Evidence for Androgenic Influences on Self-Rated Health

Abstract

Background: According to most studies, males self-report being physically and mentally healthier than females. The present study sought to determine if androgens might influence health.

Methods: Self-reports of physical and mental health were obtained from college students in Malaysia (N = 2,058) and the United States (N = 2,511). Androgen exposure was assessed based on five self-reported measures that were then factor analyzed. A clear two-factor solution resulted from the analysis: muscularity, physical strength, and athletic ability loaded onto a muscular coordination factor, while adult height and 2D:4D finger length measure loaded onto a bone growth factor.

Results: As hypothesized, for males and females in both countries, self-rated physical and mental health were both positively correlated to a significant degree with the muscular coordination androgen factor. The only significant correlation between self-rated health and the bone growth androgen factor was negative among the Malaysian sample.

Conclusions: Androgenic influences on muscular coordination appear to coincidentally alter self-rated physical and mental health. This conclusion conflicts with proposals that men and women would provide the same self-ratings of health if it were not for sex role training and discrimination.

Citation

Ellis L, Hoskin AW (2020) Evidence for Androgenic Influences on Self-Rated Health. J Sexual Med Reprod Health 3: 9.

Introduction

Most studies have found self-reported physical health to be higher among males than among females [1-8], although some have failed to find significant differences, particularly studies based on college student samples [9,10]. Research suggests that the sex difference is found not only for perceptions of overall health, but for reports of symptoms and for rates of morbidity [11]. Whereas men tend to have higher rates of chronic disease and mortality, women tend to experience illnesses of a less serious and more transient nature [12].

In most studies of self-rated mental health, ratings by males are also higher than those provided by females [13-16]. Paradoxically, high self-rated health by males flies in the face of evidence that in nearly all countries men die 4 to 5 years earlier than women [17-19]. (It is true that some of the life expectancy difference between males and females is due to greater risk taking among young males – a fact that would not be reflected in self-rated levels of health)

Three plausible explanations have been offered for sex differences in self-perceived health: First, some have asserted that the main cause is sex discrimination along with sex role training. For example, Molarius [7], argued that women’s self-rated health would be the same as that for men “if they had similar financial security as men and were not treated in a condescending manner to a larger extent than men”. Similar proposals have been made in recent years by Borrell [20,21]. In the case of sex differences in self-reported mental health, proposals that sex discrimination may also be an important determinant, especially regarding depression, have also been made [20,22-24].

Second, sex differences in self-assessed health have been attributed to differences in levels of activity and exercise [25]. Specifically, studies indicate that regular exercise is associated with elevated mood, reduced stress, and improved physical health [26-31]. This coincides with numerous studies showing that males are more physically active and more likely to regularly exercise than females [32].

A third proposal is that exposure to androgens (male sex hormones) could contribute to average sex differences in self-reported health [33]. Support for this view is currently fragmentary. It includes studies linking various physical disorders with measures of 2D:4D finger length ratio, a reputed measure of prenatal testosterone exposure (as will be discussed in more detail below). For example, high 2D:4D finger length ratios have been found associated with high ratings of various types of joint pain, including osteoarthritis [34], and temporomandibular joint (TMJ) disorders [35]. Four direct lines of evidence linking self rated health and androgens were located. One came from a study of women in which a significant positive correlation was found between circulating testosterone and self-rated physical health as well as a reduction in depression symptoms [36]. Another was a study of men in which circulating testosterone was positively correlated with self-rated health [37]. The remaining two studies were of elderly men, both reporting significant positive correlations between age-controlled circulating testosterone and self-rated health [38,39]. Men might report high levels of physical and mental health due to testosterone’s reduction in sensitivity to aches and pain, and to its tendency to elevate mood [33,40].

Given that androgen studies of self-rated health have been limited to circulating levels of testosterone, the present study was undertaken to explore the relationship between organizational androgens and self-assessed health. This was done by obtaining self-reported measures of five biomarkers for high androgen exposure (2D:4D, adult height, muscularity, physical strength, and athletic ability) along with self-ratings of physical health and mental health. We hypothesized that self-ratings of physical and mental health would be positively correlated with androgen exposure, even within each sex.

Method

The study’s sample was comprised of undergraduate college students in Malaysia (N = 2,059) and the United States (N = 2,247). These two populations were chosen in order to see if results would be robust across two very different cultures. The proportional representation of respondents in terms of gender, marital status, and ethnicities are shown in Table 1 along with their average ages. Greater numbers of females than males in both countries were largely due to more females attending college in both Malaysia and the United States in recent years [41,42] (Table1).

