The Hormone – Joint Pain Connection for Men and Women
Joint pain is commonly written off by most doctors as just “arthritis” because you are getting older. But the truth is far more complex than just getting older, or the usual “wear and tear” explanation. Likewise, there are many more helpful, integrative and comprehensive approaches to joint pain relief than just taking Tylenol, Aleve, Advil, or aspirin. As I said in last week’s Health Tip, joint pain does not always begin with an injury or joints getting “worn-out” as we get older. More often than people realize, before the pain, there was a change in the hormonal balance—particularly with our sex hormones—that is a critical factor explaining why familiar activities suddenly hurt, morning stiffness lasts longer, or several joints become uncomfortable at once.
I want to help you avoid the pitfall of simply dismissing new pain as a sign of age and accepting that all you can do is take pain medicine. The truth rarely discussed in most doctors’ offices is that there are many different contributors to joint pain, from leptin signaling in overweight individuals to declining estrogen and testosterone during menopause and andropause to other medical conditions and medications that dramatically drop or completely block hormone receptors leading to painful joints and other life-altering symptoms.
So, today’s Health Tip expands on last week’s article on the overlooked connection between leptin and joint pain as I discuss this even bigger and tragically overlooked connection contributing to painful joints – decline or imbalance in your sex hormones: estradiol and testosterone women, testosterone and estradiol for men. Yes, women have testosterone and men have estradiol although the healthy, optimal balances vary based on biological sex chromosomes (XX or XY) present.
Our sex hormones have many roles in the health of our joints and the connective tissues and muscles that stabilize and help the joints work normally and without pain: lubrication, blood flow, healthy joint lining, nerve function, strength and flexibility of tendons and ligaments, reducing inflammation from daily use, improving repair processes from microtraumas each day, wound healing after injury, coordination, balance and proprioception.
Our sex hormones play key roles in ALL these functions! It is a lot – and most doctors never even mention it when patients come in describing painful joints, loss of mobility and strength. I’ll talk about these functions in more detail today –and give you some practical Tips to help with creative approaches to treatment.
Understanding Joint Function and Health: More than “wear and tear”: what actually hurts?
A joint functions as a system. Cartilage covers the ends of bones; the synovium, or joint lining, helps maintain the joint environment; tendons connect muscles to bones; and ligaments provide stability. Muscles control movement and help the body tolerate load.
I listed above the many ways our sex hormones affect multiple aspects of this carefully designed integrated system. Sex hormones also change how readily sensory nerves respond to inflammatory signals and how strongly the spinal cord and brain amplify those signals. Consequently, hormonal imbalance (estradiol deficit, progesterone excess, testosterone excess or deficit, DHEA excess), can result in significant increase in pain even without an equivalent increase in structural damage.
This distinction is fundamental: pain and joint deterioration are related, but they are not interchangeable. A person may experience significant relief because inflammation, tendon irritation, or nerve sensitivity improves—not because cartilage has regenerated.
Estrogen and Testosterone role in Joint Pain
Both hormones clearly influence multiple functions that affect the strength and integrity of the tissues that surround and support joints, the signals that regulate inflammation, and the nervous system’s response to pain. Both women and men produce both hormones, but the balance of E2 and testosterone in men and women obviously differ.
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Testosterone: muscle support, bone health, & pain modulation
Testosterone is present in both sexes in different amounts, and also shares similar functions for men and women to maintain health of connective tissue, muscle, bone and joint health. Hypogonadism is the medical term for clinically significant testosterone deficiency in men, regardless of age or cause (medical conditions, medications, trauma, cancer, alcohol or drug use, etc). Menopause is the general medical term used to describe the loss of ovarian hormones in women. In natural menopause, estradiol declines more rapidly, while ovarian testosterone declines more gradually. Adrenal glands continue to make adrenal androgens (DHEA and DHEA-S, small amounts of testosterone) in women after menopause, but without functioning ovaries, precursor DHEA cannot be converted to the end hormones of estradiol and testosterone. Taking DHEA supplements in post-menopausal women just adds unwanted symptoms of androgen excess but without estradiol or the right amount of testosterone to balance it. After hysterectomy with removal of both ovaries, or surgical menopause, women immediately and abruptly lose both estradiol and ovarian androgens (testosterone, DHEA and DHEA-S). Removal of the ovaries in women is the same catastrophic loss of hormones as castration by removal of testes in men.
