Health maintenance through hormone replacement therapy

Low DHEA Levels Linked to Burnout
In study after study DHEA has shown anti-stress benefits
By Will Block

Dehydroepiandrosterone (DHEA) exists in the human body in sulfate form (DHEA-S), where it operates as an important anabolic protective hormone for health maintenance, as many studies have shown. DHEA-S (hereafter DHEA) levels peak in young adults and decline thereafter with age. For this and other reasons it is known as the youth hormone (see Fig. 1). DHEA has previously been shown to be lower in individuals reporting prolonged stress. Extending that finding, a new investigational study has discovered that DHEA levels are low in patients with clinical burnout, a disorder caused by long-term psychosocial stress.1

In the new Swedish study, 122 patients suffering from clinical burnout (51% men) and 47 controls (51% men) in the age range of 25-54 years were divided into three 10-year-interval age groups. DHEA levels were compared between patients and controls in the whole sample and within each of the groups.


A new investigational study has
discovered that DHEA levels are low
in patients with clinical burnout, a
disorder caused by long-term
psychosocial stress.


Women’s Burnout Exceeds Men’s

In the youngest age group (25-34 years), DHEA levels were on average 25% lower in the burnout group compared to the healthy controls. Also, the differences in DHEA levels between patients and controls were more pronounced among female than male participants (on average 32% and 13% lower, respectively). There were no differences in DHEA levels between patients and controls in the age group 35-44 years or 45-54 years or when analyzing all age groups together. This may be due to the great falloff in DHEA that comes with age (see Fig. 1).


In the youngest age group (25-34
years), DHEA levels were on average
25% lower in the burnout group
compared to the healthy controls.


Supporting this, the new study indicates that levels of the health promoting “youth” hormone DHEA are low in younger burnout patients. The fact that healthy younger adults have much higher DHEA levels and more pronounced inter-subject variability in DHEA levels than older individuals might explain why burnout status differentiates patients from controls only among the youngest patients included in this study. To see this effect, it would be necessary to restore youthful levels of DHEA through supplementation.


Burnout is defined as a negative
affective state consisting of emotional
exhaustion, cognitive weariness and
physical fatigue, which is caused by
chronic psychosocial stress.


What’s Burnout and Who Suffers from It?

Burnout is defined as a negative affective state consisting of emotional exhaustion, cognitive weariness and physical fatigue, which is caused by chronic psychosocial stress. It is actually a syndrome, a group of medical signs and symptoms that are connected with each other and, quite often, with a specific disease. The Burnout Syndrome derives from the Greek word for “concurrence.”


In addition to being a precursor to
androgens and estrogens, DHEA is an
active hormone in its own right, with
many effects.


Burnout frequently leads to loss of the ability to work and consequently long-term sick leave. It is frequently attended by depression and anxiety. Besides the weariness and mental health burden, it is also associated with increased risk of adverse physical health.

DHEA Postpones Aging in Rats

In a new study the effect of chronic administration of DHEA on steroid hormones and antioxidant parameters in aged rats was investigated. Three groups of rats were compared: 1) young (3 months of age) untreated; 2) aged (19 months old) untreated; and 3) aged rats treated with 20 mg/kg DHEA for 8 weeks.

Major organs of aged rats in the untreated group demonstrated physiological atrophy (gradual decline in effectiveness or vigor), compared to the young rats; this effect appeared to have been partially reversed by DHEA treatment.

Testosterone and estradiol contents were significantly decreased and aldosterone significantly increased in aged untreated, compared to young untreated rats.


DHEA administration may have
effects on steroid hormone levels
and antioxidant parameters in aged
rats and result in postponement of
the aging process.


Steroid hormone levels were clearly reversed, however, in aged rats treated with DHEA. Additionally, superoxide dismutase activity in serum, brain, heart, and liver was decreased, and malic dialdehyde content in heart was markedly increased in untreated aged, compared to young, rats. Importantly, these changes in brain and heart of aged rats were reversed by DHEA treatment. These results indicate that chronic DHEA administration may have effects on steroid hormone levels and antioxidant parameters in aged rats and result in postponement of the aging process.