Table 1: Demographic composition of the samples

The questionnaire

The questionnaire used in this study was developed and refined in English. It was then translated into Bahasa Malaysia, Malaysia’s official language since its independence from Great Britain in 1957. To ensure that the Malaysian translation was equivalent to the English version, the Malaysian questionnaire was back-translated into English until discrepancies were eliminated. Both questionnaires were four pages in length and covered a wide variety of topics, only a few of which are part of the present study.

Androgen-Influenced variables

Since it was first identified as a likely biomarker of prenatal androgen exposure in the late 20th Century [43], a subtle but fairly easily observed trait known as the 2D:4D ratio (or simply 2D:4D) has come to be widely utilized in research on traits that are suspected as being influenced by prenatal androgens. Among the findings are that there are well-established sex differences in 2D:4D, with males having lower ratios, meaning that the relative length of their 4th finger compared to their 2nd finger is slightly longer than for most females [44-49]. These sex differences are present even among newborns, albeit to a slightly lesser degree than among adults [50,51].

Studies have also shown 2D:4D to be statistically associated with several other sexually dimorphic physical traits such as birth weight [52,53], adult height [54,55], physical strength and muscularity [56-58], and athletic ability [59-62]. Consequently, it is reasonable to consider them physical biomarkers for androgen exposure. In the research questionnaire, respondents were asked to provide estimates of 2D:4D as well as estimates of their height, physical strength, muscularity, and athletic ability.

The r2D:4D Measure

Most studies that have compared the relative finger lengths on both hands have concluded that the right hand provides a more reliable measure of prenatal androgen exposure than does the the left hand [49,63-67].Therefore, we limited our measurement to the right hand, and will use the term r2D:4D to reference it.

Exactly how the relative lengths of the second and fourth digits are altered by perinatal androgen exposure remains to be fully explained, but it is well established that testosterone promotes bone growth [68-71]. Also, a period when prenatal androgens normally rise seems to coincide with a growth spurt in the fourth digit [55,63,72].

Using a variety of research designs, several studies have confirmed that 2D:4D is a relatively valid biomarker for perinatal androgen exposure [48,63,73,74]. At least when measured with precise instruments, it is a reliable measure [75], but researchers have characterized it as “valid, though weak” [76], and “a very ‘noisy’ indicator” [77].

Although it is infrequently used, the “gold standard” for measuring the relative lengths of the 2nd and 4th digits involves obtaining X-ray images [67,78]. Much more common methods involve physically measuring the distance between the tip of the finger to the basal crease where the finger connects to the palm [79]. Additional measures have been obtained from photocopies or scanned images of the hand and then using calipers to estimate their relative lengths [55,80,81]. A few studies have relied on various self-estimates made by respondents themselves [66,82,83].

In the present study, respondents were asked to provide a self-estimate. They did so after reading the following: Hold up the back of your right hand so that you can see all five fingers. With your thumb as the first finger, compare the lengths of your 2nd (pointing) finger with your 4th (ring) finger. Which is longer? (check one of the five responses below)

____ Index (pointing) finger considerably longer

____ Index (pointing) finger slightly longer

____ They are almost exactly the same length

____ Ring (4th) finger slightly longer

____ Ring (4th) finger considerably longer

For a subsample of 215 of the U.S. respondents, we obtained both the self-estimate just described and a measure using calipers of scanned images of the right hand. This yielded a modest positive correlation of r = .30 between the two measures. While highly significant statistically, and both measures no doubt contain measurement error, this coefficient suggests that our self-report measure was only modestly reliable.

In order to minimize confusion in interpreting the results, we inverted the r2D:4D self-ratings (relative to how they are normally presented). Thus, the higher r2D:4D ratios reflect higher androgen exposure. This pattern means that high r2D:4D scores conform to high scores for the other four androgen-influenced traits discussed below; all are in the positive direction.

Four additional androgen-Influenced traits

As noted above, 2D:4D appears to be a valid indicator of prenatal androgen exposure although its reliability has been disappointingly low. Therefore, four additional biomarkers of androgen exposure were utilized, all of which have been found to be inversely correlated with 2D:4D: height [54,55], physical strength and muscularity [56-58], and athletic ability [59,61,62].

Adult height was measured by simply asking all respondents to report their height. In Malaysia, reports were provided in metrics, while the U.S. sample responded in feet and inches which were converted to metrics.

The remaining three traits were physical strength, muscularity, and athletic ability. To obtain these measurements, respondents were asked to use an eleven-point scale with the following instructions: Being as objective as possible, rate yourself on the following traits (0 meaning “not at all” to 10 meaning “the most extreme degree possible”):

Physical strength _____

Being muscular _____

Athletic ability _____

From the standpoint of accuracy, it obviously would have been preferable to have had each of these traits measured with objective instruments overseen by trained researchers. However, to provide anonymity, and to save time and expense given large sample sizes in both countries, we relied entirely on self-reports.

