ESPE Abstracts

Background: There is an emerging evidence that the ovary may be an important site where genes such as LIN28b, whose polymorphisms has been strongly associated to age at menarche, could modulate the timing of puberty. Recent data suggest that the endocannabinoid system plays a role in folliculogenesis and ovulation, through cannabinoid receptor 2 (CB2) expressed in the ovary. On the other hand childhood obesity is associated with increased likelihood of early menarche, probably for the increased bioavailability of sex hormones.

Objective and Hypotheses: We aimed to investigate the association of the functional variant Q63R of CB2 in influencing age at menarche in obese girls.

Method: We studied 240 girls (age, 11.9±3 years; BMI z-score, 2.8±0.8). Age at menarche was recorded at the time of the visit if already occurred or asked by phone-call. The CNR2 rs35761398 variant has been detected by TaqMan assay.

Results: One hundred and five patients were homozygous for R allele (R63), 113 were Q63R and 22 were Q63. Variance analysis showed a significantly earlier age of menarche in subjects carrying the Q allele, also adjusting for BMI z-score (11±1.2 vs 11.6±1.2 years; P: 0.0016). Logistic regression analysis showed that carriers of the Q allele had 2.05 times higher risk (OR 2.05; CI: 1.21–3.45; P: 0.0068) to present with an early menarche (age at menarche, <12 years).

Conclusion: We demonstrated for the first time the association between rs35761398 polymorphism in CNR2 gene and age at menarche in a cohort of Italian obese girls. We hypothesize that the CB2 receptor may be part of the pathway that mediates the ovary response to peripheral estrogens and the more functional variant (Q63) could enhance the ovary response to estrogens. In obese girls this mechanism may contribute in determining early menarche both affecting the initiation of puberty and the rate of progression through puberty.