Whether for men or women, loss of testosterone gradually leads to reduced muscle mass, loss of bone mass, loss of strong connective tissue around joints, and decline in physical stamina and strength. Together, these changes make everyday activity more difficult and more painful because testosterone also interacts with pain-processing pathways and plays a role in deep restorative sleep for men that helps repair muscle and connective tissue from the microtraumas that occur over a day of activity. Estradiol plays a similar and crucial role in maintaining the normal, restorative sleep pathway in women.
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Estradiol: Critical for joint, bone and muscle health in both men and women
Estradiol (E2), or 17-besta estradiol, is the primary, metabolically active form of estrogen prior to menopause, and it is present in women but also in smaller amounts in men. Estradiol shares similar functions on bone, connective tissue, nerves, brain and other organs in both sexes.
Men produce estradiol largely by converting testosterone through an enzyme called aromatase. In men, estradiol plays an important role in maintaining bone; treatments that lower testosterone can also lower estradiol leading to bone loss in men. In fact, studies in the bone and mineral research field from 30 years ago found that both men and women need a critical blood level of 17-beta estradiol of about 60 pg/ml to maintain normal bone preservation pathways.
It is critical to understand this connection between the hormones and joint health vs. deterioration and pain because the roles these hormones play opens the door to therapeutic options for better pain management. I am not saying that every painful joint reflects a hormone deficiency, or that hormone replacement by itself rebuilds damaged or missing cartilage. I do know from 40+ years of practice in this field of reproductive hormones effects on our total health that effective treatment for painful joints must start with assessing the current state of hormone balance, along with the other medical and nutritional factors I assess in all my new patients. It is part of my careful evaluation to determine the root causes and apply appropriate integrated medical-endocrine-nutritional and lifestyle strategies that I tailor to each person’s treatment plans.
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Estradiol influences connective tissue
Estradiol signaling affects collagen formation—the structural protein that gives tendons, ligaments, and other connective tissues their mechanical properties. It influences collagen production, increases collagen content of connective tissue, increases collage cross-linking and elasticity, which help determine how tendons and ligaments respond to stretching and loading. In muscle and bone, estradiol primarily improves strength and function. In tendons and ligaments, estradiol decreases stiffness, and increases elasticity, which directly affects performance and injury rates.
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Estradiol influences inflammation and pain processing
Estradiol receptors act as cellular signal receivers. They are present in tissues and neural pathways involved in pain. Estradiol can modify inflammatory gene activity, sensory-neuron excitability, and signaling in the spinal cord and brain. This means that depending on the tissue, estradiol may have differing effects—reducing pain sensitivity in some, and in others, facilitating pain transmission. The response depends on receptor type, tissue, hormonal context, and the underlying pain disorder. Estradiol is a regulator of pain pathways in ways that modulates and can reduce pain and is important in pain management, but it is not a “painkiller” like NSAIDS or opiates.
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Estradiol affects hyaluronic acid production
Hyaluronic acid is a glycosaminoglycan: a large, water-binding molecule found in the extracellular matrix—the material surrounding cells. Hyaluronic acid is one of the body’s important moisturizing molecules. It helps tissues retain water and maintain their cushioning, flexibility, and viscoelasticity. Depending on its location, such as vaginal tissue, it also contributes to lubrication. In skin and mucosal tissues, it contributes to a hydrated extracellular environment. And in joints, it helps give synovial fluid the viscoelastic properties needed for smooth movement and fluid retention.
In our younger years, estradiol maintains hyaluronic acid and other glycosaminoglycans. When estradiol declines, hyaluronic acid and the other glycoaminoglycans production and maintenance declines, reducing tissue hydration and lubrication affecting not only joint health but dryness in skin, eyes, mucosal tissue lining the sinuses, mouth, GI tract, and vagina.
Men also need estradiol signaling to maintain hyaluronic acid. Most estradiol in men is supplied through conversion of testosterone to estradiol by the enzyme aromatase.
THE BOTTOM LINE: Testosterone has anabolic effects to build both bone and muscle in both sexes; estradiol helps maintain bone in both sexes by facilitating calcium being absorbed and deposited into bone and preventing excess bone breakdown in the remodeling process needed to maintain strong bones. The combined musculoskeletal benefits of both estradiol and testosterone involve maintain healthy muscle, bone, and connective tissue plus pain regulation and improving lubrication of joints.
