Oestrogen and pregnanediol excretion through childhood, menarche and first ovulation

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Abstract
Summary Urinary oestrogen and pregnanediol values were measured in 24 boys and 38 girls between the ages of 2 and 13 years. Longitudinal studies were conducted on eight girls, two of whom collected for periods of 4 and 5 years which included menarche and in one case establishment of ovulation. Highly sensitive assay methods were developed for measuring the very small amounts of oestrone, oestradiol and oestriol and pregnanediol present in the urine of young children. The total oestrogen values were within the submicrogram range of 0·1–0·5 μg/24 hr in the children aged 2–8 years, with no differences seen between the boys and girls. After the age of 8 years, oestrogen values above 1 μg/24 hr began to be encountered and by age 11½ years the majority of subjects were recording oestrogen values above this figure. The rise in the oestrogen values was more rapid in the girls than in the boys. Evidence was presented that a value of approximately 1 μg/24 hr represents the minimum oestrogen production for the initiation of breast development. The oestrogen values were fluctuating with irregular periodicities at all ages and the gradual general rises seen after the age of 8 years could be arrested at any stage for a year or more. Menarche was preceded by marked periodic fluctuations in oestrogen output which peaked above 15 μg/24 hr. In all subjects studied, the initial bleeding cycles were anovulatory as judged by the low pregnanediol values, the usual pattern being one of fluctuating oestrogen production. One subject was studied fully through to the establishment of ovulation, which first occurred 12 months after menarche. The approach of ovulation was indicated by pre-menstrual rises in pregnanediol which increased in amplitude from 0·4 mg/24 hr until finally 2 mg/24 hr was exceeded (the value accepted for ovulation). Evidence was presented that the interval from menarche to ovulation in different individuals was very variable, extending from ovulation at menarche itself to periods of more than a year. Recording of self-observed symptoms of production of cervical mucus could be of considerable value in documenting these events in larger populations.