Advertisement

The effects of oral contraceptives on androgen levels and their relevance to premenstrual mood and sexual interest: a comparison of two triphasic formulations containing norgestimate and either 35 or 25 ��g of ethinyl estradiol

  • Teri Greco
    Affiliations
    Department of Medicine, Regenstrief Institute for Health Care, Indiana University School of Medicine, Indianapolis, IN 40202, USA

    Department of Medicine, Division of Women's Health, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA
    Search for articles by this author
  • Cynthia A. Graham
    Correspondence
    Corresponding author. Oxford Doctoral Course in Clinical Psychology, Isis Education Centre, Warneford Hospital, Headington, Oxford OX3 7JX, UK. Tel.: +44 1865 226431; fax: +44 1865 226364.
    Affiliations
    Oxford Doctoral Course in Clinical Psychology, Isis Education Centre, Warneford Hospital, OX3 7JX Oxford, UK

    The Kinsey Institute for Research in Sex, Gender, and Reproduction, Indiana University, Bloomington, IN 47405-2501, USA
    Search for articles by this author
  • John Bancroft
    Affiliations
    The Kinsey Institute for Research in Sex, Gender, and Reproduction, Indiana University, Bloomington, IN 47405-2501, USA
    Search for articles by this author
  • Amanda Tanner
    Affiliations
    Department of Applied Health Science, Indiana University, Bloomington, IN 47405-7109, USA
    Search for articles by this author
  • Helen A. Doll
    Affiliations
    Department of Public Health, University of Oxford, OX3 7LF Oxford, UK
    Search for articles by this author

      Abstract

      Purpose

      This study compared two oral contraceptives (OCs) with the same triphasic regimen of progestin (norgestimate 0.18, 0.215 and 0.25 mg) but differing doses of ethinyl estradiol (EE) ��� 25 and 35 ��g EE ��� in their effects on androgens, mood and sexual interest in women starting on OCs.

      Methods

      Total testosterone (T), free testosterone (FT), sex-hormone-binding globulin (SHBG) and dehydroepiandrosterone sulphate (DHEA-S), together with measures of mood [Beck Depression Inventory (BDI)], sexual interest [Dyadic and Solitary subscales of the Sexual Desire Inventory (SDI)] and self-reported side effects were assessed before starting on the OC and again after 3 months of use.

      Results

      Sixty women, all university students, were randomized to receive either the 25 ��g EE (N/EE25) or the 35 ��g EE (N/EE35) pill; 12 women discontinued, leaving 48 who completed the 3-month study. Their mean age was 19.7 years (18���30) and they were predominantly white and single. Both OCs produced reductions in mean T [N/EE35: from 1.33 to 0.60 nmol/L, p<.001; N/EE25: from 1.12 to 1.02 nmol/L; nonsignificant (NS)] and FT (N/EE35: from 41.3 to 4.4 pmol/L, p<.001; N/EE25: from 25.4 to 7.9 pmol/L, p<.01), but the reduction in both T and FT was significantly greater with the higher EE dose (N/EE35) (p=.05 and p=.03, respectively). DHEA-S was also reduced with both formulations (N/EE35: from 7.26 to 5.22 ��mol/L); N/EE25: from 7.50 to 5.39 ��mol/L), although the reduction was only significant in the N/EE35 group (p<.02). Considerable variability in changes in mood was evident with both OCs, with some women showing predominantly negative effects (10 in N/EE35, 5 in N/EE25); others, positive effects (9 in N/EE35, 17 in N/EE25) and some, no change (four in each group). Women using N/EE25 were significantly more likely to show improvement in premenstrual mood than those in the N/EE35 group (p<.02), although there was no correlation between changes in BDI and FT or DHEA-S. Sexual interest scores did not change significantly from baseline to posttreatment with either OC (N/EE35: dyadic, from 40.5 to 39.6, NS; solitary, from 5.9 to 6.4, NS; N/EE25: dyadic, from 36.7 to 37.0, NS; solitary, from 5.0 to 4.2, NS).

