DHEA for Menopause

Updated Dec. 2013
by Etsuko Ueda
According a 2011 Clinical review: DHEA replacement for postmenopausal women. by Davis SR, Panjari M, Stanczyk FZ, Dehydroepiandrosterone (DHEA) and/or its sulfate, DHEAS is a hormone secreted in large amount by adrenal gland, and in addition, brain produces its own DHEA and DHEAS (together, DHEA/S from here on), so do the ovary and testis, and even some peripheral tissues. DHEA and DHEAS convert to each other and to other androgens (including testosterone) and then to estrogens (estrone and estradiol) in various tissues according to the enzymes available locally.
The amount of DHEA/S found in blood circulation decreases dramatically with age as shown in the graph below, although the levels of other adrenal cortex hormones (cortisol=glucocorticoid and aldosterone=mineralcorticoid) do not change much with aging. Actually, menopausal symptoms such as hot flushes elevate cortisol level (see Pituitary hormones during the menopausal hot flash. D R Meldrum, et. al. 1999). DHEA/S is also produced in brain along with other neurosteroid/sex hormones, and when measured in cerebrospinal fluid, DHEA/S does not go down with age (Changes with aging of steroidal levels in the cerebrospinal fluid of women. K Murakami, et. al. 1999), which may be an indication of its importance in brain.
Figure From Regulation of the adrenal androgen biosynthesis. Rainey WE, Nakamura Y. 2008
Because of this age related sharp decline, the decline of DHEA has been thought to drive aging process, and various studies have been conducted to examine its role in aging related declines and diseases (DHEA deficiency syndrome: a new term for old age? J P Hinson and P W Raven 1999). However, the individual differences are so large that individual DHEA/S level cannot be used as a marker of aging.
According to a 2003 review, Dehydroepiandrosterone - is the fountain of youth drying out? (Celec P, Stárka L), when DHEA is measured alone in relation to degenerative disease processes such as cancer, cardiovascular diseases, insulin resistance, diabetes, osteoporosis, etc., the association is not always clear. However, when cortisol is taken into account, the cortisol/DHEA ratio seems more closely associated with the degenerative disease processes, indicating the destructive power of cortisol and protective role of DHEA against it.
Despite its promising profile, DHEA research is not as advanced as you would imagine. According to Celec and Stárka "There are two important reasons for this scientific delay of the general information about DHEA functions:
1)    DHEA is an endogenous metabolite that cannot be patented so that pharmaceutical companies are not interested in supporting research in this field.
2)    DHEA can be described as a "human molecule" because other investigated species have much lower concentrations. Especially the classical rodent laboratory animals are not suitable for experiments with DHEA. Moreover, even non-human primates produce only about 10 % of the "human amounts" of DHEA.
The conclusion they reached from studies available at the time was that a lower DHEA seems to be associated with a poorer health and increased health risks, but a lack of adrenal DHEA/S is not critical (a loss of DHEA from adrenal cortex does not lead to any particular diseases including cardiovascular and immunological diseases), except, DHEA supplementation is known to dramatically improve connective tissue diseases such as systemic lupus erythematosus and rheumatoid arthritis (The connective tissue diseases and the overall influence of gender. R G Lahita, 1996).
While Celec and Stárka were rather cautious about the use of DHEA supplementation, a group of Canadian researchers at Laval University (F Labrie. et. al.) has been more enthusiastic about DHEA supplementation. They have been focusing on the metabolic conversion of DHEA, coining a term "Intracrinology" as opposed to Endocrinology. Their enthusiasm is based on their understanding that "All the enzymes required to transform DHEA into androgens and/or estrogens are expressed in a cell specific manner in a large series of peripheral target tissues, thus permitting all androgen-sensitive and estrogen sensitive tissues to make locally and control the intracellular levels of sex steroids according to local needs." and the synthesis of active steroids takes place "in peripheral target tissues where the action is exerted in the same cells where synthesis takes place" and "they are released from these target cells only after being inactivated" (DHEA and its transformation into androgens and estrogens in peripheral target tissues: intracrinology. 2001). This understanding has lead them to:
1.     The development of combined androgen blockade which uses a pure antiandrogen added to chemical or surgical castration to block simultaneously the androgens of both testicular and adrenal origin at the start of treatment of prostate cancer. Similarly, the use of aromatase inhibitors or antiestrogen to block estrogen in breast cancer (Intracrinology: role of the family of 17 beta-hydroxysteroid dehydrogenases in human physiology and disease., F Labrie. et. al. 2000).