DHEA—Historical Data

DHEA is major steroid hormone produced by the adrenal zona reticularis. One of its main characteristics is its age-dependent secretion pattern; production begins during fetal life and then steadily declines at a rate of 2 to 5% per year to a total decline of up to 80% in old age.2

A Number of Beneficial Effects

Clinically, a number of beneficial effects of DHEA treatment have been described and include improved mood states in the clinically depressed,3 improved psychological well-being in the elderly4 and correction of hormone levels in patients with adrenal deficiencies.5

Administration of large doses of DHEA to rodents has demonstrated a multitude of beneficial effects including reduced incidence of cancer, heart disease, diabetes, and obesity.6 Its availability as a food supplement in the USA has resulted in large-scale self-administration of DHEA as an “anti-ageing” drug, in the absence of medical supervision.

In aging individuals, endocrine changes result in decreased hormone secretion by peripheral glands.7 DHEA appears to serve as a prohormone, and could be rapidly metabolized within target tissues into biologically active steroids, including androstenedione, testosterone, and estradiol4,8,9 and, in aged adults, dietary supplementation with DHEA may have protective effects on the brain and heart.10

A study already mentioned4 assessed the effect of a large dose (100 mg) of DHEA for a prolonged duration (6 months), on circulating sex steroids in age-advanced men and women, and demonstrated that testosterone was increased to levels above young adult ranges. Previously it was demonstrated that serum concentrations of testosterone, estradiol and aldosterone were markedly increased in testis tissues of rats following treatment with DHEA.11 Androstenedione and testosterone levels have also been shown to be significantly increased in aged adults, following treatment with DHEA4,9 Taken together, these findings suggest that the restoration of DHEA may alter hormone contents, and potentially have anti-aging effects.

References

  1. Yin FJ, Kang J, Han NN, Ma H. Effect of dehydroepiandrosterone treatment on hormone levels and antioxidant parameters in aged rats. Genet Mol Res. 2015 Sep 22;14(3):11300-11. doi: 10.4238/2015.September.22.24.
  2. Genazzani AD, Lanzoni C and Genazzani AR. Might DHEA be considered a beneficial replacement therapy in the elderly? Drugs Aging. 2007;24:173-85.
  3. Wolkowitz OM, Reus VI, Roberts E, Manfredi F, et al. Dehydroepiandrosterone (DHEA) treatment of depression. Biol Psychiatry. 1997;41:311-8.
  4. Morales AJ, Haubrich RH, Hwang JY, Asakura H, et al. The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol. 1998;49:421-432.
  5. Hunt PJ, Gurnell EM, Huppert FA, Richards C, et al. Improvement in mood and fatigue after dehydroepiandrosterone replacement in Addison’s disease in a randomized, double blind trial. J. Clin. Endocrinol. Metab. 2000;85:4650-6.
  6. Bacsi K, Kosa J, Lazary A, Horvath H, et al. (2007). Significance of dehydroepiandrosterone and dehydroepiandrosterone sulfate in different diseases. Orv Hetil. 2007;148:651-7.
  7. Chahal HS and Drake WM. The endocrine system and ageing. J Pathol. 2007;211:173-80.
  8. Arlt W, Haas J, Callies F, Reincke M, et al. Biotransformation of oral dehydroepiandrosterone in elderly men: significant increase in circulating estrogens. J Clin Endocrinol Metab. 1999;84:2170-6.
  9. Labrie F, Belanger A, Belanger P, Berube R, et al. Metabolism of DHEA in postmenopausal women following percutaneous administration. J Steroid Biochem Mol. Biol. 2007;103:178-88.
  10. Arlt W. Dehydroepiandrosterone and ageing. Best Pract Res Clin Endocrinol Metab. 2004;18:363-80.
  11. Song L, Tang X, Kong Y, Ma H, et al. The expression of serum steroid sex hormones and steroidogenic enzymes following intraperitoneal administration of dehydroepiandrosterone (DHEA) in male rats. Steroids. 2010;75:213-8.