Correlating and factor analyzing the Androgen Influenced traits

As already documented, 2D:4D is inversely associated with adult height, physical strength, muscularity, and athletic ability. Such findings are predictable since all of these traits are influenced by exposing the body to testosterone and/or other androgens [53,84]. Table 2 provides confirmation of these findings with respect to the present study. Specifically, in both Malaysia and the U.S., the inverted r2D:4D variable positively correlates with adult height, physical strength, muscularity, and athletic ability, and these variables in turn all positively correlate with one another. All but two of these correlations were statistically significant, i.e., in the Malaysian sample, the associations between physical strength and the inverted r2D:4D and height variables both fell slightly short of statistical significance.

Table 2: Spearman rank correlations between the five androgen-influenced traits for the Malaysian sample in the upper right portion and for the U.S. sample in the lower left portion.

To determine how closely linked the five androgen-influenced traits were interrelated, we subjected them to factor analysis. Because we inverted all of the r2D:4D scores, all five androgen influenced traits were in the same direction: i.e., high scores for each trait meant high androgen exposure.

The results of the factor analysis appear in Table 3 for each sex.

Table 3: Factor loadings for the five self-assessed androgen-influenced traits using principal component analysis with varimax rotation. Analyses were run on males and females separately and in combination. (All loadings above .50 are bolded. Eigenvalues: Factor 1 = 2.096; Factor 1 = 1.075).

Without having any limits imposed regarding the number of factors to be extracted, the same factors emerged for both males and females. Our inverted r2D:4D measure loaded very heavily along with adult height onto Factor 2. Since both of these traits pertain to skeletal structures (i.e., growth of the fingers and growth of the body as a whole), we named this second factor the bone growth factor.

The remaining three androgen-influenced traits – physical strength, muscularity, and athletic ability – all loaded unambiguously onto Factor 1. The communality of these three traits suggested that they would be appropriately named the muscular coordination factor. Even though androgens play important roles in affecting both skeletal growth and muscularity, our findings are consistent with evidence that bone growth and muscular coordination result from substantially different androgenic regimens and/or biochemical pathways [85,86].

Dependent variables

To assess health, research participants were asked to answer the following two questions: Being as objective as possible, rate yourself on the following traits (0 meaning “not at all” to 10 meaning “the most extreme degree possible”):

Physical health _______

Mental health _______

Data analyses

In order to determine how well the androgen-influenced traits were associated with one another and with the health measures, we used correlation. Spearman correlation was used since the relevant variables were measured at the ordinal level. Two-tailed tests of significance were utilized throughout.

As noted earlier, to make interpretation of findings easier, the scores for the r2D:4D measure were inverted. Therefore, our r2D:4D measure is henceforth referred to as inverted r2D:4D. The androgen-influenced traits (and factors) were correlated with the two self-ratings of health.

Results

Before addressing the study’s hypotheses, attention is drawn to Table 4.

Table 4: Sex differences in the androgen-influenced traits and the physical and mental health measures by country and gender.

This provides a comparison of averages for all of the variables (and factors) according to gender and country. As one would expect, scores for the five of the independent variables (and for the two factors derived from these variables) were all significantly higher for males than for females. However, only physical health for the U.S. sample was significantly higher in males. As noted in the introduction, this is similar to a couple of other studies limited to college student populations [9,10].

Androgen biomarkers and self-rated physical health

The evidence bearing on the hypothesis that self-rated physical health would be postively correlated with androgen exposure is presented in Table 5a.

Table 5a: Spearman ranks between self-rated physical health and the five androgen-influenced traits (and the two derived factors) by country and gender.

According to this table, statistically significant positive correlations exist with respect to Factor 1 (the muscular coordination factor), comprised of physical strength, muscularity, and athletic ability. However, Factor 2 (the bone growth factor – comprised of adult height and the 2D:4D measure), was not correlated with self-rated physical health. The pattern holds for both countries sampled and for both males and females.

Androgen biomarkers and self-rated mental health

Table 5b presents evidence bearing on the possible relationship between self-rated mental health and androgen exposure. Its results are similar to those for self-rated physical health. Factor 1 – incorporating physical strength, muscularity, and athletic ability – is significantly and positively correlatedwith with mental health self-ratings. As with physical health ratings,this pattern holds for both countries and for both sexes and it holds true for all three androgen measures comprising Factor 1.

Table 5b: Spearman rank correlations between self-rated mental health and the five androgen-influenced traits (and two derived factors) by country and gender.

