DHEA is a steroid precursor to testosterone and estrogen that may play important roles in fertility, brain function, and aging. It also has one FDA-approved use which can significantly improve the quality of life of menopausal women. Read on to learn more.
What are DHEA and DHEA-S?
DHEA and DHEA-S are steroid hormones. They should be used with caution and only with the prescription or recommendation of a medical professional. Do not use DHEA as a replacement for any therapy that your doctor recommends.
DHEA is a steroid hormone that is produced in the adrenal gland, gonads, and brains. It is a precursor to other hormones, namely estrogen and testosterone. DHEA levels are highest after birth and continue to lower as you age [1].
DHEA-sulfate (DHEA-S) is a sulfite derivative of DHEA. The body also turns it into androgen hormones. Not a lot of studies have been done on DHEA-S and its long-term effects, so it is not recommended for supplementation [2].
Snapshot
Proponents:
- Approved for vaginal atrophy
- May improve cognitive function
- May reduces blood pressure
- May prevent osteoporosis
- May improve sleep quality
- May improve fertility
Skeptics:
- Can contribute to substance abuse
- Might cause cancer
- Risk factor for psychotic symptoms
- Can cause anxiety and hyperactivity for some
- Limited safety data
- Lacking in quality clinical studies for most purported benefits
Important Mechanisms
- Inhibited proliferation of spleen cells and IFN-у production, therefore it’s a Th1 suppressant [3]. Increased Th2, decreased Th1 and Th17 cells in the spleen and lymph nodes, respectively [3].
- Decreased expression of IL-6 and TGF-β [3].
- Reduces the accumulation of reactive oxygen species (ROS) in response to H2O2 [4].
- Stimulated the activation of Nrf2, which led to the expression of an antioxidant response gene, HO-1 [4].
- Increased expression levels of the beta 3 adrenergic receptor (beta(3)AR) and PGC-1a [5].
Approved Use of DHEA
While the FDA has approved the use of DHEA for women with vaginal atrophy, it should never be used without the prescription or recommendation of a medical professional. Talk to your doctor before using DHEA for any purpose.
1) Vaginal Atrophy
After menopause, some women experience vaginal pain during sexual intercourse or severe dryness of the vagina. Intravaginal administration of DHEA administered led to improved vaginal health and lessened pain [6].
In 2016, the FDA approved Intrarosa, a DHEA suppository, for menopausal women with vaginal atrophy and pain during sex [7].
Potential Uses of DHEA
DHEA has not been approved by the FDA for any medical use other than vaginal atrophy. Researchers are investigating its potential for a number of other purposes, but larger and more powerful clinical trials are still required for all of them. Talk to your doctor before using DHEA, and do not use DHEA in place of an approved medication or therapy.
2) Fertility
DHEA levels affect testosterone and estrogen levels because it is a precursor to these hormones. Low DHEA is also associated with sexual dysfunction [1, 8].
Women sometimes take DHEA as a supplement during menopause to increase their level of estrogen [8].
Ovarian reserve is the capacity for the ovaries to produce a healthy egg that is ready for fertilization. Women with poor ovarian reserve who also did not respond well to IVF were given DHEA. These women had a higher rate of pregnancy and higher ovarian reserve than the group who did not take DHEA [9].
This study only included 30 volunteers. Larger and more robust clinical trials are needed to determine the role of DHEA in fertility.
3) Brain Function & Mental Health
DHEA stimulates neurons and inhibits cortisol. In humans, salivary DHEA increases with cognitive tasks and working memory [10].
DHEA also participates in the emotional regulation of memory and the connections between the amygdala and hippocampus (memory center) [11].
In a rat model of Alzheimer’s, DHEA supplements reduced symptoms and improved memory [12].
DHEA levels in the brain are also involved in visual processing, awareness, and attention [13].
Depression
DHEA has anti-cortisol properties and protects against depression [14].
In a meta-analysis of 22 studies, DHEA improved depressive symptoms in both old and young patients. However, only 3 of these studies were focused on young patients. The authors of this analysis called the use of DHEA in depression “promising,” but more robust clinical trials are still needed [15].
4) Aging Skin
Topical application of DHEA improved markers associated with skin aging in a pilot study of 40 postmenopausal women [16].
In another study of 280 older men and women, an oral DHEA supplement restored blood levels of DHEA to levels expected in younger people and improved the appearance and structure of the skin [17].
The results from these studies were promising, but they must be repeated in larger and more robust trials.
Insufficient Evidence
Researchers are investigating the role of DHEA in a number of other health conditions, but the clinical evidence here is considered insufficient to determine whether it is effective. In all cases, larger and more robust studies are required. Talk to your doctor before using DHEA, and never use DHEA in place of your doctor’s prescription or recommendations.
5) Heart Health
Low levels of DHEA are associated with heart disease in men [18].
