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Human Olfactory Contrast Changes During the Menstrual Cycle

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Human Olfactory Contrast Changes During the Menstrual Cycle Japanese Journal of Physiology, 52, 353–359, 2002 Human Olfactory Contrast Changes during the Menstrual Cycle Kyoko WATANABE*, Kana UMEZU*, and Takashi KURAHASHI*,† * Department of Biophysical Engineering, Osaka University, Toyonaka, 560–8531 Japan; and † Precursory Research for Embryonic Science and Technology (PRESTO), Japan Science and Technology Corporation (JST), Toyonaka, 560–8531 Japan Abstract: Several lines of studies have re- patch clamp experiment that uses the solitary ol- ported that olfactory perception is influenced by factory receptor cell. The results obtained from physical and hormonal conditions. In the present 18 trials (15 subjects) showed that olfactory con- study, we investigated changes of olfactory per- trast was significantly enhanced at the ovulatory ception during the menstrual cycle of the human. and/or menstrual phases. It is suggested that ol- Cyclopentadecanolide vapor was used and its factory contrast, which we defined as a new pa- perception intensity was measured by 6-point rameter, provides a useful tool in many kinds of category scale methods. We especially focused studies exploring the olfactory perceived ability. on a novel concept termed “olfactory contrast” [Japanese Journal of Physiology, 52, 353–359, that has been just very recently derived from the 2002] Key words: sensory system, olfaction, receptor cell, sex pheromone, menstrual cycle. Chemoreception is generally believed to be a very also confirmed the rhythmic change of the olfactory primary sensation, equipped in a wide variety of or- sensitivity during the menstrual cycle [5]. The detec- ganisms. In higher animals olfaction is tightly related tion thresholds of pentalide and androstenol varied to mating and feeding behaviors [1]. Therefore it has during the menstrual cycle [6]. In contrast, conflicting long been discussed that olfactory sensitivities are reports suggest that olfactory sensitivity is not rhyth- strongly dependent on the animal situation: Sensitivity mically changed throughout the menstrual cycle. becomes high when the animal seeks foods (see, e.g., Hummel et al. detected no changes in the olfactory Takagi [2]). Also, human olfaction has been thought sensitivity during the menstrual cycle when examin- to be influenced by body and external conditions ing it with phenylethyl alcohol, androstenone, and [3–8]. One amusing example is the relation between nicotine [7]. Furthermore, it was reported that thresh- the olfactory sensitivities and the menstrual cycles of old values against citral were uncorrelated with the women. menstrual cycle, but olfactory-related events obtained Several studies have investigated the olfactory sen- from the brain (CSERP: chemosensory event–related sitivity during the menstrual cycle, but the experimen- potentials) showed a remarkable change around the tal results express diverse variations among studies. It ovulatory phase [8]. was reported that women in ovulatory and premen- In the present study, we investigated the changes of strual phases could detect a lower concentration of olfactory perception during the menstrual cycle from Exaltolide, and during or just after menstruation the a different viewpoint. We carried out this study by fo- sensitivity became duller [3]. The olfactory sensitivity cusing on an index termed “olfactory contrast,” which is higher at ovulation than at menstruation when ex- has been just very recently derived from physiological amined with three involatile esters (pentadecalactone, experiments on the olfactory receptor cell [9]. Olfac- coumarin, and cinnamyl butylate) [4]. Doty et al. have tory contrast is defined as a slope of the dose–re- Received on May 23, 2002; accepted on July 25, 2002 Correspondence should be addressed to: Takashi Kurahashi, Physiological Laboratory, Department of Frontier Biosciences, Osaka Univer- sity, Toyonaka, 560–8531 Japan. Tel and Fax: 181–6–6850–6540, E-mail: [email protected] Japanese Journal of Physiology Vol. 52, No. 4, 2002 353 K. WATANABE, K. UMEZU, and T. KURAHASHI sponse relation and therefore provides recognition in regard to temperature), we would sometimes read- ability for the changed intensity of odorant. In the pre- just the air-conditioning so make the subject more sent work, we obtained it from females with psy- comfortable. chophysical tests. Our purposes for this work are (1) Cyclopentadecanolide (CPD; oxacyclohexadecan- to determine if olfactory contrast is a useful index to 2-one, known as Exaltolide or Pentalide, donated from evaluate human sensation, (2) to determine if olfac- Soda Aromatic was used as an odorant). CPD solution tory contrast changes during the menstrual cycle, and was diluted to 0.1 g/ml by ethanol (99.5%, Katayama (3) to provide information regarding correlation be- Chemical Industries) 12 steps of concentration was tween the olfactory perception and change in the en- made by binary serial dilution. It was stocked in glass