madman
Super Moderator
Abstract
Estradiol, an estrogen steroid hormone, serves as the dominant female hormone and its levels fluctuate during its lifetime. In women, after menopause, all estrogens and almost all androgens are locally developed in the peripheral tissues from dehydroepiandrosterone (DHEA). However, the effect of DHEA supplementation on estradiol levels in women is unclear as previously published data has resulted in conflicting findings. Thus, we conducted the present dose-response meta-analysis of randomized controlled trials (RCTs) evaluating the influence of DHEA on estradiol concentrations in women. The PubMed/Medline, Embase, Web of Science, and Scopus databases were systematically searched for articles published on this topic until May 10, 2021. No time or language restrictions were applied. The data were expressed as weighted mean differences (WMDs) and 95% confidence intervals (CI), and a P-value of less than 0.05 was considered to be statistically significant. The pooled results were obtained using the generic inverse of variance method with a random-effects model. A total of 21 arms, including 1223 participants (case=610, and control=613), reported estradiol concentrations as an outcome measure. The overall results demonstrated that estradiol significantly increased following the administration of DHEA (WMD: 7.02 pg/mL, 95% CI: 5.43, 8.62, P=0.000). The stratified analyses revealed that the elevation of estradiol concentrations was more pronounced in subjects aged ≥60 years old (WMD: 8.56 pg/mL, 95% CI: 6.97, 10.16, I2=94%) and in those receiving DHEA supplements for ≥26 weeks (WMD: 7.30 pg/mL, 95% CI: 6.28, 8.32, I2=61%). Moreover, estradiol levels increased significantly with DHEA dosages of 50 mg/day (WMD: 7.75 pg/mL, 95% CI: 9.12, 9.39, I2= 94%) and when DHEA was prescribed to postmenopausal women (WMD: 7.61 pg/mL, 95% CI: 5.97, 9.24, I2=93%). This meta-analysis has provided a comprehensive overview of the effects of DHEA administration on circulating estradiol levels, far beyond the available evidence from different RCTs. Subsequent on DHEA dosages of 50 mg/day and those receiving DHEA for ≥26 weeks registered a more pronounced elevation of the circulating estradiol levels.
Introduction
Dehydroepiandrosterone (DHEA) is an important prohormone secreted by the adrenals in large quantities in humans and other primates, but not in smaller species [1, 2]. DHEA is generated by the adrenal glands in humans and is employed by many tissues, including the brain, liver, kidneys, and gonads. Based on the tissue for which it is necessary, DHEA is metabolized to 5-androstene3β,17β-diol, 4-androstene-3,17-dione, testosterone, estrogen, and other biologically active steroids [3-5].
Estradiol, which is the dominant female hormone, fluctuates during its lifetime and, at different times, during the menstrual cycle [6]. Estradiol (E2) serves as a strong feedback molecule between the ovaries and the hypothalamic neurons which generate the gonadotropin-releasing hormone (GnRH), and exerts both positive and negative regulatory actions on the GnRH synthesis and secretion [7]. In women, after menopause, all estrogens and almost all androgens are locally developed in the peripheral tissues from DHEA, and have indirect effects on the bone structure, adiposity levels, muscles, insulin and glucose metabolisms, skin, libido, and well-being [8, 9].
As estradiol is the dominant female hormone, maintaining its concentrations within normal limits, including during menopause, is important for a normal status of health in women. Several trials have reported that the production of estradiol could be stimulated by DHEA [10-14]. Thus, it has been suggested that supplementation with DHEA could influence estradiol levels [14-16]. Nonetheless, the relationship between DHEA supplementation and estradiol levels remains administration on estradiol concentrations remains unclear to this date [10, 12, 13, 17-19]. The discrepancies could be attributed to several items, such as the duration of intervention and the DHEA dosage, among others. In addition, before issuing a recommendation of DHEA supplementation to increase estradiol concentrations, we must keep in mind that a synthesis of high-quality, RCT-derived data is warranted to prevent any potential harms of such an intervention in women, as well as to identify the subjects who would benefit the most from DHEA prescription. Thus, we aimed to clarify the effects of DHEA supplementation on estradiol levels in females and we conducted the present dose-response meta-analysis of randomized controlled trials (RCTs) evaluating the influence of DHEA on estradiol concentrations in women.
This review has provided a comprehensive overview of the effect of DHEA administration on circulating estradiol levels, far beyond the available evidence in different RCTs. Subsequent subgroup analyses revealed that postmenopausal women, females aged 60 years and above, those on DHEA dosages of 50 mg/day, and those receiving DHEA supplements for ≥26 weeks, exhibited a more pronounced elevation of the circulating estradiol concentrations. To the authors’ knowledge, this study is the first meta-analysis to investigate the effects of DHEA administration on estradiol levels and, thus, represents a milestone for future practice and research to build upon. These studies are needed to understand the optimal DHEA doses for the treatment of postmenopausal women to avoid the potentially deleterious effects of excessive estradiol elevations. In the meantime, due to its significant impact on increasing circulating estradiol levels, DHEA supplementation may be an attractive option for improving or preserving bone health in older women.
