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Supplementation of dehydroepiandrosterone (DHEA) in pre-and postmenopausal women — position statement of an expert panel of Polish Menopause and Andropause Society
ABSTRACT
Dehydroepiandrosterone (DHEA) concentration decreases with age, therefore, DHEA has been considered a hormone that reduces the symptoms associated with aging, so the usefulness of DHEA in premenopausal and postmenopausal women, and the options of hormone therapy have received a large amount of attention. The effectiveness of DHEA in premenopausal women remains unclear, while in postmenopausal women with coexisting estrogen deficiency is controversial. Despite many years of study, the use of DHEA is still controversial, especially regarding its effectiveness. The aim of the present article was to evaluate DHEA-specific effects on metabolic parameters, bone mineral density, and insulin resistance as well as the therapeutic potential of DHEA in pre-and postmenopausal women using measures of sexual activity, cognition, and well-being. The summary of this article is the position statement of an expert group of the Polish Menopause and Andropause Society regarding the efficacy and safety of DHEA supplementation in women. We concluded, that currently available clinical trials and meta-analyses indicate that DHEA supplementation is effective in women with adrenal insufficiency and chronically treated with exogenous glucocorticoids, postmenopausal women with low bone mineral density and/or osteoporosis, premenopausal women with sexual disorders and low libido, and in women with vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause. Currently, available clinical trials also suggest that DHEA supplementation is probably effective in postmenopausal women with hypoactive sexual disorders, infertile women with diminished ovarian reserve, women suffering from depression and anxiety, and women with obesity and insulin resistance. No serious adverse effects have been reported.
DHEA IN HUMAN PHYSIOLOGY
Dehydroepiandrosterone (DHEA) is an endogenous androgen produced in the zona reticularis of the adrenal cortex (30%), thecal cells in the ovary (20%), and from peripheral conversion of DHEAS (30%).
In peripheral tissues, DHEA is converted to more active androgens and estrogens: estrone and testosterone and later to estradiol and dihydrotestosterone (DHT) respectively. The contribution is remarkable since in postmenopausal women 40–75% of the testosterone and 90% of estrogens are derived from adrenal androgens [1]. DHEA-S serves as a circulating reservoir of DHEA. DHEA can be reversely transformed in many tissues by sulphatases from its sulfate (DHEA-S). Together with its sulfate, DHEA is the most concentrated hormone and the most abundant steroid in peripheral blood, thus it became clear that it is more than just an intermediate in steroid hormone synthesis. Serum DHEA concentrations range from 0.2 to 0.9 mcg/dL (7 to 31 nmol/L). Due to its remarkable and gradual decrease that occurs with aging, DHEA was considered an anti-aging elixir, and the concept of dietary supplementation of DHEA was promoted and administration was introduced in the 1980s [2]. As primary effects improvement in sexual function, well-being, metabolic parameters, immune response, and cognition were suggested. Noteworthy many initial studies regarding anti-aging properties and mechanisms of DHEA were conducted on rodents that naturally do not secrete DHEA from adrenal glands, thus may be irrelevant [3]. DHEA also plays an important role in reproductive endocrinology. Like other androgens, DHEA is important in follicular steroidogenesis and oogenesis in the ovary. Described effects on ovarian folliculogenesis include the upregulation of insulin-like growth factor-1 (IGF-1) [4], sensitization to gonadotropins, and reduction of follicular arrest [5].
*SUPPLEMENTATION OF DHEA AS A HORMONE REPLACEMENT THERAPY IN PREMENOPAUSAL AND POSTMENOPAUSAL WOMEN
-Osteoporosis, metabolic health, and muscular strength
-Depression, anxiety, cognitive function, and mood improvement
-Libido and sexual satisfaction
-Cosmetic Dermatology
*SUPPLEMENTATION OF DHEA IN WOMEN WITH ADRENAL INSUFFICIENCY AND CHRONICALLY TREATED WITH EXOGENOUS GLUCOCORTICOIDS
*SUPPLEMENTATION OF DHEA IN WOMEN WITH VULVOVAGINAL ATROPHY
*SUPPLEMENTATION OF DHEA FOR FERTILITY IMPROVEMENT
-Supplementation of DHEA in IVF cycles
-Supplementation of DHEA in natural cycles
*SIDE EFFECTS OF DHEA SUPPLEMENTATION AND CONTRAINDICATIONS
CONCLUSIONS
Currently, available clinical trials and meta-analyses indicate that DHEA supplementation is effective in the following cases:
• Adrenal insufficiency and chronically treated with exogenous glucocorticoids
• In postmenopausal women with low bone mineral density and/or osteoporosis
• In premenopausal women with sexual disorders and low libido
• Vaginally in women with vulvovaginal atrophy of menopause or genitourinary syndrome of menopause (GSM)
Currently, available clinical trials suggest that DHEA supplementation is probably effective in some of the following cases:
• Postmenopausal women with hypoactive sexual disorders
• Infertile women with diminished ovarian reserve (DOR)
• Women suffer from depression and anxiety
• Women with obesity and insulin resistance
Usual daily doses of DHEA that are administrated in clinical trials and regular off-label use are summarized in Table 1. In the majority of conditions, an oral dose of 25 mg of DHEA given two or three times a day is often implemented.
