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Is A Little Person's Genitals The Same Size As A Regular Size Person

  • Periodical List
  • Proc Natl Acad Sci U Due south A
  • v.110(17); 2013 April 23
  • PMC3637716

Proc Natl Acad Sci U Due south A. 2013 Apr 23; 110(17): 6925–6930.

Development

Penis size interacts with body shape and height to influence male attractiveness

Brian Due south. Mautz

aResearch School of Biology, Australian National University, Canberra, Human action 0200, Australia;

Bob B. Chiliad. Wong

bSchool of Biological Sciences, Monash University, Melbourne, VIC 3800, Australia; and

Richard A. Peters

cDepartment of Zoology, La Trobe University, Bundoora, VIC 3086, Australia

Michael D. Jennions

aInquiry Schoolhouse of Biology, Australian National University, Canberra, ACT 0200, Australia;

Supplementary Materials

Supporting Information

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Abstract

Compelling evidence from many animal taxa indicates that male genitalia are oftentimes nether postcopulatory sexual choice for characteristics that increase a male'southward relative fertilization success. There could, still, too be straight precopulatory female person mate selection based on male genital traits. Earlier clothing, the nonretractable human penis would accept been conspicuous to potential mates. This observation has generated suggestions that human penis size partly evolved because of female choice. Hither we evidence, based upon female cess of digitally projected life-size, computer-generated images, that penis size interacts with torso shape and height to determine male sexual attractiveness. Positive linear selection was detected for penis size, but the marginal increase in bewitchery eventually declined with greater penis size (i.e., quadratic selection). Penis size had a stronger result on attractiveness in taller men than in shorter men. At that place was a like increase in the positive outcome of penis size on attractiveness with a more masculine body shape (i.e., greater shoulder-to-hip ratio). Surprisingly, larger penis size and greater meridian had almost equivalent positive effects on male bewitchery. Our results back up the hypothesis that female person mate option could have driven the evolution of larger penises in humans. More than broadly, our results show that precopulatory sexual choice can play a part in the evolution of genital traits.

Keywords: genital development, multivariate bewitchery, multiple cues

Male person genitalia show great variation amid closely related species (one). This variation is typically attributed to copulatory and postcopulatory sexual selection to increment male fertilization success under sperm contest (2) or cryptic female choice (3). At that place might, however, also exist premating sexual selection on male ballocks. Precopulatory processes tin influence genital morphology (4, 5), simply it is unknown whether these results are due to direct female selection or sexual conflict. In species where genitalia are externally visible, sexual selection might likewise act if females adopt males with specific genital morphology. Despite this potential effect, relatively little research has tested whether principal sexual characters influence male bewitchery (6–8).

How female person pick acts on any given male trait, and hence the forcefulness and direction of choice, can be influenced by several, nonmutually exclusive factors. First, females use multiple cues during the mate pick procedure (9). Overall male person attractiveness is unlikely to be adamant by private traits (e.grand., refs. 10 and eleven), so manipulating traits in isolation can atomic number 82 to faulty conclusions about internet male person bewitchery (but encounter also ref. 12). Second, traits within individuals are phenotypically and genetically correlated. These relationships can influence evolution via correlational option (xiii). Third, there might be a size contrast issue such that female person assessment of attractiveness varies if the trait of involvement is viewed differently in relation to other traits, analogous to the Ebbinghaus–Titchener consequence (xiv). For example, the same sized penis might exist perceived differently on brusk and tall men. Finally, a female's own phenotype might influence her mate pick decisions. Humans mate assortatively based on numerous traits, including pinnacle (15), facial symmetry (sixteen), and body shape (17, 18). Hence, information technology is probable that how a female rates a male's attractiveness will partly depend upon her ain phenotype.

The upright body posture and protruding, nonretractable genitalia of male humans make the penis particularly conspicuous, even when flaccid. This observation has generated suggestions by evolutionary biologists that the comparatively large human penis evolved under premating sexual selection (19, 20). Furthermore, novels, magazines, and pop articles ofttimes allude to the existence of a relationship between penis size and sexual attractiveness or masculinity (21, 22). Many cultures take style items, similar penis sheaths and codpieces, that describe attention toward male genitalia (20), highlighting the potential for female choice to influence the development of male person genitalia. There are numerous psychological studies straight asking females for their preference regarding male penis size. The results are mixed, with studies finding that females prefer longer penises (23), wider penises (24, 25), or that penis size is unimportant (26). These studies, all the same, all employ self-reported, direct questioning and are therefore susceptible to biases of self-censorship and pressure to arrange to socially desirable responses to sensitive issues (due east.grand., refs. 27–29).