In the case of the remaining two androgen exposure measures – i.e., those comprising Factor 2 (the bone growth factor) – there is actually a negative correlation for the Malaysian sample, but not for the U.S. sample. This finding is contrary to our hypothesis, and the lack of relevant research leaves us unable to explain the unexpected

Discussion

As noted in the introduction, most studies have found that males report being healthier than females, both physically and mentally, with a few exceptions involving samples drawn from college students. In the present study of college students, U.S. males rated their physical health significantly higher than did females, but no significant difference was found amongst the Malaysian students regarding physical health. Self-ratings of mental health were not significant different for males and females in either country (Table 4). Obviously, there is a need to discover why sex differences are found in self-rated health among broad populations but sometimes not among college students.

The main purpose of this study was to determine if variations in physical and mental health self-ratings could be partly due to exposure to organizational androgens. Five androgen exposure measures were utilized: 2D:4D, adult height, physical strength, muscularity, and athletic ability. These measures were factor analyzed and shown to load unambiguously onto two factors: Factor 1, termed the muscular coordination factor, and Factor 2, named the bone growth factor. For this study, values for the 2D:4D measure were inverted, so that high scores would correspond with high androgen exposure. In all cases, males scored significantly higher than females on all five androgen measures and on both androgen exposure factors (Table 4).

Results from this study strongly support the conclusion that androgens do have effects on self-ratings of both physical health and mental health. This conclusion directly contradicts those who argue that sex differences in self-ratings of health can actually be entirely explained in terms of sex role training and societal discrimination [7,21]. Our findings are also consistent with the view that organizational androgens improve health indirectly via increased physical exercise.

The strongest apparent effects of androgens on self-rated health were positive, as we hypothesized. This finding coincides with three prior studies indicating that circulating testosterone levels are positively correlated with self-rated health [36,38,39]. However, the positive effects we observed were based on indirect, rather than direct, measures of androgens, and our findings indicate that only the effects of androgen regimens pertaining to muscular coordination affected self-ratings of health. At least in our Malaysian sample, there was also a weak but still significant negative effect of androgen regimens associated with bone growth factor that also appears to have affected self-rated health. This was entirely unexpected and obviously needs to be replicated.

Without attempting to offer a detailed explanation for these findings, it is almost certainly relevant to note that the biochemical pathways whereby androgens promote muscular development and skeletal growth are not the same [86,87]. For example, to promote bone growth, testosterone needs to be converted to estradiol (via the enzyme aromatase). After making this conversion, estradiol operates in conjunction with the human growth hormone, to elongate and strengthen the bones [88-91]. As a steroid, testosterone appears to promote muscular development and functioning more directly, although estrogens may still have some role to play in the process [91-95].

Among the limitations of this study are that measures are based on single-item, self-rated responses. This is all but unavoidable for measuring self-reported health in a non-clinical setting, but the androgen-influenced traits could have been measured more precisely with physiologically-based instruments. Nonetheless, as an exploratory study, our findings are suggestive with respect to some new directions that may be taken to understand how androgens may influence traits such as self-assessed health. We also see our indirect measurement of androgens as actually being advantageous over direct measurements of testosterone and other androgens, since direct measures only tap into the levels of these hormones over a short period of time. Our indirect measurements gage much more long term prenatal exposure to androgens.

Another limitation was that only college students were sampled. Because a significant sex difference in self-rated health was found only among the U.S. male sample, our study probably provides a minimal estimate of the extent to which androgens play a role in self-rated health. Moreover, the 2D:4D digit ratio is recognized as a “noisy” biomarker of androgen exposure, thus providing a low-reliability marker for prenatal androgen exposure. Nonetheless, evidence presented here that androgens are related to physical and mental health suggests that further research along these lines is in order.

Acknowledgements

The following individuals assisted in recruiting research participants for this study: Drew H. Bailey, David Geary, Richard D. Hartley, Richard Lippa, Emi Prihatin, Anthony Walsh, and Alan Widmayer. Funding for the collection of data utilized in this study was provided in part by a research grant from the University of Malaya to its Department of Anthropology and Sociology (Number RG143-10HNE) while the first author was there as a visiting professor.

References

1. Chemaitelly H, Kanaan C, Beydoun H, Chaaya M, Kanaan M, Sibai AM. The role of gender in the association of social capital, social support, and economic security with self-rated health among older adults in deprived communities in Beirut. Qual Life Res. 2013; 22, 1371-1379.

2. Hosseinpoor AR, Williams JS, Amin A, De Carvalho IA, Beard J, Boerma T, et al. Social determinants of self-reported health in women and men: understanding the role of gender in population health. PLoS One, 2012; 7: e34799.

3. Kroenke K, Spitzer RL. Gender differences in the reporting of physical and somatoform symptoms. Psychosomatic Med. 1998; 60: 150-155.

