Thursday, September 29, 2016

Effects of prenatal (fetal) testosterone on the (human) body

General effects of testosterone on the human body

"[Apart from the right-hand 2D:4D ratio, f]our additional traits known to be influenced by androgen exposure [...]: muscularity, physical strength, [...] athletic ability [and] height. [The higher the androgen exposure, the greater the muscularity, physical strength, athletic ability and height]." 
(Ellis, Lee, Anthony W. Hoskin, and Malini Ratnasingam. "Testosterone, Risk Taking, and Religiosity: Evidence from Two Cultures." Journal for the Scientific Study of Religion 55.1 (2016): 153-173.)
"Physiological traits such as muscularity, physical strength, and low voice timbre have been shown to be androgen promoted (...)."
(Ellis, Lee, and Anthony W. Hoskin. "The evolutionary neuroandrogenic theory of criminal behavior expanded." Aggression and violent behavior 24 (2015): 61-74.)

"Testosterone/estrogen ratio in males and females gives reason for differences in skin thickness and texture. Male epidermis for example is 20% thicker than female epidermis, being able to bind a larger amount of moisture, and containing more collagen in all ages, thus, making male skin more dense and vigorous.
Androgens stimulate sebum production. Therefore, due to higher androgen levels male seborrheic glands produce more sebum leading to fatty glow and coarser pores of the skin. Consequently, acne, acneiform eruptions, and blemishes are more common in seborrheic areas (face, back, upper thorax, shoulders).
(...) [T]estosterone has proven negative effect on the [skin] barrier function, making male skin particularly more sensitive than female skin [to dryness and eczema]. (...)
On one hand, male skin regenerates more quickly than female skin due to testosterone controlled higher cellular turnover, on the other hand wound healing turns out to occur more slow than in females, due to higher testosterone levels.
Androgens play an important role in androgenic hair loss, even if androgen levels are within normal ranges, as androgen sensitivity of the hair follicles varies individually due to genetic determination. (...) [In males: ] On the scalp hair follicles miniaturize according to the androgensensitivity of the individual, thus, leading to the clinical appearance of androgenetic alopecia presenting a receding frontal hairline as well as vertex and total balding. (...)
[In females: ] female androgenetic alopecia, causing a certain phenotype gradually developing sparse hair in parietal areas (...). Androgentic female hair loss is most likely retaining the frontal hairline. (...) Hirsute females must not necessarily show increased Testosterone levels (...)."
(Kopera D (2015) N, Impact of Testosterone on Hair and Skin. Endocrinol Metab Syndr 4:187. doi:10.4172/2161-1017.1000187) 

"Prior to puberty, there is no sex difference in circulating testosterone concentrations or athletic performance but from puberty onwards sex difference in athletic performance emerges as circulating testosterone concentrations rise in men because testes produce 30 times more testosterone than before puberty with circulating testosterone exceeding 15-fold those of women at any age. There is a wide sex difference in circulating testosterone concentrations and reproducible dose-response relationship between circulating testosterone and muscle mass and strength as well as circulating hemoglobin in both men and women. These dichotomies largely accounts for the sex differences in muscle mass and strength and circulating hemoglobin levels resulting in at least an 8-12% ergogenic advantage in men. Suppression of elevated circulating testosterone of hyperandrogenic athletes results in negative effects on performance, which are reversed when suppression ceases."
(Handelsman, David J., Angelica Lindén Hirschberg, and Stephane Bermon. "Circulating testosterone as the hormonal basis of sex differences in athletic performance." Endocrine Reviews (2018).)

Conference by John T. Manning

Testosterone may be involved in brain seizures

"A number of experiments with laboratory animals have shown that exposure to androgens (or its metabolite estradiol) decreases the threshold at which the brain will seizure (...). However, under some conditions, testosterone can also have anti-convulsant effects if its conversion to estradiol is blocked (...). Even though brain seizures are not involved in the commission of most crimes, they do seem relevant to a small percentage of offenses that are unusually “irrational” and bizarre. For example, many instances of kleptomania and sadistic crimes of passion may be the result of brain
seizures, particularly seizure in or around the limbic system."
(Ellis, Lee, and Anthony W. Hoskin. "The evolutionary neuroandrogenic theory of criminal behavior expanded." Aggression and violent behavior 24 (2015): 61-74.)

High testosterone levels linked to higher pain tolerance

"[E]xperiments with humans as well as other animals [show] that pain tolerance is enhanced by exposing the brain to testosterone and/or its metabolites."
"[E]xposing the brain to testosterone (or its metabolites) appears to have analgesic (pain reducing) and anxiolytic (anxiety reducing) effects. [...]"  
(Ellis, Lee, and Anthony W. Hoskin. "The evolutionary neuroandrogenic theory of criminal behavior expanded." Aggression and violent behavior 24 (2015): 61-74.)

In females 2D:4D ratios (left and right) were negatively correlated with waist and hip circumference and waist-to-chest ratio 

"Significant negative correlations were found between female’s left and right hand 2D:4D, waist and hip circumference, and WCR (waist-to-chest-ratio). In males, BMI was found to be positively related to digit ratio but remained significant only for left hand 2D:4D. Generally, the relationships were stronger for females than for males."
In other words: in females, low 2D:4D ratio goes together with high waist and hip circumference and high waist-to-chest ratio.
(source: Second to fourth digit ratio, body mass index, waist-to-hip ratio, and waist-to-chest ratio: their relationships in heterosexual men and women, B. Finka, N. Neaveb & J. T. Manning, pages 728-738, Annals of Human Biology, Volume 30, Issue 6, 2003, retrieved July 1st 2016)

High waist to hip ratio linked to low 2D:4D ratio

"[M]others with high waist to hip ratios, a trait that is positively associated with maternal testosterone levels, have been shown to have low 2D:4D ratios (Manning, Trivers, Singh, & Thornhill, 1999)."

(Liu, Jianghong, Jill Portnoy, and Adrian Raine. "Association between a marker for prenatal testosterone exposure and externalizing behavior problems in children." Development and psychopathology 24.03 (2012): 771-782.)

Males with lower righthand 2D:4D ratio have higher grip strength

"for righthand 2D:4D (but not left-hand 2D:4D), the LGS (Low Grip Strength of the hand) men had higher 2D:4D than the HGS (High Grip Strength) men"

(source: Digit Ratio and Hand-Grip Strength in German and Mizos Men: Cross-Cultural Evidence for an Organizing Effect of Prenatal Testosterone on Strength, BERNHARD FINK, VANLAL THANZAMI, HANNA SEYDEL, AND JOHN T. MANNING, AMERICAN JOURNAL OF HUMAN BIOLOGY 18:776–782 (2006), retrieved July 1st 2016)

"Using a cross-sectional design, this study quantified the relationship between the digit ratio (2D:4D) and muscular strength in 57 adolescent boys. 2D:4D was very likely a moderate negative correlate of handgrip strength, even after adjustment for age and body size."
(Tomkinson, Jordan M., and Grant R. Tomkinson. "Digit ratio (2D: 4D) and muscular strength in adolescent boys." Early Human Development 113 (2017): 7-9.)

Whites, non-chinese Asians and Mid-Easterners have higher 2D:4D ratios than Chinese and Black 

"[M]ean 2D:4D varied across ethnic groups with higher ratios for Whites, Non-Chinese Asians, and Mid-Easterners and lower ratios in Chinese and Black samples."

(source: The effects of sex, ethnicity, and sexual orientation on self-measured digit ratio (2D:4D), Manning JT, Churchill AJ, Peters M., Arch Sex Behav. 2007 Apr;36(2):223-33, retrieved July 1st 2016)

"The cross-sectional data included 90 adolescents and 240 nonadolescents. White women had a significantly higher 2D:4D than other ethnic groups."
(Brabin, Loretta, et al. "The second to fourth digit ratio (2D: 4D) in women with and without human papillomavirus and cervical dysplasia." American Journal of Human Biology 20.3 (2008): 337-341.)

Chinese Hui and Han ethnic groups have lower mean 2D:4D ratio than Brits

"The mean values of 2D:4D of the Hui and the Han in Ningxia are lower than those in European countries like Britain."

(Lu, Hong, et al. "Study on the digit ratio of Hui and Han ethnic groups in Ningxia." Acta Anatomica Sinica 39.2 (2008): 267.)