2.     The realization that the active hormone levels measured by blood test does not reflect the tissue levels. To measure how much DHEA is converted to active estrogens and androgens in the tissues, blood levels of their metabolites have to be measured. (Physiological changes in dehydroepiandrosterone are not reflected by serum levels of active androgens and estrogens but of their metabolites: intracrinology. Labrie F, et. al. 1997).
Note: It is not accurate to say that the androgens and estrogens converted from DHEA do not show up in blood circulation. This conclusion was drown from their 14 day trial, replicating a 28 day trial (The effects of oral dehydroepiandrosterone on endocrine-metabolic parameters in postmenopausal women. J F Mortola, et. al. 1990) where only testosterone was detected to rise in serum (its peak was reached within a week or two). However, trials longer than 3 months show serum increase of estrogens and DHT as well as testosterone ( Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids. Alessandro D Genazzani, et. al. 2003).
3.     The promotion of DHEA for hormone replacement therapy: By running 12 month transdermal DHEA supplementation study with post menopause women, they have demonstrated that it stimulates bone formation and vaginal maturation, increases skin oil secretion, and decreases insulin resistance and menopausal symptoms, all without stimulating uterine lining buildup (Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. Labrie F, et. al. 1997), clear indications of conversion of DHEA to androgens (skin oil secretion) and estrogens (vaginal maturation) and more, without systemic impact (no uterine lining buildup).
Advantage of adding DHEA to transdermal estradiol + progesterone therapy
Together with other researchers' studies and their own, Labrie's group has pointed out the advantage of DHEA alone or adding DHEA to standard ERT (estrogen replacement therapy) or HRT (estrogen + fake progesterone) (Is dehydroepiandrosterone a hormone? by F Labrie, et. al. 2005). However, their assertion of "When used as replacement therapy, DHEA is free of the potential risk of breast and uterine cancer" is not warranted and inconsistent with their claim made in #1. So long as DHEA turns into estrogens inside certain cells, only way to safeguard against breast cancer or any other estrogen driven cancer as well as blood clots and cardiovascular diseases is to counterbalance it with progesterone (see Safe Use of Hormones: the Hard Evidence and Menopause: Cardiovascular Health). Like wise, their assertion that "almost all present therapies are limited to a reduction of bone loss" and that DHEA is a rare exception is simply not true. That can only be true when you ignore the proper low dose transdermal estradiol + progesterone supplementation regimen (see Bone: Sad State of Progesterone Research and Hormone overdose: How can you tell?). Most of all, DHEA alone may not be enough to take care of the menopausal symptoms for most people, especially during the menopausal transition. It can take 2 to 3 months for its full effects to take place, in any case, particularly for the estrogen level, hot flushes, and the reduction of cortisol level (Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause. M Stomati, et. at. 2000).
One of the interesting studies about the role of DHEA/androgens for menopausal women comes from Androgens and estrogens in relation to hot flushes during the menopausal transition. (Øverlie et al. 2002). They concluded "high levels of testosterone and DHEA-S seemed to protect against vasomotor symptoms. Our most important finding was, that among women who achieved hot flushes at the first assessment postmenopause, the high androgen level was a significant predictor of recovery from hot flushes at the last assessment, 1 year later." Also from Japan, Effect of Korean red ginseng on psychological functions in patients with severe climacteric syndromes. (T Tode, et. al., 1999) reported that DHEA-S levels in postmenopausal women with menopausal syndrome were about a half of those without menopausal syndrome (By the way, Red ginseng did not restore the DHEA level, but cortisol and cortisol/DHEA ratio decreased significantly).