DHEA is synthesized from cholesterol, and DHEA levels gradually decline as people age. One study found that DHEA relaxed the blood vessels (thereby decreasing blood pressure) and that DHEA levels were inversely associated with cardiovascular disease; the authors suggested that it could be a valuable hormone in the prevention and treatment of CVD. However, additional studies are required [19].
6) Weight Management
DHEA-S only had affected the weight of obese men, but not women. DHEA-S supplementation led to weight loss and reduced blood insulin levels [20].
Dogs that took DHEA supplements lost more weight than ones that took a placebo. They also had lower cholesterol [21].
DHEA supplementation led to huge weight loss in rats and also increased their energy usage [5].
On the other hand, anorexic women treated with 100 mg of DHEA experienced greater improvements than those who received placebos. Their weight increased, as did their mood [22].
DHEA may play a role in weight management and balance, but many more studies will be required to flesh out our understanding of that role.
7) Insulin Resistance
Elderly humans that underwent six months of DHEA replacement therapy had decreased insulin resistance and improved glucose tolerance [23].
In obese rats, DHEA administration combined with exercise helped lower insulin resistance and increased weight loss. Blood glucose and insulin sensitivity improved [24].
Many more clinical studies will be required to clarify the effect of DHEA on insulin sensitivity.
8) Sleep Quality
DHEA administration improved sleep quality in 10 young men. REM sleep, which is associated with memory formation, increased [25].
Because this is a single study on only ten people in one demographic, many more clinical studies will be required to understand the role of DHEA in sleep.
9) Bone Density
In a study of over a thousand South Korean men, DHEA increased bone mass and reduced the symptoms of osteoporosis [26].
DHEA may increase bone (osteoblast) formation and inhibits bone (osteoblast) cell death, thereby increasing bone volume and bone mineral density. Some researchers have suggested using DHEA in menopausal women with osteoporosis [27].
Areas of Future Research
No valid clinical evidence supports the use of DHEA for any of the conditions listed in this section. Below is a summary of the existing animal and cell-based research, which should guide further investigational efforts. However, the studies listed below should not be interpreted as supportive of any health benefit. As always, talk to your doctor before using DHEA.
10) Inflammation
Low DHEA levels are associated with inflammatory states in human patients; however, it is currently unclear whether taking DHEA could reduce inflammation [28].
Animal and cell studies have been largely promising, if limited. DHEA stops inflammation and restored normal colon length. It balanced the immune responses from bowel disease that cause damage [3].
DHEA reduced inflammation due to HIV and prevented neuron degeneration [29].
In the feline model of HIV (called FIV), DHEA also prevented neuron loss [29].
DHEA tends to be reduced in people with asthma. According to some researchers, it may reduce inflammation in the lungs and prevent the hyperreactivity of the airways [30].
Nevertheless, the exact role of DHEA in inflammatory states is unclear. Additional studies will be required to clarify.
11) Muscle Repair
In a cell study, DHEA protected against oxidative stress and prevented apoptosis (programmed death) in muscle cells. It increased the effects of antioxidants and stopped the processes that lead to atrophy [4].
This effect has yet to be investigated in animals or humans.
Cancer Research
The spread of cancer to other organs (metastasis) is a leading cause of cancer-related deaths. Some researchers have suggested a role for DHEA in preventing metastasis of colon cancer, but this inference is speculative and based entirely on cell studies [31].
DHEA & Lupus
According to a meta-analysis of 842 patients, DHEA does not appear to provide any significant benefit to patients with lupus and produced more adverse events than the placebo. Furthermore, long-term effects and safety are very poorly studied [32].
Other
DHEA helps relieve tuberculosis symptoms in patients. It clears bacteria and prevents tissue damage [33].
Conventional doctors will look at high or low DHEA levels and not mention anything, but these can indicate that certain processes in the body aren’t optimal.
Negative Effects & Safety Concerns
Remember that the only FDA-approved use of DHEA is as a suppository for menopausal women suffering from vaginal atrophy. We advise against using DHEA unless your doctor has specifically recommended it.
Some reported side effects of DHEA include acne and excessive hair growth [34].
Because DHEA can increase testosterone in the body, it is prohibited in some professional sports [35].
Long-term safety data, especially in women, is generally lacking [2].
1) Cancer
Post-menopausal women with higher levels of DHEA and DHEA-S in their blood also developed breast cancer at a higher rate [36].
An excessive amount of DHEA (more than 50mg daily) may stimulate the growth of cancer [37].
2) Mental Disorders
Patients with schizophrenia had higher levels of cortisol and DHEA-S compared to healthy patients, but they also were more likely to respond to antipsychotic treatment [38].
A high level of DHEA might be a risk factor for psychotic symptoms. Patients with high levels of DHEA were more likely to have a family history of major depressive disorders or psychotic symptoms [39].
3) Addiction
DHEA might contribute to substance abuse (drug-seeking behavior) through effects on the parts of the brain that regulate emotion and motivation [40].
