Psychological effects of subthreshold exposure to the putative human pheromone 4,16-androstadien-3-one

Research on human putative pheromones has recently focused on the effects of exposure to 4,16-androstadien-3-one (androstadienone). This steroid has been observed in the skin, axillary hair, and blood plasma, primarily in males. In addition to effects of the steroid on measures of physiological arousal and brain blood flow, positive mood effects have also been reported. The current study further investigated mood effects of androstadienone exposure (250 microM) in women in two experiments. Through psychophysical testing of each individual we controlled for whether any observed mood effects could be related to sensory detection of the steroid. In both experiments, we observed positive changes of women's feeling of being focused, which could not be related to sensory detection of the steroid. Overall, the patterns of results were significantly correlated between the two experiments. In conclusion, this study corroborates earlier findings suggesting that androstadienone exposure yields effects on women's mood; the feeling of being focused. The mood effects were not dependent on menstrual cycle phase. Further, these effects are replicable and occur also when androstadienone detection is rigorously controlled for across variation in menstrual cycle.     

Evidence that androstadienone, a putative human chemosignal, modulates women's attributions of men's attractiveness

Considerable research effort has focused on whether specific compounds found within human body odor influence the behavior or physiology of other individuals. The most intensively studied is 4,16-androstadien-3-one, a chemical which is known to modulate mood and have activational effects in the sympathetic nervous system in a context-dependent manner, but whose action in mate-choice contexts remains largely untested. Here we present evidence that this androgen steroid may modulate women’s judgments of men’s attractiveness in an ecologically valid context. We tested the effects of androstadienone at a speed-dating event in which men and women interacted in a series of brief dyadic encounters. Men were rated more attractive when assessed by women who had been exposed to androstadienone, an effect that was seen in two out of three studies. The results suggest that androstadienone can influence women’s attraction to men, and also that research into the modulatory effects of androstadienone should be made within ecologically valid contexts.     

Putative human pheromone androstadienone attunes the mind specifically to emotional information

The putative human pheromone Δ4,16-androstadien-3-one (androstadienone), a non-androgenic steroid found in sweat and saliva, modulates psychological, physiological and hormonal responses without detection as an odor. To determine the specific psychological processes altered by androstadienone, four studies were completed by 50 men and women after solutions of 250 μM androstadienone or clove-odor control carrier, on separate days, were applied to their upper lip: (1) face pairs were subliminally presented, with one face neutral and the other happy or angry. Androstadienone accelerated speed to locate a subsequent dot probe appearing on the same side as emotional faces, without affecting overall reaction times, indicating that androstadienone specifically enhanced automatic attention to emotional information. (2) In two Stroop paradigms, emotional or mismatched color words interfered with ink color identification. Androstadienone slowed ink color identification of emotional words, demonstrating greater allocation of attentional resources towards emotional information, with no effect on the cognitive Stroop. (3) To test effects on social cognition, participants performed two working memory tasks with distinct stimuli, neutral faces or shapes. Androstadienone did not alter attention to either the social or nonsocial images. (4) The ameliorative effects of androstadienone on self-reported attentiveness were replicated, consistent with increased attention to emotional visual stimuli. Moreover, androstadienone did not alter positive or negative mood, as participants were alone during testing, which removed emotional stimuli from social interactions with a tester. Taken together, these findings demonstrate that subliminal androstadienone guides psychological resources to specifically engage stimuli with emotional significance and does not alter attention to social or general cognitive information.     

Heterosexual men and women both show a hypothalamic response to the chemo-signal androstadienone

The odorous steroid compound 4,16-androstadien-3-one (androstadienone), found in axillary sweat, was previously reported to evoke hypothalamic activation in heterosexual women, but not in heterosexual men. However, subjects were exposed to the pure crystalline form of androstadienone, which raised the question whether the observed hypothalamic response is physiologically relevant. Therefore, in the present study, we asked whether sexually dimorphic hypothalamic responses could be measured when subjects were exposed to lower, more physiologically relevant concentrations of androstadienone. A total of 21 women and 16 men, all heterosexual, participated in our functional magnetic resonance imaging study (fMRI). Three different concentrations of androstadienone diluted in propylene glycol (10 mM "high," 0.1 mM "medium" and 0.001 mM "low") were delivered to the subjects' nostrils using a computer-controlled stimulator. When exposed to the "high" androstadienone concentration, women showed stronger hypothalamic activation than men. By contrast, men showed more hypothalamic activation when exposed to the "medium" androstadienone concentrations in comparison to women. Thus, we replicated that smelling the chemo-signal androstadienone elicits a hypothalamic activation. However, this effect does not seem to be gender-specific, because androstadienone activated the hypothalamus in both men and women, suggesting that androstadienone exerts specific effects in heterosexual individuals of both sexes.     

