YHBEH-03499; No. of pages: 6; 4C: Hormones and Behavior xxx (2013) xxx–xxx Contents lists available at SciVerse ScienceDirect Hormones and Behavior journal homepage: www.elsevier.com/locate/yhbeh The relationship between oral contraceptive use and sensitivity to olfactory stimuli Kaytlin J. Renfro ⁎, Heather Hoffmann Psychology Department, Knox College, 2 East South Street, Galesburg, IL 61401-4999, USA article info abstract Article history: The present study examined differences in olfactory sensitivity between 16 naturally cycling (NC) women Received 2 March 2012 and 17 women taking monophasic oral contraceptives (OCs) to six odors: lemon, peppermint, rose, musk, Revised 20 November 2012 androstenone and androsterone. Thresholds were assessed twice for both groups of women (during the Accepted 2 January 2013 periovulatory and luteal phases of their cycles) via a forced-choice discrimination task. NC women in the Available online xxxx periovulatory phase were significantly more sensitive to androstenone, androsterone, and musk than women taking OCs. These findings give support to odor-specific hormonal modulation of olfaction. Further, Keywords: Oral contraceptives due to the social and possibly sexual nature of these odors, future work should address whether there is a re- Olfaction lationship between decreased sensitivity to these odors and reported behavioral side effects among women Odor taking OCs. Ovarian steroids © 2013 Elsevier Inc. All rights reserved. Threshold Introduction problems, such as stroke (Seibert et al., 2003). Women taking OCs have also reported many behavioral side effects, such as emotional la- There are a number of physiological, perceptual, and behavioral bility and decreased sexual desire (Battaglia et al., 2012; Caruso et al., changes that have been reported to co-occur with ovulation in 2004; Sanders et al., 2001; Warner Chilcott, 2009, but see Alexander women; these changes have largely been attributed to the hormonal et al., 1990). fluctuations that characterize ovulation (i.e. the pre-ovulatory spikes Recent studies have elucidated the effects of OCs on the sensory in luteinizing hormone (LH) and estradiol) (e.g. Fehring, 2002; systems, reporting increases in auditory and olfactory thresholds, Gueguen, 2009; Parlee, 1983). Because women taking oral contracep- indicating decreased auditory and olfactory sensitivity, among OC tives (OCs) do not experience hormonal fluctuations as naturally cy- users as compared to nonusers (Caruso et al., 2001, 2003; Snihur cling (NC) women do, and do not ovulate, they provide a and Hampson, 2012). Caruso et al. (2001) tracked women's olfacto- particularly good opportunity to assess which of these mid-cycle ry thresholds across their menstrual cycles, both before they began changes are specifically related to hormonal influences (Cohen and using OCs and then again during the period of use. Participants' Katz, 1979; Elkind-Hirsch et al., 1992). thresholds were significantly higher after beginning a pill regimen. Approximately 82% of women between the ages of 15 and 44 in Before beginning use of OCs, the women showed fluctuations in the United States have at one point in time regularly used an oral con- sensitivity to the olfactory stimuli across their menstrual cycles— traceptive pill as a form of birth control (Mosher and Jones, 2010). becoming more sensitive to many of the olfactory stimuli during The combination pill, containing an estrogen and a progestin, is re- the periovulatory and follicular phases of their cycles, as compared portedly the most common form of the pill in use (Sanders et al., to the luteal phases. However, when on OCs, the women's thresh- 2001). The combination pill targets the hypothalamus and pituitary, olds rose to luteal phase levels, and remained at these levels altering hormone levels, to prevent ovulation. The estrogen component throughout the months. It is presumed that the steroid hormones suppresses the follicle stimulating hormone (FSH), preventing the de- of the pill are responsible for the women's decreased olfactory sen- velopment of a follicle, and the progestin component suppresses the sitivity; however, the specific mechanism underlying these effects LH surge necessary for ovulation (Speroff and Darney, 2010). remains unclear. One possibility is that because thresholds rise to Exogenous hormones can have various physiological effects on luteal phase levels, and the luteal phase of the cycle is character- women's bodies, such as inducing nausea and promoting weight ized by heightened levels of progesterone, it is the progestin in gain, as well as putting women at risk for more serious health the pill driving these effects (Caruso et al., 2001). It is also possible that the decrease in sensitivity is due to the decrease in estradiol in OC users, as NC women experience increases in estradiol through- ⁎ Corresponding author at: Psychology Department, Emory University, 36 Eagle Row, out the follicular phase, and a sharp increase in estradiol just pre- Atlanta, GA 30322, USA. Fax: +1 404 727 0372. E-mail addresses: [email protected] (K.J. Renfro), [email protected] ceding ovulation, both of which are absent in OC users (Cohen (H. Hoffmann). and Katz, 1979; Elkind-Hirsch et al., 1992). 