docrine factors. bottles and covered tightly at room temperature. The range of concentration prepared was 3 log. According MATERIALS AND METHODS to our preliminary experiments, we confirmed that the lowest concentration used in this study was lower than Subjects. By questionnaires and their basal the detection threshold. Before testing, both the exper- body temperature monitored for a month before the imenter and the subject washed their hands with a fra- investigation, we recruited 15 healthy oriental women grance-free soap. The odor solution (2 ml) was infil- (from among 17) as subjects who had stable menstrual trated into a filter paper 5 mm wide. After the com- cycles and who did not smoke, use perfume, or con- plete evaporation of ethanol vapor (40–60 s), the filter sume highly seasoned foods. The subjects included paper was presented to the subject. The stimulants people from different genetic origins: 11 Japanese, 2 were inhaled by their sniffing. Chinese, 1 Taiwanese, and 1 Singaporean. In the pre- Psychophysical procedure. The olfactory sent study, however, we obtained no systematic rela- perceived strength was rated by using a 6-point cate- tion between olfactory perception and their back- gory scale that was anchored with the phrases “no ground. The mean age was 22.8 years (range519–32, smell” (leftmost word: zero) and “extremely strong” SD54.1). All subjects were nonparous, and none were (rightmost word: five) at both ends (in Japanese). The taking oral contraceptives. The average length of men- odorants were presented with the ascending series. In strual cycle was 31.463.9 d. a lower concentration, a three-force choice method To avoid emotional artifact during the measure- was used in parallel. We odorized only one filter paper, ments, we did not inform the patients of the purpose then presented it with two nonodor (only ethanol) fil- of our experiment. Before the experiments, however, ter paper as the blank. The subject judged which filter protocols and species of smell (musk) were explained paper had an odorant, and she rated the intensity of so that the subjects completely agreed to paricipate in stimuli. However, if the subject made a wrong judg- the measurement. All subjects signed a letter of intent ment or couldn’t determine which paper had the odor, to establish voluntary consents. After the series of in- the intensity of concentration was judged to be zero. vestigations were completed, a detail of our study was When the subject could make a correct judgment for a explained individually to each subject. Throughout the sequential three presentations, the intensity values of experiments, we found no subject to be affected by a stimuli were recorded from the lowest concentration health problem caused by the experimental procedure. of those three presentations. In the present experi- Stimulus delivery. We asked subjects not to ment, we allowed subjects to use decimal numbers to use any fragrance on the day of the test. The tests increase the resolution for the results. This was were performed around noon (from 9 A.M. to 1 P.M.), needed especially in the present experiment because more than 2 h after breakfast and before lunch. During we had to obtain a slope of the dose–response rela- this 2-h interval, the subjects were not allowed to con- tionship. To avoid adaptation, filter papers were pre- sume any food or drink except for water and tea. The sented to the subjects at intervals of 60–180 s, and the time needed for one series of test was approximately subjects were allowed to smell the presented odor 30 min. Subjects who had more than 5 h of sleep par- with only one sniff. For a comparison, some experi- ticipated in the examination. Alcohol and spicy foods ments were performed on male subjects (n53). Essen- were completely suppressed during the day before tially, the same protocols for the females were applied. tests. For all subjects, the tests were done in isolated The test was performed every other day during one rooms with the same environment. The condition of menstrual cycle. If a subject became unable to partici- each room was adjusted to a temperature of 23–27°C, pate (for example, a cold prevented smelling), we moisture 42–45%, and light 750–1,000 lx. But when a stopped the test until she recovered and started an- subject expressed uncomfortable feelings (especially other term of experiments over a single menstruation 354 Japanese Journal of Physiology Vol. 52, No. 4, 2002 Olfaction during the Menstrual Cycle Fig. 1. (A) Relation between the concentration of the odorant and the perceived intensity. The horizon- tal axis is log concentration of odor (mM, at the filter paper). The vertical axis represents olfactory-perceived in- tensity rated by the category scale. A series of plots was fitted by a Sig- moidal function: y5A11(A22A1)/{11 (log x02x p 10 ) }, where A1 is the bottom as- ymptote, A2 is the top asymptote, p is the Hill coefficient, and log x0 is the x value where y becomes (A11A2)/2. (B) Derivative of the curve obtained in A. Note that the curve is monotonic, expressing a remarkable peak.
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