The commonly used dosage range of DHEA supplementation in the therapy of diverse medical conditions. The most prevalent dose was bolded. Daily doses above 25 mg are usually split into 2–3 parts. Please note that the table summarizes an example of doses administered in clinical practice that may differ from those recommended by the manufacturer or are utilized in off-label treatment. Administration and dose of every drug should rely on current medical knowledge and individual clinical assessment.
A recent statement of experts from the Polish Menopause and Andropause Society and the Polish Society of Aesthetic and Reconstructive Gynecology provides a comprehensive literature review that supports the use of intravaginal DHEA supplementation. Clinical studies with a high level of evidence prove that topical treatment is effective, safe, and well-tolerated long-term therapy for vulvovaginal atrophy [63].
In a Cochrane Systemic Review [64] regarding the supplementation of DHEA in peri- and postmenopausal women, the authors questioned the effectiveness of DHEA in women, but the overall quality of the studies analyzed in this review was moderate to low. It was unclear if the supplementation of DHEA decrease symptoms of menopause since the study outcomes were inconsistent and could not be pooled to obtain an overall effect due to versatile types of measurement. Insufficient results were available to estimate the quality of life and menopausal symptoms during DHEA supplementation as well as, and there were inadequate reports accessible to compare the effects of DHEA replacement to hormone therapy (HT) for quality of life, menopausal symptoms, and adverse effects.
ABSTRACT
Dehydroepiandrosterone (DHEA) concentration decreases with age, therefore, DHEA has been considered a hormone that reduces the symptoms associated with aging, so the usefulness of DHEA in premenopausal and postmenopausal women, and the options of hormone therapy have received a large amount of attention. The effectiveness of DHEA in premenopausal women remains unclear, while in postmenopausal women with coexisting estrogen deficiency is controversial. Despite many years of study, the use of DHEA is still controversial, especially regarding its effectiveness. The aim of the present article was to evaluate DHEA-specific effects on metabolic parameters, bone mineral density, and insulin resistance as well as the therapeutic potential of DHEA in pre-and postmenopausal women using measures of sexual activity, cognition, and well-being. The summary of this article is the position statement of an expert group of the Polish Menopause and Andropause Society regarding the efficacy and safety of DHEA supplementation in women. We concluded, that currently available clinical trials and meta-analyses indicate that DHEA supplementation is effective in women with adrenal insufficiency and chronically treated with exogenous glucocorticoids, postmenopausal women with low bone mineral density and/or osteoporosis, premenopausal women with sexual disorders and low libido, and in women with vulvovaginal atrophy due to menopause or genitourinary syndrome of menopause. Currently, available clinical trials also suggest that DHEA supplementation is probably effective in postmenopausal women with hypoactive sexual disorders, infertile women with diminished ovarian reserve, women suffering from depression and anxiety, and women with obesity and insulin resistance. No serious adverse effects have been reported.
DHEA IN HUMAN PHYSIOLOGY
Dehydroepiandrosterone (DHEA) is an endogenous androgen produced in the zona reticularis of the adrenal cortex (30%), thecal cells in the ovary (20%), and from peripheral conversion of DHEAS (30%).