Interestingly, SWAN (Study of Women’s Health Across the Nation, a longitudinal study of menopause) researchers have found out that most women have some ability to increase DHEA secretion when ovaries stop secreting hormones at menopause.
    Androstenediol complements estrogenic bioactivity during the menopausal transition. Lasley BL, Chen J, Stanczyk FZ, El Khoudary SR, Gee NA, Crawford S, McConnell DS. Menopause. 2012
    Circulating dehydroepiandrosterone sulfate levels in women who underwent bilateral salpingo-oophorectomy during the menopausal transition. Lasley BL, Crawford SL, Laughlin GA, Santoro N, McConnell DS, Crandall C, Greendale GA, Polotsky AJ, Vuga M. Menopause. 2011
    Circulating dehydroepiandrosterone sulfate concentrations during the menopausal transition. Crawford S, Santoro N, Laughlin GA, Sowers MF, McConnell D, Sutton-Tyrrell K, Weiss G, Vuga M, Randolph J, Lasley B. J Clin Endocrinol Metab. 2009
    The relationship of circulating dehydroepiandrosterone, testosterone, and estradiol to stages of the menopausal transition and ethnicity. Lasley BL, Santoro N, Randolf JF, Gold EB, Crawford S, Weiss G, McConnell DS, Sowers MF. J Clin Endocrinol Metab. 2002
This is consistent with the observations that DHEA/S increases during a period of distress (Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). Maninger N, Wolkowitz OM, Reus VI, Epel ES, Mellon SH. Front Neuroendocrinol. 2009), and the late perimenopause and early post menopause are the periods when menopausal symptoms are most severe.
Most of us are not that lucky to have strong enough adrenal to cope with menopausal transition without menopausal symptoms. Nearly 90% of women experience menopausal symptoms (Bresilda Sierra, et.al. 2005). They start about 2 years before the final menstrual period, and last for many years. Nearly 50% of all women reported vasomotor symptoms 4 years after their final menstrual period, and 10% of all women reported symptoms as far as 12 years after final menstrual period. 1 year following the final menstrual period (late perimenopause, while you are wondering if the menses would ever come back) seems the most difficult time in terms of bothersome symptoms (Revisiting the Duration of Vasomotor Symptoms of Menopause: A Meta-Analysis. Mary Politi, Mark Schleinitz, Nananda Col 2008).
So for most of us, it is safe to assume that we have some degree of adrenal insufficiency by the age we start to have menopausal symptoms, and it may be wise to supplement DHEA. DHEA supplementation studies clearly indicate its positive effects on menopausal symptom reduction (Effect of 12-month dehydroepiandrosterone replacement therapy on bone, vagina, and endometrium in postmenopausal women. Labrie F, et. al. 199; Long-term low-dose dehydroepiandrosterone oral supplementation in early and late postmenopausal women modulates endocrine parameters and synthesis of neuroactive steroids. Genazzani, et. al. 2003), although it may not be adequate in most cases (Clinical review: DHEA replacement for postmenopausal women. Davis SR, Panjari M, Stanczyk FZ. 2011). When that is not enough, you can always add an ultra low dose of transdermal estradiol. The worst thing you can do is to let the menopausal symptoms linger. It will increase stress hormones that ravage your bones (see Bone: Destructive Power of Stress Hormones).
Caution: Either way, you need to supplement progesterone (real, natural, bio-identical progesterone in cream form) preferably as soon as a sign of transition or decline appears (at around 35 years of age for many people) before starting any other hormone to avoid estrogen dominance related risks (see Estrogen dominance: it's not just a theory and Safe Use of Hormones: the Hard Evidence).
