| Dahir and Travers-Gustafson, 2014 | Determine effect of DHEA on sexual health | Quasi-experimental pilot (4 weeks) | Women with breast cancer taking AI therapy
n = 12
Race/ethnicity not reported
Age (mean): 59.7 years | DHEA vaginal cream;
300 μg/daily | Exclusion criteria described | Female Sexual Function Index (FSFI) survey | Compared to baseline, improvements in individual domain scores of desire (P = 0.000), arousal (P = 0.002), lubrication (P = 0.018), orgasm (P = 0.005), satisfaction (P = 0.001), and pain (P = 0.000)
No recurrence or progression of breast cancer over 3 years | Authors reported that no serious adverse events occurred | Narrow time frame for enrollment and follow-up
Small sample size
Excluded surgical menopause under the age of 50 and women with recurrent G. vaginalis infection
Sexual functioning may have been affected by history or events such as relationship conflict, stress, or vacation
Absence of a randomized control group |
| Davis et al., 2018 | Determine effect of testosterone on sexual satisfaction, vaginal symptoms | Randomized double-blind, placebo-controlled (26 weeks) | Postmenopausal women taking an AI with VVA symptoms
n = 44
Race/ethnicity not reported
Age (mean): 57.7 years (treatment) 55.1 years (placebo) | Testosterone intravaginal cream;
300 μg/dose | Exclusion criteria described
Treatment schedule: Daily for 2 weeks and then 3x/week for 24 weeks | FSFI survey Female Sexual Distress Scale–Revised (FSDS-R), Profile of Female Sexual Function
Questionnaire for UI Diagnosis; serum levels of sex steroids | Greater improvements seen in treatment group in FSFI satisfaction scores (P= 0.043); FSDS-R scores (P = 0.02); sexual concerns (P < 0.001); sexual responsiveness (P < 0.001); vaginal dryness (P = 0.009); dyspareunia (P = 0.014)
No between-group differences in serum levels of sex steroids at baseline or posttreatment
No between-group differences in reported UI symptoms at 26 weeks, adjusted for baseline status | Authors did not report on adverse events for this study | Higher dropout rate in control group
Low power to assess additional domains of sexual function
Recruitment was limited by patient concerns about the safety of hormone therapy after a diagnosis of breast cancer |
| Glaser et al., 2011 | Determine effect of testosterone on somatic, psychological and urogenital symptoms | Cohort (12 weeks) | Pre- and postmenopausal women
n = 300
Race/ethnicity not reported
Age (mean):
42.7 years (premenopausal)
53.0 years (postmenopausal) | Testosterone pellet (3.1 mm)
Initial dose varied across patient based on their weight (ranged from 75 mg to 160 mg)
Subsequent dose adjustments based on weight, avoidance of adverse events, and adequacy of clinical response | Exclusion criteria described | Menopause Rating Scale (MRS)
Total scores and psychological, somatic, and urogenital subscale scores
Health-Related Quality of Life (HRQOL) | Premenopausal women: Higher testosterone doses correlated with greater improvement in MRS total score (P < 0.05) and urogenital subscore (P < 0.01)
Higher testosterone doses did not correlate with greater improvement in either the psychological or somatic subscores (P > 0.05)
Postmenopausal women: Higher testosterone doses correlated with greater improvement in MRS total score and three subscores: somatic, psychological, and urogenital (P < .001) | Authors reported that no serious adverse events occurred | Short-term study
Absence of a randomized control group or comparison group |
| Jankowski et al., 2006 | Determine effect of DHEA on BMD and body composition | Randomized, double-blind, placebo-controlled (12 months) | Older men and women
Participants were primarily White
Women
n = 70 (36 DHEA; 34 placebo)
Age (mean): 68 years
Men
n = 70 (35 DHEA; 35 placebo)
Age (mean): 69 years | Oral DHEA; 50 mg/daily | Exclusion criteria described | BMD measured at baseline and 12 months | Men and women: Greater increase in BMD in DHEA group: Total hip (1.0%, P = 0.05), trochanter (1.2%, P = 0.06), and shaft (1.2%, P = 0.05)
Women only: DHEA increased lumbar spine BMD (2.2%, P = 0.04; sex-by-treatment interaction, P = 0.05) | Placebo: One death (unrelated to study); one hospitalization for coronary artery stenting
DHEA: One hospitalization for transient ischemic attack and one hospitalization for urinary tract infection | Small sample size
Patient use of other reproductive steroids
Short duration of the therapy |
| Kenny et al., 2010 | Determine effect of DHEA and exercise on bone mass, strength, and physical function | Randomized, double-blind, placebo-controlled (6 months) | Women over 65 with DHEA levels < 550 ng/dL
n = 99 (assigned)
Participants were primarily White
Age (mean): 76.6 years | Treatment arm 1: Oral DHEA 50 mg/d supplemented with yoga
Treatment arm 2: Oral DHEA 50 mg/d supplemented with aerobics
Control arm 1: Placebo supplemented with yoga
