The Menstrual Cycle

A patient with menstrual cycles between 26 days and 30 days comes to your office for evaluation. You tell her that the phase of the menstrual cycle that most influences cycle length is the

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· The menstrual cycle occurs in three phases: follicular (proliferative), ovulatory, and luteal (secretory). Menstruation is part of the follicular (proliferative) phase and does not affect the length of the menstrual cycle. During the follicular phase, folliculogenesis and selection of a dominant follicle occurs. Estradiol is produced and is responsible for the proliferation of the endometrial lining of the uterus. Ovulation occurs in response to a surge in luteinizing hormone. During the ovulatory phase, ovulation takes place approximately 24-36 hours after the LH peak.

· Most people have a menstrual cycle length between 25 and 30 days, with the median duration being 28 days. The variability in length of the menstrual cycle is based on the variable length of the follicular phase; the luteal phase is constant in most people at 14 days in length.

· The luteal phase starts after ovulation. The granulosa cells in the dominant follicle become the corpus luteum, which predominantly secretes progesterone and converts proliferative endometrium into secretory endometrium in preparation for implantation should pregnancy occur. If pregnancy does not occur, the corpus luteum involutes and a decrease in progesterone leads to instability and shedding of the endometrium.

The physiologic event that induces completion of the first meiotic division of the oocyte is the

Appearance of progesterone secretion

Intercycle rise in follicle-stimulating hormone (FSH)

Midcycle luteinizing hormone (LH) surge

Increase in frequency of pulsatile gonadotropin releasing hormone (GnRH)

Ovulation-associated drop in estradiol

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· As the ovary nears the time of ovulation, a pool of primordial follicles develops in response to FSH. It is unclear what signals determine the single follicle that develops into the dominant follicle, but it has an increased number of FSH receptors, and FSH stimulates aromatase activity and estradiol secretion. The follicle then develops LH receptors and becomes responsive to LH. When estradiol secretion has reached a sufficient threshold and duration, an LH surge is triggered.

· The events of ovulation are stimulated by the LH surge. The oocyte had previously been suspended in the first meiotic division. After the LH surge, the oocyte completes its first meiotic division and a metaphase II oocyte is created. The granulosa cells in the follicle then favor progesterone secretion over estradiol secretion and progesterone receptor expression increases. This activates expression of proteases responsible for follicular rupture 24-36 hours after the onset of the LH surge.

· The intercycle rise in FSH starts the recruitment of a pool of follicles. Progesterone secretion is a result of the LH surge, but does not directly affect the oocyte. The decrease in estradiol occurs because of follicular rupture, and does not induce changes in oocyte function.

You are seeing a patient in clinic who has infrequent menses and has been diagnosed with polycystic ovary syndrome. She would like more information about cyclic progesterone. How is cyclic progesterone administered, and who is a good candidate? What relationship does it have to the physiologic menstrual cycle?

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· The administration of cyclic progesterone includes providing oral progesterone such as medroxyprogesterone acetate (Provera) for 10-14 days every 1-3 months. This simulates secretion of progesterone by the corpus luteum during the luteal phase of the menstrual cycle. Following completion of the course results in decreasing serum progestin levels, mimicking the involution of the corpus luteum. This results in induced menses to avoid prolonged unopposed estrogen, which can increase the risk of endometrial hyperplasia and malignancy, and anovulatory bleeding, which can be unpredictable and heavy.

· Cyclic progesterone does not prevent ovulation and therefore is not effective as a contraceptive method. It may be effective in those who are not at risk of pregnancy and would like to use an oral medication to manage irregular, anovulatory menses that does not have to be taken continuously. It is also often used in conjunction with oral ovulation induction methods to cause menses when ovulation and pregnancy did not occur.

· Other options for managing anovulation include combined hormonal contraceptives (if no contraindications), a levonorgestrel IUD, or continuous daily oral progestin-only pills. These options all also act as contraceptives.