Han children have higher 2D:4D ratio than Berber and Uygur children, who have higher 2D:4D ratio than Jamaican children

"The 2D:4D ratio was measured from photocopies of the right hand of Berber children from Morocco, Uygur [from Turkey] and Han children from the North-West province of China, and children from Jamaica.The Han children had the highest mean values of 2D:4D (0.954F 0.032), they were followed by the Berbers (0.950 F0.033), then the Uygurs (0.946 F0.037), and the Jamaican children had the lowest mean 2D:4D (0.935 F0.035). These differences in mean 2D:4D across the ethnic groups were significant."

(source: Sex and ethnic differences in 2 to 4 digit ratio of children, Manning, Stewart, Bundred, Trivers, in Early Human Development 80(2):161-8 · December 2004, retrieved July 1st 2016)

Lithuanians have low 2D:4D ratio

"seen in an international perspective, the average 2D:4D in Lithuania is low"
(Voracek, Martin, Albinas Bagdonas, and Stefan G. Dressler. "Digit ratio (2D: 4D) in Lithuania once and now: testing for sex differences, relations with eye and hair color, and a possible secular change." Collegium antropologicum 31.3 (2007): 863-868.)

Mean 2D:4D ratios by country

"[M]ost UK studies yielded [an average righthand 2D : 4D value for men] of 0.97 or 0.98 [...]. [M]ale mean 2D : 4D levels are 0.93 in Finland (Manning et al., 2000), 0.95 in Sweden (Sanders et al., 2005), 0.95 in Lithuania (Manning, 2002), 0.955 in Belgium (Millet and Dewitte, in press), 0.96 in Germany (Manning et al., 2000; Kempel et al., 2005) and 0.99 in Poland (Manning et al., 2000). [...] [A] sample [...] comprised of 30 unselected Austrian men, aged 19–39 years [gave] the following results: mean (SD) 2D : 4D was 0.953 for [direct measurement]."

(source: Martin Voracek and Stefan G. Dressler, "High (feminized) digit ratio (2D : 4D) in Danish men: a question of measurement method?", Hum. Reprod. (May 2006) 21 (5): 1329-1331. doi: 10.1093/humrep/dei464)

Indian, Malay and Chinese male science and management students have roughly the same 2D:4D ratio as their female counterparts (+/-0.98)

(Idris, Siti Khadijah, and Gargi Soni. "Second Digits To Fourth Digits Ratio In Management And Science University Students: Sexual Dimorphism.")

Lower right-hand 2D:4D ratios associated with higher sperm counts and blood testosterone levels in males; higher ratios associated with high blood levels of oestrogen, luteinizing hormone and prolactin in males and females

"Lower 2D:4D ratios in the right hand have been associated with higher sperm counts and blood testosterone levels in males whilst higher ratios have been associated with high blood levels of oestrogen, luteinizing hormone and prolactin in males and females (Manning et al. 1998)."

Low 2D:4D ratio strongly related to efficiency in aerobic exercise (endurance), weakly to strength

"Speed in endurance races is strongly related to 2D:4D, and may be one factor that underlies the link between sport and 2D:4D, but nothing is known of the relationship between 2D:4D and sprinting speed. Here we show that running times over 50 m were positively correlated with 2D:4D in a sample of 241 boys (i.e. runners with low 2D:4D ran faster than runners with high 2D:4D). The relationship was also found for 50 m split times (at 20, 30, and 40 m) and was independent of age, BMI, and an index of maturity. However, associations between 2D:4D and sprinting speed were much weaker than those reported for endurance running. This suggests that 2D:4D is a relatively weak predictor of strength and a stronger predictor of efficiency in aerobic exercise."

(source: Digit ratio (2D:4D) and sprinting speed in boys, J.T. Manning, M.R. Hill, 2008, DOI: 10.1002/ajhb.20855)

Higher 2D:4D ratio in men linked to higher risk for myocardial infarction

"In men with myocardial infarction (MI), 2D:4D and 3D:4D ratios were significantly higher than the respective ratios in healthy men (2D:4D: right hand, P = 0.001; left hand, P < 0.05; 3D:4D: right hand, P < 0.05; left hand, P = 0.001), but no significant differences were observed in the ratios between women with MI and healthy women.
Conclusions: Digit ratios that include ring-finger length (ie, 4D) may be useful biomarkers for predisposition to MI in Greek men, but not in Greek women.[...]"
(Kyriakidis, Ioannis, et al. "Digit ratios and relation to myocardial infarction in Greek men and women." Gender medicine 7.6 (2010): 628-636.)

Low 2D:4D ratio linked to auto-immune disease SLE

"We measured 2D4D ratios in 100 patients with SLE and 200 normal healthy controls (NHC).
Results: Patients with SLE had a lower 2D4D ratio than NHC.
Conclusion: Our study suggests that patients with SLE have experienced high prenatal testosterone and low prenatal estrogen."
(Doe, Kentaro, et al. "Second-to-fourth Digit Ratio in Systemic Lupus Erythematosus." The Journal of rheumatology 42.5 (2015): 826-828.)

"Systemic lupus erythematosus (SLE), also known simply as lupus, is an autoimmune disease in which the body’s immune system mistakenly attacks healthy tissue in many parts of the body.[1] Symptoms vary between people and may be mild to severe. Common symptoms include painful and swollen joints, fever, chest pain, hair loss, mouth ulcers, swollen lymph nodes, feeling tired, and a red rash which is most commonly on the face. Often there are periods of illness, called flares, and periods of remission when there are few symptoms."

(source: Wikipedia, retrieved 5/8/2016)

Low 2D:4D ratio risk factor for MS

"During the prenatal period, low androgens could represent a risk factor for MS (multiple sclerosis)."

(Bove, Riley, et al. "The 2D: 4D ratio, a proxy for prenatal androgen levels, differs in men with and without MS." Neurology 85.14 (2015): 1209-1213.)

Higher incidence of prostate cancer in men with low 2D:4D ratio

"The PCA (prostate cancer) group presented significantly lower right and left 2D:4D (...) in comparison to healthy controls, [...] [M]ales with prostate cancer present lower 2D:4D than healthy subjects. On the other hand, 2D:4D does not appear to be associated with the severity of prostate cancer."
(Mendes, P. H. C., et al. "Comparison of digit ratio (2D: 4D) between Brazilian men with and without prostate cancer." Prostate cancer and prostatic diseases 19.1 (2016): 107-110.)

Low 2D:4D ratio linked to male alopecia (loss of hair in patches)

"The 2D:4D ratios in patients with androgenetic alopecia were significantly lower than those of healthy controls for the right hand; however, no significant difference was found for the left hand. Average 2D:4D ratios in androgenetic alopecia patients were also lower than in controls. No significant relationship was observed between androgenetic alopecia severity and 2D:4D ratios."
(Bilgic, Özlem, et al. "Are 2D: 4D finger-length ratios an indicator of androgenetic alopecia in males?." Anais brasileiros de dermatologia 91.2 (2016): 156-159.)

Testosterone reduces effectiveness of immune system

"[T]estosterone acts like a ‘double-edged sword’. It is required for the expression of all secondary sexual traits [...], but it is also a powerful immunosuppressant that reduces the effectiveness of a male's immune system. [...]"
(Johnston, Victor S. "Mate choice decisions: the role of facial beauty." Trends in cognitive sciences 10.1 (2006): 9-13., Part 1Part 2)

Low 2D:4D in women linked to menstrual irregularity.

"[L]ow 2D:4D women [...] reported more menstrual irregularity."
(Johnston, Victor S. "Mate choice decisions: the role of facial beauty." Trends in cognitive sciences 10.1 (2006): 9-13., Part 1Part 2)

Sex ratio of offspring (males : females) increases with prenatal testosterone of both parents

"We present evidence from three populations (English, Spanish and Jamaican) that 2D:4D is negatively related to sex ratio, independent of the sex and ethnicity of the parents."
(Manning, J. T., et al. "2nd to 4th digit ratio and offspring sex ratio." Journal of Theoretical Biology 217.1 (2002): 93-95.)