4. Li H, Zhu Y. Income, income inequality, and health: Evidence from China. Journal of Comparative Economics. 2006; 34: 668-693.

5. Kawada T, Wakayama Y, Katsumata M, Inagaki H, Otsuka T, Hirata Y, et al. Patterns in self-rated health according to age and sex in a Japanese national survey, 1989-2004. Gender Med. 2009; 6: 329-334.

6. Malmusi D, Artazcoz L, Benach J, Borrell C. Perception or real illness? How chronic conditions contribute to gender inequalities in self-rated health. Eur J Public Health. 2012; 22: 781-786.

7. Molarius A, Granstrom F, Feldman I, Blomqvist MK, Pettersson H, Elo S, et al. Can financial insecurity and condescending treatment explain the higher prevalence of poor self-rated health in women than in men? A population-based cross-sectional study in Sweden. Int J Equity Health. 2012; 11: 50-57.

8. Todorova IL, Tucker KL, Jimenez MP, Lincoln AK, Arevalo S, Falcón LM. Determinants of self-rated health and the role of acculturation: implications for health inequalities. Ethnicity & Health. 2013; 18: 563 585.

9. Castrén J, Huttunen T, Kunttu K. Users and non-users of web-based health advice service among Finnish university students–chronic conditions and self-reported health status (a cross-sectional study). BMC Med Inform Decision Making. 2008; 8: 8.

10. Noor NM, Rahman SA, Farooqui J, Nasr AM, Noon HM. Psychological profiles of effeminate, male, and female students. Psychologia. 2003; 46: 235-245.

11. Gove WR, Hughes M. Possible causes of the apparent sex differences in physical health: An empirical investigation. Am Sociol Rev. 1979; 126-146.

12. Gijsbers van Wijk CMT, Kolk AMM, van den Bosch WJHM, van den Hoogen HJM. Male and female morbidity in general practice: The nature of sex differences. Social Science & Medicine. 1992; 35: 665 678.

13. Hutton K, Nyholm M, Nygren JM, Svedberg P. Self-rated mental health and socio-economic background: A study of adolescents in Sweden. BMC Public Health. 2014; 14: 394-402.

14. Kim BJ, Harris LM. Social capital and self-rated health among older Korean immigrants. J Applied Gerontol. 2013; 32: 997-1014.

15. O’Regan C, Cronin H, Kenny RA. Mental health and cognitive function. In A. Barrett G. Savva V. Timonen & R. A. Kenny (Eds), Fifty Plus in Ireland, 155-166. Dublin: Irish Longitudinal Study on Ageing. 2011.

16. Hicks T, Miller E. College life styles, life stressors and health status: Differences along gender lines. J College Admission. 2006; 192: 22-29.

17. Idler EL, Benyamini Y. Self-rated health and mortality: A review of twenty seven community studies. J Health Soc Behav. 1997; 38: 21-37.

18. Ng N, Hakimi M, Santosa A, Byass P, Wilopo SA, Wall S. Is self-rated health an independent index for mortality among older people in Indonesia? PloS one. 2012; 7: e35308.

19. Oksuzyan A, Juel K, Vaupel JW, Christensen K. Men: Good health and high mortality. Sex differences in health and aging. Aging Clinical and Experimental Research. 2008; 20: 91-102.

20. Borrell C, Muntaner C, Gil-González D, Artazcoz L, Rodríguez-Sanz M, Rohlfs I, et al. Perceived discrimination and health by gender, social class, and country of birth in a Southern European country. Preventive Medicine. 2010; 50: 86-92.

21. Lee SY, Kim SJ, Yoo KB, Lee SG, Park EC. Gender gap in self-rated health in South Korea compared with the United States. Int J Clin Health Psychol. 2016; 16: 11-20.

22. Horwitz AV. Sex-role expectations, power, and psychological distress. Sex Roles. 1982; 8: 607-623.

23. Radloff L. Sex differences in depression. Sex roles. 1975; 1: 249-265.

24. Rosenfield S. The effects of women’s employment: Personal control and sex differences in mental health. J Health Social Behav. 1989; 30: 77-91.

25. Ross CE, Bird CE. Sex stratification and health lifestyle: consequences for men’s and women’s perceived health. J Health and Social Behav. 1994; 35: 161-178.

26. Arai SM, Mock SE, Gallant KA. Childhood traumas, mental health and physical health in adulthood: Testing physically active leisure as a buffer. Leisure. 2011; 35: 407-422.

27. Fox KR, Stathi A, McKenna J, Davis MG. Physical activity and mental well-being in older people participating in the Better Ageing Project. Eur J applphysiol. 2007; 100: 591-602.