The just scientific studies to attempt to test experimentally whether flaccid penis length affects male attractiveness asked women to rate five images created by modifying a single drawing of a male person effigy so that the exam figures differed only in penis length (30–32). These of import studies were not designed to quantify directly the relative effect of penis length on bewitchery compared with other sexually selected male person traits, such equally height and body shape (30–32). Therefore, it is notwithstanding unknown whether penis size affects attractiveness when there is substantive variation in other, arguably more than important, trunk traits, or whether interactions between these traits and penis size make up one's mind internet bewitchery. For example, does a given increase in penis length accept an equivalent effect on the attractiveness of a brusque and alpine man? In addition, the use of small photographs to quantify size-based preferences might pb to different estimates than those obtained when viewing fully life-sized male person bodies.

To accost these issues, nosotros presented a sample of heterosexual Australian women with projected life-size, calculator-generated male figures (Fig. 1). Each figure was an animated four-s video in which the figure rotated xxx° to each side to allow participants to more easily evaluate the figure. We tested for the furnishings of flaccid penis size, body shape (shoulder-to-hip ratio), and height on male sexual attractiveness. The latter two traits have regularly been investigated and are known to influence male bewitchery or reproductive success [tiptop (15, 33–35), shape (18, 36, 37)]. Each trait had seven possible values that were within the natural range (±2 SD) based on survey data (36, 39). We generated figures for all 343 (= viiiii) possible trait combinations by varying each trait independently. This procedure eliminated any correlation between the three traits across the set of figures. Penis width did, yet, covary positively with length in the program used to generate the figures, and so we refer to overall "penis size" (merely encounter also Materials and Methods). The women (n =105), who were not told which traits varied, were and so asked to sequentially view a random subset of 53 figures, including iv of the same control effigy, and to charge per unit their attractiveness as sexual partners (Likert scale: i–vii). Effigy rating was conducted in the absence of an interviewer and was completely anonymous. We then used a standard evolutionary choice analyses to estimate multivariate linear, nonlinear, and correlational (interactive) selection (using the bewitchery score as a measure of "fitness") arising from female sexual preferences (e.g., ref. 38).

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Figures representing the nearly extreme height, shoulder-to-hip ratio, and penis size (±two SD) (Right and Left) in comparing with the average (Center effigy) trait values.

Results

Pick Analysis.

There were highly significant positive linear furnishings of meridian, penis size, and shoulder-to-hip ratio on male attractiveness (Table i). Linear selection was very strong on the shoulder-to-hip ratio, with weaker pick on superlative and penis size (Table 1). There were diminishing returns to increased height, penis size, and shoulder-to-hip ratio (quadratic selection: P = 0.010, 0.006 and < 0.0001) ["B" in Table 1] and, given the good fit of the linear and quadratic models, the optimum values appear to lie outside the tested range (i.e., maxima are >2 SD from the population mean for each trait) (Fig. two). A model using only linear and quadratic pick on the shoulder-to-hip ratio accounted for 79.six% of variation in relative attractiveness scores (centered to remove differences among women in their average attractiveness scores). The explanatory ability of height and penis size when added separately to this model was almost identical. Both traits significantly improved the fit of the model (log-likelihood ratio tests: height: χ2 = 106.5, df = three, P < 0.0001; penis: χ2 = 83.7, df = three, P < 0.0001). Each trait, respectively, explained an extra 6.one% and 5.ane% of the total variation in relative attractiveness.

Table 1.

Linear selection gradients and the matrix of quadratic and correlational selection gradients based on boilerplate rating for each of the 343 figures and means of gradients generated separately for each participant

An external file that holds a picture, illustration, etc.  Object name is pnas.1219361110unfig01.jpg

An external file that holds a picture, illustration, etc.  Object name is pnas.1219361110fig02.jpg

Relationship between attractiveness and penis size decision-making for height and shoulder-to-hip ratio (95% conviction intervals) indicating quadratic pick interim on penis size.