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Progesterone: Crucial differences between pregnancy and menopause effects for women
Studies on progesterone over the years have found minimal benefits on building bone and muscle, but progesterone has significant benefits to increase ligament laxity (elasticity or “stretchiness) in women during the luteal phase of the menstrual cycle in ovulating women and even more pronounced in pregnancy. Increasing the elasticity of ligaments in the pelvic girdle allows for expansion of the pelvic bones during pregnancy to accommodate the growing baby and then allow the pelvic bones to separate enough for the baby’s head to pass through the birth canal during delivery. That is major adaptive advantage during pregnancy.
Menopause, however, is a different story and older women have very different needs from women during pregnancy. Ligaments that are looser, or more elastic, during the luteal phase of the menstrual cycle is one of the factors that contributes to more frequent knee and hip injuries in young women athletes. In older women taking daily progesterone for hormone therapy, progesterone-induced ligament laxity can be a significant problem leading to knee, hip, ankle, shoulder and elbow injuries, since older women are losing tendon and ligament strength to support their joints as they age. Progesterone excess in older women has many negative effects, particularly if they also have inadequate estradiol and testosterone benefits to build stronger muscles, tendons and ligaments.
BOTTOM LINE: Hormone changes can alter tissue biology, strength, elasticity, inflammatory activity, hyaluronic acid quality, and pain processing. All of these factors can contribute to joint pain that may be helped with properly designed hormone interventions integrated with other approaches.
Why Joint Pain Increases Around Menopause
During the menopause transition, or early menopause triggered by the COVID shots for example, the decline and fluctuations in estradiol leads to changes in the environment in which joints, tendons, and muscles function. At the same time, age-related changes, previous injuries, medication side effects, developing osteoarthritis, sleep disruption, and reduced activity also contribute to joint pain symptoms. Multiple mechanisms can overlap and intensify combined effects:
- Changes in connective-tissue turnover and mechanical behavior.
- Changes in inflammatory and sensory-nerve signaling.
- Reduced muscular capacity to tolerate everyday activity.
- Disrupted sleep that impairs normal tissue repair overnight
- Greater sensitivity to an existing joint or tendon problem.
This helps explain why a woman may report new widespread aching or stiffness around menopause without having a single new injury. It also explains why hormonal changes can aggravate a problem that was previously manageable.
Can menopausal hormone therapy help?
In my medical practice, with optimal hormone therapy tailored to an individual’s needs and activity level, I typically see significant reduction in joint pain, particularly with the integrated approach combining the strategies I am discussing here. The degree of benefit depends in large part on type of menopausal hormone therapies used and whether the doses are titrated to optimal levels for an individual woman. For example, in my medical practice since 1985 I have only used bioidentical forms of ovarian hormones (whether FDA-approved commercial ones or individually compounded options), so I have seen significantly positive results on muscle and joint pain reduction with hormone therapy in my patients. But in The Women’s Health Initiative (WHI), published in 2002 that gave hormone therapy such a bad rap, there were not such significant results. I think that is directly related to the very different hormone products used in that study. The WHI used conjugated equine estrogens derived from pregnant mare’s urine that provided a lot of horse estrogens and very little of the human 17-beta estradiol, and it was given with a high dose synthetic progestin (Provera, or medroxyprogesterone acetate) that negated on average 50-60% of the estrogen benefits. Even in the conjugated equine estrogen only arm of the WHI (in women had a hysterectomy and did not need progestin therapy), there was only about a 3% positive difference between joint pain in women on the horse estrogen compared to women on placebo. Pain severity was also slightly lower with estrogen. So the results were encouraging but not the marked improvements I have seen over my career treating women with bioidentical hormones and optimal dosing tailored to each patient rather than a one-size-fits-all dose. And I have never prescribed the oral conjugated equine estrogens. Unfortunately, to this day, we have never had a head-to-head study comparing oral conjugated equine estrogens and bioidentical 17-beta estradiol products.
Cancer treatment: major impact on hormone balance—A factor in musculoskeletal pain
Cancer therapies that suppress hormone production or signaling provide a clinically important example of just how important the hormone-pain connection can be. Many of the cancer chemotherapy agents as well as radiation treatments for cancer cause early menopause in women or hypogonadism (low testosterone) in men undergoing cancer treatment. The resulting hormone losses for men and women can be significant factors in new onset joint pain, muscle soreness, bone loss, loss of connective tissue strength, and sleep disruption—all of which contribute to pain.
