~Depression, Part 3 - Natural Hormone Replacement

Natural Hormone Replacement

  • DHEA
  • Progesterone
  • Pregnenolone
  • Testosterone


Only 20-30% of postmenopausal women in the United States take conventional HRT (using estrogen alone or in combination) even though proper hormone modulation can prevent degenerative disease and improve physical and emotional functioning. Why? The reason is that many women are concerned about the life-threatening effects of synthetic hormones. There are, however, natural hormone therapies available to both men and women who may be suffering the consequences of a deficiency in certain hormones. Scientific studies continue to show that depression is often one of the consequences of hormonal deficiency.

DHEA. Dehydroepiandrosterone (DHEA) is produced by the adrenal glands and gonads. It serves as a parent compound for estrogen and testosterone. It is important for brain function. The brain contains six and a half times more DHEA than any other organ. From puberty, DHEA levels rise steadily, peaking at about the age of 25. By age 70 or 80, there is only about 10% of that peak amount left. Thus, it may be helpful for many people to take supplemental DHEA. Preliminary research suggests that it is helpful in treating adrenal insufficiency and in improving well-being in menopausal women and elderly men (Yen et al. 1995; Morales et al. 1998; Hunt et al. 2000).

Researchers have different theories about how DHEA alleviates depression. Both DHEA and DHEA sulfate (DHEA-S) can cross the blood-brain barrier and interact with the brain directly. DHEA can affect serotonin, GABA receptors, and other brain factors. A 1999 study indicates it might modulate the serotonin signaling pathway (Inagaki et al. 1999). In addition, DHEA is the precursor for estrogen and testosterone which have been reported to enhance mood.

DHEA also has anti-stress effects that may be part of its antidepressant action. Research shows that cortisol, the stress hormone, is elevated in major depression. DHEA counteracts cortisol. Calmness appears to be associated with higher levels of DHEA. People who practice transcendental meditation have higher levels of DHEA than those who do not. People who took part in a stress reduction program were able to increase their DHEA by 100%. At the same time, they reduced their stress hormone by 23%.

Preliminary research suggests that DHEA supplementation in people with adrenal insufficiency and in postmenopausal women and older men improves, among other things, psychological well-being (Hoeger et al. 1999; Hunt et al. 2000; Rigaud et al. 2001). A 1997 study conducted at the University of California at San Francisco School of Medicine found that elderly patients with depression and low DHEA levels respond well to DHEA supplementation, with dosing ranging between 30-90 mg a day (Wolkowitz et al. 1997).

In the first double-blind, placebo-controlled study on DHEA's potential as an antidepressant, 11 patients with major depression were given up to 90 mg a day of DHEA for 6 weeks, and 11 were given a placebo. One week before the study actually started, all patients were given a placebo to weed out people who would respond to a sugar pill. People getting the DHEA received 30 mg a day for the first 2 weeks; 60 milligrams the second 2 weeks; and 90 milligrams the last 2 weeks. The idea of the graduated dose was to bring patients up to the DHEA levels they had when they were 20-30 years old (DHEA declines with age). Although the amount of DHEA was not adjusted individually, the graduated dose approximates what it takes to reach a "youthful" level in most people, according to Dr. Owen Wolkowitz, principle investigator of the study (Wolkowitz et al. 1999).

Some of the participants were taking antidepressants. For these people, the antidepressants were either working partially or not at all. Only people who had been on the same antidepressant for at least 6 weeks without changing were allowed in the study, and no changes could be made in anyone's medication during the study.

After 6 weeks, psychological tests indicated that about half the participants responded to DHEA therapy, with an overall enhancement of mood scores by 30.5%. This is close to the response rate of antidepressant drugs (Wolkowitz et al. 1999).

A study by Bloch et al. (1999) at the National Institute of Mental Health found that 90 mg a day of DHEA for 3 weeks significantly lessened depression among 15 dysthymic patients who were 45 years old and older. A battery of psychological tests was administered, including the Hamilton Depression Rating Scale, the Beck Depression Inventory, a visual analogue scale, and the Cornell Dysthymia Scale. (In addition, a day's worth of cognitive function tests were given, but DHEA did not show a significant effect on cognition in this study. However, the researchers note a trend toward better cognition that could have played out if the study had lasted longer.) Seven symptoms in particular got much better: lack of pleasure; low energy; low motivation; emotional numbness; sadness; inability to cope; and excessive worry. DHEA worked for most people within 10 days. If the supplement was stopped, symptoms came back. Overall, the response rate was 60% which is better than what antidepressants usually do for dysthymia (Bloch et al. 1999).

The researchers subsequently gave patients 450 mg of DHEA a day for 3 more weeks, but found that it was not necessary to go to such a high dose in order to improve mood.

Caution: DHEA supplementation is contraindicated in men and women with hormone-related cancers. Consult the DHEA Replacement Therapy protocol for more information. A blood test can determine if DHEA levels are low. If you need supplementation, periodic blood monitoring can determine whether your DHEA levels have risen to the youthful normal range.

