Anti-Aging Hormone Supplements: Hope or Hype?

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By Dace L. Trence, MD, FACE
Pharmacist discussing a medication with an elderly couple

Emphasis on looking youthful and feeling energetic surrounds us all. Whether in magazine ads, on TV, or the Internet, photos of people who appear to look decades younger than they reportedly are and articles about vigorous 90- and even 100-year-olds with energy that seems boundless – who cannot help thinking, “I want some of what they have!”

We’ve all heard about hormones that claim to offer the benefits of a proverbial fountain of youth. But what is behind these claims? What support or hard science is there behind those ads for DHEA, growth hormone, estrogen and testosterone? Here we examine the facts.

DHEA

DHEA, or dehydroepiandrosterone, is a hormone that is normally produced by your adrenal glands. Blood levels of DHEA naturally decrease after about age 25 to 30, and by age 70, DHEA levels typically have fallen by about 80 percent. People with certain major chronic diseases tend to have more rapid declines in DHEA, so it’s tempting to wonder if replacing DHEA to match that of younger age levels could be beneficial. To that end, DHEA supplements are sold as over-the-counter, non-prescription medication in the U.S. – which many people think are safe to use. However, in other countries such as Canada, DHEA is only available by prescription.

DHEA is typically advertised as an aid for people who want to “reverse” aging, boost their immunity, improve their brain function and mental sharpness, and improve muscle strength. But studies do not support DHEA actually providing any benefit for these functions. DHEA has been studied as a treatment for uses ranging from preventing the development of cardiovascular disease to delaying or treating the symptoms of menopause. Even prevention of Alzheimer’s disease has been proposed as a DHEA benefit, although clinical results are murky at best.

The appeal seems to be that DHEA, at times called a “parent” or “master” hormone, is converted into other hormones, specifically testosterone and estrogen. Many of its so-called benefits (and possible risks) are attributed to its potential conversion to these hormones.

"…Overall sexual function and quality of life were no different between the testosterone group versus the group taking a placebo."

However, DHEA does not have the same effect in everyone. The chemistry is complex, and the results can vary considerably and can be unpredictable. One of the better studies on DHEA took place approximately a decade ago. In this study, elderly men and women were given daily DHEA – 75 milligrams for men and 50 milligrams for women – to achieve blood levels present in young people of the same gender. Measurements were taken over the course of two years for muscle strength, exercise tolerance, quality of life, and measures of insulin sensitivity. The expansive study did not support claims that taking DHEA showed benefits.

It was noted, however, that the elderly women in the DHEA group had a small but significant increase in bone density at the wrist, while men in the DHEA group had an increase in bone density at the hip. Study investigators felt that the very limited bone effect did not support the value of DHEA for either preventing or treating osteoporosis in elderly men or women, but they added that there did not appear to be any side effects with the medication.

One form of DHEA supplement known as 7-Keto has been advertised as an aid for reducing body fat and increasing metabolism. The idea is that leaner body tissue and higher metabolism will burn calories more efficiently, making it easier to not only lose weight, but to keep it off as well. Unfortunately, most studies have shown little effect from DHEA in losing weight or increasing metabolism.

Plus, there are the potential side effects to be considered:

  • Oily skin and acne, as well as skin thickening
  • Hair loss
  • Upset stomach
  • High blood pressure
  • Changes in menstrual cycle
  • Facial hair in women
  • Deepening of the voice in women
  • Fatigue
  • Rapid or irregular heart beat
  • Insomnia
  • Unfavorable changes in cholesterol levels

What About Testosterone?

Many drug commercials promise instant relief from a decreased sex drive, loss of energy and moodiness for men who have low testosterone levels. It appears that message has hit home as use of testosterone replacement therapy has skyrocketed during the past 10 to 15 years. As men age, it is natural for the amount of testosterone in their bodies to gradually decrease. This decline begins after the age of 30 and continues throughout life. According to the American Urological Association, as many as four in 10 men older than 45 have lower-than-normal levels of testosterone. This decline has been associated with symptoms such as loss of energy, reduced sex drive, erectile dysfunction, loss of muscle mass, loss of strength, loss of bone mineral density, increase in body fat, decreased sense of well-being, and several other undesirable effects that can dramatically decrease quality of life.

But, the results of replacing testosterone in those with low levels have been mixed. For example, the TEAAM study, a well-done investigation with rigorous qualifications, researched whether testosterone administration for three years would improve mind sharpness and other physical factors in men 60 years and older who had baseline low or low-to-normal serum testosterone concentrations.

The study findings included no significant change in how open major blood vessels were. Additionally, overall sexual function and quality of life were no different between the testosterone group versus the group taking a placebo (a substance that has no therapeutic effect, used as a control in testing drugs). But men in the testosterone group had side effects, including increased hemoglobin in the blood and increased concentrations of prostate-specific antigen (PSA), which can be an early indication of prostate cancer.