DHEA for Health Maintenance and Restoration

In addition to being a precursor to androgens and estrogens, DHEA is an active hormone in its own right, with many effects. Indeed, DHEA has a regenerative and protective role important for maintenance and restoration of health. As an example, DHEA enhances the activity of the body’s own antioxidant system, prevents atherosclerosis by stimulating the production of nitric oxide (NO) in blood vessels and stimulates neurite growth, neurogenesis, and neural survival.2 DHEA is produced in the zona reticularis area of the adrenal cortex in response to adrenocorticotrophic hormone (ACTH). The production peaks in young adulthood. Thereafter, the levels decline progressively by 2–4% per year (see Fig. 1).


Independently of age, low levels of
DHEA have mostly been reported to
be associated with both subjective
perception of poor health and
different disease states.


DHEA and Disease States

Independently of age, low levels of DHEA have mostly been reported to be associated with both subjective perception of poor health and different disease states. The Swedish researchers (along with scientists around the world) have previously reported that DHEA levels are lower in individuals reporting undergoing psychosocial stress.

Since burnout is a consequence of long-term stress, and since it is a syndrome associated with both psychological and physiological adverse health, the researchers thought it would be important to investigate DHEA levels in burnout.


Higher levels of DHEA are associated
with participating in and enjoying
pleasurable activities.



LEM1511Fig1_254.jpg
(click on thumbnail for full sized image)

Low DHEA levels in these patients constitute one of the links between stress and adverse health associated with burnout. Nonetheless, out of four previous publications on DHEA levels in burnout, three reported no difference between burnout subjects and controls3,4,5 and one publication reported higher DHEA levels in the individuals with burnout.6 The present study aimed to investigate DHEA levels in patients with clinical burnout compared to healthy controls without burnout symptoms. The relatively large sample of patients in the study allows for separate analyses in different age groups, which is an advantage since DHEA is strongly age-related.

In conclusion, the present study indicates that levels of the health promoting “youth” hormone DHEA are low in younger burnout patients. The fact that younger adults have much higher DHEA levels and more pronounced inter-subject variability in DHEA levels than older individuals might explain why burnout status differentiates patients from controls only among the youngest. Low DHEA levels in these patients may constitute one of the links between stress and adverse health associated with burnout.


DHEAS levels are lowest in those
patients (both men and women)
being treated for depression.


DHEA is Anti-Stress

Dr. Ward Dean, Life Enhancement’s Medical Editor has written (see “What You Should Know About DHEA” in the December 2013 issue):

“Abnormally low levels of DHEA have been reported to be related to a number of diseases, including cancer, diabetes, coronary artery disease, obesity, and Alzheimer’s. Conversely, supplemental DHEA has been reported in study after study to have immunoregulatory, anti-diabetic, anti-cancer, anti-obesity and anti-stress activity, and to be involved in the prevention of atherosclerosis, hypertension, hypercholesterolemia, Alzheimer’s disease and multiple sclerosis [emphasis added].”7,8


The patients receiving DHEA
were less depressed than those
who were not.


DHEA Levels Up; Cortisol Down

In a study published in 1996, scientists measured DHEA and cortisol in 62 subjects aged 3-85 years old, 36 of whom were males and 36 females. Also noteworthy, the researchers determined that the ratio of cortisol to DHEA increased with age in the brain. Due to the decrease in DHEA, the result was relative hyper-cortisolemia. Because cortisol tends to exacerbate stress, and DHEA to lessen it (DHEA has antiglucocorticoid activity), relative hyper-cortisolemia is an ominous sign of the inevitable ravages of the aging process that may be ameliorated with DHEA supplementation.9

Improved Moods with Higher DHEA Levels

There have been a number of studies that suggest a direct role between elevated DHEA and improved mood in patients with clinical depression. For example, depression is more common in women with nondetectable DHEA levels than in women with detectable levels. Another study has shown that in institutionalized patients, DHEA levels are lowest in those patients (both men and women) being treated for depression.10


The levels of beta-endorphin
(the principal “feel-good” hormone)
tripled, and the levels of cortisol
(the principal stress hormone)
fell by about 35%.