Control arm 2: Placebo supplemented with aerobics | Exclusion criteria described
All received calcium and Vitamin D supplements | BMD measured at baseline and 6 months | There were no significant changes in BMD or bone turnover markers between groups | Author did not report on adverse events for this study | Small sample size
Short duration of therapy |
| Leonetti et al., 1999 | Determine effect of progesterone on vasomotor symptoms, BMD | Randomized, double-blind, placebo-controlled (12 months) | Healthy women within 5 years of menopause
n = 90 (assigned)
All participants were White
Age (mean): 52 years | 20 mg transdermal progesterone cream; applied daily | Exclusion criteria described
All received daily multivitamins and 1,200 mg of calcium | Weekly symptom diaries (self-report)
BMD measured in the lumbar spine, femoral neck, and hip | Symptoms: Greater self-reported improvement in vasomotor symptoms found in treatment group compared to placebo (83% versus 19%); (P < 0.001)
BMD: No significant difference between group comparisons | Author did not report on adverse events for this study | Limited consumer access to the custom-compounded preparation
Limited generalizability of research results |
| Mahmud, 2010 | Determine effect of Bi-est, progesterone, testosterone and/or DHEA on menopausal symptoms | Observational (average 30 month follow-up) | Postmenopausal women
n = 189 (assigned)
Race/ethnicity not reported
Age (mean): 53.7 years | Treatment arm 1: transdermal Bi-est cream (estradiol 1 mg plus estriol 4 mg per gram) and sublingual progesterone (50–100 mg) and testosterone perivaginal cream
Participants began with a 0.5 gm twice daily dose of Bi-est cream, which was increased or decreased as needed to control hot flashes and breast tenderness
Total testosterone was maintained around 25 ng/dl with dose adjustments as needed based on blood levels
Adjustments to progesterone doses were made to achieve blood levels close to 4 ng/ml
Treatment arm 2: Transdermal Bi-est cream (estradiol 1 mg plus estriol 4 mg per gram) and sublingual progesterone (50–100 mg) and DHEA
Participants began with a 0.5 gm twice daily dose of Bi-est cream, which was increased or decreased as needed to control hot flashes and breast tenderness
Adjustments to progesterone doses were made to achieve blood levels close to 4 ng/ml
Participants received DHEA if levels were determined to be low. Average dose began at 25 mg/day and was typically reduced to 25 mg every other day to maintain the desired level (approx. 120 μg/dl) | No exclusion criteria provided | Patient outcomes assessed over an average follow-up of 30 months
Common symptoms assessed: hot flashes, night sweats, insomnia, lack of energy, low libido, and minor stiffness or achy joints | 122 patients reported improvement in all common symptoms, 49 patients reported relief of most symptoms; 13 patients reported some improvements; 5 patients reported little to no improvement in symptoms | One patient was found to have an ER+ and PR+ breast cancer after 6 months of treatment
Prior to joining this study the patient had been taking Premarin for 10 years, which the researchers believe may have caused the development of breast cancer in this patient | Absence of a randomized control group
Lack of predetermined dosage formulation, participant outcomes, and statistical analysis of results
Multiple dosage forms of treatments (subset of patients switched from Bi-est cream to sublingual route) |
| Morales, 1998 | Determine effect of DHEA on steroid levels, body composition and muscle strength | Randomized double-blind, placebo-controlled crossover (12 months) | Older men and women
Women
n = 10 (assigned)
Race/ethnicity not reported
Age (mean): 54.5 years
Men
n = 9 (assigned)
Race/ethnicity not reported
Age (mean): 55.6 years | Oral DHEA; 100 mg/daily | Exclusion criteria described
2-week washout period between crossover | BMD measured at baseline and 6 months | There were no significant changes from baseline in the BMD of the hip and spine in men or women | Author reported that no serious adverse events occurred | Small sample size |
| Narkwichean et al., 2017 | Determine effect of DHEA on In-Vitro Fertilization (IVF) outcomes | Randomized, double-blind, placebo-controlled pilot trial (2 years) | Women receiving IVF with diminished ovarian reserves
Treatment group: n = 27
All White British women
Age (mean) = 36.8 years
Placebo group: n = 25
84% White British women
Age (mean) = 35.2 years | Oral DHEA; 75 mg/day; 12 to 20 weeks before starting ovarian stimulation | Exclusion criteria described
Long protocol using hMG 300 IU/day | Number of oocytes retrieved; live birth rates; mRNA expression of developmental biomarkers in granulosa and cumulus cells | Treatment did not improve the response to controlled ovarian hyperstimulation or oocyte quality or live birth rate during IVF