28. Jewett R, Sabiston CM, Brunet J, O’Loughlin EK, Scarapicchia T, O’Loughlin J. School sport participation during adolescence and mental health in early adulthood. J Adolescent Health. 2014; 55, 640 644.

29. Niemann C, Wegner M, Voelcker-Rehage C, Holzweg M, Arafat AM, Budde H. Influence of acute and chronic physical activity on cognitive performance and saliva testosterone in preadolescent school children. Mental Health and Physical Activity. 2013. 6: 197-204.

30. Salmon P. Effects of physical exercise on anxiety, depression, and sensitivity to stress: a unifying theory. Clin Psychol Rev. 2001; 21: 33 61.

31. Ströhle A. Physical activity, exercise, depression and anxiety disorders. J Neural Transm. 2009; 116: 777-784.

32. Ellis L, Hershberger S, Field E, Wersinger S, Pellis S, Geary D, et al. Sex differences: Summarizing more than a century of scientific research. New York: Psychology Press. 2008.

33. Fillingim RB. Sex, gender, and pain: Women and men really are different. Curr Rev Pain. 2000; 4: 24-30.

34. de Kruijf M, Kerkhof HJ, Peters MJ, Bierma-Zeinstra S, Hofman A, Uitterlinden AG, et al. Finger length pattern as a biomarker for prenatal androgen exposure and the risk for osteoarthritis and pain. Osteoarthr Cartil. 2013; 21: S266.

35. Sanders AE, Slade GD, Bair E, Fillingim RB, Knott C, Dubner R. General health status and incidence of first-onset temporomandibular disorder: The OPPERA prospective cohort study. J Pain. 2013; 14: T51-T62.

36. Santoro N, Torrens J, Crawford S, Allsworth JE, Finkelstein JS, Gold EB, Korenman S. Correlates of circulating androgens in mid-life women: the study of women’s health across the nation. J Clin Endocrinol Metab. 2005; 90: 4836-4845.

37. LeBlanc ES, Wang PY, Lee CG, Barrett-Connor E, Cauley JA, Hoffman AR. Higher testosterone levels are associated with less loss of lean body mass in older men. J Clin Endocrinol Metab. 2011; 96: 3855 3863.

38. Eskelinen SI, Vahlberg TJ, Isoaho RE, Kivelä SL, Irjala KM. Associations of sex hormone concentrations with health and life satisfaction in elderly men. Endocr Pract. 2007; 13: 743-749.

39. Hsu B, Cumming RG, Blyth FM, Naganathan V, Le Couteur DG, Seibel MJ, et al. Longitudinal and cross-sectional relationships of circulating reproductive hormone levels to self-rated health and health-related quality of life in community-dwelling older men. J Clin Endocrinol Metab. 2014; 99: 1638-1647.

40. Barrett-Connor E, Von Mühlen DG, Kritz-Silverstein D. Bioavailable testosterone and depressed mood in older men: the Rancho Bernardo Study. J Clin Endocrinol Metab. 1999; 84: 573-577.

41. Diprete TA, Buchmann C. Gender-specific trends in the value of education and the emerging gender gap in college completion. Demography. 2006; 43: 1-24.

42. Shawn F. Dorius, Glenn Firebaugh. Trends in global gender inequality. Soc Forces. 2010; 88: 1941-1968.

43. Manning JT, Scutt D, Wilson J, Lewis-Jones DI. (1998). The ratio of 2nd to 4th digit length: A predictor of sperm numbers and concentrations of testosterone, luteinizing hormone and oestrogen. Hum Reprod. 1998; 13: 3000-3004.

44. Gillam L, McDonald R, Ebling FJ, Mayhew TM. Human 2D (index) and 4D (ring) finger lengths and ratios: Cross-sectional data on linear growth patterns, sexual dimorphism and lateral asymmetry from 4 to 60 years of age. J Anat. 2008; 213: 325-335.

45. Hönekopp J, Watson S. Meta-analysis of digit ratio 2D:4D shows greater sex difference in the right hand. Am J Hum Biol. 2010; 22: 619 630.

46. Lippa R A. Finger lengths, 2D:4D ratios, and their relation to gender related personality traits and the Big Five. Biol Psychol. 2006; 71: 116 121.

47. Manning JT, Stewart A, Bundred PE, Trivers RL. Sex and ethnic differences in 2nd to 4th digit ratios of children. Early Hum Dev. 2004; 80: 161-168.

48. Okten A, Kalyoncu M, Yariş N. The ratio of second-and fourth-digit lengths and congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Early Hum Dev. 2002; 70: 47-54.