Subliminally perceived odours modulate female intrasexual competition: an eye movement study

Background

Evidence suggests that subliminal odorants influence human perception and behavior. It has been hypothesized that the human sex-steroid derived compound 4,16-androstadien-3-one (androstadienone) functions as a human chemosignal. The most intensively studied steroid compound, androstadienone is known to be biologically relevant since it seems to convey information about male mate quality to women. It is unclear if the effects of androstadienone are menstrual cycle related.

Methodology/Principal Findings

In the first experiment, heterosexual women were exposed to androstadienone or a control compound and asked to view stimuli such as female faces, male faces and familiar objects while their eye movements were recorded. In the second experiment the same women were asked to rate the level of stimuli attractiveness following exposure to the study or control compound. The results indicated that women at high conception risk spent more time viewing the female than the male faces regardless of the compound administered. Women at a low conception risk exhibited a preference for female faces only following exposure to androstadienone.

Conclusions/Significance

We contend that a woman''s level of fertility influences her evaluation of potential competitors (e.g., faces of other women) during times critical for reproduction. Subliminally perceived odorants, such as androstadienone, might similarly enhance intrasexual competition strategies in women during fertility phases not critical for conception. These findings offer a substantial contribution to the current debate about the effects that subliminally perceived body odors might have on behavior.     

Psychological effects of musky compounds: comparison of androstadienone with androstenol and muscone

Previously, we have shown that delta4,16-androstadien-3-one modulates psychological state, reducing negative mood and increasing positive mood (Jacob and McClintock, 2000; Jacob et al., 2001a). In order to determine whether similar musky compounds also produce these effects, we compared the effects of androstadienone to those of androstenol and muscone, measuring the psychological states of 37 participants. Androstenol and muscone were chosen because they too have a musky odor at high concentrations, while androstenol is a steroid like androstadienone and muscone is not. In a controlled laboratory setting, we conducted a double-blind, within-subject, repeated-measures experiment counterbalanced for order of presentation. Under each participant's nose, a nanomolar amount of each compound was presented, masked by clove oil to minimize perceptible olfactory differences. Participants completed a baseline psychological battery and twice again at 25-min intervals after exposure. Androstadienone's effects on psychological state were unique in comparison with those of androstenol and with muscone. Exposure through passive inhalation, rather than dermal contact, was sufficient for these effects. Although this is additional evidence that androstadienone may be a pheromone, it is yet to be determined whether humans exude concentrations into the air adequate for social communication or process this chemical information within natural social contexts.     

Gas chromatographic-mass spectrometric study of metabolites of C21 and C19 steroids in neonatal porcine testicular microsomes.

Microsomal fractions obtained from testes of 3-week-old piglets have been incubated, separately, with progesterone, 17-hydroxyprogesterone, 5-pregnene-3 beta,20 beta-diol, 16 alpha-hydroxypregnenolone, 5-androstene-3 beta,17 alpha-diol and dehydro-epiandrosterone. The metabolites, after derivatization, have been separated by capillary gas chromatography and identified by mass spectrometry. Quantification was by selected ion monitoring. Progesterone was shown to be 17-hydroxylated and also converted into 4,16-androstadien-3-one (androstadienone). The major metabolite of 17-hydroxyprogesterone was 4-androstene-3,17-dione (4-androstenedione), but little, if any, androstadienone was formed, indicating that this particular biosynthesis did not require 17-hydroxylation. The metabolites of 5-pregnene-3 beta, 20 beta-diol were found to be 17-hydroxypregnenolone, 3 beta-hydroxy-5,16-pregnadien-20-one (16-dehydropregnenolone) and 5,16-androstadien-3 beta-ol. Dehydroepiandrosterone and 5-androstene-3 beta,17 alpha-diol were interconvertible but neither steroid acted as a substrate for 16-androstene formation. However, dehydroepiandrosterone was metabolized to a small quantity of 4-androstenedione. Under the conditions used, no metabolites of 16 alpha-hydroxypregnenolone could be detected. The present results, together with those obtained earlier, indicate that the neonatal porcine testis has the capacity to synthesize weak androgens, mainly by the 4-en-3-oxo steroid pathway. Although 16-androstenes cannot be formed from C19 steroids, progesterone served as a substrate and may be converted directly to androstadienone, without being 17-hydroxylated first. The pathway to 5,16-androstadien-3 beta-ol, however, involves 17-hydroxypregnenolone and 16-dehydropregnenolone as intermediates.     

