Due to this inconsistency the goal of the current study was to assess the association between women’s general and reproductive health and 2D:4D. For instance, several large studies found a negative association between 2D:4D and age at menarche 20, 22, 23, while another found a positive association 21. Not all studies however found an association between 2D:4D in women and reproductive 39, 40, 41, 42, 43 and health characteristics 44, 45 and there is some inconsistency in the literature regarding the direction of the association.

As for general health characteristics, 2D:4D was associated with various cancers 32, 33, idiopathic pulmonary hypertension 34 and other morbidities such as systemic lupus erythematosus 35, autism spectrum disorders 36, and congenital adrenal hyperplasia 37, 38.

Several studies found 2D:4D to be associated with reproductive cancers 25, 30, 31. Various studies found associations between 2D:4D and reproductive characteristics in humans, including age at menarche 20, 21, 22, 23, puberty characteristics 24, reproductive period 20, age at menopause 25, polycystic ovary syndrome 26, severity of premenstrual symptoms 27 and estradiol levels across menstrual cycle 28, 29. Therefor other methods have been used to evaluate prenatal androgen exposure, such as 2D:4D 7. Conversely, some studies found no support for such association 17, 18, 19.Īssessing the prenatal hormonal environment directly from the fetus in utero is challenging because of the risk for the fetus. Previous research showed association between prenatal hormonal environment and exposure to endocrine disrupting chemicals and 2D:4D in animals 12, 13 and humans 2, 10, 14, 15, 16. Considering this, it was suggested that there may be an association between prenatal hormonal function and digit formation, and 2D:4D was proposed as an indicator of first trimester testosterone and estrogen levels, reflecting the Hox genes’ action on differentiation 9, 10.Įnvironmental exposure to toxicants is critical during early development stages, such as the perinatal period, in which there is a heightened vulnerability to exposures due to potential permanent effect on health and development 11. Homeobox genes Hox a and Hox d may indirectly influence the prenatal production of androgen by controlling the differentiation of the urogenital system as well as digit development. Relative digit length is considered steady at ages 2 to 25 6, although other studies suggest that 2D:4D does mildly increase during childhood but remains steady during puberty 7, 8.ĢD:4D was suggested to be associated with Hox gene family 2, 3. 2D:4D is observed at as early as the end of the first trimester 4, 5. 2D:4D is sexually dimorphic, and males’ 2D:4D is relatively shorter than females’ 2, 3. The ratio between lengths of the second and the fourth digits (index and ring fingers) (2D:4D) is a putative biomarker of prenatal testosterone and estrogen exposure 1. Further studies are required to support our findings. These findings support the association between the intrauterine period and reproductive characteristics. There is an association between 2D:4D and sub optimal reproductive characteristics, including later age at menarche, heavier menses bleeding and dysmenorrhea. Higher 2D:4D was also associated with heavier menses bleeding and dysmenorrhea. 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. The mean age at menarche was 12.9 ± 1.4 years. Mean age of the participants was 30.7 ± 4.9 years. Multivariable linear and logistic models were used to study the associations between digit ratio and the studied health characteristics. 2D:4D was measured directly in both hands using a digital caliper. This analysis was conducted within a prospective pregnancy cohort study. The aim of the study was to examine the association between 2D:4D and women’s general and reproductive health. The ratio between the length of second and fourth digits (2D:4D) is a putative biomarker for prenatal testosterone and estrogen exposure.

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