A menstrual cycle is defined as that period of time from the first day of menstrual period to the first day of the next menstrual flow. On the basis of current understanding, the menstrual cycle may be described by the response of the pituitary (i.e., FSH and LH levels), the ovary (follicular, ovulatory, and luteal phases), and the endometrium (proliferative and secretory phases).
FSH and LH are secreted in a pulsatile manner, with frequency varying between 1 and 2 hours in the follicular and luteal phases, respectively. The pulsatile spikes are higher in amplitude during the luteal phase. The pulsatile secretion of FSH and LH are secondary to the pulsatile secretion of GnRH from the hypothalamus. The pulsatile release of GnRH can be modulated by estradiol and progesterone feedback. Neurotransmitters (i.e., dopamine, norepinephrine) and endorphins (opioids) also play a role in modulating GnRH secretion. Menstrual irregularities that occur with weight loss, stress, exercise, and drugs may be secondary to the effect of these compounds on the hypothalamus.
The physiological mechanisms of the menstrual cycle can be divided into three descriptive phases: the follicular phase, the ovulatory phase, and the luteal phase.
1) Follicular Phase
The duration of the follicular phase is usually 14 days, but the length is highly variable (range 7 to 22 days). This phase begins with the onset of menses and ends with ovulation. The duration of the follicular phase is the major determinant of menstrual cycle length.
- During the end of the prior menstrual cycle, corpus luteum involution occurs, with resulting decreasing levels of estradiol and progesterone. The low levels stimulate the hypothalamic release of GnRH, which in turn increases the pituitary's release of FSH and LH.
- FSH stimulates the recruitment of ovarian follicles.
- At present, it is believed that LH stimulates ovarian theca cells to produce androgens, which are then converted to estrogens in the granulosa cells of the ovary under the influence of FSH (Fig. 49.2). Estradiol increases FSH binding to granulosa cell receptors, leading to amplification of the FSH effect, allowing one follicle to predominate.
- Under the influence of estrogen, the proliferative phase of the endometrium occurs. The binding of estradiol to its receptor sites on the endometrium results in the production of growth factors that stimulate marked proliferation within the glandular and stromal compartments of the endometrium. The height of the endometrium increases from approximately 1 mm at the time of menstruation to 5 mm at the time of ovulation. The major effect of estrogen on the endometrium is that of growth. Estrogen also increases the number of estrogen and progesterone receptors in endometrial cells.
- Estrogen causes maturation of vaginal basal cells into superficial squamous epithelial cells and the formation of watery vaginal mucus, which can be strung out (spinnbarkeit) or dried, forming a ferning pattern.
- In response to rising estradiol levels in the middle and late follicular phase, FSH release begins to fall.
2) Ovulatory Phase
- A preovulatory estradiol surge leads to a midcycle LH surge which initiates ovulation approximately 10 to 16 hours after the LH surge. An estradiol level of approximately 200 pg/mL or higher for at least 2 days is needed to induce ovulation. A small preovulatory rise in progesterone is required to induce the FSH surge.
- A mature follicle releases an oocyte and becomes a functioning corpus luteum.
- At this stage there are copious, clear vaginal secretions, with maximum spinnbarkeit and a positive fern test result.
3) Luteal Phase
The luteal phase begins with ovulation and ends with the menstrual flow. This phase is more constant, lasting approximately 14 ± 2 days, reflecting the life of the corpus luteum.
- The corpus luteum produces large amounts of progesterone, as well as increased levels of estrogen. Granulosa cells are exposed to low-density lipoprotein (LDL) cholesterol as a result of the invasion of blood vessels into the collapsed follicle. LDL acts as a substrate for progesterone synthesis. A progesterone serum level of >3 ng/mL is a presumptive evidence of ovulation. Rising levels of estrogen and progesterone lead to falling levels of FSH and LH.
- Progesterone antagonizes the action of estrogen by reducing estrogen receptor sites and increasing conversion of estradiol to estrone, a less potent estrogen. Progesterone halts the growth of the endometrium and stimulates differentiation into a secretory endometrium. The secretory phase is characterized histologically by increased tortuosity of glands and spiraling of blood vessels. Secretory activity is maximal, and stromal edema occurs. The secretory endometrium is prepared for implantation.
- Local progesterone produced by the corpus luteum suppresses follicular development in the ipsilateral ovary so that ovulation in the following month usually occurs in the contralateral ovary.
- The cervical mucus becomes thick during the luteal phase, owing to the influence of progesterone, and no ferning or spinnbarkeit occurs.
- Unless there is fertilization with subsequent production of human chorionic gonadotropin, the corpus luteum involutes after approximately 10 to 12 days. Sloughing of the endometrium occurs secondary to a loss both of estrogen and of supportive progesterone. Local prostaglandins cause vasoconstriction and uterine contractions.
- The decreased levels of estrogen and progesterone lead to increased levels of FSH and LH, providing the positive feedback loop required to initiate another menstrual cycle.
Conclusion
Menarche is that time in the female life cycle denoting the beginning of menses and the commencement of orderly cyclic hormonal changes. Normal menstrual cycles require an orchestrated sequence of events to occur between the hypothalamus, pituitary, ovaries, and the endometrium. Abnormal menstrual cycles are not uncommon and require appropriate clinical assessment and evaluation to determine etiology. Common menstrual disorders experienced by adolescents, including dysmenorrhea, dysfunctional uterine bleeding, and amenorrhea will be discussed in the following chapters.
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