In peripheral tissues, DHEA is converted to more active androgens and estrogens: estrone and testosterone and later to estradiol and dihydrotestosterone (DHT) respectively. The contribution is remarkable since in postmenopausal women 40–75% of the testosterone and 90% of estrogens are derived from adrenal androgens [1]. DHEA-S serves as a circulating reservoir of DHEA. DHEA can be reversely transformed in many tissues by sulphatases from its sulfate (DHEA-S). Together with its sulfate, DHEA is the most concentrated hormone and the most abundant steroid in peripheral blood, thus it became clear that it is more than just an intermediate in steroid hormone synthesis. Serum DHEA concentrations range from 0.2 to 0.9 mcg/dL (7 to 31 nmol/L). Due to its remarkable and gradual decrease that occurs with aging, DHEA was considered an anti-aging elixir, and the concept of dietary supplementation of DHEA was promoted and administration was introduced in the 1980s [2]. As primary effects improvement in sexual function, well-being, metabolic parameters, immune response, and cognition were suggested. Noteworthy many initial studies regarding anti-aging properties and mechanisms of DHEA were conducted on rodents that naturally do not secrete DHEA from adrenal glands, thus may be irrelevant [3]. DHEA also plays an important role in reproductive endocrinology. Like other androgens, DHEA is important in follicular steroidogenesis and oogenesis in the ovary. Described effects on ovarian folliculogenesis include the upregulation of insulin-like growth factor-1 (IGF-1) [4], sensitization to gonadotropins, and reduction of follicular arrest [5].
*SUPPLEMENTATION OF DHEA AS A HORMONE REPLACEMENT THERAPY IN PREMENOPAUSAL AND POSTMENOPAUSAL WOMEN
-Osteoporosis, metabolic health, and muscular strength
-Depression, anxiety, cognitive function, and mood improvement
-Libido and sexual satisfaction
-Cosmetic Dermatology
*SUPPLEMENTATION OF DHEA IN WOMEN WITH ADRENAL INSUFFICIENCY AND CHRONICALLY TREATED WITH EXOGENOUS GLUCOCORTICOIDS
*SUPPLEMENTATION OF DHEA IN WOMEN WITH VULVOVAGINAL ATROPHY
*SUPPLEMENTATION OF DHEA FOR FERTILITY IMPROVEMENT
-Supplementation of DHEA in IVF cycles
-Supplementation of DHEA in natural cycles
*SIDE EFFECTS OF DHEA SUPPLEMENTATION AND CONTRAINDICATIONS
CONCLUSIONS
Currently, available clinical trials and meta-analyses indicate that DHEA supplementation is effective in the following cases:
• Adrenal insufficiency and chronically treated with exogenous glucocorticoids
• In postmenopausal women with low bone mineral density and/or osteoporosis
• In premenopausal women with sexual disorders and low libido
• Vaginally in women with vulvovaginal atrophy of menopause or genitourinary syndrome of menopause (GSM)
Currently, available clinical trials suggest that DHEA supplementation is probably effective in some of the following cases:
• Postmenopausal women with hypoactive sexual disorders
• Infertile women with diminished ovarian reserve (DOR)
• Women suffer from depression and anxiety
• Women with obesity and insulin resistance
Usual daily doses of DHEA that are administrated in clinical trials and regular off-label use are summarized in Table 1. In the majority of conditions, an oral dose of 25 mg of DHEA given two or three times a day is often implemented.
The commonly used dosage range of DHEA supplementation in the therapy of diverse medical conditions. The most prevalent dose was bolded. Daily doses above 25 mg are usually split into 2–3 parts. Please note that the table summarizes an example of doses administered in clinical practice that may differ from those recommended by the manufacturer or are utilized in off-label treatment. Administration and dose of every drug should rely on current medical knowledge and individual clinical assessment.
A recent statement of experts from the Polish Menopause and Andropause Society and the Polish Society of Aesthetic and Reconstructive Gynecology provides a comprehensive literature review that supports the use of intravaginal DHEA supplementation. Clinical studies with a high level of evidence prove that topical treatment is effective, safe, and well-tolerated long-term therapy for vulvovaginal atrophy [63].
In a Cochrane Systemic Review [64] regarding the supplementation of DHEA in peri- and postmenopausal women, the authors questioned the effectiveness of DHEA in women, but the overall quality of the studies analyzed in this review was moderate to low. It was unclear if the supplementation of DHEA decrease symptoms of menopause since the study outcomes were inconsistent and could not be pooled to obtain an overall effect due to versatile types of measurement. Insufficient results were available to estimate the quality of life and menopausal symptoms during DHEA supplementation as well as, and there were inadequate reports accessible to compare the effects of DHEA replacement to hormone therapy (HT) for quality of life, menopausal symptoms, and adverse effects.
