The 2D:4D ratio, a proxy for prenatal androgen levels, differs in men with and without MS.
OBJECTIVE
To determine whether the 2D:4D ratio (ratio of the second and fourth digit lengths), a proxy for lower prenatal androgen to estrogen ratio, differs in men with and without multiple sclerosis (MS) using a case-control study design.


METHODS
We obtained 2 digital scans of the right hand for men with MS presenting to a scheduled clinic visit at a large MS referral center, and for men without autoimmune or endocrine diseases. All individuals were aged 18 to 65 years, right-handed, and reported no prior digit trauma. We calculated a mean 2D:4D ratio using digital calipers. In participants with MS, we assessed age at first MS symptoms, MS type, and the MS Severity Score; 51 had provided a testosterone level within 10 years of symptom onset. Our primary analysis was a cross-sectional comparison of the 2D:4D ratio between men with and without MS, using a 2-sample t test for independent samples assuming unequal variance.


RESULTS
In total, we scanned 137 men with MS and 145 men without MS. A statistically significant association between 2D:4D ratio and MS status was observed in the univariate logistic regression model (p<0.05). These differences were not associated with age or race, which differed between the 2 groups. In participants with MS, the 2D:4D ratio was not correlated with MS type, age at first symptoms, or MS Severity Score (p>0.15 for each), and it was not correlated with adult testosterone levels (r=0.06, p=0.68, n=51).


CONCLUSIONS
During the prenatal period, low androgens could represent a risk factor for MS.
From the Partners Multiple Sclerosis Center (R.B., M.T.M., C.D.-C., A.C., T.J.S., D.B., E.G., B.I.G., B.C.H., T.C.), Department of Neurology, Brigham and Women's Hospital, Brookline; Harvard Medical School (R.B., B.I.G., B.C.H., T.C.), Boston; Ann Romney Center for Neurologic Diseases (R.B., D.B., B.I.G., B.C.H., T.C.), Harvard Medical School, Boston; and Massachusetts General Hospital Biostatistics Center (B.C.H.), Boston, MA.
Riley
R
Bove
From the Partners Multiple Sclerosis Center (R.B., M.T.M., C.D.-C., A.C., T.J.S., D.B., E.G., B.I.G., B.C.H., T.C.), Department of Neurology, Brigham and Women's Hospital, Brookline; Harvard Medical School (R.B., B.I.G., B.C.H., T.C.), Boston; Ann Romney Center for Neurologic Diseases (R.B., D.B., B.I.G., B.C.H., T.C.), Harvard Medical School, Boston; and Massachusetts General Hospital Biostatistics Center (B.C.H.), Boston, MA.
Muhammed T
MT
Malik
From the Partners Multiple Sclerosis Center (R.B., M.T.M., C.D.-C., A.C., T.J.S., D.B., E.G., B.I.G., B.C.H., T.C.), Department of Neurology, Brigham and Women's Hospital, Brookline; Harvard Medical School (R.B., B.I.G., B.C.H., T.C.), Boston; Ann Romney Center for Neurologic Diseases (R.B., D.B., B.I.G., B.C.H., T.C.), Harvard Medical School, Boston; and Massachusetts General Hospital Biostatistics Center (B.C.H.), Boston, MA.
Camilo
C
Diaz-Cruz
From the Partners Multiple Sclerosis Center (R.B., M.T.M., C.D.-C., A.C., T.J.S., D.B., E.G., B.I.G., B.C.H., T.C.), Department of Neurology, Brigham and Women's Hospital, Brookline; Harvard Medical School (R.B., B.I.G., B.C.H., T.C.), Boston; Ann Romney Center for Neurologic Diseases (R.B., D.B., B.I.G., B.C.H., T.C.), Harvard Medical School, Boston; and Massachusetts General Hospital Biostatistics Center (B.C.H.), Boston, MA.
Alicia
A
Chua
From the Partners Multiple Sclerosis Center (R.B., M.T.M., C.D.-C., A.C., T.J.S., D.B., E.G., B.I.G., B.C.H., T.C.), Department of Neurology, Brigham and Women's Hospital, Brookline; Harvard Medical School (R.B., B.I.G., B.C.H., T.C.), Boston; Ann Romney Center for Neurologic Diseases (R.B., D.B., B.I.G., B.C.H., T.C.), Harvard Medical School, Boston; and Massachusetts General Hospital Biostatistics Center (B.C.H.), Boston, MA.
Taylor J
TJ
Saraceno
From the Partners Multiple Sclerosis Center (R.B., M.T.M., C.D.-C., A.C., T.J.S., D.B., E.G., B.I.G., B.C.H., T.C.), Department of Neurology, Brigham and Women's Hospital, Brookline; Harvard Medical School (R.B., B.I.G., B.C.H., T.C.), Boston; Ann Romney Center for Neurologic Diseases (R.B., D.B., B.I.G., B.C.H., T.C.), Harvard Medical School, Boston; and Massachusetts General Hospital Biostatistics Center (B.C.H.), Boston, MA.
David
D
Bargiela
From the Partners Multiple Sclerosis Center (R.B., M.T.M., C.D.-C., A.C., T.J.S., D.B., E.G., B.I.G., B.C.H., T.C.), Department of Neurology, Brigham and Women's Hospital, Brookline; Harvard Medical School (R.B., B.I.G., B.C.H., T.C.), Boston; Ann Romney Center for Neurologic Diseases (R.B., D.B., B.I.G., B.C.H., T.C.), Harvard Medical School, Boston; and Massachusetts General Hospital Biostatistics Center (B.C.H.), Boston, MA.
Emily
E
Greeke
From the Partners Multiple Sclerosis Center (R.B., M.T.M., C.D.-C., A.C., T.J.S., D.B., E.G., B.I.G., B.C.H., T.C.), Department of Neurology, Brigham and Women's Hospital, Brookline; Harvard Medical School (R.B., B.I.G., B.C.H., T.C.), Boston; Ann Romney Center for Neurologic Diseases (R.B., D.B., B.I.G., B.C.H., T.C.), Harvard Medical School, Boston; and Massachusetts General Hospital Biostatistics Center (B.C.H.), Boston, MA.
Bonnie I
BI
Glanz
From the Partners Multiple Sclerosis Center (R.B., M.T.M., C.D.-C., A.C., T.J.S., D.B., E.G., B.I.G., B.C.H., T.C.), Department of Neurology, Brigham and Women's Hospital, Brookline; Harvard Medical School (R.B., B.I.G., B.C.H., T.C.), Boston; Ann Romney Center for Neurologic Diseases (R.B., D.B., B.I.G., B.C.H., T.C.), Harvard Medical School, Boston; and Massachusetts General Hospital Biostatistics Center (B.C.H.), Boston, MA.
Brian C
BC
Healy
From the Partners Multiple Sclerosis Center (R.B., M.T.M., C.D.-C., A.C., T.J.S., D.B., E.G., B.I.G., B.C.H., T.C.), Department of Neurology, Brigham and Women's Hospital, Brookline; Harvard Medical School (R.B., B.I.G., B.C.H., T.C.), Boston; Ann Romney Center for Neurologic Diseases (R.B., D.B., B.I.G., B.C.H., T.C.), Harvard Medical School, Boston; and Massachusetts General Hospital Biostatistics Center (B.C.H.), Boston, MA. tchitnis@partners.org.
Tanuja
T
Chitnis
D000328:Adult; D000367:Age Factors; D000368:Aged; D000728:Androgens / Q000378:metabolism*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000378:metabolism*; D012727:Sex Characteristics
D000728:Androgens