Happiness Prevails with DHEA

Of importance, the reverse of this situation is also true. Higher levels of DHEA are associated with participating in and enjoying pleasurable activities. In fact, one research paper consolidates information from a number of trials by reporting that, “… higher serum levels of DHEA and DHEAS have been associated with greater amount, frequency, and enjoyment of leisure activities; higher ‘dominance’ and ‘expansive personality’ ratings; and greater ‘sensation-seeking’ attributes.”11 In other words, happiness is more prevalent in those with high blood levels of DHEA.


DHEA treatment significantly
improved overall well-being as well as
scores for depression, anxiety, and
their physical correlates.


DHEA Improves Mood in Patients with Major Depression

To investigate the effect of DHEA on depression, researchers at the University of California, San Francisco, performed a six-week study involving 22 severely depressed patients.12 Eleven patients received DHEA (30 mg/day for two weeks, followed by 60 mg/day for two weeks, followed by 90 mg/day for the last two weeks), and 11 patients received matching placebos for the entire six weeks. Based on a standardized clinical analysis, the patients receiving DHEA were less depressed than those who were not. Specifically, five of the 11 DHEA patients showed a 50% or greater decrease in depressive symptoms, whereas no patients in the control group posted this degree of improvement.

DHEA for Tripling the Feel Good Hormone

In 2003, an Italian research group published the results of a study on 20 healthy early-postmenopausal (50–55) and late-postmenopausal (60–65) women.13 In this study, they evaluated the effects of a lower dose of DHEA (25 mg per day) for 12 months. The substances targeted for measurement were 17 hormones (mostly steroids, and a few neuropeptides and proteins)—including DHEA.

The results showed that the 25-mg/day DHEA treatment had similarly positive (though not as strong) hormonal effects as did the 50 mg/day dose used in a previous study (and a number of other studies as well). There were 3- to 4-fold increases in the plasma levels of estrogen and testosterone, and progesterone levels more than doubled. The levels of beta-endorphin (the principal “feel-good” hormone) tripled, and the levels of cortisol (the principal stress hormone) fell by about 35%, suggesting, in the authors’ words, “a sort of neuroprotective (antistress) role for exogenous [as a supplement] DHEA administration [emphasis added].”


It’s quite possible that boosting your
DHEA levels—especially if you’re
getting on in years—will make you
feel more like you used to in the
untroubled days of your youth.


Sexual Interest and the Level of Satisfaction with Sex

In an adrenal insufficiency study,14 German researchers investigated the effects of DHEA replacement in 24 women with primary and secondary adrenal insufficiency employing a double blind, placebo-controlled, randomized crossover design. In the study, 50-mg/day of DHEA or placebo were given over the course of four months. Then, following a washout period, those who got the DHEA received placebo and vice versa.

Treatment with DHEA raised the initially low serum concentrations of DHEA, DHEAS, androstenedione, and testosterone into the normal range. DHEA induced a slight increase in serum IGF-I, but only in patients with primary adrenal insufficiency, suggesting a growth hormone-mediated effect. DHEA treatment significantly improved overall well-being as well as scores for depression, anxiety, and their physical correlates. Furthermore, DHEA significantly increased both sexual interest and the level of satisfaction with sex.

DHEA replacement had no influence on cognitive performance, which was already on a high level at baseline. In conclusion, DHEA replacement improves well-being and sexuality in women with adrenal insufficiency. Were the women happier? What do you think?

