Hormone replacement therapy and joint disease

In this article we discuss the use of estrogen and testosterone for their roles in accelerating joint repair and  healing.

Prolotherapy doctors have long recognized that hormones are a required part of injury and wound healing. New research supports the use of hormones in chronic pain patients.

Hormones drive the immune system and help repair damaged joints. A patient who experiences thinning hair, loss of sex drive, decreased muscle tone, dry skin, menstrual cramping, irregular menses, chronic fatigue, decreased body temperature, and a feeling of coldness has a hormone deficiency until proven otherwise.

Like everything else in our bodies, hormone levels need to be balanced. The “correct balance” can change, based on our gender and age, but everyone needs their hormones balanced in order for their bodies to function the way they were meant to function. When your hormones are off balance, it is a sign that the body is not working correctly. When the body does not function optimally, it cannot heal the way it is supposed to heal. For instance, having high estradiol levels can decrease the ability of the body to make fibroblasts, the cells needed to make connective tissue. This is a consideration for women who are on birth control, as it can hamper healing ability. Low hormone levels can most definitely alter your ability to heal, let alone make you feel sluggish and unhealthy.

The science connection between hormone levels and chronic pain

  • Recently doctors at the University of Oxford found that post-menopausal women who underwent a Total Knee Replacement or Total Hip Replacement had a 40% reduction in the need for a second “corrective” surgery after they went on Hormone Replacement Therapy.1
  • In animal study research at the University of Gothenburg, doctors looking at the Jekyll/Hyde aspects of estrogen on joint destruction (estrogens are both anabolic – builders – and catabolic – destroyers) found that the positive values of estrogen relieved both synovitis and joint destruction.2
  • Research lad by doctors at Austrialia’s University of Tasmania and Monash University found that women with low serum levels of endogenous estradiol, progesterone and testosterone are associated with increased knee swelling-synovitis and possibly other osteoarthritis-related structural changes.10
  • At Wake Forrest University, doctors found estrogen replacement therapy increases the production of IGFBP-2 (Insulin-like growth factor-binding protein 2 – simply as it names implies a growth factor for repair) and the synthesis of Proteoglycan (a joint lubricant) by chondrocytes (cartilage building cells found in the extracelluar matrix). The study concludes that estrogen can have a direct positive effect on adult articular cartilage.3
  • Doctors at Monash University in Australia writing in the medical journal Osteoarthritis Cartilage examined the Relationship between circulating sex steroid hormone concentrations and incidence of total knee and hip arthroplasty due to osteoarthritis in men. They found that higher concentrations of androstenedione (testosterone) were associated with a decreased risk of total knee and hip arthroplasty for osteoarthritis in overweight and obese men. They concluded their study by suggesting that circulating sex steroids (testosterone) may play a role in preventing the development of osteoarthritis in men.4

There is a connection between painkillers and hormone replacement therapy that makes pain worse

  • Doctors at Virginia Commonwealth University writing in the medical journal Opioid endocrinopathysuggested that:
    • Opioids appear to affect multiple endocrine pathways leading to abnormal levels of different hormones such as testosterone, cortisol, and prolactin.
    • Opioids appear to affect each of the pituitary hormone pathways in addition to altering bone metabolism.
    • The most commonly reported and substantial effect was hypogonadism (low testosterone) in both sexes; however, suppression of the adrenal axis may be more common than initially thought. (The hypothalamic–pituitary–adrenal axis is the interactions among three endocrine glands: the hypothalamus, the pituitary gland and the adrenal glands).
    • The doctors concluded that more research is needed to determine which opioids are more likely to cause endocrine dysfunction and which patients need to be screened and treated. Also unknown is the length of time to the development of hormonal changes after starting opioid therapy and if ending opioid therapy can normalize hormone levels.5
  • Doctors of the Research Program in Men’s Health: Aging and Metabolism, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School,  Boston University School of Public Health,  and the University of Pittsburgh School of Medicine found that men with androgen deficiency (low testosterone) brought on by overuse of painkillers and other pain medications, showed improvements in pain, sexual desire, body composition, and aspects of quality of life when put on a testosterone replacement program.6
  • A Swedish study recently focused on the effects of testosterone on chondrocytes (regrowing cartilage). The research concluded that testosterone promotes differentiation of chondrocytes (producing cartilage cells) and increases collagen production.7

Many people believe that testosterone is only a male hormone, but it plays a pivotal role in the female body chemistry as well. Man or women, if one has a low testosterone level, then they will likely experience more difficulty healing.