49. Williams TJ, Pepitone ME, Christensen SE, Cooke BM, Huberman AD, Breedlove NJ, et al. Finger-length ratios and sexual orientation. Nature. 2000; 404: 455-456.

50. Knickmeyer RC, Woolson S, Hamer RM, Konneker T, Gilmore JH. 2D:4D ratios in the first 2 years of life: Stability and relation to testosterone exposure and sensitivity. Horm Behav. 2011; 60: 256-263.

51. Ventura T, Gomes MC, Pita A, Neto MT, Taylor A. Digit ratio (2D: 4D) in newborns: Influences of prenatal testosterone and maternal environment. Early Hum Dev. 2013; 89: 107-112.

52. Danborno B, Adebisi S, Adelaiye A, Ojo S. Relationship between digit ratio (2D:4D) and birth weight in Nigerians. Anthropologist. 2010; 12: 127-130.

53. Klimek M, Galbarczyk A, Nenko I, Alvarado LC, Jasienska G. Digit ratio (2D: 4D) as an indicator of body size, testosterone concentration and number of children in human males. Ann Hum Biol. 2014; 41: 518 523.

54. Fink B, Neave N, Manning JT. Second to fourth digit ratio, body mass index, waist-to-hip ratio, and waist-to-chest ratio: Their relationships in heterosexual men and women. Ann Hum Biol. 2003; 30: 728-738.

55. Lutchmaya S, Baron-Cohen S, Raggatt P, Knickmeyer R, Manning JT. 2nd to 4th digit ratios, fetal testosterone and estradiol. Early Hum Dev. 2004; 77: 23-28.

56. Fink B, Thanzami V, Seydel H, Manning JT. Digit ratio and hand-grip strength in German and Mizos men: Cross-cultural evidence for an organizing effect of prenatal testosterone on strength. Am J Hum Biol. 2006; 18: 776-782.

57. Halil M, Gurel EI, Kuyumcu ME, Karaismailoglu S, Yesil Y, Ozturk ZA, et al. Digit (2D:4D) ratio is associated with muscle mass (MM) and strength (MS) in older adults: Possible effect of in utero androgen exposure. Arch Gerontol Geriatr. 2013; 56: 358-363.

58. Liana S.E. Hone, Michael E. Mc Cullough. 2D: 4D ratios predict hand grip strength (but not hand grip endurance) in men (but not in women). Evolution and Human Behavior. 2012; 33: 780-789.

59. Bennett M, Manning JT, Cook CJ, Kilduff LP. Digit ratio (2D:4D) and performance in elite rugby players. J Sports Sci. 2010; 28: 1415-1421.

60. Giffin NA, Kennedy RM, Jones ME, Barber CA. Varsity athletes have lower 2D:4D ratios than other university students. J Sports Sci. 2012; 30: 135-138.

61. Hönekopp J, Schuster M. A meta-analysis on 2D:4D and athletic prowess: Substantial relationships but neither hand out-predicts the other. Personality and Individual Differences. 2010; 48: 4-10.

62. Pokrywka L, Rachoń D, Suchecka-Rachoń K, Bitel L. The second to fourth digit ratio in elite and non-elite female athletes. Am J Hum Biol. 2005; 17: 796-800.

63. Brown WM, Finn CJ, Breedlove SM. Sexual dimorphism in digit-length ratios of laboratory mice. Anatomical Record. 2002; 267: 231-234.

64. Grimbos T, Dawood K, Burriss RP, Zucker KJ, Puts DA. Sexual orientation and the second to fourth finger length ratio: A meta analysis in men and women. Behav Neurosci. 2010; 124: 278-287.

65. Kastlunger B, Dressler SG, Kirchler E, Mittone L, Voracek M. Sex differences in tax compliance: Differentiating between demographic sex, gender-role orientation, and prenatal masculinization (2D:4D). J Economic Psychology. 2010; 31: 542-552.

66. Manning JT, Morris L, Caswell N. Endurance running and digit ratio (2D:4D): Implications for fetal testosterone effects on running speed and vascular health. Am J Hum Biol. 2007; 19: 416-421.

67. Xi H, Li M, Fan Y, Zhao L. A comparison of measurement methods and sexual dimorphism for digit ratio (2D:4D) in Han ethnicity. Arch Sexual Behavior. 2014; 43: 329-333.

68. Ebeling PR. Androgens and osteoporosis. Curr Opin Endocrinol Diabetes Obes. 2010; 17: 284-292.

69. McIntyre MH, Ellison PT, Lieberman DE, Demerath E,Towne B. The development of sex differences in digital formula from infancy in the Fels Longitudinal Study. Procedings of the Biological Sciences. 2005; 272:1473-1479.