As a treatment for menopausal symptoms, estradiol+progesterone is a clear winner over DHEA alone. However, there are areas of benefits that DHEA may further enhance or add to the benefits of estradiol+progesterone therapy. Although we do not know the full impact of DHEA decline with aging or adrenal insufficiency, the Mother nature gave it to us for a reason and it is better to have an adequate level of DHEA, I believe. At least, for post menopausal women, it boosts androgens which neither estradiol nor progesterone can. Since stimulation of skin oil secretion requires androgens, this is important for people who tend to have dry skin. For some people, it may also improve libido beyond estradiol+progesterone can.
Caution: Because of this effect on skin oil secretion, DHEA can cause skin/hair problems when overdosed. Therefore, my guideline for DHEA dosage is: if you start to have oily hair/skull or pimples, it is too much. For most people, 5 to 10mg/day (oral or transdermal) may be a safe and effective level.
One-year therapy with 10mg/day DHEA alone or in combination with HRT in postmenopausal women: Effects on hormonal milieu.(Nicola Pluchino, et. al. 2008) seems to agree. The good news is that a long term use of DHEA strengthens the adrenal gland's capacity to produce DHEA in response to adrenocorticotropic hormone (ACTH).
More difficult to evaluate is the supplemented DHEA's impact on brain. Since brain can produce its own DHEA/S, it  may be difficult to determine how much impact a long term low dose DHEA may have on brain of a healthy person. Nonetheless, according to Neurobiological and neuropsychiatric effects of dehydroepiandrosterone (DHEA) and DHEA sulfate (DHEAS). (Maninger, et. al. 2009), the major biological actions of DHEA/S in brain involve neuroprotection, neurite growth, neurogenesis and neuronal survival, apoptosis, catecholamine synthesis and secretion, as well as anti-oxidant, anti-inflammatory and anti-glucocorticoid (cortisol) effects, and "Beneficial treatment effects are more likely to be seen in medically or neuropsychiatrically ill patients than in healthy individuals."

Personally, the first time I tried DHEA (30mg/day), I tried it because someone told me it might help me with my menopausal symptoms after I stopped estrogen. After 1 month, I did not feel any effect and discontinued. The second time, I tried it in addition to estradiol patch + progesterone cream without knowing what to expect, except that it might improve overall hormonal milieu. After about 3 months of 30mg/day DHEA, I noticed my hair getting oily, and started to see pimples near my hairline (androgen effect). I also noticed my vaginal wall felt more "alive" (estrogen + androgen effect ?). I could go back to sleep more often after waking up too early. I am not sure why, but may have something to do with reduced cortisol. The link between time of awakening and the level of morning cortisol has been reported by Association between time ofawakening and diurnal cortisol secretory activity. (Edwards S, Evans P, Hucklebridge F, Clow A. 2001), The diurnal patterns of the adrenal steroids cortisol and dehydroepiandrosterone (DHEA) in relation to awakening. (Hucklebridge F1, Hussain T, Evans P, Clow A. 2005) . Perhaps the easing of early wakening problem is an indication of reduced cortisol through a mechanism different from that of estradiol + progesterone.

1 comment:

  1. Thank you! I went on DHEA (oral dose 100mg daily) to combat Sjogren's Syndrome-7 years ago to combat a diagnosis that was causing me to lose my health and sight and life!

    It was Italian medical journals I turned to for information, American medical prgress is woefully inadequate. I became a hated PARIAH for holding to my own medical research and course of actions, I was FIRED as a patient (GOOD!-I AM ALIVE-NO THANKS TO 'YOU WORTHLESS "PHYSICIANS") I 'saved' myself. Others can too-thank you for your blog.


Before you post your HRT questions, please try what I think safe and effective for at least 3 months: estradiol 0.025~0.050mg/day patch, with 20~40mg/day progesterone cream (about 1000mg progesterone in 2oz cream). You can also add DHEA 5~10mg /day.
That is the only recommendation you will get from me.