      Conclusion

      The lower EE pill reduced FT less and was associated with greater improvement in premenstrual mood. A causal relation between these two effects is uncertain.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Contraception
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kay C.R.
        The Royal College of General Practitioners' Oral Contraception Study: some recent observations.
        Clin Obstet Gynecol. 1984; 11: 759-786
        • Bancroft J.
        • Sartorius N.
        The effects of oral contraceptives on well-being and sexuality.
        Oxf Rev Reprod Biol. 1990; 12: 57-92
        • Oinonen K.A.
        • Mazmanian D.
        To what extent do oral contraceptives influence mood and affect?.
        J Affect Disord. 2002; 70: 229-240
        • Bancroft J.
        The premenstrual syndrome ��� a reappraisal of the concept and the evidence.
        Psychol Med Monogr. 1993; 24: 1-47
        • Sanders S.A.
        • Borsos A.
        • Graham C.A.
        • Bass J.
        • Bancroft J.
        A prospective study of the effects of oral contraceptives on sexuality and well-being and their relationship to discontinuation.
        Contraception. 2001; 64: 51-58
        • Apter D.
        • Borsob A.
        • Baumgartner W.
        • et al.
        Effect of an oral contraceptive containing drospirenone and ethinylestradiol on general well-being and fluid-related symptoms.
        Eur J Contracept Reprod Health Care. 2003; 8: 37-51
        • Graham C.A.
        • Sherwin B.
        The relationship between mood and sexuality in women using an oral contraceptive as a treatment for premenstrual symptoms.
        Psychoneuroendocrinology. 1993; 18: 273-281
        • Freeman E.W.
        • Kroik R.
        • Rapkin A.
        • et al.
        Evaluation of a unique oralcontraceptive in the treatment of premenstrual dysphoric disorder.
        J Womens Health Gend Based Med. 2001; 10: 561-570
        • Graham C.A.
        • Ramos R.
        • Bancroft J.
        • Maglaya C.
        • Farley T.M.M.
        The effects of steroidal contraceptives on the well-being and sexuality of women: a double-blind, placebo-controlled, two-center study of combined and progestogen-only methods.
        Contraception. 1995; 52: 363-369
        • Anderson D.C.
        Sex-hormone-binding globulin.
        Clin Endocrinol. 1974; 3: 69-96
        • Cawood E.H.H.
        • Bancroft J.
        Steroid hormones, the menopause, sexuality and well-being of women.
        Psychol Med. 1996; 26: 925-936
        • Bell R.J.
        • Donath S.
        • Davison S.L.
        • Davis S.R.
        Endogenous androgen levels and wellbeing: differences between pre- and postmenopausal women.
        Menopause. 2005; 13: 65-71
        • Bancroft J.
        The endocrinology of sexual arousal. Starling review.
        J Endocrinol. 2005; 186: 411-427
        • Coenen C.M.H.
        • Thomas C.M.G.
        • Borm G.F.
        • Hollanders J.M.G.
        • Rolland R.
        Changes in androgens during treatment with four low-dose contraceptives.
        Contraception. 1996; 53: 171-176
        • Boyd R.A.
        • Zegarac E.A.
        • Posvar E.L.
        • Flack M.R.
        Minimal androgenic activity of a new oral contraceptive containing norethindrone acetate and graduated doses of ethinyl estradiol.
        Contraception. 2001; 63: 71-76
        • Akerlund M.
        • Rode A.
        • Westergaard J.
        Comparative profiles of reliability, cycle control and side effects of two oral contraceptive formulations containing 150��g desogestrel and either 30��g or 20��g ethinyl oestradiol.
        Br J Obstet Gynaecol. 1993; 100: 832-838
        • Endrikat J.
        • Muller U.
        • Dusterberg B.
        A twelve-month comparative clinical investigation of two low-dose oral contraceptives containing 20��g ethinylestradiol/75��g gestodene, and 30��g ethinylestraiol/75��g gestodene, with respect to efficacy, cycle control, and tolerance.
        Contraception. 1997; 55: 131-137