The effects of the three traits on relative attractiveness were not contained because of correlational choice (all P < 0.013) ["B" in Table 1]. Controlling for tiptop, there was a small-scale but pregnant difference in the rate of increase in relative bewitchery with penis size for a given shoulder-to-hip ratio (Fig. iiiA ). More compellingly, after controlling for shoulder-to-hip ratio, greater penis size elevated relative attractiveness far more strongly for taller men (Fig. threeB ).

An external file that holds a picture, illustration, etc.  Object name is pnas.1219361110fig03.jpg

Contour map of the fettle surface (red: more than attractive) for (A) penis length and shoulder-to-hip ratio (meridian controlled) and (B) penis length and height (shoulder-to-hip ratio controlled) (1 = mean attractiveness).

Participant and Response Time Analysis.

The average historic period of female participants was 26.two ± 6.viii SD y old. The participants were 71.eight% European, 20.9% Asian, and 7.3% from elsewhere with respect to ethnic origins. Female height was positively correlated with the linear upshot that male person peak had on her rating of his relative attractiveness (i.e., the linear choice slope for height calculated separately for each female person) (Pearson'southward r = 0.292, P < 0.0001) (Table 2). Females that were heavier than expected for their height (i.e., high relative weight/body mass alphabetize) showed a stronger linear issue of penis size on their rating of a male person's relative attractiveness (Pearson's r = 0.227, P < 0.021) (Tabular array 2). Female age was not correlated with the linear effect that whatsoever of the three male traits had on her rating of a male's relative attractiveness (all P > 0.164) (Table 2). At that place was no result of either the utilise of hormonal contraception or menstrual country on the linear effect of any of the iii male traits on how a female person rated relative attractiveness (all P > 0.166) (Table S1). We notation, yet, that these tests have limited power to detect a cycle effect, as women were non repeatedly surveyed during both the high and depression fertility phases.

Table 2.

Correlations betwixt female person traits and the strength of linear choice on male traits

Male trait Female traits
Elevation Weight Relative weight Age
Penis size −0.119 0.159 0.227* 0.074
Shoulder-to-hip ratio −0.069 −0.186 −0.173 −0.138
Height 0.292 *** 0.181 0.068 −0.056

The average latency to respond and rank a figure when pooled across all trials was three.08 ± 0.028 s (hateful ± SD) (n = five,142). Decision-making for baseline variation in response time among women, the response time was significantly greater for figures with a larger penis (F 1, 5034 = fifteen.099, P < 0.001), greater elevation (F 1, 5034 = 23.819, P < 0.001), and a greater shoulder-to-hip ratio (F 1, 5034 = 316.878, P < 0.001). Given that all three male traits were positively correlated with relative attractiveness, information technology is non surprising that, on average, there was also a significant positive correlation betwixt a female's attractiveness rating for a effigy and her response fourth dimension (mean correlation: r = 0.219, t 104 = eight.734, P < 0.001, north = 105 females). Decision-making for differences amidst women in their average bewitchery scores (i.e., using relative attractiveness), we plant meaning repeatability of the ratings given to the 343 figures (northward = 14–16 ratings per figure) (F 342, 4799 = six.859, P < 0.001; intraclass correlation: r = 0.281). For example, the accented departure in the rating score for the showtime and terminal (fourth) presentation of the command effigy to the aforementioned female was i.21 ± 0.10 (mean ± SE) (due north = 105) on a 7-point scale. This is a high level of repeatability, equally well-nigh figures had six adjacent figures that were identical except that they differed for one trait by 0.66 of a SD.

Word

We found that flaccid penis size had a significant influence on male attractiveness. Males with a larger penis were rated as being relatively more bonny. This relationship is nonlinear, even so, indicating that the proportional increase in bewitchery begins to decrease after a size of ∼seven.6 cm (Fig. two), which is an under-boilerplate penis size based on a large-scale survey of Italian men (39). Although we detected quadratic option on penis size, whatsoever potential peak (i.eastward., the most bonny penis size) appears to fall outside the range used in our study. A preference for a larger-than-boilerplate penis is qualitatively consequent with some previous studies (30–32), but our results differ in showing that the virtually attractive size appears to lie more than 2 SDs from the mean (i.e., no prove for stabilizing sexual selection, in contrast to refs. 30–32). Our results are further supported past the analysis of response time. We establish a significantly positive, admitting small, correlation between penis size and response time. This finding is consistent with a pattern in adults whereby attractive stimuli are viewed for a longer periods (forty). A trend to view attractive stimuli for longer is a generalized phenomenon that starts in infancy (41, 42).