In sheep, high prenatal testosterone causes intrauterine growth retardation and increased prepubertal growth rate in female offspring

"Experimental elevation of maternal testosterone (T) from 30 to 90 days of gestation leads to intrauterine growth retardation (IUGR) and increased prepubertal growth rate in female lambs."
(Crespi, E. J., Steckler, T. L., MohanKumar, P. S. and Padmanabhan, V. (2006), Prenatal exposure to excess testosterone modifies the developmental trajectory of the insulin-like growth factor system in female sheep. The Journal of Physiology, 572: 119–130. doi:10.1113/jphysiol.2005.103929)

With increasing androgen levels asymmetry decreases

"Three main types of asymmetry can be distinguished: antisymmetry, directional asymmetry (DA) and fluctuating asymmetry (FA) [13,14].
Antisymmetry is defined as a pattern of bilateral variation in a sample of individuals where a statistically significant difference between sides occurs, but where the larger side varies at random among individuals [15,16].
Directional asymmetry (DA) refers to a pattern of bilateral variation in a sample of individuals where a statistically significant difference exists between sides, but the larger side is mainly the same side for all individuals of the sample [16]. Among humans a typical example of DA is found for upper limb dimensions [17,18,19,20,21]. In general, the right upper limbs exhibit larger dimensions than the left ones. This DA among Homo sapiens is mainly interpreted as a result of handedness [19,21,22].
Fluctuating asymmetry (FA)—the third variant of asymmetry—is a widespread phenomenon in nature referring to small random deviations from perfect symmetry in bilaterally-paired structures, which are symmetrical at population level [13]. Under normal conditions FA is minimal, but it is increased under stressful events."
A study among !Kung San and Kavango males from northern Namibia revealed the following:
"FA was indicated by ear length, ear breadth, foot length and foot breadth. Concerning directional asymmetry, only hand breadth, hand length, hand circumference and wrist breadth could be analyzed. (...)
[W]ith increasing androgen levels (FA and DA) asymmetry decreased."
(Kirchengast, Sylvia, and Kerrin Christiansen. "Androgen Levels and Body Size Are Associated with Directional as Well as Fluctuating Asymmetry Patterns in Adult! Kung San and Kavango Males from Northern Namibia." Symmetry 9.5 (2017): 72.)

Both low and high 2D:4D are associated with increased asymetry

"Our data show that both low 2D:4D (a marker of high prenatal testosterone) and high 2D:4D (a marker of high prenatal oestrogen) are associated with elevated levels of asymmetry and this relationship applies particularly to finger asymmetry."
(Manning, John T., et al. "The second to fourth digit ratio and asymmetry." Annals of human biology 33.4 (2006): 480-492.)

High 2D:4D digit ratio correlated to some forms of lower infertility in men

"The percentage of cases (males) with a 2D:4D ratio equal to or greater than 1 was specially higher among vasal agenesis and hypogonadotropic hypogonadism groups and some statistically significant differences were detected."
The other groups of male infertility that were studied (namely low sperm count and Klinefelter syndrome) showed no statistically significant differences.

Klinefelter syndrome = affected individuals typically have small testes that do not produce as much testosterone as usual, other symptoms include undescended testes (cryptorchidism) and micropenis.
Vassal agenesis = lack of blood vessel development
Hypogonadism = diminished functional activity of the gonads (which in men are the testes)

(Akinsal, Emre Can, Abdullah Demirtas, and Oguz Ekmekcioglu. "Comparison of the Ratio of the Lenght of the Second and Fourth Digits in Subgroups of Fertile and Infertile Cases." Urology Journal 14.3 (2017): 3081-3084.)

Elite wrestlers have lower 2D:4D digit ratio

"The 2D:4D ratios of elite wrestlers were lower compared to non-elite athletes (...) and the control group ...)."
(Keshavarz, Mohammad, et al. "The Second to Fourth Digit Ratio in Elite and Non-Elite Greco-Roman Wrestlers.", DOI: 10.1515/hukin-2017-0097)

Patients with low 2D:4D ratio have less chance of succesfull prostate cancer treatment outcome

"This study explored the prognostic significance of digit ratio in prostate cancer patients. We reviewed the progressive status and survival of 382 prostate cancer patients who had received hormone therapy at our institutions. Survival of clinicopathological variables analyzed as categorical variables were determined by the log-rank test. According to Cox’s proportional hazards analysis, R2D:4D, L2D:4D, PSA [Prostatic Specific Antigen] at 6 month, bone metastasis were significant independent factors for prostate cancer. The risk of any progression of prostate cancer similarly depressed with increasing 2D:4D, for any progression (R2D:4D HR = 0.71, p = 0.003; L2D:4D HR = 0.67, p = 0.001), for cancer-specific death (R2D:4D HR = 0.67, p = 0.025; L2D:4D HR = 0.74, p = 0.036). Digit ratio may not only have predictive value in risk but also prognosis of prostatic cancer. This finding suggests that low 2D:4D can be used as prognostic factors to identify patients with a poor prognosis. These patients may benefit from more aggressive management."
(Li, Guanjian, et al. "Prognostic significance of the digit ratio after hormone therapy for prostate cancer: a prospective multicenter study." Scientific Reports 7 (2017).)

In rats, high prenatal tesosterone linked to increased anogenital distance and nipple retention

"Anogenital distances (AGD), nipple retention, reproductive tract, and external genitalia are morphological parameters organized by prenatal androgens and are predictive of altered masculinized/defeminized phenotype in adult female mice and rats. (...)  Female offspring exposed to [testosterone in utero] displayed increased AGD at postnatal day (PND) 2 and decreased nipples at PND 13 and as adults. TP-induced changes in neonatal AGD and infant areola number were reliable indicators of permanently altered adult phenotype in female rats. Further, females in the two high-dose groups displayed increased incidences of external genital malformations and the presence of prostatic tissue, not normally found in female rats."
(Hotchkiss, Andrew K., et al. "Prenatal testosterone exposure permanently masculinizes anogenital distance, nipple development, and reproductive tract morphology in female Sprague-Dawley rats." Toxicological Sciences 96.2 (2007): 335-345.)

In men (after controlling for BMI) the higher the 2D:4D ratio, the higher the neck circumference

"A significant positive correlation between 2D:4D and NC (neck circumference) was found for men but not for women after controlling for body mass index (BMI); the higher the ratio the higher the NC."
(Fink, Bernhard, J. T. Manning, and Nick Neave. "The 2nd-4th digit ratio (2D: 4D) and neck circumference: implications for risk factors in coronary heart disease." International Journal of Obesity 30.4 (2006): 711.)

High 2D:4D ratio linked to gynecomastia in men

"2D:4D in men with gynecomastia ([median quartiles)]: 1.03 (1.01-1.04) for right hand and 1.03 (1.01-1.03) for left hand) was significantly different than the ratio in control men [0.97 (0.95-0.99)] for right and left hand) (p < 0.0001) and similar to the ratio found in control women [1.02 (1-1.03)] for right and left hand) (p = 1)."
Gynecomastia is a common disorder of the endocrine system in which there is a non-cancerous increase in the size of male breast tissue.

(Kasielska-Trojan, Anna, and Bogusław Antoszewski. "Can digit ratio (2D: 4D) studies be helpful in explaining the aetiology of idiopathic gynecomastia?." Early human development 91.1 (2015): 57-61.)

Low 2D:4D ratio linked to Dupuytren disease

"We found that compared with control group, the Dupuytren disease group had significantly lower phalanx and combined 2D:4D. These findings suggest that endogenous prenatal androgens could contribute to the development of Dupuytren disease, leading to its characteristic clinical presentation predominantly in men and affecting the ulnar rays."
Dupuytren's contracture is a condition in which one or more fingers become permanently bent in a flexed position.
(Yokoi, Takuya, et al. "Low second to fourth digit ratio in Dupuytren disease." Medicine 96.33 (2017): e7801.)

Male pattern baldness linked to low left-hand 2D-4D digit ratio

"Androgenetic alopecia is a common form of hair loss in both men and women. In men, this condition is also known as male-pattern baldness. Hair is lost in a well-defined pattern, beginning above both temples. Over time, the hairline recedes to form a characteristic "M" shape. Hair also thins at the crown (near the top of the head), often progressing to partial or complete baldness.
The pattern of hair loss in women differs from male-pattern baldness. In women, the hair becomes thinner all over the head, and the hairline does not recede."