70. Sims NA, Brennan K, Spaliviero J, Handelsman DJ, Seibel MJ. Perinatal testosterone surge is required for normal adult bone size but not for normal bone remodeling. Am J Physiol Endocrinol Metab. 2006; 290: E456-E462.

71. Vanderschueren D, Vandenput L, Boonen S, Lindberg MK, Bouillon R, Ohlsson C. Androgens and bone. Endocr Rev. 2004; 25: 389-425.

72. Malas MA, Dogan S, Hilal Evcil E, Desdicioglu K. Fetal development of the hand, digits and digit ratio (2D:4D). Early Hum Dev. 2006; 82: 469 475.

73. Putz DA, Gaulin SJ, Sporter RJ, McBurney DH. Sex hormones and finger length: What does 2D:4D indicate? Evolution and Human Behavior. 2004; 25: 182-199.

74. Zheng Z, Cohn MJ. Developmental basis of sexually dimorphic digit ratios. Procedings of the National Academy of the Sciences. 2011; 108: 16289-16294.

75. Allaway HC, Bloski TG, Pierson RA, Lujan ME. Digit ratios (2D: 4D) determined by computer-assisted analysis are more reliable than those using physical measurements, photocopies, and printed scans. Am J Human Biol. 2009; 21: 365-370.

76. Hampson E, Ellis CL, Tenk CM. On the relation between 2D:4D and sex dimorphic personality traits. Arch Sexual Behav. 2008; 37:133-144.

77. Hell B, Päßler K. Are occupational interests hormonally influenced? The 2D:4D-interest nexus. Personality and Individual Differences. 2011; 51: 376-380.

78. Paul SN, Kato BS, Cherkas LF, Andrew T, Spector TD. Heritability of the second to fourth digit ratio (2D:4D): A twin study. Twin Res Hum Genet. 2006; 9: 215-219.

79. Manning JT. The finger book: Sex, behaviour and disease revealed in the fingers. London: Faber and Faber. 2008.

80. McFadden D, Loehlin JC, Breedlove SM, Lippa RA, Manning JT, Rahman Q. A reanalysis of five studies on sexual orientation and the relative length of the 2nd and 4th fingers (the 2D:4D ratio). Arch Sex Behav. 2005; 34: 341-356.

81. Trivers R, Manning J, Jacobson A. A longitudinal study of digit ratio (2D:4D) and other finger ratios in Jamaican children. Hor Behav. 2006; 49: 150-156.

82. Hönekopp J. Relationships between digit ratio 2D: 4D and self reported aggression and risk taking in an online study. Personality and Individual Differences. 2011; 51: 77-80.

83. Kemper CJ, Schwerdtfeger A. Comparing indirect methods of digit ratio (2D:4D) measurement. Am J Hum Biol. 2009; 21: 188-191.

84. Majumder J, Bagepally BS. The right hand second to fourth digit ratio (2D:4D) and its relationship with body composition indicators among young population. Asian J Med Sci. 2014; 6:78-84.

85. Notelovitz M. Androgen effects on bone and muscle. Fertil Steril. 2002; 77: S34-S41.

86. Selye H, Bajusz E. Effect of denervation on experimentally induced changes in the growth of bone and muscle. Am J Physiol. 1958; 192: 297-300.

87. Bertelloni S, Baroncelli G, Mora S. Bone health in disorders of sex differentiation. Sexual Development. 2010; 4: 270-284.

88. Horstman AM, Dillon EL, Urban RJ, Sheffield-Moore M. The role of androgens and estrogens on healthy aging and longevity. J Gerontology Series A: Biological Sciences and Medical Sciences. 2012.

89. Rochira V, Carani C. Aromatase deficiency in men: A clinical perspective. Nat Rev Endocrinol. 2009; 5: 559-568.

90. Veldhuis JD, Roemmich JN, Richmond EJ, Rogol AD, Lovejoy JC. Endocrine control of body composition in infancy, childhood, and puberty. Endocrinol Rev. 2005; 26: 114-146.

91. Hansen L, Bangsbo J, Twisk J, Klausen K. Development of muscle strength in relation to training level and testosterone in young male soccer players. J Applied Physiol. 1999; 87:1141-1147.

92. Kerr JM, Congeni JA. Anabolic-androgenic steroids: Use and abuse in pediatric patients. Pediatric Clinics of North America. 2007; 54: 771 785.

93. Firebaugh G, Dorius SF. Trends in global gender inequality. Social Forces. 2010; 88: 1941-1968.

94. Iacobucci D. Mediation analysis. Thousand Springs, CA: Sage. 2008.

95. Manning JT,Taylor RP. Second to fourth digit ratio and male ability in sport: Implications for sexual selection in humans. Evol Hum Behav. 2001; 22: 61-69