Tiptop and shoulder-to-hip ratio also influenced a male'southward relative bewitchery with taller men and those with a greater shoulder-to-hip ratio being rated as more than attractive by women. Equally with penis size, the proportional increase in attractiveness declined as both male height and their shoulder-to-hip ratio increased. These results are consistent with previous findings of sexual selection on male tiptop based on prove from attractiveness rankings and patterns of actual mate choice (15, 37; but see as well refs. 43 and 44). Our results approve previously reported quadratic relationships between male person height and reproductive success (34, 45; merely run across besides refs. 33 and 35). Our results for shoulder-to-hip ratio are also broadly consequent with previous attractiveness studies on body shape (36, 46–48). Again, the correlations between response time and elevation and shoulder-to-hip ratio, respectively, were both significantly positive, indicating the females made quicker decisions when viewing less attractive figures (twoscore).

Our study plant no significant divergence in the proportion of variance deemed for in our model by penis size and elevation (6.1% vs. 5.1%), indicating that both traits had equivalent effects on relative bewitchery. This finding is intriguing given that height is ane of the virtually widely investigated and well-documented traits known to affect male reproductive success (15, 33–35, 37, 43, 44). The finding suggests that choice on penis size is potentially equally strong as choice on stature. The shoulder-to-hip ratio, however, accounted for a much larger proportion of variance in bewitchery in our model (79.6%). This issue might exist considering of our figures extending also far into the feminine range of body shapes (36), as those with a low shoulder-to-hip ratio were highly unattractive. Nevertheless, given increasing waistlines (49), the values we used are well within the range at present seen in many Western countries.

Nosotros detected correlational selection between all three traits, and then the effects of each trait on attractiveness were not independent of i another. The effect of penis size on bewitchery varied with both acme and body shape (Fig. 3B ). After decision-making for the shoulder-to-hip ratio, larger penis size had a greater result on attractiveness for taller men. This effect could be because perceived penis size was smaller when assessed relative to the summit of a taller man; or because of full general bigotry against brusk men irrespective of the value of other traits, and so that even a larger penis did petty to increase their cyberspace bewitchery. A similar relationship between penis size and shoulder-to-hip ratio was also detected (Fig. 3A ).

Attractiveness scores were not independent of the female participant'due south phenotype. Most chiefly, a female person's height was significantly positively correlated with the strength of her tendency to rate taller men as being relatively more attractive. This result is consistent with testify that humans mate assortatively based on height (15). In that location was also a weak, admitting pregnant (P = 0.021), positive relationship betwixt a female'southward relative weight (comparable to body mass index) and the outcome that penis size had on her cess of male person attractiveness. This human relationship was far stronger if nosotros included ii outliers (>four SD from mean; r = 0.333, P = 0.001, due north = 105). The human relationship was also stronger if we used a more stringent benchmark to exclude four outliers (>2 SD from mean; r = 0.296, P < 0.01, due north = 101). This result is intriguing simply should exist viewed with caution given that nosotros conducted multiple tests.

In sum, nosotros show that flaccid penis size alongside its interaction with shoulder-to-hip ratio and tiptop significantly influenced a male's relative attractiveness. Our results directly contradict claims that penis size is unimportant to nigh females (22, 26, fifty). Some studies betoken that preference for a larger penis might arise because penis size is associated with college rates of vaginal orgasm (23, 51). In turn, vaginal orgasms are associated with higher levels of associated sexual satisfaction (52). The proximate ground of the decisions leading to the reported attractiveness scores is unknown. General preexisting aesthetic preferences, either innate or caused through cultural norms, might account for the observed patterns. Another possibility is that females apply previous sexual experiences to infer a link between penis size and desirable male properties [eastward.yard., the likelihood of (vaginal) orgasm]. Arguing against this theory is the lack of a correlation between a woman's age and the magnitude of the effect of penis size on her rating of male attractiveness. Regardless of the exact mechanism, still, our results show that female person mate choice could accept played a role in the development of the relatively large human male penis. More than broadly, our study adds to growing bear witness from several species that precopulatory sexual selection tin influence the development of principal sexual traits in animals (four–8).