"The left-hand 2D:4D ratios of AGA group (0.893 ± 0.267) were significantly lower than healthy controls (0.971 ± 0.028). No significant relationships were found between AGA severity, age of onset,and digit ratios.
The left-hand digit ratio 2D:4D is lower in AGA patients, and therefore, left-hand digit ratio 2D:4D can be used as an estimation tool for AGA development in future. There is not any correlation between digit ratio and age of onset. Also, there is no correlation between digit ratio 2D:4D and AGA severity."


Women with low 2D:4D digit ratio suffer more from osteoarthritis

"Each hand was visually classified on X-ray as either type 1—index finger longer than the ring finger; type 2—index and ring finger equal in length; or type 3—index finger shorter than the ring finger. (...) Females with a type 3 finger length pattern showed significantly higher hand OA (OsteoArthritis) values than those with types 1 and 2."
(Kalichman, L., V. Batsevich, and E. Kobyliansky. "2D: 4D finger length ratio and radiographic hand osteoarthritis." Rheumatology International (2017): 1-6.)

Low 2D:4D digit ratio correlates with early onset of puberty in males

"Among the males, there was a significant difference in digit ratios between individuals who experienced early, average, and late onset of puberty. In the males, we observed a positive relationship between 2D:4D and age of pubertal onset for both right and left hands. There were no significant differences in 2D:4D among the three groups of female maturers. We observed no significant association between digit ratios and age at menarche."
(Gooding, Diane C., and Blake H. Chambers. "Age of pubertal onset and 2nd to 4th digit ratios: Preliminary findings." Early Human Development 116 (2018): 28-32.)

Elevated maternal testosterone levels during human pregnancy are associated with growth restriction in utero

"Elevated maternal testosterone levels at week 17 and 33 were both associated with lower birth weights and lengths. (...) Conclusions: Elevated maternal testosterone levels during human pregnancy are associated with growth restriction in utero. Our results support animal studies, which have indicated that maternal androgen levels influence intrauterine offspring environment and development."
(Carlsen, S. M., G. Jacobsen, and P. Romundstad. "Maternal testosterone levels during pregnancy are associated with offspring size at birth." European Journal of Endocrinology 155.2 (2006): 365-370.)

High maternal testosterone associated with lower birth weight of male infants and accelerated infant weight gain after 6 months

"Elevated maternal morning testosterone level was associated with lower birth weight Z-scores adjusted for gestational age and sex, and greater infant weight gain between birth and 6 months. Although maternal testosterone levels did not differ by fetal sex, relations were sex-specific such that maternal testosterone had a significant impact on weight for male infants; among female infants associations were nonsignificant. Results highlight the opposing influence of maternal androgens during pregnancy on decreased growth in utero and accelerated postnatal weight gain."
(Voegtline, K. M., et al. "Sex-specific associations of maternal prenatal testosterone levels with birth weight and weight gain in infancy." Journal of developmental origins of health and disease 4.4 (2013): 280-284.)

Low digit ratio among Chinese women with coronary artery disease

"CAD (Coronary Artery Disease) group had significantly lower 2D:4D, 2D:5D in both hands and 3D:4D in left hand than controls."
(Wang, Lu, et al. "Digit ratio (2D: 4D) and coronary artery disease in north Chinese women." Early Human Development 116 (2018): 64-67.)

Injection of pregnant rats with testosterone prevents male-typical muscle to develop in female offspring

"[T]he study was performed on litters of albino rats. Their pregnant mothers received on embryonic days (E16- E20) subcutaneous injection of 2mg of testosterone propionate. The spinal nucleus of bulbocavernosus was examined in control group, female litters with and without prenatal testosterone injection. Results: It was demonstrated that perinatal injection of testosterone prevented the
involution of spinal nucleus of bulbocavernosus in the female rats."
(Al-Marsoummi, Sarmad I., and Anam R. Al-Salihi. "Sexual Differentiation of the Spinal Nucleus of Bulbo-Cavernosus Muscle (Onuf's Nucleus).")

Low 2D:4D associated with higher incidence of prostate cancer, gastric cancer and brain tumors; high 2D:4D with breast cancer risk and cervical dysplasia

"The 2D:4D ratio was studied in prostate cancer, breast cancer, testicular cancer, gastric cancer, oral cancer, brain tumors and cervical intraepithelial neoplasia. Low 2D:4D was associated with prostate cancer, gastric cancer and brain tumors, while high 2D:4D with breast cancer risk and cervical dysplasia."
(Bunevicius, Adomas. "The association of digit ratio (2D: 4D) with cancer: a systematic review and meta-analysis.")

In sheep, prenatal testosterone excess influences insulin sensitivity

"Relative to earlier findings of reduced insulin sensitivity of prenatal T-treated females during early life and adulthood, these findings of increased insulin sensitivity and reduced adiposity postpubertally are suggestive of a period of developmental adaptation. The disruption observed in free fatty acid metabolism a few months later correspond to a time point when the insulin sensitivity indices of prenatal T-treated animals appear to shift toward insulin resistance."
(Veiga-Lopez, A., et al. "Developmental programming: impact of prenatal testosterone excess on insulin sensitivity, adiposity, and free fatty acid profile in postpubertal female sheep." Endocrinology 154.5 (2013): 1731-1742.)

Low testosterone may be linked to increased risk of multiple sclerosis (MS)

"Several studies have demonstrated lowered testosterone levels in up to 40% of men with MS."
(Chitnis, Tanuja. "The role of testosterone in MS risk and course." Multiple Sclerosis Journal 24.1 (2018): 36-41.)

Higher incidence of gastric cancer among Chinese women with low 2D:4D digit ratio

"The GCA (gastric cancer) group presented significantly lower 2D:4D than controls (left: P < .01; right: P < .05). (...) Decreased 2D:4D (especially of the left hand) may suggest a higher prenatal testosterone (lower prenatal estrogen) exposure in north Chinese women with GCA."
(Wang, Lu, et al. "Digit ratio (2D: 4D) in Chinese women with gastric cancer." American Journal of Human Biology (2018).)

In rats, excessive prenatal androgen exposure negatively impacts cardiovascular function and causes gut microbial dysbiosis

"We found that prenatal exposure to excess androgen negatively impacted cardiovascular function by increasing systolic and diastolic blood pressure and decreasing heart rate. Prenatal androgen was also associated with gut microbial dysbiosis and altered abundance of bacteria involved in metabolite production of short chain fatty acids. These results suggest that early-life exposure to hyperandrogenemia in daughters of women with PCOS may lead to long-term alterations in gut microbiota and cardiometabolic function."
(Sherman, Shermel, et al. "Prenatal Androgen Exposure Causes Hypertension and Gut Microbiota Dysbiosis." Gut Microbes just-accepted (2018): 01-45.)

Low 2D:4D ratio associated with higher static and explosive strength in males, and with greater height and more body fat in females

"A negative correlation between right hand 2D:4D and vertical jumping, standing long jump, 20 m sprint, 10x5 agility and right hand grip strength in the males. As for the females, although a negative correlation was detected between right hand 2D:4D and height, a positive correlation was found between the same variable and body fat ratio (p<0.05). It can be concluded that while a low 2D:4D ratio was correlated with static and explosive strength, speed and agility in the males, it was correlated with height and body fat ratio in the females."
(Eler, Nebahat. "The correlation between right hand finger ratio (2D: 4D) and the parameters of anthropometric and physical fitness in children." Journal of Human Sciences 15.1 (2018): 656-664.)

2D:4D ratio may correlate with voice pitch

"We also found that the right-hand ratio of the length of their index to ring finger (2D:4D digit ratio), which has been proposed to constitute an index of prenatal testosterone exposure, was positively correlated with F0 [voice pitch fundamental frequancy], at both 4 months and 5 years of age."
(Levrero, Florence, Nicholas Mathevon, Kasia Pisanski, Erik Gustafsson, and David Reby. "The pitch of babies’ cries predicts their voice pitch at age five." Biology Letters (2018).)

Hyperandrogenism over-represented in elite athletics

"There is a wide sex difference in circulating testosterone concentrations and reproducible dose-response relationship between circulating testosterone and muscle mass and strength as well as circulating hemoglobin in both men and women. These dichotomies largely accounts for the sex differences in muscle mass and strength and circulating hemoglobin levels resulting in at least an 8-12% ergogenic advantage in men. Suppression of elevated circulating testosterone of hyperandrogenic athletes results in negative effects on performance, which are reversed when suppression ceases. (...) [W]omen with mild hyperandrogenism including that of polycystic ovarian syndrome, (...) are over-represented in elite athletics (...)."
(Handelsman, David J., Angelica Lindén Hirschberg, and Stephane Bermon. "Circulating testosterone as the hormonal basis of sex differences in athletic performance." Endocrine Reviews (2018).)

