What is the normal progression of puberty and the start of menstruation?

Updated: Jan 08, 2019
  • Author: Kristi A Tough DeSapri, MD; Chief Editor: Richard Scott Lucidi, MD, FACOG  more...
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Answer

The orderly progression of puberty begins with breast budding (thelarche), accelerated growth, and menses (menarche). Adrenarche, sexual hair growth, is independent from GnRH function and typically occurs between breast budding and accelerated growth but may occur anywhere along the puberty timeline.  Secretion of dehydroepiandrostenedione (DHEA) initiates adrenarche. In the United States, the average age of girls at menarche is 12.6 years, with a range of 9-15 years. (Age 15 years is 2 standard deviations above the mean, while age 16 years is 3 standard deviations above.)  Progression of puberty requires exposure to estrogens.

 Menses occurring on a predictable cyclic pattern are associated with follicle development and ovulation.  At birth, female infants have a predetermined number of primordial follicles. During the first trimester of pregnancy, fetal oogonia increase in number by rapid mitosis.   By the 16 to 20th week of pregnancy, up to 6 million oogonia are present and mitosis halts. After reaching a maximum number of oogonia cells at 20 weeks, supporting cells envelop the oocyte forming the primordial follicle. The oocyte within the primordial follicle will enter into meiosis I, arresting at the diplotene stage of prophase. Over the remaining 20 weeks of pregnancy, over 4 million oocytes will undergo spontaneous atresia resulting in 2 million oocytes available at birth. Atresia continues such that only 300,000 oocytes remain at the time of puberty. Up to 500 oocytes will ovulate during a woman’ reproductive  life with the remainder undergoing apoptosis. The oocytes will remain arrested at Meiosis I unless the oocyte is chosen to progress to a primary follicle and eventual the dominant follicle chosen for ovulation. Upon the LH surge associated with ovulation, the oocyte is stimulated to complete meiosis 1 with subsequent arrest at metaphase of meiosis 2.  Completion of meiosis 2 occurs after fertilization of a single sperm. At birth, female infants have a predetermined number of primordial follicles that are arrested during meiosis 1 at the diplotene stage of prophase until stimulation at puberty. Until puberty, the hypothalamus is in a quiescent state. At approximately age 8 years, the GnRH pump is reactivated under the primary control of Kisspeptin {ref 85}.

Menarche and sustained menstrual cycles requires normal function of the endocrine axis comprising the hypothalamus, pituitary, and ovaries (see the image below). Any disruption in this axis may result in amenorrhea. Defining the level of primary dysfunction is critical in determining the pathophysiology of amenorrhea.

Hypothalamus, pituitary and ovaries form a functio Hypothalamus, pituitary and ovaries form a functional endocrine axis, known as HPO axis with hormonal regulations and feedback loops.

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