Materials and Methods

MakeHuman (v0.9.1RC1) was used to generate anatomically correct wire-frame figures. Body shape, height, and flaccid penis size were manipulated on each frame. We aimed to generate figures that encompassed the typical range of variation in these three traits in populations of Caucasian males. The penis and peak values used stem from a big-scale study of an Italian male population, merely these values fit within the standard range for Caucasians (reviewed in ref. 39). These values should capture ∼95% of the variation that females are probable to meet, although they do not encompass the full range of variation, and the mean values are known to vary amongst different man populations. For height and penis length, seven values were evenly spaced between ±two SD of the population mean (range: height: 1.63–1.87 m; flaccid penis: 5–xiii cm) (39). Using this program we could not generate penises that only increased in length, then nosotros refer to penis "size," as at that place was a slight increase in width of one.ii cm betwixt the shortest and longest penis, whereas at that place was an 8-cm alter in length. Body shapes were generated as seven evenly spaced values along the "masculinity" function of MakeHuman. We and so summarized these figures using the shoulder-to-hip ratio in our analysis (range: i.thirteen–1.45; i.e., pear to Five-shaped). These values cruel inside the natural range (36). Figures were imported into LightWave 3D (v9.six), colored grayness, modified to reduce pixilation, and standardized for testicle size. We so generated videos where a forrad facing effigy took four s to rotate xxx° to each side. Rotation increased the ability of participants to gauge penis size. Full details are available upon request.

Female participants were recruited at Monash University and the Australian National University (students, staff, and nonuniversity). The experiment was briefly described to participants as a study of male person attractiveness, but they were not told which male traits varied. Females were instructed to stand half dozen.five k straight in front of a wall where figures were projected at full (life) size. Before data collection and after the interviewer left the room, participants filled out a questionnaire and were asked about their height, weight, and age (SI Text). A scale and tape measure (for height) were provided in the room. The participants were too asked whether they were using chemical/hormonal contraception and what stage of their menstrual cycle they were in. After the questionnaire, and earlier data collection began, all participants viewed the aforementioned set of xiii videos that spanned the range in male trait values to gain familiarity with the figures. Before testing, participants were then asked: "Delight rate each figure based on how sexually attractive they are to you" (Likert calibration: i–vii). During the test, each participant was shown a unique, randomly ordered set of 53 videos: 49 test videos and 4 command (all traits at hateful) videos. After the participant entered a rating score (by pressing a keyboard button) the next figure in the sequence appeared. The organization automatically recorded the time between the effigy commencement appearing and a score for it being entered. We obtained data from 105 participants who self-identified as (i) heterosexual or (two) exclusively attracted to men in a pretest questionnaire (information from other participants were excluded: n = thirteen). Hence, all 343 figures were each viewed past approximately fifteen women (n = 5,145 ratings). Stimuli were displayed at life size using a digital projector in a private viewing room. Data were nerveless using SuperLab (v4.5). Data collection was anonymous then that no answers could be traced back to participants. Ideals approval was granted through Monash University (MUHREC Approval CF11/1378–2011000764).

Data Analysis.

Data on attractiveness were analyzed using standard multivariate selection procedures (xiii, 53). Our analyses clearly showed strong nonlinear and correlational selection, then we did non conduct canonical rotations of the data to generate eigenvectors (e.thou., refs. 53–55). We conducted two analyses. First, nosotros used a standard analysis based on a multiple regression of "relative bewitchery" on standardized trait values (mean = 0, SD = 1). We centered the rating scores from each participant (i.e., the hateful rating for each participant was then zero). This process generated participant-corrected scores to command for variation amidst participants in their tendency to requite higher or lower than average scores. For relative bewitchery we then calculated the mean participant-corrected attractiveness score for each of the 343 figures (an average of 15 participants viewed each figure). The mean score of the 343 figures is 0, so we added i to each figure's score to generate the last relative attractiveness score. This addition was done purely for presentation reasons, as the convention in selection analyses is that the average private has a value of 1. Adding 1 does not change estimates of selection gradients (i.e., regression coefficients). The relative attractiveness score is the dependent variable that we used every bit a surrogate mensurate of "fitness." We estimated pick gradients (13, 54) and associated P values from standard tests for regression coefficients (13) [encounter "A" in Table 1]. Considering nosotros present the results as a selection analysis, the regression coefficient for the squared product of individual traits are doubled (54). The selection gradients in Table one can therefore exist read as the increase in attractive score (on the original ane–7 scale) with a one SD increase in the focal trait.