- Breast cancer: aromatase inhibitors versus tamoxifen
Aromatase inhibitors—anastrozole, letrozole, and exemestane—block the enzyme that converts testosterone to estradiol in the overall pathway that increases estrogen synthesis. Many patients on taking these drugs develop a recognized syndrome involving joint pain (shoulder, knees, hips, low back), morning stiffness, tendon irritation, “trigger finger,” “tennis elbow,” or carpal tunnel symptoms.
Tamoxifen works differently. It blocks estrogen receptors in breast tissue but can exert estrogen-like effects elsewhere, particularly in postmenopausal bone. It generally causes fewer joint symptoms than aromatase inhibitors, although it can still cause musculoskeletal pain. In the ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial, joint symptoms occurred in 35.6% of anastrozole users and 29.4% of tamoxifen users.
- Prostate cancer: lowering testosterone also affects estradiol
Androgen-deprivation therapy, or ADT, reduces testosterone production as well as androgen signaling. Men on ADT commonly experience significant loss of muscle mass, accelerated bone loss, increased fat mass, and weakness, loss of stamina, and increased fractures. Lower testosterone also reduces the substrate available for estradiol production, which adversely affects memory, sleep and further contribute to musculoskeletal symptoms and reduced tolerance for activity. For both groups, the goal is to manage symptoms while preserving effective cancer treatment. Patients should not stop hormone-blocking therapies on their own, and should not add reproductive hormones on their own without extensive discussion with their personal physicians.
Current guidelines in the US do not recommend hormone therapy for men or women after treatment for prostate or breast cancer, but actual research data actually shows that hormone therapy may have benefits and not increase risk of cancer recurrence. These are lengthy discussions beyond the scope of this short Health Tip, but they are discussions and review of the medical studies that I have with my own men and women patients who want to consider hormone therapy after successfully treated cancer. This is also where alternative pain management strategies including nutrition, exercise and specific nutraceuticals can play an important role.
FISH OIL: complementary strategy to reduce pain and inflammatory signaling
Adding Fish Oil is one of my pain-reduction strategies for appropriate patients. Fish oil supplies EPA and DHA, long-chain omega-3 fatty acids that become incorporated into cell membranes. They change the substrates available for producing inflammatory lipid signals and provide starting materials for pathways that help resolve inflammation.
Mechanism 1: changing the inflammatory “message mix”
EPA competes with arachidonic acid in enzyme pathways that produce eicosanoids—short-lived lipid messengers involved in inflammation and pain. This changes the balance of mediators that sensitize sensory nerves. If those nerves become less reactive, ordinary movements hurt less even when the underlying joint structure remains unchanged.
Mechanism 2: supplying materials for inflammation resolution
EPA and DHA serve as precursors for specialized mediators that reduce inflammation:
- EPA contributes to E-series resolvins.
- DHA contributes to D-series resolvins, protectins, and maresins.
These molecules help decrease inflammatory pain by coordinating the clearance of inflammatory cells and debris that trigger pain rather than simply blocking inflammation’s initiation.
Mechanism 3: reducing nerve sensitization
In laboratory and animal research, resolvins reduce activity in pain-related ion channels and dampen exaggerated spinal signaling. These findings help explain the pain relief effects of fish oil in humans.
Fish Oil may complement estradiol’s pain-reducing benefits
Estradiol has multiple effects on pain pathways and significant effects to help reduce pain overall via modifying hormone-sensitive inflammatory and neural pathways, while EPA and DHA alter lipid signaling and supply inflammation-resolution substrates. Their actions complement one another and are a combination I often find beneficial in my menopausal patients.
Based on my clinical experience over many years of medical practice seeing improved pain after adding EPA/DHA to a stable estradiol regimen, I do think it is worth considering even if we don’t have controlled trials confirming that estradiol plus fish oil provides a synergistic joint-pain benefit in menopausal women. Here is where mechanistic plausibility and clinical experience provides guidance for shared decision-making with patients who need help now, before we have formal studies to confirm physiologically plausible benefits.
My recommendations: TruOmegaPure™ and TruSynovial Support™.
If you want to try adding Fish Oil, I don’t recommend just any fish oil off the drug store or warehouse shelf. It is important to select a product with documented sourcing and purity of high quality ingredients and formulated in a way to enhance bioavailability. I found two products that I think meet these standards to put in the Truth for Health foundation store: TruOmega Pure and TruSynovial Support™.
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