Peri-pubertal high caffeine exposure increases ovarian estradiol production in immature rats

- High caffeine significantly delays female sexual maturation.
- High caffeine exposure increases serum estradiol levels during puberty.
- High caffeine enhances in vivo and in vitro estradiol production.
- High caffeine directly modulates aromatase expression.
- High caffeine exposure may induce an endocrine imbalance during puberty.

Chronic caffeine consumption exerts a negligible effect on the reproductive organs of normal adult females, but it is not known whether this is also true for children and adolescents. Here, we investigated the effects of high caffeine exposure on sexual maturation and ovarian estradiol production in immature female rats. Immature female SD rats were divided into controls and caffeine groups fed 120 and 180 mg/kg/day for 4 or 8 weeks. There was a significant delay in vaginal opening in the caffeine-fed groups. In addition, serum estradiol levels were elevated in the caffeine-fed animals after 2 and 4 weeks of exposure. Estradiol secretion as well as aromatase expression also increased significantly in the ovarian cells in response to caffeine. These results demonstrate that peripubertal exposure to high caffeine increases estradiol production in the ovary; this may disturb the coordinated regulation of the hypothalamo-pituitary-ovarian axis, thereby interfering with sexual maturation.

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