Within-sex differences in 2D:4D ratio correlate with functional characteristics (eg. handgrip strength)

"We analyzed a group of Russian males (N = 169) and females (N = 193) aged between 17 and 27 years (with mean ages of 18.6±1.50 and 18.9±1.85, respectively) for the association between the 2D:4D ratio and a wide range of morphological characteristics, some of which were considered in this aspect for the first time. The 2D:4D ratio in males was significantly lower than in females (p ˂ 0.000). A highly statistically significant correlation was found between 2D:4D and sexually dimorphic morphological traits in the total sample. The association of 2D:4D ratio with morphological signs of masculinity/femininity within male and female samples were revealed only as a trend, which was more distinct for the functional indicators (handgrip strength)."
(Bakholdina, Varvara Yu, Alla A. Movsesian, and Marina A. Negasheva. "Association of the digit ratio (2D: 4D) with sexually dimorphic morphological traits." European Journal of anatomy 22, no. 4 (2018): 317-322.)

Men (not women) with high 2D:4D digit ratio have more asymmetrical larynxes

"in men, a correlation between larynx asymmetry and digit ratio was found that was marginally significant (r = .36, p = .063). That means that men with a high digit ratio, which means low testosterone in utero (Manning, 2002), had more asymmetrical larynxes."
(Lange, B. P., H. A. Euler, K. Neumann, E. Zaretsky, and V. Ungericht. "More symmetrical larynxes in men are associated with higher voice attractiveness and mate-choice relevant anthropometric measures. Poster at the 30th annual meeting of the Human Behavior and Evolution Society, University of Amsterdam, Netherlands, July 4-7, 2018.")

Male tobacco chewers with higher digit ratio have higher risk of developing oral cancer

"male tobacco chewers with a higher digit ratio, have higher risk of developing oral cancer."

Females with acne have lower 2D:4D ratios

Two studies found a correlation between acne and low 2D:4D in females:
"In total, 215 female AV patients and 92 healthy controls, aged 18-35 years, were enrolled in this study. (...) The 2D:4D ratios of the AV (Acne Vulgaris) patients were significantly lower than those of the controls, for both hands."
(Bilgiç, Özlem, Cevdet Altınyazar, Hüseyin Hıra, and Murat Doğdu. "investigation of the Association of the Second-to-fourth Digit Ratio with Skin Sebum Levels in Females with Acne Vulgaris." American journal of clinical dermatology 16, no. 6 (2015): 559-564.)

"Data of 251 patients with AV (Acne Vulgaris) (67.7% female) and 120 healthy controls (72.5% female), aged 16-40 years, were analysed. The 2D : 4D ratios of female patients with AV were significantly lower than healthy females in both hands. However, there was no significant difference between male acne cases and controls."
(Bilgiç, Ö., M. Doğdu, G. Kaya İslamoğlu, and C. Altınyazar. "The relationship between the second to fourth digit ratio and acne vulgaris." Journal of the European Academy of Dermatology and Venereology 28, no. 10 (2014): 1340-1343.)

Another study found no correlation:
"The 2D:4D ratio was not significantly different between the group with AV (Acne Vulgaris) and the control group independent of sex. Also, we did not observe a significant association with age of onset, severity of disease, or family history."
(Unal, Mehmet, Gulbahar Urun Unal, Sukru Balevi, Hüseyin Tol, and Mehmet Uyar. "The second to fourth digit ratio in acne vulgaris." Pediatric dermatology 32, no. 5 (2015): 651-655.)

Women who play overhand throwing sports have smaller 2D:4D ratios

"[W]e found no significant differences between the digit ratios of women that (1) were athletes and non-athletes, (2) were varsity or club sport athletes, (3) had played or were currently playing individual or team sports, (4) played contact and non-contact sports, (5) played sports involving a ball and those that do not, (6) played sports where the outcome was determined by a score or the outcome of direct physical competition or subjectively by judges, or (7) were starters or reserves on their teams. However, women that played overhand throwing sports softball and water polo had significantly smaller digit ratios than did women that played other sports. These differences were not due to scaling effects. (...) We suggest that the organizational consequences of prenatal testosterone exposure may influence the anatomy and physiology of women that leads to success playing overhand throwing sports."
(Lombardo, Michael P., Sango Otieno, and Adam Heiss. "College-aged women in the United States that play overhand throwing sports have masculine digit ratios." PLOS ONE 13, no. 9 (2018): e0203685.)

Women with low 2D:4D ratio at risk of lower bone density

"Based on the findings from the present study, the 2D:4D value seems to be positively associated with the QUS-SOS (the speed of sound of the calcaneus by quantitative ultrasound). This phenomenon suggests that it may be possible to screen university students with a relatively low 2D:4D value of the left hand to identify those who are at risk for a low bone density."
(Takahata, Yoko, and Kumi Hirokawa. "Relationship between the Second to Fourth Finger Length Ratio and Calcaneus Quantitative Ultrasound." Scientific Reports 8, no. 1 (2018): 14603.)

2D:4D not significantly correlated with height and body weight, body mass index, waist and hip circumference, the waist-to-hip ratio, handgrip strength; only to skinfold thickness of females on forearm and abdomen

"Aims: To evaluate the value of the 2D:4D ratio in a Mordovian sample and to test the associations between the 2D:4D ratio and sexually dimorphic morphological traits, such as height and body weight, body mass index, waist and hip circumference, the waist-to-hip ratio, handgrip strength and the skinfold thickness.
Subjects and methods: The sample studied included 106 individuals of Mordovian ethnicity: 58 males and 48 females, 16–23 years old. The associations between the 2D:4D ratio and morphological traits were evaluated by multivariate regression analysis and correlation analysis.
Results: The 2D:4D ratio in males was significantly lower than in females. Most of the associations of the 2D:4D ratio with morphological traits were statistically insignificant. The 2D:4D ratio is only significantly correlated with skinfold thickness of the forearm and the abdomen in females."
(Bakholdina, Varvara Yu, Alla A. Movsesian, and Marina A. Negasheva. "Association between the digit ratio (2D: 4D) and body fat distribution in Mordovian students." Annals of human biology (2018): 1-5.)

Low 2D:4D associated with more prognathic jaws, and less malocclusion

"There was a positive correlation between low 2D:4D ratio, i.e., high prenatal androgen levels and high caries index. It was concluded that the hormones have an impact on taste perception and dietary preferences, which in turn influence their caries index.
Low 2D:4D ratio was seen in prognathic mandible cases. These findings suggested that testosterone plays an important role in mandibular growth.
Another study was conducted by Priyanka et al.,[1] to depict the role of hormonal fingerprints in the early detection of malocclusion, caries, and the influence of Basal Metabolic Index (BMI) on malocclusion and caries. (...) The rate of occurrence of malocclusion increased with increase in the value of 2D:4D ratio, whereas higher BMI values were associated with normal occlusal conditions and lower 2D:4D ratio. High caries incidence was reported in children with malocclusion."
(Issrani, Rakhi, Abdalwhab MA Alzwiri, Namdeo Prabhu, and Ahmed Shawkat Hashem. "Hormonal fingerprints: A potential screening tool." Journal of International Oral Health 10, no. 5 (2018): 220.)

High salivary testosterone associated with lower voice in males; no relation with 2D:4D

"Results supported previous findings for a negative relationship between circulating levels of testosterone and fundamental frequency, with higher testosterone indicating lower fundamental frequency(...). Diurnal variation in testosterone and fundamental frequency, but not formant dispersion was reported, together with a trend towards an association between the fall in testosterone and the rise in fundamental frequency. Finally, there was no relationship between 2D:4D and the vocal parameters."
(Evans, Sarah, Nick Neave, Delia Wakelin, and Colin Hamilton. "The relationship between testosterone and vocal frequencies in human males." Physiology & Behavior 93, no. 4-5 (2008): 783-788.)

