Androgen Restored Contraception

Abstract

Combined oral contraceptives (COCs) reduce androgen levels, especially testosterone (T), by inhibiting ovarian and adrenal androgen synthesis and by increasing levels of sex hormone-binding globulin (SHBG). Possible consequences of this androgen loss are diminished sexual function and mood disturbances. Androgen Restored Contraception (ARC) is a novel concept of oral contraception aiming to maintain physiological androgen levels in women using a COC by the addition of the natural human adrenal hormone dehydroepiandrosterone (DHEA). In the context of this thesis, a systematic review was performed to evaluate the effect of COCs on concentrations of total T, free T and sex hormone-binding globulin (SHBG) in healthy women. As there is general concern about the quality of T assays, especially at low levels, special attention was paid in this thesis to the comparison of different methods to measure T. The clinical studies included in this thesis evaluated the suppression of androgens during COC use and its clinical implications and investigated the endocrine and clinical effects of ARC with the following conclusions: 1.All COC users experience a loss of androgens, especially free T. 2.COC use suppresses sexual function. 3.Total T measurements during COC use are unreliable when performed with assays sensitive to the SHBG concentration. The free T level is the most important parameter to evaluate the androgen status during COC use. 4.Co-administration of 50 mg DHEA per day to a COC containing EE and DRSP does not affect the pharmacokinetic properties of EE and DRSP. Therefore, it will most likely not affect its contraceptive efficacy. 5.By adding DHEA to a COC the loss of androgens can be restored without inducing side effects. 6.Apart from the ability of DHEA to normalise T levels, favourable clinical effects were observed on several aspects of sexual function and mood, especially menstrual cycle related symptoms. 7.The ARC pill is suitable for all women since all COC users experience a serious loss of T. 8.Further research should reveal whether it is possible to determine at the start of COC use which women benefit also clinically from DHEA.