Concordant preferences for opposite-sex signals? Human pheromones and facial characteristics.

We have investigated whether preferences for masculine and feminine characteristics are correlated across two modalities, olfaction and vision. In study 1, subjects rated the pleasantness of putative male (4,16-androstadien-3-one; 5alpha-androst-16-en-3-one) and female (1,3,5 (10),16-estratetraen-3-ol) pheromones, and chose the most attractive face shape from a masculine-feminine continuum for a long- and a short-term relationship. Study 2 replicated study 1 and further explored the effects of relationship context on pheromone ratings. For long-term relationships, women's preferences for masculine face shapes correlated with ratings of 4,16-androstadien-3-one and men's preferences for feminine face shapes correlated with ratings of 1,3,5(10),16-estratetraen-3-ol. These studies link sex-specific preferences for putative human sex pheromones and sexually dimorphic facial characteristics. Our findings suggest that putative sex pheromones and sexually dimorphic facial characteristics convey common information about the quality of potential mates.     

Chemosignals,hormones and mammalian reproduction

Many mammalian species use chemosignals to coordinate reproduction by altering the physiology and behavior of both sexes. Chemosignals prime reproductive physiology so that individuals become sexually mature and active at times when mating is most probable and suppress it when it is not. Once in reproductive condition, odors produced and deposited by both males and females are used to find and select individuals for mating. The production, dissemination and appropriate responses to these cues are modulated heavily by organizational and activational effects of gonadal sex steroids and thereby intrinsically link chemical communication to the broader reproductive context. Many compounds have been identified as “pheromones” but very few have met the expectations of that term: a unitary, species-typical substance that is both necessary and sufficient for an experience-independent behavioral or physiological response. In contrast, most responses to chemosignals are dependent or heavily modulated by experience, either in adulthood or during development. Mechanistically, chemosignals are perceived by both main and accessory (vomeronasal) olfactory systems with the importance of each system tied strongly to the nature of the stimulus rather than to the response. In the central nervous system, the vast majority of responses to chemosignals are mediated by cortical and medial amygdala connections with hypothalamic and other forebrain structures. Despite the importance of chemosignals in mammals, many details of chemical communication differ even among closely related species and defy clear categorization. Although generating much research and public interest, strong evidence for the existence of a robust chemical communication among humans is lacking.     

Conversion of 5 alpha-pregnane-3,20-dione, 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 beta-hydroxy-5 alpha-pregnan-20-one to delta 16-C19 steroids by the reconstituted delta 16-C19-steroid synthetase system

The substrate specificity of the reconstituted delta 16-C19-steroid synthetase system, which catalyzes the formation of 5,16-androstadien-3 beta-ol or 4,16-androstadien-3-one from pregnenolone or progesterone, respectively, was studied. The reconstituted system consisted of a partially purified cytochrome P-450, NADPH-cytochrome P-450 reductase, cytochrome b5 and NADH-cytochrome b5 reductase all from pig testicular microsomes. It was found that 5 alpha-reduced C21 steroids such as 5 alpha-pregnane-3,20-dione, 3 alpha-hydroxy-5 alpha-pregnan-20-one and 3 beta-hydroxy-5 alpha-pregnan-20-one can be substrates for the enzyme system, resulting in the formation of 5 alpha-androst-16-en-3-one, 5 alpha-androst-16-en-3 alpha-ol and 5 alpha-androst-16-en-3 beta-ol, respectively. The results suggest that 5 alpha-reduced delta 16-C19 steroids might be synthesized from pregnenolone and progesterone via 5 alpha-reduced C21 steroids as intermediates. The pathways would bypass 5,16-androstadien-3 beta-ol and 4,16-androstadien-3-one which have been assumed as obligatory intermediates in the formation of 5 alpha-reduced delta 16-C19 steroids from pregnenolone and progesterone.     