Low 2D:4D ratio associated with predisposition for osteoarthritis of the knee

"The type 3 finger length pattern (index finger shorter than ring finger) is associated, to a statistically significant degree, with OA (osteoarthritis) of the knee. The type 3 finger length pattern (ring finger longer than index finger) appears to be an indicator of OA predisposition."
(Ferraro, B., F. V. Wilder, and P. E. Leaverton. "Site specific osteoarthritis and the index to ring finger length ratio." Osteoarthritis and cartilage 18, no. 3 (2010): 354-357.)

Low 2D:4D ratio associated with higher neck circumference in adolescents (except in obese individuals)

"There was a significant negative correlation between NC [neck circumference] and 2D:4D ratios of the individuals with normal BMI [Body Mass Index]. However, no statistically significant correlation between NC and 2D:4D ratios was observed in overweight and obese individuals."
(Jeevanandam, Saravanakumar, and K. M. Prathibha. "Measurement Of 2D: 4D ratio and neck circumference in adolescents: Sexual dimorphism and its implications in obesity–A cross sectional study." Indian Journal of Endocrinology and Metabolism 22, no. 6 (2018): 724.)

Lower 2D:4D ratio in women associated with higher content of muscle mass, lean body mass and water

"The BMI, muscle mass, lean body mass and water in the body demonstrated higher values in men than in women. However, the fat content in men was low. It was found that the relationship exists between muscle mass, lean mass and total water content in the body and the 2D:4D finger length ratio in the left hand in women. A higher level of fetal testosterone, characterized by lower values of the 2nd to 4th finger length ratio, may be associated with a higher content of muscle mass, lean body mass and water in the body of adult women leading a similar lifestyle."
("Sex differences in relationship between body composition and digit length ratio (2D:4D) in students of military courses", Anthropological Review • Vol. 81(4), 393–403 (2018), Marek Kociuba, Zofia Ignasiak, Anna Sebastjan, Katarzyna Kochan, Ireneusz Cichy, Andrzej Dudkowski, Marcin Ściślak, Sławomir Kozieł)

No relation between 2D:4D and BMI, anaerobic power or athletic ability scores in young male athletes

"Two hundred and fifty well-trained young male athletes were recruited as participants. Anthropometric measurements (body height, weight, and digit length) vertical jump and athletic ability tests were performed on each participant, for data analysis, correlation analysis was used. Data analyses indicated that the means of 2D:4D ratio was not correlated with BMI, anaerobic power and  athletic ability scores (p < .05). According to the findings of this study, the 2D:4D ratio does not seem to be an indicator parameter to predict the physical performance and athletic abilities of young athletes."
("The Relationship between Digit Ratio (2D:4D), Anaerobic Power and Athletic Ability of Young Athletes", Hüseyin Özden Yurdakul, Gökmen Özen, Hürmüz Koç, Faculty of Sport Sciences, Çanakkale Onsekiz Mart University, Çanakkale, Turkey, Universal Journal of Educational Research 6(12):2913-2917, 2018, DOI: 10.13189/ujer.2018.061226)

"[T]he 2D:4D digit ratio has no relationship with height, weight or BMI of an individual from the people of the Ebira tribe of Nigeria."
(Ibegbu, Augustine Oseloka, Zubair Chegede Danjuma, Wilson Oliver Hamman, Uduak Emmanuel Umana, Daniel Ikyembe, and Sunday Abraham Musa. "Association of the index (2nd) and ring (4th) digit ratios with some physical attributes in Ebira Ethnic Group of Nigeria." Applied Innovations and Technologies 7, no. 2 (2012): 46-54.)

High 2D:4D ratio associated with higher risk of allergic rhinitis in women

"The study consisted of surveys and measurement data collected from 768 female university undergraduates. One hundred and sixty eight undergraduates (21.9%) had been diagnosed with allergic rhinitis. The results of logistic regression show that in women with a high digit ratio, indicating exposure to a higher estrogen level in the prenatal period, the risk of allergic rhinitis was almost twice as high as that in those with an average value of the ratio. The difference in the digit ratio was greater for the right than left hand. (...) We conclude that a higher digit ratio is suggestive of a propensity to allergies in adulthood plausibly having to do with greater exposure to estrogen at early stages of ontogenetic development."
(Kliś, Katarzyna, and Iwona Wronka. "Association of estrogen-related traits with allergic rhinitis." In Influenza and Respiratory Care, pp. 71-78. Springer, Cham, 2017.)

High 2D:4D associated with phimosis (tight foreskin)

"We assert that our results present sufficient evidence that higher 2D:4D ratio is a risk factor for phimosis in the early human development."
(Li, Guanjian, Ying Huo, Ke Sun, Xiaodong Wang, Hao Li, Le Gao, and Bin Ma. "2D: 4D indicates phimosis risk: A study on digit ratio and early foreskin development." Early human development 99 (2016): 21-25.)

Men and women with lower 2D:4D ratio are better at endurance running

"Digit ratio (2D:4D) was used as a proxy for prenatal androgenisation in 439 males and 103 females, while a half marathon race (21km), representing a distance/duration comparable with that of persistence hunting, was used to assess running ability. Digit ratio was significantly and positively correlated with half-marathon time in males (right hand: r = 0.45, p<0.001; left hand: r = 0.42, p<0.001) and females (right hand: r = 0.26, p<0.01; left hand: r = 0.23, p = 0.02). Sex-interaction analysis showed that this correlation was significantly stronger in males than females, suggesting that androgenisation may have experienced stronger selective pressure from endurance running in males."
(Longman, Daniel, Jonathan CK Wells, and Jay T. Stock. "Can persistence hunting signal male quality? A test considering digit ratio in endurance athletes." PloS one 10, no. 4 (2015): e0121560.)

Low 2D:4D ratio associated with smaller and shorter forehead, thicker eyebrows, wider and shorter nose, and larger lower face

"Using geometric morphometrics, we show a significant relationship between facial shape and 2D : 4D before the onset of puberty (explaining 14.5% of shape variation; p = 0.014 after 10 000 permutations, n = 17). Regression analyses depict the same shape patterns as in adults, namely that the lower the 2D : 4D, the smaller and shorter the forehead, the thicker the eyebrows, the wider and shorter the nose, and the larger the lower face."
Figure 2.

(Meindl, Konstanze, Sonja Windhager, Bernard Wallner, and Katrin Schaefer. "Second-to-fourth digit ratio and facial shape in boys: the lower the digit ratio, the more robust the face." Proceedings of the Royal Society of London B: Biological Sciences (2012): rspb20112351.)

Higher scrotal pigmentation and higher right arm circumference are markers of higher prenatal androgen exposure in boys

"Prenatal sex steroid exposure plays an important role in determining child development. Yet, measurement of prenatal hormonal exposure has been limited by the paucity of newborn/infant data and the invasiveness of fetal hormonal sampling. Here we provide descriptive data from the MIREC-ID study (n=173 girls; 162 boys) on a range of minimally invasive physical indices thought to reflect prenatal exposure to androgens [anogenital distances (AGDs); penile length/width, scrotal/vulvar pigmentation], to estrogens [vaginal maturation index (VMI) – the degree of maturation of vaginal wall cells] or to both androgens/estrogens [2nd-to-4th digit ratio (2D:4D); areolar pigmentation, triceps/sub-scapular skinfold thickness, arm circumference]. VMI was found to be associated with triceps skinfold thickness (β=0.265, P=0.005), suggesting that this marker may be sensitive to estrogen levels produced by adipose tissue in girls. Both estrogenic and androgenic markers (VMI: β=0.338, P=0.031; 2D:4D – right: β=−0.207, P=0.040; left: β=−0.276, P=0.006; AGD-fourchette − β=0.253, P=0.036) were associated with areolar pigmentation in girls, supporting a role for the latter as an index of both androgen and estrogen exposure. We also found AGD-penis (distance from the anus to the penis) to be associated with scrotal pigmentation (β=0.290, P=0.048), as well as right arm circumference (β=0.462, P<0.0001), supporting the notion that these indices may be used together as markers of androgen exposure in boys. In sum, these findings support the use of several physical indices at birth to convey a more comprehensive picture of prenatal exposure to sex hormones."
(Nguyen, T. V., P. Monnier, G. Muckle, S. Sathyanarayana, E. Ouellet, M. P. Velez, L. Dodds, and T. E. Arbuckle. "Androgenic and estrogenic indices in human newborns and infants: the MIREC-ID study." Journal of Developmental Origins of Health and Disease: 1-9.)

