General Medical Information

Initiation of Gonadarche

Sander S. Shapiro and Joel S. Krasnow

The alterations in physical characteristics that occur around puberty are largely dependent on sex steroid production by the gonads. The process of ovarian follicular growth and atresia is a continuous process initiated in utero. Both ultrasound and autopsy studies have documented cystic changes in the ovaries from birth to puberty. It is not uncommon to note ovarian follicular cysts, in utero or in the neonatal period, that regress spontaneously following chorionic gonadotropin withdrawal. Throughout childhood, follicles continue to develop and undergo atresia, resulting in a gradual increase in ovarian stromal tissue but with only minimal estrogen secretion. The initiation of follicular development is thought to occur independent of pituitary gonadotropin stimulation. Sustained progression of follicular development to the antral stage with significant estrogen production does, however, require gonadotropins.

After reactivation of the HPG axis at puberty, multiple (more than five) follicles develop to a size larger than 4 mm. With maturation of the neuroendocrine unit, gonadotropin pulse frequency increases and ovarian follicles develop to a progressively larger size. As follicular maturation progresses, steroidogenic competency develops. There is a direct relationship between follicular size and steroid-synthesizing capacity. Follicular development to 16 mm in diameter may be expected to provide sufficient estrogen for endometrial proliferation. The earliest follicles to attain this degree of maturation usually fail to induce an LH surge and, therefore, undergo atresia without effecting ovulation. This, in turn, causes estrogen withdrawal followed by endometrial involution and menstrual bleeding. Thus, menarche follows and is usually the result of nonovulatory cycling. The length of the menstrual cycle is quite variable during the first year after menarche, with only about 15% being ovulatory. However, should ovulation take place during the initial cycle, pregnancy would be possible without the onset of a first menses.

Even after ovulatory competence has been achieved, abnormalities of the luteal phase (short luteal phase, inadequate luteal phase) commonly occur. These abnormalities are thought to be the result of inadequate follicular stimulation by the pituitary and provide evidence that the HPG axis has not achieved full maturity. With complete maturation of the HPG axis, a dominant follicle develops in each cycle, becomes fully mature, and ovulates.

Both the onset and rate of progression through puberty correlate with the age of menarche and the age at which regular ovulatory menstrual cycles are established. Progression from Tanner stage II breast and pubic hair to menarche occurred in 1.4 ± 0.1 years and 1.1 ± 0.2 years, respectively, in Finnish girls experiencing menarche prior to age 13 years. The majority of menstrual cycles were ovulatory within 18 months of menarche. In contrast, those girls experiencing menarche after age 13 years progressed through these same developmental stages in 2.1 ± 0.2 years and 2.0 ± 0.2 years, respectively. In this group, only 50% of all menstrual cycles were ovulatory by the fifth year after menarche. Other investigators have found a trend in essentially the opposite direction, with those girls undergoing early onset of puberty experiencing a longer pubertal interval. This observation is thought to reflect the variable velocity at which integration of the HPG axis occurs.