Individual differences in sensitivity to the odor of 4,16-androstadien-3-one

Individual differences in sensitivity to the putative human pheromone androstadienone were investigated in three experiments. In experiment 1, the absolute detection threshold for androstadienone was determined to be 211 micro M using the method of constant stimuli. Detection for the related compound estratetraenol was also investigated but a threshold could not be determined. In experiment 2, using an adaptive threshold test on 100 participants, the sensitivity distribution for androstadienone, but not for the reference odor phenylethyl alcohol, was bimodal, with a smaller group of individuals with a high sensitivity to androstadienone (supersmellers). A lack of correlation between thresholds for androstadienone and phenylethyl alcohol further suggested that the bimodality for androstadienone was not due to individuals with a high general olfactory sensitivity. In line with an earlier observation, there was a statistical tendency for women to be more sensitive to androstadienone than men. Results of experiment 3 preclude the possibility that the bimodal sensitivity distribution for androstadienone would depend on individual differences in trigeminal activation. Altogether, the current study suggests that olfactory sensitivity to androstadienone is bimodally distributed in the population with a subgroup consisting of highly sensitive people.     

Simultaneous quantification of five odorous steroids (16-androstenes) in the axillary hair of men

Five 16-androstenes have been simultaneously quantified in extracts of the axillary hair of men (age range 18-40 years) using combined capillary gas chromatography-mass spectrometry, with specific ion monitoring. Quantities found (pmol/mg.hair, with approximate 24-h totals in parentheses) were: 5 alpha-androst-16-en-3-one, 0-15 (0-433); 4, 16-androstadien-3-one, 0-143 (0-4103); 5,16-androstadien-3 beta-ol, 0-3.5 (0-728); 5 alpha-androst-16-en-3 alpha-ol, 0-17 (0-1752) and 5 alpha-androst-16-en-3 beta-ol, 0-4 (0-416). There were no significant relationships with age of the subjects for any of the steroids measured but significant relationships were found between the amounts of the two ketones and between 5 alpha-androst-16-en-3 alpha- and 3 beta-ols. These findings may indicate the existence of a pathway of metabolism in axillary bacteria in which 4,16-androstadien-3-one is reduced to 5 alpha-androst-16-en-3-one and thence to the 3 alpha- and 3 beta-alcohols. The data are discussed in the context of axillary odour because of the low olfactory thresholds of several of the 16-androstenes measured and because of the relatively large quantities found in some subjects.     

Synthesis of 2-carboxy-11 beta, 17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one and related compounds

A series of 2-carboxy-1, 4-androstadien-3-one derivatives and their alkyl esters, were prepared by high-yield syntheses. The compounds were structurally identified by physical methods. All these steroids are characterized by a marked antiglucocorticoid activity that proved long-acting in the case of the ester derivatives. 2-Carboxy-11 beta, 17 beta-dihydroxy-17-methyl-1, 4-androstadien-3-one or roxibolone, and its n-decylester or decylroxibolone, are the most promising derivatives in consideration of their pharmacological properties.     

Social chemosignals from breastfeeding women increase sexual motivation

Human pheromones, a type of social chemosignal, modulate endocrine function by regulating the timing of ovulation. In animals, pheromones not only regulate ovulation but also female reproductive motivation and behavior. There is no extant evidence that humans produce social chemosignals that affect human sexual motivation or reproductive behavior as occurs in other mammals. Here, we demonstrate that natural compounds collected from lactating women and their breastfeeding infants increased the sexual motivation of other women, measured as sexual desire and fantasies. Moreover, the manifestation of increased sexual motivation was different in women with a regular sexual partner. Those with a partner experienced enhanced sexual desire, whereas those without one had more sexual fantasies. These results are consistent with previous pheromonal effects on endocrine function, and warrant further study of these social chemosignals as candidates for pheromonal processes, including their effects on other aspects of motivation and behavior.     

GC-MS studies of 16-androstenes and other C19 steroids in human semen.

