatment
Dive deeper with this review article on the potential benefits of melatonin supplementation as a healthspan extension strategy.
In both sexes, alterations in anterior pituitary structure and function result in a decreased production of growth hormone (GH). In healthy, young adults, GH stimulates growth and cell reproduction; it also stimulates IGF-1 release from the liver, which helps regulate blood sugar as well as cell growth and development. As a result of decreases in GH, we have an increased risk for developing sarcopenia and central adiposity, which can result in loss of mobility, function, and independence as we get older. Furthermore, research suggests that loss of muscle mass is a good predictor of mortality and central adiposity is associated with an increased risk for metabolic syndrome, diabetes, and heart disease.
While we need GH as a signal to our muscles to grow, declines in GH have been linked to lifespan extension in animal models. For example, this review on the applicability of GH therapy as an anti-aging treatment, suggests that aging is slowed or delayed in mice who have reduced GH signaling due to certain mutations. This is also thought to be related to GH’s effect on the production of IGF-1.
The mixed nature of the research can make this topic confusing. What seems to be clear is that excessive elevation of GH levels can result in increased risk for certain diseases like cancer. In the context of healthspan we think the key priority should be in mitigating the age-related risk for muscle loss and increased abdominal fat without relying on above normal GH levels.
Click here to learn more about sarcopenia and how to combat it with resistance training.
Additional hormones that may impact healthspan if their levels fluctuate above/below normal are:
- Cortisol—Changes to the composition of the adrenal glands decreases production of cortisol, though blood levels stay relatively stable. Consistently elevated cortisol levels (i.e., due to factors such as chronic stress) have been shown to prime the body for chronic diseases like obesity, heart disease, and diabetes.
- T3 & T4—Changes in the anterior pituitary reduce production of thyroid-stimulating hormone which is needed to produce T3 & T4 in the thyroid gland. Decreases in the levels of T3 & T4 can produce effects such as slowed metabolism, increased adiposity (fat gain), and temperature dysregulation (due to reduced metabolic rate).
- Parathyroid Hormone—Changes in the parathyroid glands increase production of parathyroid hormone in the blood. This can result in increased calcium resorption from the bones. The combination of increased parathyroid and menopause puts women at higher risk of osteoporosis due to decreased functionality of calcitonin (which prevents bone resorption).
- Insulin—Glucose metabolism changes with age and becomes less effective. While circulating levels of insulin remain relatively stable, impaired glucose metabolism can put you at risk for type 2 diabetes as well as cardiovascular and neurodegenerative diseases.
For a more exhaustive list of hormonal changes and an in-depth analysis of the mechanisms behind these changes, check out these academic sources:
- The Role of Androgens and Estrogens on Healthy Aging and Longevity
- The Physiology of Endocrine Systems with Aging
- Endocrine Changes with Aging
Do I Need to Check My Hormone Levels?
We all experience hormonal shifts as we age and, as highlighted above, some of these shifts can impact our healthspan. However, as is the case with many biomarkers relevant to aging, checking hormone levels is not something that doctors commonly do unless you are experiencing persistent symptoms. These may include:
- Exercise-resistant weight gain
- Chronic fatigue
- Muscle pain or stiffness
- Dry skin
- Thinning, brittle hair
- Sexual dysfunction
If you are experiencing any of these you should ask your primary care doctor to run the appropriate tests to determine if there is a hormone imbalance.
Alternatively, there are a good number of direct-to-consumer companies offering at-home testing of the levels of different hormones. Here are four highly-rated at-home hormone tests that we explored:
- For Thyroid—LetsGetChecked Thyroid Test ($99)
- For Menopause—MyLabBox Postmenopause Test ($99)
- For Andropause—Imaware Testosterone Monitoring Test ($69)
- For Melatonin and Sleep—Everlywell Sleep and Stress Test ($199)
How Can I Address Changes in My Hormones?
Much remains to be researched on the connection between hormonal changes and healthy aging. While many practitioners suggest that there isn’t much that can be done about age-related hormone changes, we did find a few interesting strategies in our research that we felt were worth sharing.
If you have low estrogen and progesterone…
- Hormone replacement therapy
- Topical estrogens
- Non-hormone treatments for hot flashes
- Healthy lifestyle behaviors (e.g., balanced diet, daily exercise, managing stress)
If you have low testosterone…
- Testosterone replacement therapy
- Healthy lifestyle behaviors (e.g., balanced diet, daily exercise, managing stress)
If you have low melatonin…
- Melatonin supplements
- Natural light exposure
- Tryptophan-rich foods like oats, turkey, cheese, nuts and seeds (precursor to melatonin)
- Sleep hygiene
If you have low growth hormone…
Altering your hormones without physician supervision can result in adverse health outcomes. Check with your doctor to see if any of these options are right for you before adding them to your longevity protocol.
Share your experiences with age-related hormone changes with us or anything we may have left out: firstname.lastname@example.org
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