Increase Your DHEA Levels through Supplementation

So here we can summarize. Not only does DHEA supplementation decrease anxiety, stress, and depression. It improves sexuality (especially in women), acts as a “feel good” hormone, and promotes happiness.

If (remember burnout; the subject of the Swedish study) you suffer from emotional exhaustion, cognitive weariness and physical fatigue, and psychosocial stress, DHEA may be for you, whatever your age. You can restore your DHEA to its youthful levels through supplementation, an approach that may help you to reconnect with a positive mental attitude. And even if you don't fall within either of these categories, it’s quite possible that boosting your DHEA levels—especially if you’re getting on in years—will make you feel more like you used to in the untroubled days of your youth.

References

  1. Lennartsson AK, Theorell T, Kushnir MM, Jonsdottir IH. Low Levels of Dehydroepiandrosterone Sulfate in Younger Burnout Patients. PLoS One. 2015 Oct 6;10(10):e0140054. doi: 10.1371/journal.pone.0140054. eCollection 2015. PubMed PMID: 26441131.
  2. Traish AM, Kang HP, Saad F, Guay AT. Dehydroepiandrosterone (DHEA)—a precursor steroid or an active hormone in human physiology. J Sex Med. 2011 Nov;8(11):2960-82.
  3. Grossi G, Perski A, Evengard B, Blomkvist V, Orth-Gomer K. Physiological correlates of burnout among women. J Psychosom Res. 2003; 55(4):309–16.
  4. Moch SL, Panz VR, Joffe BI, Havlik I, Moch JD. Longitudinal changes in pituitary adrenal hormones in South African women with burnout. Endocrine. 2003; 21(3):267–72.
  5. Langelaan S, Bakker AB, Schaufeli WB, van Rhenen W, van Doornen LJ. Do burned-out and work-engaged employees differ in the functioning of the hypothalamic-pituitary-adrenal axis? Scand J Work Environ Health. 2006 Oct;32(5):339-48.
  6. Mommersteeg PM, Heijnen CJ, Kavelaars A, van Doornen LJ. Immune and endocrine function in burnout syndrome. Psychosom Med. 2006 Nov-Dec;68(6):879-86.
  7. Kalimi M, Regelson W, eds. The Biologic Role of Dehydroepiandrosterone (DHEA). Berlin, New York: Walter de Gruyter, 1990.
  8. Bellino FL, Daynes RA, Hornsby PJ, Lavrin DH, Nestler JE, eds. Dehydroepiandrosterone (DHEA) and Aging. Vol 774. New York: NY Acad Sci; 1995.
  9. Guazzo EP, Kirkpatrick PJ, Goodyer IM, Shiers HM, Herbert J. Cortisol, DHEA, and DHEAS in the CSF fluid of man: Relation to blood levels and the effects of age. J Clin Endo Met. 1996;81:3951–60.
  10. Yaffe K, Ettinger B, Presseman A, et al. Neuropsychiatric function and dehydroepiandrosterone sulfate in elderly women: a prospective study. Biol Psychiatry. 1998;43:694-700.
  11. Legrain S, Berr C, Frenoy N, et al. Dehydroepiandrosterone sulfate in a long-term-care aged population. Gerontology. 1995;41:343-51.
  12. Wolkowitz OM, Reus VI, Keebler A, et al. Double-blind treatment of major depression with dehydroepiandrosterone. Am J Psychiatry. 1999;156:646-9.
  13. Genazzani AD, Stomati M, Bernardi F, Pieri M, Rovati L, Genazzani AR. Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids. Fertil Steril. 2003;80(6):1495-1501.
  14. Arlt W, Callies F, Allolio B. DHEA replacement in women with adrenal insufficiency—pharmacokinetics, bioconversion and clinical effects on well-being, sexuality and cognition. Endocr Res. 2000 Nov;26(4):505-11.


Will Block is the publisher and editorial director of Life Enhancement magazine.

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