In a subset of the participants, tests that evaluated mind sharpness and thinking ability showed no significant difference between the group taking testosterone and the group taking a placebo. These negative findings are the best evidence so far regarding the lack of effect of testosterone treatment on cognition in fairly healthy older men with low testosterone. One could argue that perhaps the results could be different in less healthy men, men with chronic illness, or perhaps even an older-aged group, but those studies remain to be done.

Possible side effects of testosterone therapy in men include:

  • Increased acne
  • Fluid retention
  • Increased urination
  • Breast enlargement
  • Decreased testicular size
  • Decreased sperm count
  • Increased aggressive behaviors

What About Estrogen?

Estrogen is another hormone that normally decreases with time in women and is known to be associated with bone density loss, skin changes, hair thinning and (perhaps) changes in mind sharpness. At menopause, hot flashes, sleep disturbances and vaginal dryness can prompt many women to consider whether hormone replacement therapy could be helpful for them.

By age 50, most women will have half the amount of estrogen they started with, and levels continue to fall after menopause. Why some women have severe low-estrogen symptoms and others don’t is unclear. In the 1990s, two of the largest studies of hormone replacement therapy were initiated. One was a randomized trial in the U.S. [Women’s Health Initiative (WHI)], and one was an observational questionnaire study conducted in the U.K. [the Million Women Study (MWS)]. The published results of these studies during 2002 and 2003 raised concerns regarding the safety of hormone replacement therapy (HRT). These concerns emphasized two main issues:

  1. That the extended use of HRT may increase the risk of breast cancer, and;
  2. The use of HRT may increase (and not decrease, as was commonly thought at the time) the risk of heart disease.

Subsequent analyses, particularly of the U.S. study results, have suggested that the results show a more complex picture than initially realized. The apparent increased risk for breast cancer was only found in those who had taken HRT before entering the study. In addition, the age of the participants made a huge impact in the results of hormone replacement. Re-analyses of different age groups showed no increase in heart disease in women starting hormonal replacement within 10 years of menopause.

Subsequently, a large controlled trial from Denmark in 2012 demonstrated that healthy women taking combined hormonal therapy for 10 years immediately after menopause had a reduced risk of heart disease and of dying from heart disease.

Studies regarding estrogen’s possible effects on mental sharpness have been contradictory, but generally do not suggest a benefit.

The effects of estrogen use on skin – increased skin thickness and improved skin moisture – have had the most positive results. In menopause, as estradiol levels decline, skin thickness decreases by over 1 percent each year for the first five years, while collagen – a protein in the body that helps give structure to our skin – decreases yearly by 2 percent. Wrinkles are caused by a reduction in elasticity secondary to loss of connective tissue, which decreases 1.5 percent each year. And the face is preferentially involved, as estrogen receptors are higher in the face than in the breast or thigh, for example.

Many wonder if skin changes are reversible with estrogen use. In one study, an estrogen cream applied to the face for 24 months produced significant increases in skin thickness and decreases in wrinkles, while a different study in which subjects took 0.01 percent estradiol (manufactured estrogen) versus 0.3 percent estriol for six months produced no changes in systemic hormone status, but both dosages increased skin elasticity, skin moisture and firmness, and reduced wrinkles.

Still, you may not need estrogen to enjoy this type of benefit. In study participants given either 0.01 percent estradiol, or 15 percent glycolic acid alone or in combination with estradiol, epidermal (skin) thickness was increased 23 percent by estradiol alone, 27 percent by glycolic acid alone, and 38 percent by both in combination. Glycolic acid, a weak acid with small molecules that penetrate the skin easily, dissolves oil gland secretions and other substances that hold superficial skin cells together, which encourages new cell development. Other agents with a better safety profile continue to be researched.

What Truly Keeps Us Youthful?

There are countless books, blogs and articles that offer advice on how to stay forever young. Some of the common themes include keeping physically active, eating more plant-based and low-fat foods, decreasing stress levels, and staying engaged socially.

Researchers at University College London asked approximately 6,500 men and women who were age 52 and older the question, “How old do you feel you are?” Of the group (whose collective age averaged 65 years), about 70 percent felt three or more years younger than their actual age. Twenty-five percent felt close to their actual age, and 5 percent felt more than one year older than their actual age. The really interesting association came eight years later, when the same researchers looked at who was still living.

The results showed:

  • 75 percent of those who felt older than their age were still alive
  • 82 percent of those who felt their actual age were still living, and
  • 86 percent of those who felt younger than their age were alive

Suffice it to say, a positive attitude may not be the key to eternal youth, but it clearly can make an impact on how we age.