0018-506X/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.yhbeh.2013.01.001 Please cite this article as: Renfro, K.J., Hoffmann, H., The relationship between oral contraceptive use and sensitivity to olfactory stimuli, Hor- mones and Behavior (2013), http://dx.doi.org/10.1016/j.yhbeh.2013.01.001 2 K.J. Renfro, H. Hoffmann / Hormones and Behavior xxx (2013) xxx–xxx Hormonal modulation of olfaction has previously been evidenced Table 1 in work focusing on sex differences in olfactory ability and in research Comprehensive list of the brand names of the oral contraceptives (OCs) used by women in the study (n=17). Manufacturer and dosage of the OC are provided in parentheses. examining changes in women's olfactory sensitivity across the men- strual cycle. The majority of research that has reported sex differences Oral contraceptive brand name and dosage Number of in olfactory sensitivity has shown that, compared to men, women are participants more sensitive to a range of odors and have greater accuracy in Yaz (Bayer)/Gianvi (generic, Teva Pharmaceuticals) 6 odor-identification (for review, see Doty and Cameron, 2009). How- (3 mg of drospirenone and 0.02 mg of ethinyl estradiol) ever, there are disparities in the literature, where some have failed Loestrin 24Fe (Warner Chilcott) 4 fi (1 mg of norethindrone acetate and 0.02 mg of ethinyl estradiol) to nd sex differences in sensitivity. This is similarly the case with ol- Microgestin 1.5/30 (Watson Pharmaceuticals, Inc.) 2 factory fluctuations across the menstrual cycle. Although many stud- (1.5 mg of norethindrone/0.03 mg of ethinyl estradiol) ies have reported that women become more sensitive to odors during Levora (Watson Pharmaceuticals, Inc.) 1 the ovulatory phases of their cycles, this does not appear to hold true (0.15 mg of levenorgestrel and 0.03 mg of ethinyl estradiol) Sronyx (Watson Pharmaceuticals, Inc.) 1 for all odors. It has been suggested that these inconsistent findings are (0.1 mg of levonorgestrel and 0.02 mg of ethinyl estradiol) due to the nature of the odors used in the studies (for discussion, see Yasmin (Bayer) 1 Doty and Cameron, 2009). Whereas, for example, significant sex dif- (3 mg of drospirenone and 0.03 mg of ethinyl estradiol) ferences and menstrual phase differences have been found for sensi- Necon 1/35 (Watson Pharmaceuticals, Inc.) 1 tivity to citral, anise, Exalotide (musk), and coumarin, no differences (1 mg of norethindrone and 0.035 mg of ethinyl estradiol) Desogen (Merck & Co., Inc.) 1 have been found in regard to safrol, n-butanol, amyl-acetate (ba- (0.15 mg of desogestrel and 0.03 mg of ethinyl estradiol) nana), and eucalyptus (Caruso et al., 2001; Le Magnen, 1952; Mair et al., 1978; Navarrete-Palacios et al., 2003; Oberg et al., 2002). Lundstrom et al. (2006) provided data indicating that hormones Materials may have differential effects on olfactory sensitivity, dependent upon the reproductive significance of the odor. Specifically, they showed Time of ovulation for NC women was determined with Answer Quick women in the periovulatory phase of their cycles to be more sensitive & Simple One-Step Ovulation Tests (Church & Dwight Co., Inc., Princeton, to androstadienone, a social odor, than to phenyl-ethyl alcohol (PEA— NJ, USA). Each ovulation test kit contained seven test sticks with the scent of roses); whereas women on OCs were more sensitive to luteinizing hormone (LH) antibodies designed to detect the LH surge PEA, an environmental odor, than the social odor. The authors suggest that occurs approximately 24–36 hours before ovulation. According to that these differences in olfactory sensitivity may be explained by dif- the manufacturer, these tests have a 98% accuracy at detecting the LH ferences in the hormonal profiles of the women, as women taking OCs surge, and thus at predicting ovulation. During each laboratory session, do not ovulate, and thus increased sensitivity to odors of potential olfactory thresholds were determined for four general odors: lemon mates would not prove beneficial. However, this was a cross-sectional (McCormick Pure Lemon Extract, McCormick & Co., Inc. Hunt Valley, study, and NC women's time of ovulation was estimated, not directly MD, USA), peppermint (Tone's Imitation Peppermint flavor, ACH Food measured via blood or urine analyses; therefore, more precise evalua- Companies, Inc. Memphis, TN, USA), rose (Rose Water, Nielson-Massey tion of this hypothesis is warranted. Vanilla's, Inc. Waukegan, IL, USA), and musk (Mystic Memories' Witch The present study sought to further explore hormonal influences Fae Perfume Oil with Genuine Amethyst, Mayfield Heights, OH, USA) on odor sensitivity, and tested the claims that women taking OCs odorants, as well as 5α-androst-16-en-3-one (androstenone), an andro- would have decreased olfactory sensitivity to a range of odors com- gen metabolite found in male bodily secretions (i.e.