The gonads in utero exist in an undifferentiated state until the seventh week of fetal life, at which time the primitive ovary can be differentiated from the testis. Estrogen formation in the ovary begins between weeks 8 and 10, and by 10 to 11 weeks of gestation, some oognia in the developing ovarian cortex begin developing into primary oocytes.
The ovary contains a finite number of germ cells. The maximal number of about 7 million oogonia being reached by the fifth to sixth month of gestation. Afterward, the germ cells decrease in number through a process of atresia such that only 1 million remain at birth, 400,000 are present at the time of menarche, and only a few remain at menopause. Two X chromosomes are required for normal development of the ovary. In individuals with a 45,X karyotype, ovarian development occurs, but the rate of atresia (ovarian dealth) is accelerated so that only a fibrous streak remains at the time of birth.
Final maturation of ovarian follicles commences during puberty. The two major hormones that regulate follicular development are the pituitary gonadotropins - follicle stimulating hormone (FSH) and luteinizing hormone (LH).
As the time of puberty nears, a decrease in the sensitivity of the hypothalamic-pituitary system allows for increased secretion of FSH and LH, possibly secondary to increased episodic or pulsatile secretion of luteinizing hormone releasing hormone (LHRH) by the hypothalamus. An increase in estrogen secretion subsequently exerts a positive feedback which leads to an exaggeration of the pulsatile release of LH and eventually to ovulation and the menarch, after which average plasma gonadotropin concentrations reach adult values in which day and night levels are similar.
The culmination of puberty is the onset of predictable, cyclic menses. The average time between the beginning of breast development and the onset of menses is 2 years. During the first few years after menarche, menstrual cycles are often irregular and unpredictable due to anovulation (similar to perimenopause). The age of menarch is variable and is determined in part by socioeconomic and genetic factors as well as general health. The mean age in the United States has decreased at a rate of 3 to 4 months per decade over the last 100 years and is now around 13 years old.
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