Treatment with long protocol in women predicted to have poor ovarian reserve | Author reported that no serious adverse reactions occurred | No power calculation to determine sample size |
| Panjari et al., 2009 | Determine safety of DHEA used to improve sexual function | Randomized, double-blind, placebo-controlled parallel group trial (52 weeks) | Postmenopausal women with low libido
Race/ethnicity not reported
Treatment group: n = 47 (assigned; age (mean) = 55.1 years
Placebo group: n = 46 (assigned); age (mean) = 53.9 years | Oral DHEA; 50 mg/day | Exclusion criteria described | DHEA versus placebo on androgenic side effects, lipid profile, insulin–glucose homeostasis, and the endometrium were assessed over 52 weeks | DHEA did not significantly alter lipid profile or insulin sensitivity in postmenopausal women
The pattern of breakthrough bleeding did not substantially differ between the DHEA and placebo groups, and no significant adverse endometrial effects were apparent | Author reported that no serious adverse events occurred | Length of study is insufficient to have confidence in the reported endometrial safety outcomes
Endpoint for endometrial effects was not sufficiently powered |
| Virkki et al., 2010 | Effect of DHEA on Sjorgren's syndrome-related fatigue | Multicentered, randomized, double-blind, placebo-controlled crossover trial (9 months) | Men and women with primary Sjorgren's Syndrome (reported as one group)
n = 107 (including 7 men)
Race/ethnicity not reported
Age (range): 18–80 years | Oral DHEA; 50 mg/day | Exclusion criteria described
1 month washout period between crossover (2 treatment groups lasting 4 months each) | General fatigue using the 20-item Multiple Fatigue Inventory (MFI-20); Health-Related Quality of Life (HRQOL) | All of the MFI-20 subscales and the fatigue Visual Analog Scale showed improvements from baseline levels as a result of treatment (P < 0.001)
No significant differences between placebo and DHEA treatment | Placebo Treatment: One case of pneumonia and pneumococcal sepsis
Other serious events resulting in patient dropout: (1) unilateral numbness, (2) suspected transient ischemic attack, and (3) exanthema
DHEA treatment: Serious events resulting in patient dropout: muscle cramps in the calves and maculae on the back and cheek, (suspected as being discoid lupus erythematosus lesions) | Owing to increased number of statistical analyses of the MFI-20s six subscale variables, there is an increased risk of analyses resulting in statistical significance by chance |
| Wiser et al., 2010 | Effect of DHEA on IVF outcomes | Prospective, randomized, open-labeled, controlled trial (19 months) | Women with poor ovarian response to previous IVF cycles
Race / ethnicity not reported
Treatment group: n = 17; age (mean) = 36.9 years
Control group: n = 16; age (mean) = 37.8 years | Oral DHEA; 75 mg/day, at least 6 weeks before starting first cycle of IVF ovulation
Women who did not conceive took DHEA for at least 16–18 weeks | Exclusion criteria described
All patients received long-protocol IVF | Estradiol levels, number of retrieved oocytes, quality and number of embryos, pregnancy and birth rate | Live birth rate for women in the DHEA group for both IVF treatment cycles = 23.1%; Live birth rate from women in the control group = 4.0%. (p = 0.05) | Author reported that no serious adverse events occurred | Small sample size
Outcomes may have been affected by variations in IVF protocol |
| Witherby et al., 2011 | Effect of vaginal testosterone on estradiol and testosterone levels, and vaginal atrophy in breast cancer patients on AIs | Observational (28 days) | Women undergoing treatment with an AI in early stage breast cancer with reported vaginal itching, dryness, or dyspareunia
Ethnicity not reported
n = 20 (divided into two treatment groups)
Age (range): 45–69 years | Group 1 (n = 10): 300 μg intravaginal testosterone cream compounded with 13.5 mg of testosterone propionate
Group 2 (n =10): 150 μg intravaginal testosterone cream compounded with 6.75 mg of testosterone propionate | Exclusion criteria described | Assessment of hormone levels to confirm estradiol suppression
Clinical effect based on analyses of serial questionnaire results
Pathologic improvement of vaginal atrophy was analyzed based on a comparison of baseline and posttreatment maturation index, pH, and clinical examination | No significant difference in median serum estradiol levels before and after treatment (P = 0.91)
No difference in posttreatment estradiol levels between dosing levels (P >0.99)
Significant improvement in mean total symptom score for vaginal atrophy (P < 0.001) and remained low at 1 month post-therapy (P = 0.003)
No significant difference between dosing levels
Posttreatment maturation values were significantly higher for 300 μg group (P = 0.005) | Author reported that no serious adverse events occurred | Lack of a randomized control group
Recruitment of subjects was not systematic
Small sample size |