Progesterone. Women experience a gradual loss of the critical sex hormone progesterone throughout adult life. This decline becomes significant as women get closer to menopause. Symptoms of a progesterone deficit include premenstrual discomfort, night sweats, and hot flashes, along with feelings of depression. During and after menopause, natural progesterone synthesis often grinds to a halt, setting the stage for a host of menopausal miseries and degenerative diseases. In addition to making people feel better, progesterone may help to prevent the mental decline that occurs with aging. Progesterone has been shown to increase neuronal energy production and to protect brain cells.

Dr. John Lee (one of the world's foremost experts on progesterone therapy) has found studies showing that 20 times more progesterone is concentrated in brain cells than blood serum levels. He postulates that progesterone may help prevent mental decline in the elderly and that recovery after brain trauma is better if progesterone levels are higher.

Dr. Lee also has pointed out that progesterone has been shown to increase brain cell energy production while suppressing hyperexcitotoxicity. Excitotoxicity occurs when too much (or too little) of neurotransmitters such as glutamate is released from brain cells. This type of toxicity is now considered a cause of brain aging and degenerative neurological disease.

The issue of synthetic versus natural hormones is as important with progesterone as it is with estrogen. Just as the pharmaceutical industry created their dangerous estrogen drug Premarin, they produced a pseudoprogesterone named Provera. As with Premarin, the warning label on Provera is full of dangers including the possibility of birth defects, breast cancer, blood clots, fluid retention, acne, rashes, weight gain, and depression. Such drugs as Provera are classified as "progestins," not as progesterones. The side effects of Premarin and Provera may be the main reason women stop taking their replacement hormones and are the reason that HRT has such a questionable and spotty reputation.

An alternative to progestins is using natural progesterone products. Products like Life Extension's Pro-Fem use progesterone synthesized from soybeans. Not only are such soy-derived natural progesterones far safer than synthetic drugs, they are as easily utilized as the real progesterone manufactured within the human body. The preferable forms of natural progesterone are creams that are rubbed into appropriate areas of soft tissue such as the chest, breast, underarms, face, abdomen, buttocks, or inner thighs. This route of administration bypasses the liver and allows hormone delivery to the place where it is needed the most. For example, progesterone cream applied to the breasts slows cell proliferation and eases breast pain. As for safety, according to Northrup (1994), "there is virtually no danger of overdose."

In a study conducted at the Mayo Clinic, 176 women using hormone replacement therapy were changed from synthetic progesterone to natural progesterone. Of the total, 147 were menopausal. The remainder of the women were premenopausal with amenorrhea. Women reported significant improvement in eight of nine domains tested in the study, including sleep disturbance; anxiety; depression; somatic symptoms; menstrual problems; cognitive difficulties; sexual functioning; and vasomotor symptoms. The majority of respondents (80%) reported excellent satisfaction with the natural progesterone; 65% thought it was better than any other previous regimen they followed; and more than 70% believed that the current regimen would reduce future health risks (Fitzpatrick et al. 2000). (Consult the Female Hormone Modulation Therapy protocol for additional information on natural hormone replacement.)

Pregnenolone. Pregnenolone is another hormone produced by the ovaries and by the adrenal glands in men and women. It can be very useful for treating depression. Some studies have shown that depressed people have less than normal amounts of pregnenolone in their spinal fluid. Pregnenolone likely works by preventing the brain from being overwhelmed by GABA (gamma-aminobutyric acid) and other hormones that slow its activity.

Although pregnenolone may help relieve depression, it may earn its greatest accolades through its beneficial effect upon the mind, especially the memory. Studies have shown that giving this hormone to older men and women improves their performance on tests of memory and concentration. Research, moreover, indicates that pregnenolone:

  • Improves the ability to remember and retrieve information
  • Increases the ability to handle stress
  • Has a beneficial effect on the myelin sheath membranes, which protect the brain and nervous system
  • Helps to keep the nervous system on an even keel


Testosterone. As men enter their 40s, hormonal changes occur that often produce a noticeable effect on physical, sexual, and cognitive energy levels, as well as a loss of feeling of well being. Until recently, these changes were attributed to "growing old," and men were expected to accept the fact that their body was entering into a long degenerative process that would some day result in death.

Data gathered over the last few years indicates that many of the diseases that men begin experiencing over age 40, including depression, abdominal weight gain, prostate, and heart disease, are directly related to hormone imbalances that are correctable with currently available drug and nutrient therapies. Unfortunately, conventional doctors typically prescribe antidepressant, cholesterol-lowering, and other drugs to correct symptoms of a possible hormone imbalance. If doctors checked their male patient's blood levels of estrogen, progesterone, testosterone, prolactin, thyroid, and DHEA (instead of prescribing drugs to treat symptoms), they might be surprised to learn that many problems could be eliminated by adjusting hormone levels to fit the profile of a healthy 21 year old.