Testosterone is made by men in the testicles, and females the ovaries. There is also a small production that is created in the adrenal glands. Although the adrenal gland is able to produce a small amount of testosterone, many patients of both genders suffer from depleted adrenals as a result of stress. This stress can arise from pain, lack of sleep, and a myriad of personal issues. So sometimes treating adrenal fatigue to optimize hormone production is called for.

Hormone serum abnormalities are biomarkers of severe, uncontrolled pain

Dr. Forest Tennant, MD, DrPH, wrote in the medical journal Postgraduate Medicine:

Some patients with severe and chronic pain failed to obtain adequate pain relief with standard pain medications, including low to moderate dosages of opioids.

To help characterize these individuals and develop treatment strategies for them, a serum hormone profile consisting of adrenocorticotropin (ATCH), cortisol, pregnenolone, progesterone, dehydroepiandrosterone (DHEA), and testosterone was obtained on 61 chronic pain patients who failed standard treatments; 49 patients (80.3%) demonstrated hormone abnormality and 7 patients (11.5%) showed a severe pituitary-adrenal-gonadal deficiency as indicated by deficient serum levels of adrenocorticotropin and  more than 2 adrenal-gonadal hormones.

These results suggest that hormone serum abnormalities are biomarkers of severe, uncontrolled pain, and, in a patient who has failed standard treatment, they are an indicator that enhanced pain killers are required and that hormone replacement may be indicated.8

A clear connection between hormone levels, stress hormones, and chronic pain can be mode.



1. Prieto-Alhambra D, Javaid MK, Judge A, Maskell J, Cooper C, Arden NK; COASt Study Group. Hormone replacement therapy and mid-term implant survival following knee or hip arthroplasty for osteoarthritis: a population-based cohort study. Ann Rheum Dis. 2015 Mar;74(3):557-63. doi: 10.1136/annrheumdis-2013-204043. Epub 2014 Jan 22.
2. Engdahl C, Börjesson AE, Forsman HF, Andersson A, Stubelius A, Krust A, Chambon P, Islander U, Ohlsson C, Carlsten H, Lagerquist MK. The role of total and cartilage-specific estrogen receptor alpha expression for the ameliorating effect of estrogen treatment on arthritis. Arthritis Res Ther. 2014 Jul 15;16(4):R150. doi: 10.1186/ar4612.
3. Richmond RS, Carlson CS, Register TC, Shanker G, Loeser RF. Functional estrogen receptors in adult articular cartilage: estrogen replacement therapy increases chondrocyte synthesis of proteoglycans and insulin-like growth factor binding protein.
4 Hussain SM, Cicuttini FM, Giles GG, Graves SE, Wang Y. Relationship between circulating sex steroid hormone concentrations and incidence of total knee and hip arthroplasty due to osteoarthritis in men. Osteoarthritis and Cartilage. 2016 Aug 31;24(8):1408-12.
5. Demarest S, Gill R, Adler R. Opioid endocrinopathy. Endocrine Practice. 2014 Dec 22;21(2):190-8.
6. Basaria S, Travison TG, Alford D, Knapp PE, Teeter K, Cahalan C, Eder R, Lakshman K, Bachman E, Mensing G, Martel MO, Le D, Stroh H, Bhasin S, Wasan AD, Edwards RR. Effects of testosterone replacement in men with opioid-induced androgen deficiency: a randomized controlled trial. Pain. 2015 Feb;156(2):280-8.
7. Lorentzon M, Swanson C, Andersson N, Mellstrom D, Ohlsson C. Free Testosterone is a Positive, Whereas free Estradoil Is a Negative, Predictor of Coritcal Bone Size in Young Swedish Men: The GOOD Study. Journal of Bone and Mineral Research 2005; 20(8) : 1334-1339.
8. Tennant F. Hormone abnormalities in patients with severe and chronic pain who fail standard treatments. Postgrad Med. 2015 Jan;127(1):1-4. Epub 2014 Dec 15.

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