Estradiol, an estrogen steroid hormone, serves as the dominant female hormone and its levels fluctuate during its lifetime. In women, after menopause, all estrogens and almost all androgens are locally developed in the peripheral tissues from dehydroepiandrosterone (DHEA). However, the effect of DHEA supplementation on estradiol levels in women is unclear as previously published data has resulted in conflicting findings. Thus, we conducted the present dose-response meta-analysis of randomized controlled trials (RCTs) evaluating the influence of DHEA on estradiol concentrations in women. The PubMed/Medline, Embase, Web of Science, and Scopus databases were systematically searched for articles published on this topic until May 10, 2021. No time or language restrictions were applied. The data were expressed as weighted mean differences (WMDs) and 95% confidence intervals (CI), and a P-value of less than 0.05 was considered to be statistically significant. The pooled results were obtained using the generic inverse of variance method with a random-effects model. A total of 21 arms, including 1223 participants (case=610, and control=613), reported estradiol concentrations as an outcome measure. The overall results demonstrated that estradiol significantly increased following the administration of DHEA (WMD: 7.02 pg/mL, 95% CI: 5.43, 8.62, P=0.000). The stratified analyses revealed that the elevation of estradiol concentrations was more pronounced in subjects aged ≥60 years old (WMD: 8.56 pg/mL, 95% CI: 6.97, 10.16, I2=94%) and in those receiving DHEA supplements for ≥26 weeks (WMD: 7.30 pg/mL, 95% CI: 6.28, 8.32, I2=61%). Moreover, estradiol levels increased significantly with DHEA dosages of 50 mg/day (WMD: 7.75 pg/mL, 95% CI: 9.12, 9.39, I2= 94%) and when DHEA was prescribed to postmenopausal women (WMD: 7.61 pg/mL, 95% CI: 5.97, 9.24, I2=93%). This meta-analysis has provided a comprehensive overview of the effects of DHEA administration on circulating estradiol levels, far beyond the available evidence from different RCTs. Subsequent on DHEA dosages of 50 mg/day and those receiving DHEA for ≥26 weeks registered a more pronounced elevation of the circulating estradiol levels.
Introduction
Dehydroepiandrosterone (DHEA) is an important prohormone secreted by the adrenals in large quantities in humans and other primates, but not in smaller species [1, 2]. DHEA is generated by the adrenal glands in humans and is employed by many tissues, including the brain, liver, kidneys, and gonads. Based on the tissue for which it is necessary, DHEA is metabolized to 5-androstene3β,17β-diol, 4-androstene-3,17-dione, testosterone, estrogen, and other biologically active steroids [3-5].
Estradiol, which is the dominant female hormone, fluctuates during its lifetime and, at different times, during the menstrual cycle [6]. Estradiol (E2) serves as a strong feedback molecule between the ovaries and the hypothalamic neurons which generate the gonadotropin-releasing hormone (GnRH), and exerts both positive and negative regulatory actions on the GnRH synthesis and secretion [7]. In women, after menopause, all estrogens and almost all androgens are locally developed in the peripheral tissues from DHEA, and have indirect effects on the bone structure, adiposity levels, muscles, insulin and glucose metabolisms, skin, libido, and well-being [8, 9].
As estradiol is the dominant female hormone, maintaining its concentrations within normal limits, including during menopause, is important for a normal status of health in women. Several trials have reported that the production of estradiol could be stimulated by DHEA [10-14]. Thus, it has been suggested that supplementation with DHEA could influence estradiol levels [14-16]. Nonetheless, the relationship between DHEA supplementation and estradiol levels remains administration on estradiol concentrations remains unclear to this date [10, 12, 13, 17-19]. The discrepancies could be attributed to several items, such as the duration of intervention and the DHEA dosage, among others. In addition, before issuing a recommendation of DHEA supplementation to increase estradiol concentrations, we must keep in mind that a synthesis of high-quality, RCT-derived data is warranted to prevent any potential harms of such an intervention in women, as well as to identify the subjects who would benefit the most from DHEA prescription. Thus, we aimed to clarify the effects of DHEA supplementation on estradiol levels in females and we conducted the present dose-response meta-analysis of randomized controlled trials (RCTs) evaluating the influence of DHEA on estradiol concentrations in women.
This review has provided a comprehensive overview of the effect of DHEA administration on circulating estradiol levels, far beyond the available evidence in different RCTs. Subsequent subgroup analyses revealed that postmenopausal women, females aged 60 years and above, those on DHEA dosages of 50 mg/day, and those receiving DHEA supplements for ≥26 weeks, exhibited a more pronounced elevation of the circulating estradiol concentrations. To the authors’ knowledge, this study is the first meta-analysis to investigate the effects of DHEA administration on estradiol levels and, thus, represents a milestone for future practice and research to build upon. These studies are needed to understand the optimal DHEA doses for the treatment of postmenopausal women to avoid the potentially deleterious effects of excessive estradiol elevations. In the meantime, due to its significant impact on increasing circulating estradiol levels, DHEA supplementation may be an attractive option for improving or preserving bone health in older women.