Human semen was examined for the presence of 16-androstenols, 16-androstenones and androgens. Extracts were analysed by gas chromatography-mass spectrometry after derivatization of steroids under study. In a qualitative study, 5 alpha-androst-16-en-3 alpha- and 3 beta-ols, 5,16-androstadien-3 beta-ol and 5 alpha-androstan-3 beta-ol were detected in a semen pool A. Hydroxyl groups were converted to tert-butyldimethylsilyl ethers, the ions selected for monitoring being [M-57]+, consistent with loss of the tert-butyl group. For a more detailed quantitative study, a second semen pool B was used. In this case, all hydroxyl groups were converted to trimethylsilyl ethers, while oxo groups were not derivatized. As with semen pool A, separation of steroids was achieved using capillary gas chromatography with appropriate temperature programming. Quantification was carried out by mass spectrometry using selected ion monitoring of two significant ions and appropriate internal standards. The following steroids were identified at the concentrations indicated: 5 alpha-androst-16-en-3 alpha- and 3 beta-ols and 5,16-androstadien-3 beta-ol (concentration range, 0.5-0.7 ng/ml). 5 alpha-Androst-16-en-3-one and 4,16-androstadien-3-one were also present at levels of 0.7-0.9 ng/ml. Two androgens, testosterone and 5 alpha-dihydrotestosterone were found at concentrations of 0.5 and 0.3 ng/ml, respectively. These data, showing the presence of 16-androstenes and androgens in human semen, appear to be consistent with testicular formation of these steroids. The possible significance of the odorous 16-androstenes is discussed.     

Phospholipases modulate immature pig testicular androgen and 16-androstene biosynthetic pathways in vitro.

The role of membrane phospholipids in porcine testicular androgen and 16-androstene biosynthesis was examined by monitoring the effects of phospholipase treatments on the activities of the steroid transforming enzymes. Untreated (control) microsomes from immature pig testes converted pregnenolone to 17-hydroxypregnenolone and DHA to 5,16-androstadien-3 beta-ol (andien-beta) and 4,16-androstadien-3-one (dienone) in the 16-androstene pathway, these metabolites accounting for most (65%) of the pregnenolone converted. The 4-ene steroids in the androgen pathway (progesterone, 17-hydroxyprogesterone, androstenedione and testosterone) totalled less than 10% of the pregnenolone metabolites. No estrogens or 5 alpha-reduced metabolites were detected. Treatment with phospholipase A2 or C, decreased the conversion of pregnenolone to 4-ene-3-oxo steroids but did not decrease the quantities of 5-ene-3 beta-hydroxysteroids. Confirmation of these findings was obtained by measuring the individual enzymatic steps. Phospholipases A2 and C significantly reduced the conversion of DHA to androstenedione and andien-beta to dienone but did not affect 17-hydroxylase or 'andien-beta-synthetase'. However, when the C-17, 20 lyase step was measured alone, phospholipase C decreased the quantity of androstenedione produced indicating that the side-chain cleavage reaction may involve a lipid component. The different effects of phospholipases on these enzymes suggests that pregnenolone metabolism may be regulated by alterations in the membrane microenvironment.     

From sexual attraction to maternal aggression: When pheromones change their behavioural significance

This article is part of a Special Issue “Chemosignals and Reproduction”.This paper reviews the role of chemosignals in the socio-sexual interactions of female mice, and reports two experiments testing the role of pup-derived chemosignals and the male sexual pheromone darcin in inducing and promoting maternal aggression. Female mice are attracted to urine-borne male pheromones. Volatile and non-volatile urine fractions have been proposed to contain olfactory and vomeronasal pheromones. In particular, the male-specific major urinary protein (MUP) MUP20, darcin, has been shown to be rewarding and attractive to females. Non-urinary male chemosignals, such as the lacrimal protein ESP1, promote lordosis in female mice, but its attractive properties are still to be tested. There is evidence indicating that ESP1 and MUPs are detected by vomeronasal type 2 receptors (V2R).When a female mouse becomes pregnant, she undergoes dramatic changes in her physiology and behaviour. She builds a nest for her pups and takes care of them. Dams also defend the nest against conspecific intruders, attacking especially gonadally intact males. Maternal behaviour is dependent on a functional olfactory system, thus suggesting a role of chemosignals in the development of maternal behaviour. Our first experiment demonstrates, however, that pup chemosignals are not sufficient to induce maternal aggression in virgin females. In addition, it is known that vomeronasal stimuli are needed for maternal aggression. Since MUPs (and other molecules) are able to promote intermale aggression, in our second experiment we test if the attractive MUP darcin also promotes attacks on castrated male intruders by lactating dams. Our findings demonstrate that the same chemosignal, darcin, promotes attraction or aggression according to female reproductive state.     