Low 2D:4D in women associated with higher waist circumference and higher waist-to-height ratio

"Second to fourth digit ratio (2D:4D) is sexually dimorphic, however, the hypothesis claiming that masculine digit ratio in women is connected with masculine phenotype is not fully confirmed. The aim of the present study was to investigate differences in anthropometric parameters in women in relation to the digit ratio value. Cross-sectional research was conducted among 730 Polish female university students, aged 19-25 years. Anthropometric measurements were performed and data about socioeconomic status were collected. The results showed no statistically significant relationships between both right- or left-hand 2D:4D digit ratio and body height and BMI either in univariate linear regressions or in multivariate regression when SES [socioeconomic status] was included in the models. The correlation between right-hand 2D:4D digit ratio and WHR [Waist-to-Hip Ratio] also was not statistically significant. There were significant linear negative relationships between left 2D:4D and WHR [Waist-to-Hip Ratio]. The significant linear negative relationships between both right and left 2D:4D and waist circumference and WHtR [Waist-to-Height Ratio] were found. Relationships between digit ratio and WC [Waist Circumference] and WHtR [Waist-to-Height Ratio] were also tested by multiple regression analyses with SES [socioeconomic status] included in the models. The results were statistically significant. Additionally, statistically significant differences in both right- and left digit ratios depending of the categories of waist circumference and WHtR [Waist-to-Height Ratio] were found. The lowest values of digit ratio were presented by the women with abdominal obesity. The results suggest that low values of digit ratio in women are associated with higher abdominal fat accumulation."
(Zurawiecka, M., A. Suder, A. Stangret, I. Teul, and I. Wronka. "Differences in body fat distribution in women depending on the second to fourth digit ratio value." Anthropologischer Anzeiger; Bericht uber die biologisch-anthropologische Literatur (2019).)

In females, low 2D:4D digit ratio correlates with more androgen receptors and more acne

"Aim: To investigate the relationship between second to fourth digit ratio and androgen receptor expression in female patients with acne vulgaris and to assess its association with clinical aspects of acne vulgaris.
Methods: Females patients (n = 352) with different degrees of acne vulgaris severity and 168 age-matched females were enrolled. Right, left and total second to fourth digit ratios were calculated. Biopsies from all participants were processed for androgen receptor expression by immunohistochemical method.
Results: Right, left and total second to fourth digit ratios were significantly lower in acne vulgaris patients than controls (P < 0.001 for all), and each of them had a significant negative correlation with duration of acne vulgaris (P < 0.001; P = 0.013; P < 0.001, respectively). Androgen receptors were detected in epidermal keratinocytes, hair follicles, sebaceous glands and fibroblasts. Right second to fourth digit ratio showed a negative correlation with androgen receptor H score of keratinocytes (r = −0.28;P = 0.02), hair follicles (r = −0.22;P = 0.05) and fibroblasts (r = −0.37;P = 0.001), while left second to fourth digit ratio demonstrated negative correlation with androgen receptor H score of sebocytes (r = −0.397;P < 0.000) only.
Conclusion: A masculine second to fourth digit ratio in female patients could anticipate acne vulgaris development, its duration and severity. Moreover, this ratio is associated with an upregulation of cutaneous androgen receptors."
(Farag, Azza Gaber Antar, et al. "Second to fourth digit ratio in female patients with acne vulgaris: Could it be a predictor of androgen receptor status?." (2019) - Indian Journal of Dermatology, Venereology and Leprology, ahead of print.)

Lower 2D:4D in women associated with higher risk of carpal tunnel syndrome

"Here we consider the relationship between 2D:4D and CTS in women.
Higher WHR and lower right 2D:4D increase the risk of CTS in women."
(Kasielska-Trojan, Anna, Aneta Sitek, and Bogusław Antoszewski. "Second to fourth digit ratio (2D: 4D) in women with carpal tunnel syndrome." Early Human Development 137 (2019): 104829.)

Lower 2D:4D associated with severity of seborrheic dermatitis

"The 2D:4D ratios of the patients (x = 0.977) were significantly lower than those of the controls (x = 1.050) for right hands (t = 6.948; p = 0.000; > 0.05). No similar relationship was found between the 2D:4D ratio for left hands (t = 0.901; p = 0.368; > 0.05). Seborrheic dermatitis severity was negatively correlated with 2D:4D ratios of right hands (r = -0.391; p = 0.000-0.05)."
(İslamoğlu, Zeynep Gizem Kaya. "Second-to-fourth digit ratio and seborrheic dermatitis in males: a cross-sectional study." Anais Brasileiros de Dermatologia 94, no. 3 (2019): 327-330.)

High R2D:4D associated with low waist-to-height ratio and low waist circumference in men

"Significant correlations (negative) were observed between the 2D:4D (both left and right) and WHtR; the 2D:4D ratio (both left and right) and WC in males. However, in females, these correlations were insignificant."
(ERGUL-ERKEC, Ozlem. Relaciones entre el Promedio de Dígitos 2D: 4D, Circunferencia de Cintura, Preferencias de Mano, Peso, Altura, Relación de Cintura a Altura e IMC en una Población de Turquía. International Journal of Morphology, 2019, 37.4: 1299-1304.)

Low 2D:4D ratio statistically related to longer lifespan in Russian and Abkhazian population samples

"A negative relationship was observed between longevity index and prevalence of type 1 (feminine type) ratio. In longevity samples, the prevalence of type 1 ratio was lower and the prevalence of type 3 (masculine type) ratio was higher than in the nonlongevity sample of Russians. This difference was statistically significant (P < .001) in both males and females. A similar difference between longevity and nonlongevity samples was exhibited in the Abkhazian samples. In males and females, a significantly higher prevalence of type 1 and lower type 3 finger ratios (P < .001) were shown in the nonlongevity samples."
(Kalichman, Leonid, Valery Batsevich, and Eugene Kobyliansky. "Finger length ratio in longevity populations." American Journal of Human Biology (2019): e23325.)

Increased hand digit length ratio (2D:4D) is associated with increased severity of hypospadias in pre-pubertal boys

"This study is the first to demonstrate increased 2D:4D ratios with proximal hypospadias, which also correlate with a shortened anogenital distance."
(O’Kelly, Fardod, Keara DeCotiis, Fadi Zu’bi, Walid A. Farhat, and Martin A. Koyle. "Increased hand digit length ratio (2D: 4D) is associated with increased severity of hypospadias in pre-pubertal boys." Pediatric Surgery International: 1-7.)

Low right-hand digit ratio associated with earlier menopause and less children

"One hundred sixty-nine women, who had experienced natural menopause, were enrolled in the study. (...) Age at menopause correlated significantly positively with the digitratio. A more feminine digit ratio is associated with a higher age at menopause, while a low digit ratio, interpreted as a hint of a higher androgen exposure during prenatal phase was associated with a lower age at menopause. (...)
The digit ratio of the right hand correlated highly significantly positively with the age at menopause (r=0.35;P= 0.001), and significantly with the number of children(r=0.16;P= 0.049), that is, a more feminine digit ratiowas significantly associated with a higher age at meno-pause and a higher number of children."
(Kirchengast, Sylvia, Elisabeth Dottolo, Elisa Praxmarer, and Johannes Huber. "Low digit ratio (2D: 4D) is associated with early natural menopause." American Journal of Human Biology (2019).)

In male sheep, prenatal androgen excess associated with altered genes and proteins in the liver, and predisposes for various liver and circulation problems later on in life

"We hypothesised that poor adult male health was partially attributable to aberrant androgen exposure during development. Testosterone was directly administered to developing male ovine fetuses to model excess prenatal androgenic overexposure associated with conditions such as polycystic ovary syndrome (PCOS). Such in utero androgen excess recreated the dyslipidaemia and hormonal profile observed in sons of PCOS patients. 1,084 of 15,134 and 408 of 2,766 quantifiable genes and proteins respectively, were altered in the liver during adolescence, attributable to fetal androgen excess. Furthermore, prenatal androgen excess predisposed to adolescent development of an intrahepatic cholestasis-like condition with attendant hypercholesterolaemia and an emergent pro-fibrotic, pro-oxidative stress gene and protein expression profile evident in both liver and circulation. We conclude that prenatal androgen excess is a previously unrecognised determinant of lifelong male metabolic health."
(Siemienowicz, Katarzyna J., Panagiotis Filis, Sophie Shaw, Alex Douglas, Jennifer Thomas, Sally Mulroy, Forbes Howie, Paul A. Fowler, W. Colin Duncan, and Mick T. Rae. "Fetal androgen exposure is a determinant of adult male metabolic health." Scientific Reports 9, no. 1 (2019): 1-17.)

