TY - JOUR
T1 - Restoring testosterone levels by adding dehydroepiandrosterone to a drospirenone containing combined oral contraceptive
T2 - I. Endocrine effects
AU - Zimmerman, Y.
AU - Foidart, J. M.
AU - Pintiaux, A.
AU - Minon, J. M.
AU - Fauser, B. C J M
AU - Cobey, K.
AU - Coelingh Bennink, H. J T
PY - 2015/1/1
Y1 - 2015/1/1
N2 - Objectives Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA). Study design In this randomized, double-blind, placebo-controlled study in 99 new COC starters (18-35 years old with body mass index range 18-34 kg/m2), a COC containing 30 mcg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) was used for 3 cycles, followed by 6 cycles of the same COC combined with either 50 mg/day DHEA or placebo. Total T, albumin, sex hormone-binding globulin (SHBG), DHEA-sulfate (DHEA-S), Δ4-androstenedione (AD), 3α-androstanediol glucuronide (ADG) and estradiol (E2) were measured, whereas free T and the free T index (FTI) were calculated. Assessments took place at baseline (no COC use), after the run-in period (COC use alone) and during the treatment period (DHEA or placebo). Results During COC use alone, androgen levels decreased, especially total T by 62% and free T by 86%, and SHBG increased by 243%. Total T increased with DHEA compared to placebo (change from end of run-in period to end of treatment period - 1.3±1.2 nmol/L vs. 0.0±0.4 nmol/L; p<.0001) - and was restored to baseline levels. Free T and the FTI increased significantly (p<.0001), but the free T level was still 53% below baseline levels. DHEA-S, AD and ADG increased significantly to levels above baseline (p<.0001 for each). DHEA had no effect on SHBG, albumin and E2. Conclusions An EE/DRSP containing COC strongly suppressed endogenous androgen concentrations in all users. The addition of 50 mg DHEA to a COC regimen containing EE/DRSP restored total T to baseline levels, but free T levels were restored by only 47% as most of the T remains bound to SHBG. Implications When using a COC that increases SHBG considerably, a daily dose of 50 mg DHEA is insufficient to normalize free T levels completely.
AB - Objectives Combined oral contraceptives (COCs) decrease testosterone (T) levels. This study investigated restoration of T and other androgen concentrations during COC use by 'co-administration' of dehydroepiandrosterone (DHEA). Study design In this randomized, double-blind, placebo-controlled study in 99 new COC starters (18-35 years old with body mass index range 18-34 kg/m2), a COC containing 30 mcg ethinylestradiol (EE) and 3 mg drospirenone (DRSP) was used for 3 cycles, followed by 6 cycles of the same COC combined with either 50 mg/day DHEA or placebo. Total T, albumin, sex hormone-binding globulin (SHBG), DHEA-sulfate (DHEA-S), Δ4-androstenedione (AD), 3α-androstanediol glucuronide (ADG) and estradiol (E2) were measured, whereas free T and the free T index (FTI) were calculated. Assessments took place at baseline (no COC use), after the run-in period (COC use alone) and during the treatment period (DHEA or placebo). Results During COC use alone, androgen levels decreased, especially total T by 62% and free T by 86%, and SHBG increased by 243%. Total T increased with DHEA compared to placebo (change from end of run-in period to end of treatment period - 1.3±1.2 nmol/L vs. 0.0±0.4 nmol/L; p<.0001) - and was restored to baseline levels. Free T and the FTI increased significantly (p<.0001), but the free T level was still 53% below baseline levels. DHEA-S, AD and ADG increased significantly to levels above baseline (p<.0001 for each). DHEA had no effect on SHBG, albumin and E2. Conclusions An EE/DRSP containing COC strongly suppressed endogenous androgen concentrations in all users. The addition of 50 mg DHEA to a COC regimen containing EE/DRSP restored total T to baseline levels, but free T levels were restored by only 47% as most of the T remains bound to SHBG. Implications When using a COC that increases SHBG considerably, a daily dose of 50 mg DHEA is insufficient to normalize free T levels completely.
KW - Androgens
KW - DHEA
KW - Free testosterone
KW - SHBG
UR - http://www.scopus.com/inward/record.url?scp=84921051393&partnerID=8YFLogxK
U2 - 10.1016/j.contraception.2014.11.002
DO - 10.1016/j.contraception.2014.11.002
M3 - Article
C2 - 25604900
AN - SCOPUS:84921051393
SN - 0010-7824
VL - 91
SP - 127
EP - 133
JO - Contraception
JF - Contraception
IS - 2
ER -