The search for human pheromones: the lost decades and the necessity of returning to first principles

As humans are mammals, it is possible, perhaps even probable, that we have pheromones. However, there is no robust bioassay-led evidence for the widely published claims that four steroid molecules are human pheromones: androstenone, androstenol, androstadienone and estratetraenol. In the absence of sound reasons to test the molecules, positive results in studies need to be treated with scepticism as these are highly likely to be false positives. Common problems include small sample sizes, an overestimate of effect size (as no effect can be expected), positive publication bias and lack of replication. Instead, if we are to find human pheromones, we need to treat ourselves as if we were a newly discovered mammal, and use the rigorous methods already proven successful in pheromone research on other species. Establishing a pheromone relies on demonstration of an odour-mediated behavioural or physiological response, identification and synthesis of the bioactive molecule(s), followed by bioassay confirmation of activity. Likely sources include our sebaceous glands. Comparison of secretions from adult and pre-pubertal humans may highlight potential molecules involved in sexual behaviour. One of the most promising human pheromone leads is a nipple secretion from the areola glands produced by all lactating mothers, which stimulates suckling by any baby not just their own.     

Microbial pathways leading to steroidal malodour in the axilla

Odorous steroids, specifically the 16-androstenes, 5alpha-androstenol and 5alpha-androstenone, are widely accepted as being contributors to underarm odour, but the precursors and pathways to these odorous steroids were unclear. This study demonstrated that the axillary microflora could only generate odorous 16-androstenes from precursors that already contain the C16 double bond, such as 5,16-androstadien-3-ol and 4,16-androstadien-3-one. In incubations containing 5,16-androstadien-3-ol, mixed populations of Corynebacterium spp., isolated from the axilla, could generate many different 16-androstene metabolites, several of which were odorous. Isolation of individual Corynebacterium strains, followed by pure culture incubations with 5,16-androstadien-3-ol, revealed organisms capable of efficient, rapid reactions. However, no single isolate could carry out a full complement of the observed biotransformations. 16-Androstene metabolites were identified by gas chromatography-mass spectrometry (GC-MS), either by comparison with known standards, or by prediction from molecular ion and fragmentation patterns. Based on detection of these metabolites, a metabolic map for axillary corynebacterial 16-androstene biotransformations was proposed, detailing potential enzyme activities. In summary, the formerly implicated 4,16-androstadien-3-one, 5alpha-androstenone and 5alpha-androstenol were detected, along with previously unreported hydroxy- and keto-substituted 16-androstenes, 16-androstatrienones and 16-androstatrienols. Additionally, many other metabolites with steroidal fragmentation patterns were present, but have remained unidentified.A key observation was that very low prevalences of microorganisms capable of biotransforming 16-androstenes were present on skin. For example, from a panel of 21 individuals, only 4 of 18 mixed populations of corynebacteria, and only 4 of 45 Corynebacterium isolates, could biotransform 5,16-androstadien-3-ol.This study has increased understanding of the metabolic pathways involved in steroidal malodour formation, and has demonstrated that the biotransformations are more complex than previously anticipated. However, it is clear that further research is required, both to assess the level of contribution of 16-androstenes to underarm odour, and to further elucidate the pathways and odour molecules formed by corynebacteria.     

Male axillary extracts contain pheromones that affect pulsatile secretion of luteinizing hormone and mood in women recipients

Human underarm secretions, when applied to women recipients, alter the length and timing of the menstrual cycle. These effects are thought to arise from exposure to primer pheromones that are produced in the underarm. Pheromones can affect endocrine (primer) or behavioral (releaser) responses, provide information (signaler), or perhaps even modify emotion or mood (modulator). In this study, we extracted underarm secretions from pads worn by men and placed the extract under the nose of women volunteers while monitoring serum LH and emotion/mood. Pulses of LH are excellent indicators of the release of GnRH from the brain's hypothalamus. In women, the positive influence of GnRH on LH affects the length and timing of the menstrual cycle, which, in turn, affects fertility. Here we show that extracts of male axillary secretions have a direct effect upon LH-pulsing and mood of women. In our subjects, the putative male pheromone(s) advanced the onset of the next peak of LH after its application, reduced tension, and increased relaxation. These results demonstrate that male axillary secretions contain one or more constituents that act as primer and modulator pheromones.