The lower the 2D:4D, the longer "wall sitting"

"In this exercise, subjects bend their knees and lean against a wall such that their shins are parallel to the wall and their thighs are parallel to the floor. (...) To represent fights in the experiment, we use a competitive wall sit. Here, subjects simultaneously wall sit and the winner, the person who endures longer in the position, takes the loser’s money. In contrast to prior experiments on conflict, which typically use self-reported experience of fighting [62–64] or fighting as a potential loss of money [13,16,65–67], our competitive wall sit captures key elements of real fights: it can be painful and requires both physical resilience and toughness.
198 subjects participated in our experiment (...). We recruited males between the ages of 18–40 as our subjects.
[t]he relationship between 2D:4D remains significantly negatively linked to wall sitting (...)"
(Szekely, A., & Gambetta, D. (2020). Does information about toughness decrease fighting? Experimental evidence. PLoS one, 15(2), e0228285.) 

Possible link between high androgen exposure and large breasts in women

"However, the link between high left 2D:4D and early development of gigantomastia suggests that prenatal sex hormones have a role in its development timing. High WHR, and particularly high WHR relative to BMI, may indicate that these women had at some stage of development higher circulating androgens, which may have been converted to oestrogens in breasts due to local aromatase activity."
(Kasielska-Trojan, A., Danilewicz, M., Sitek, A., & Antoszewski, B. (2020). Body size measurements, digit ratio (2D: 4D) and oestrogen and progesterone receptors’ expressions in juvenile gigantomastia. Journal of Pediatric Endocrinology and Metabolism.)

Possible association between low digit ratio and muscle dysfunction

"This study investigated the correlations of digit ratio (relative length of second and fourth fingers, 2D: 4D) and muscular strength with the progression of chronic obstructive pulmonary disease (COPD).
The right-hand digit ratio (R2D: 4D) was associated with dominant hand muscle dysfunction, non-dominant hand muscle dysfunction, and inspiratory muscle dysfunction. (...)
Lower digit ratio may be associated with higher prevalence of muscle dysfunction. This factor could be used to identify patients with COPD who are at higher risk of acute exacerbation."
(Jin, J., Li, G. J., Li, F. S., Wang, J., Jing, J., Li, Z., ... & Tao, S. M. (2020). Digit ratio as a risk factor for muscle dysfunction and acute exacerbation in patients with chronic obstructive pulmonary disease. Journal of International Medical Research, 48(2), 0300060519898059.)

Ulna-to-fibula ratio possible biomarker for pubertal sex steroids (low pubertal androgen levels may be associated with low UFR)

"In analogy to the 2D:4D bone ratio - but placing the signal carrier in the numerator instead of the denominator for easier interpretability - UFR [Ulna-to-Fibula Ratio] was thus computed by dividing ulna length by fibula length. UFR was predicted by sex while controlling for body height in a reduced model (...). UFR was normally distributed (...) and highly significantly sex-dimorphic, with larger values for men compared to women (p = .003) and an intermediate size of this effect (d = 0.55).
UFR was robustly dimorphic, with higher scores for men compared to women. (...)
In our view, our results suggest that long bone length, particularly the differential growth effect reflected in UFR, is a potential marker of pubertal organizing hormone effects. (...)
[E]arlier research provided strong indications that relative upper and lower limb length is influenced by sex steroids: Men affected by Klinefelter syndrome (i.e. having an additional X-chromosome and low androgen levels) have a height advantage compared to normal men, but the growth of the legs is much more enhanced than that of the arms (Chang et al. 2015). While this supports our basic assumption of the role of sex steroids in epiphyseal fusion, UFR’s marker function is also supported by the fact that those hypogonadic men thus show a more “female-typical” ratio. Even more, 2D:4D is also higher (“female-typical”) in Klinefelter syndrome, while finger length relative to height is reduced (Manning et al. 2013)."
(Köllner, M. G., & Bleck, K. (2020). Exploratory Evidence of Sex-Dimorphic Associations of the Ulna-to-Fibula Ratio, a Potential Marker of Pubertal Sex Steroid Exposure, with the Implicit Need for Power. Adaptive Human Behavior and Physiology, 1-26.)

High 2D:4D in women associated with older age at menarche, heavier menses bleeding and dysmenorrhea (painful periods)

"An association was found between right 2D:4D and age at menarche, with older age in women with 2D:4D ≥ mean versus 2D:4D < mean (13.2 ± 1.5 and 12.8 ± 1.3 respectively, b = 0.48, 95%CI:0.06–0.91) while controlling for ethnicity. Higher 2D:4D was also associated with heavier menses bleeding and dysmenorrhea. There is an association between 2D:4D and sub optimal reproductive characteristics, including later age at menarche, heavier menses bleeding and dysmenorrhea."
(Tabachnik, M., Sheiner, E., & Wainstock, T. (2020). The association between second to fourth digit ratio, reproductive and general health among women: findings from an Israeli pregnancy cohort. Scientific Reports, 10(1), 1-7.)

Women with multiple sclerosis (MS) have low 2D:4D

"2D:4D ratios are significantly lower in female patients with MS than in healthy controls."
(Gazioglu, S., Alkan, I., Karaman, A. G., & Boz, C. (2020). Decreased second to fourth digit ratios in female multiple sclerosis patients. Early Human Development, 144, 105039.)

Physical fitness higher in elite distant runners with lower R2D:4D

"We examined relationships between 2D:4D, aerobic fitness, physical skills, and overall physical fitness of elite adolescent boy and girl distance runners.

Subjects were top five finishers for their sex and age in 10 or more races of 10 km or longer in Michigan in 1981. We calculated 2D:4D of 15 girls and 11 boys from radiographs. Subject peak O2 consumption (VO2Peak), ventilatory threshold (VT), and point of equivalent change (PEC) were collected during intermittent treadmill protocol tests. Performances on physical skills tests (flex‐arm hang, broad jump, vertical jump, figure‐8‐run, sit ups, and sit‐and‐reach test) were collected in the laboratory.

Boys had greater VO2Peak by mass than girls. Boys with lower R2D:4D had significantly greater VO2Peak and PEC. Girls with lower R2D:4D had significantly greater VT. Factors associated with aerobic fitness explained most of the variation in composite physical fitness scores. Composite aerobic fitness, physical skills, and overall physical fitness scores of boys were negatively correlated with R2D:4D."

Masculinized right 2D:4D and Δ2D:4D are associated with a predisposition to lung cancer and/or the more aggressive forms of lung cancer

"The study included 109 patients (61 men) with lung cancer and 197 controls (78 men). In the study we found that: (i) women with lung cancer have lower 2D:4D compared to controls (the effect was independent of smoking), (ii) among women with cancer, age at diagnosis was positively related to 2D:4D, i.e. women with masculinized 2D:4D present earlier with the cancer than women with feminized 2D:4D, (iii) among men with lung cancer, those with the most aggressive form (small-cell lung cancer) had masculinized (low) Δ2D:4D compared to those with the less aggressive form (non-small cell lung cancer). The data suggests that masculinized right 2D:4D and Δ2D:4D are associated with a predisposition to lung cancer and/or the more aggressive forms of lung cancer."
(Kasielska-Trojan, A., Manning, J. T., Antczak, A., Dutkowska, A., Kuczyński, W., Sitek, A., & Antoszewski, B. (2020). Digit ratio (2D: 4D) in women and men with lung cancer. Scientific Reports, 10(1), 1-8.)

No association between 2D:4D and immune system efficacy in men

"[W]hen controlling for confounds, masculinity-related traits were in general not related to innate and adaptive immunity. Only a weak association was observed for right 2D:4D ratio and T-lymphocyte counts (but it becomes non-significant after adjustment for multiple comparisons). Our results do not support the premise that masculinity is a cue for immunological quality in men."
(Nowak-Kornicka, J., Borkowska, B., & Pawłowski, B. (2020). Masculinity and immune system efficacy in men. PloS one, 15(12), e0243777.)

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