Second, we used the aforementioned multiple-regression approach to summate a unique fitness surface for relative attractiveness for each participant. Nosotros did this to control for the fact that our first analysis did not account for participant identity. The dependent variable was simply the centered bewitchery for each participant. The 3 traits were each standardized for the prepare of figures that the participants viewed. We then calculated the hateful value for each choice gradient (i.e., each mean was based on 105 independent estimates) and used 1-sample t tests to determine whether means differed from zip (all distributions were normal, Kolomogorov–Smirnov tests, P = 0.23–0.94) [see "B" in Tabular array ane]. Both methods yielded very like estimates of selection gradients [compare "A" and "B" in Table 1]. In Figs. 2 and 3 we nowadays data based on the relative bewitchery of the 343 figures. Nosotros generated attractiveness contour maps (Fig. 3) with thin-plate splines in the fields package of R (56).

To investigate the human relationship between female traits and attractiveness scores, we used Pearson's correlations to measure the human relationship between the linear selection gradients (calculated using the second method) for each male trait (penis size, superlative, and shoulder-to-hip ratio) and each of three female traits (age, height, and weight). Weight and height are correlated (r = 0.322, P = 0.001), so to control for height, nosotros used the residuals from a regression of weight on pinnacle. These parameters tin can be considered broadly equivalent to a measure of torso mass alphabetize. We identified two females that showed a strong deviation from the regression line (residuals >4 SD). We excluded these participants from all of the results presented in Table 2. Finally, nosotros used two-sample t-tests to compare selection gradients betwixt females assigned to ane of two categories for contraception (using or not using chemical/hormonal contraception) and phase in the menstrual cycle [pinnacle of wheel (1–7 d after the start of menstrual wheel) or non peak bike (8–28 d after the showtime of the menstrual cycle)], respectively (Table S1).

Response Time and Repeatability Analysis.

We analyzed the effect of penis size on female latency to rate a figure in ii ways. First, we ran a general linear mixed model with response fourth dimension as the dependent variable and the three standardized male traits as fixed covariates. We included female participant identity as a random issue to command for multiple trials per female person. To improve the model fit, we log-transformed response fourth dimension (analyses on untransformed information yielded the same conclusions). We also ran the model excluding all cases (n = 246 of 5,142) where the response time was less than 0.ane s (this was a natural intermission in the data, as the log-transformed response time so showed a very close fit to a normal distribution). Again, the model yielded the aforementioned conclusions. Second, to decide how figure attractiveness influenced response time, we calculated the Pearson'southward correlation between the 53 bewitchery scores and log response fourth dimension for each female. These 105 correlations were then compiled and a one-sample t exam conducted to examination whether the hateful correlation was significantly unlike from nil. Use of Spearman ranked-club correlations yielded the same conclusion. Data on response time were missing for 3 of the five,145 trials.

To determine the repeatability of ratings of a figure's bewitchery across females, a repeatability analysis was performed for the 343 figures. We used participant-corrected bewitchery scores as the dependent variable in a one-fashion ANOVA (with figure identity as the chiselled gene) to estimate the intraclass correlation. This correlation is measure of the agreement among females in how they rate a effigy's attractiveness.

Meet Dataset S1 for the original data (n = five,145 ratings from 105 participants), Dataset S2 for the relative bewitchery scores and trait values for the 343 figures, and Dataset S3 for choice gradients and questionnaire responses for the 105 participants.

Supplementary Material

Acknowledgments

Nosotros thank J. Burchell, J. Irons, H. Kokko, E. McKone, and R. Reynolds for technical support; P. Backwell, I. Booksmythe, R. Catullo, and R. Lanfear for comments on previous drafts of the manuscript; and Geoff Miller and one bearding referee for their thoughtful and constructive comments on our manuscript. This project was funded by the Australian Enquiry Council; ethics blessing was granted through Monash University (MUHREC Approval CF11/1378 – 2011000764).

Footnotes

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Is A Little Person's Genitals The Same Size As A Regular Size Person,

Source: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3637716/

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