        • Caruso S.
        • Agnello C.
        • Intelisano G.
        • Farina M.
        • Di Mari L.
        • Cianci A.
        Sexual behavior of women taking low-dose oral contraceptive containing 15��g ethinylestradiol/60��g gestodene.
        Contraception. 2004; 69: 237-240
        • Caruso S.
        • Agnello C.
        • Intelisano G.
        • et al.
        A prospective study on sexual behavior of women using 30��g ethinylestradiol and 3��mg drospirenone oral contraceptive.
        Contraception. 2005; 72: 19-23
        • Dennerstein L.
        • Dudley E.C.
        • Hopper J.L.
        • Burger H.
        Sexuality, hormones and the menopausal transition.
        Maturitas. 1997; 26: 83-93
        • Talwar P.P.
        • Berger G.S.
        A prospective, randomized study of oral contraceptives: the effect of study design on reported rates of symptoms.
        Contraception. 1979; 20: 329-337
        • Beck A.T.
        • Steer R.A.
        Beck Depression Inventory (BDI).
        in: American Psychiatric Association Handbook of psychiatric measures. American Psychiatric Association, Washington (DC)2000: 519-523
        • Spector I.P.
        • Carey M.P.
        • Steinberg L.
        The Sexual Desire Inventory: development, factor structure and evidence of reliability.
        J Sex Marital Ther. 1996; 22: 175-190
        • Bancroft J.
        • Williamson L.
        • Warner P.
        • Rennie D.
        • Smith S.
        Perimenstrual complaints in women complaining of PMS, menorrhagia and dysmenorrhoea; towards a dismantling of the ���premenstrual syndrome���.
        Psychosom Med. 1993; 55: 133-145
        • Hammond G.L.
        • Abrams L.S.
        • Creasy G.W.
        • Natarajan J.
        • Allen J.G.
        • Siiteri P.K.
        Serum distribution of the major metabolites of norgestimate in relation to its pharmacological properties.
        Contraception. 2003; 67: 93-99
        • Hammond G.L.
        • Nisker J.A.
        • Jones L.A.
        • Siiteri P.K.
        Estimation of the percentage of free steroid in undiluted serum by centrifugal ultrafiltration-dialysis.
        J Biol Chem. 1980; 255: 5023-5026
        • Bachmann G.
        • Bancroft J.
        • Braunstein G.
        • et al.
        Female androgen deficiency: the Princeton consensus statement on definition, classification, and assessment.
        Fertil Steril. 2002; 77: 660-665
        • Davis S.R.
        • Davison S.L.
        • Donath S.
        • Bell R.J.
        Circulating androgen levels and self-reported sexual function in women.
        JAMA. 2005; 294: 91-96
        • Davison S.L.
        • Bell R.
        • Montalto J.G.
        • et al.
        Measurement of total testosterone in women: comparison of a direct radioimmunoassay versus radioimmunoassay after organic solvent extraction and celite column partition chromatography.
        Fertil Steril. 2005; 84: 1698-1704
        • American Psychiatric Association
        Diagnostic and Statistical Manual of Mental Disorders. 4th ed., Text Rev. American Psychiatric Association, Washington (DC)2000: 771-774
        • Walker A.
        • Bancroft J.
        The relationship between premenstrual symptoms and oral contraceptive use: a controlled study.
        Psychosom Med. 1990; 52: 86-96
        • Bancroft J.
        • Sanders D.
        • Warner P.
        • Loudon N.
        The effects of oral contraceptives on mood and sexuality: a comparison of triphasic and combined preparations.
        J Psychosom Obstet Gynaecol. 1997; 7: 1-8
        • Schmidt P.J.
        • Daly R.C.
        • Bloch M.
        • et al.
        Dehydroepiandrosterone monotherapy in midlife-onset major and minor depression.
        Arch Gen Psychiatry. 2005; 62: 154-162
        • Graham C.A.
        • Bancroft J.
        • Doll H.A.
        • Greco T.
        • Tanner A.
        Does oral contraceptive-induced reduction in free testosterone adversely affect the sexuality and mood of women?.
        Psychoneuroendocrinology. 2007; 32: 246-255