A consistent finding in the scientific literature is that testosterone replacement therapy produces an increased feeling of well-being. Published studies show that low testosterone correlates with symptoms of depression and other psychological disorders (Moger 1980; Barrett-Connor et al. 1999; Schweiger et al. 1999; Seidman et al. 1999; Rabkin et al. 1999).

A common side effect of prescription antidepressant drugs is the suppression of libido. Those with depression either accept this drug-induced reduction in quality of life or get off the antidepressant drugs so they can at least have a somewhat normal sex life. If more psychiatrists tested their patients' blood for free testosterone and prescribed natural testosterone therapies to those with low free testosterone, the need for libido-suppressing antidepressant drugs could be reduced or eliminated. As previously described, testosterone replacement often enhances libido, the opposite effect of most prescription antidepressants.

One study showed that patients with major depression experienced improvement that was equal to that achieved with standard antidepressant drugs (Rabkin et al.1999).

Androderm is one of several natural testosterone-replacement therapies that can be prescribed by doctors. A 12-month clinical trial using this FDA-approved drug resulted in a statistically significant reduction in the depression score (6.9 before versus 3.9 after). Also noted were highly significant decreases in fatigue: from 79% before the patch to only 10% after 12 months (Androderm Testosterone Transdermal System). According to Jonathan Wright, M.D., co-author of Maximize Your Vitality & Potency, the following effects have been reported in response to low testosterone levels:

  • Loss of ability to concentrate
  • Moodiness and emotionality
  • Touchiness and irritability
  • Great timidity
  • Feeling weak
  • Inner unrest
  • Memory failure
  • Reduced intellectual agility
  • Passive attitudes
  • General tiredness
  • Reduced interest in surroundings
  • Hypochondria


The above feelings can all be clinical symptoms of depression. Testosterone replacement therapy has been shown to alleviate these conditions. Testosterone thus has exciting therapeutic potential in the treatment of depression in men.

Testosterone, however, is one of the most misunderstood and mistakenly maligned hormones. Body builders tarnished the reputation of testosterone by injecting large amounts of it into their youthful bodies. Testosterone abuse can produce detrimental effects, but this has nothing to do with the benefits a man over age 40 can enjoy by properly restoring his testosterone to a youthful level.

Some early studies showed testosterone replacement therapy to be ineffective in treating the symptoms of aging because the testosterone showed only a temporary benefit, with the positive effects wearing off within a few weeks. These studies failed to identify that exogenously administered testosterone readily converts to estrogen in the body. The higher estrogen level negates the benefits of the exogenously administered testosterone. The solution to the estrogen-overload problem is to block the conversion of testosterone to estrogen in the body so that aging men can restore their strength, stamina, cognitive function, heart function, sexuality, and their outlook on life, i.e., alleviate symptoms of depression (Baker et al. 1976; Berkovitz et al. 1985). Several natural supplements described in the Male Hormone Modulation Therapy protocol will help remove excess estrogen from the blood or inhibit its formation from testosterone.

Testosterone is much more than a sex hormone. There are testosterone receptor sites in cells throughout the body, most notably in the brain and heart. Youthful protein synthesis for maintaining muscle mass and bone formation requires testosterone. Testosterone improves oxygen uptake throughout the body, helps control blood sugar, regulate cholesterol, and maintain immune surveillance. The body requires testosterone to maintain cardiac output and neurological function. Of critical concern to psychiatrists are studies showing that men experiencing depression have lower levels of testosterone than age-matched controls. For some men, elevating free testosterone levels could prove to be an effective antidepressant therapy. (Men who have depression can refer to the Male Hormone Modulation Therapy protocol). This describes safe ways of boosting free testosterone levels in a way that can alleviate or eliminate certain types of depression. Women should refer to the Female Hormone Replacement Therapy and the DHEA Replacement Therapy protocols for more information on what they can do to adjust their hormone status to improve their mood and alleviate depression.

Continued . . .


Free Shipping in the Continental U.S. on Orders over $50
The statements made here have not been evaluated by the FDA. The foregoing statements are based upon sound and reliable studies, and are meant for informational purposes. Consult with your medical practitioner to determine the underlying cause of your symptoms. Please always check your purchase for possible allergins and correct dosage on the bottle before use.

While we work to ensure that product information is correct, on occasion manufacturers may alter their ingredient lists. Actual product packaging and materials may contain more and/or different information than that shown on our Web site. We recommend that you do not solely rely on the information presented and that you always read labels, warnings, and directions before using or consuming a product. For additional information about a product, please contact the manufacturer. Content on this site is for reference purposes and is not intended to substitute for advice given by a physician, pharmacist, or other licensed health-care professional. You should not use this information as self-diagnosis or for treating a health problem or disease. Contact your health-care provider immediately if you suspect that you have a medical problem. Information and statements regarding dietary supplements have not been evaluated by the Food and Drug Administration and are not intended to diagnose, treat, cure, or prevent any disease or health condition. Life Ex Online assumes no liability for inaccuracies or misstatements about products.