Rheumatoid Arthritis

The Hormone Connection

It is well known that hormone levels are affected by arthritis, especially RA. Studies have shown that women with RA have lower levels of testosterone and DHEA, while they have normal or elevated levels of estrogen (Straub RH et al 2005). These altered levels may be due to the effects of TNF-alpha, which alters production of androgen hormones (Straub RH et al 2005). This elevated estrogen in RA patients is thought to be connected to the enzyme aromatase, which converts androgens into estrogens, including pro-inflammatory estrogens such as 17 beta-estradiol (Capellino S et al 2005). In fact, in women with RA, the entire balance of estrogen, including the ratio between 16-hydroxylated estrogen and 2-hydroxylated estrogen, seems to be upset in favor of pro-inflammatory estrogens (Cappellino S et al 2005). Finally, local levels of hormones such as insulin, aldosterone, and growth hormone, are elevated in arthritis, suggesting that these hormones also play a pro-inflammatory role (Rovensky J et al 2005).

Because of the variability in hormone levels, researchers have examined the role of DHEA in various forms of arthritis. In the body, DHEA can be converted to both estrogen and testosterone. Hoping to learn whether DHEA can help normalize hormone levels among women with arthritis, researchers have conducted human studies, giving women DHEA and carefully following their hormone levels. In one study of 26 OA patients and 24 RA patients, hormone conversion rates were analyzed. Researchers found that DHEA was converted into a variety of hormones, including anti- and pro-inflammatory estrogens and testosterone, which were further converted into anti-inflammatory metabolites (Schmidt M et al 2005).

DHEA is also known to directly suppress pro-inflammatory cytokines, including interleukin-6 and TNF-alpha, both of which contribute to the joint inflammation that characterizes RA. Research is also shedding new light on the relationship between anti-TNF-alpha drugs, such as Enbrel®, and DHEA. Studies have shown that levels of active DHEA are reduced in the synovial cells of patients with RA. After therapy with anti-TNF drugs, however, the conversion of DHEA into its active form is increased, which would help explain why these drugs have an anti-inflammatory effect (Weidler C et al 2005; Imrich R et al 2005).

The Problem with Conventional Drugs

Although nutritional approaches are the best option, many millions of people still rely on prescription medications to manage their arthritis. Unfortunately, there just isn’t a good solution when it comes to the standard prescription drugs. Even the best among them have serious drawbacks that should give pause. The following drugs are used to treat arthritis:

• NSAIDs. These drugs represent the mainstay of conventional treatment for arthritis. Over-the-counter NSAIDs, such as naproxen (Aleve®), ibuprofen, and others, operate by inhibiting the cyclooxygenase enzymes (COX-1 and COX-2), which convert arachidonic acid to pro-inflammatory PGE2. Side effects of over-the-counter NSAIDs include gastrointestinal upset because the COX-1 enzyme is also partly responsible for maintaining the mucosal lining of the stomach. In an attempt to reduce this side effect, prescription-selective COX-2 inhibitors were introduced. These drugs, including Vioxx®, Bextra®, and Celebrex®, were as effective as the older NSAIDs and did not produce the side effects. In 2004, however, Vioxx® was linked to increased risk of heart attack and cerebrovascular events. It was subsequently removed from the market by its manufacturer. Not long after, Bextra® was also voluntarily removed because of increased risk of cardiovascular events. Celebrex® is still on the market, but the Food and Drug Administration has demanded that a strong “black box” be added to its label, warning people who take this drug of the increased potential for heart attack.
• Slow-acting drugs. This type of drug includes gold compounds, penicillamine, hydroxychloroquine, and sulfasalazine. These drugs slow the progression of RA by interfering with the disease process. For example, gold compounds and penicillamine slow the formation of bone deformities. All these drugs can cause liver and kidney toxicity. Other side effects include rashes, stomach upset, and itching. They are sometimes recommended for patients who cannot tolerate NSAIDs.
• Corticosteroids. Prednisone, a corticosteroid, is used mainly as a treatment for RA, although in severe cases of OA, it will be injected directly into the affected joints. Corticosteroids work by reducing inflammation, and some evidence suggests that prednisone may slow bone erosion in RA (Kasper DL et al 2005). Whether these drugs are used as a systemic treatment (for RA), or injected directly into joints (for OA), corticosteroids have significant side effects and should be used with great caution. Injections should be spaced months apart to avoid joint degeneration. Long-term systemic corticosteroid use is associated with a wide range of metabolic abnormalities, including weight gain, osteoporosis, stress fractures, stretch marks, and adrenal gland failure.
• Immunosuppressive drugs. These drugs are sometimes used in RA to suppress the immune response that causes disease progression. Common immunosuppressive drugs used in RA include azathioprine, leflunomide, cyclosporine, and cyclophosphamide. These drugs are not considered first-line therapy. Studies have shown they are no more effective than slow-acting drugs (Kasper DL et al 2005), and they have a variety of toxic side effects, including liver damage and the increased risk of opportunistic infection because of a depressed immune system.
• Narcotics. Narcotics such as codeine and morphine are sometimes used to control pain in acute flare-ups. These drugs must be used only in the short-term because of the risk of dependency.
• Acetaminophen. Acetaminophen is a painkiller, as opposed to an anti-inflammatory. This drug is widely available over the counter, yet few people are aware of the significant danger of long-term acetaminophen use, which can cause liver toxicity. Life Extension does not recommend acetaminophen.

In addition to these medications, surgery may be suggested for patients with severely damaged joints who have not responded to aggressive treatment. In this case, joint replacement may be recommended. This is a last resort.

Product Availability

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The blood tests discussed in this section are available through Life Extension National Diagnostics, Inc. For ordering information, call anytime toll-free 1-800-208-3444, or visit us online at www.LifeExtension.com.