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A 24-year-old sexually active woman with regular 29-day menstrual cycles presents to the clinic complaining that her period is two weeks late. Physical exam reveals no abnormalities. Pregnancy is confirmed by urine test. Which of the following mechanisms is most likely responsible for her missed period?
Content Reviewers:Rishi Desai, MD, MPH
Contributors:Sam Gillespie, BSc, Brittany Norton, MFA, Jake Ryan, Robyn Hughes, MScBMC, Elizabeth Nixon-Shapiro, MSMI, CMI, Viviana Popa, MD
The endometrium is the layer of tissue lining the inside of the uterus.
The menstrual cycle actually consists of two interconnected and synchronized processes: the ovarian cycle, which centers on the development of the ovarian follicles and ovulation, and the uterine or endometrial cycle, which centers on the way in which the functional endometrium thickens and sheds in response to ovarian activity.
Menarche, which refers to the onset of the first menstrual period, usually occurs during early adolescence as part of puberty.
Following menarche, the menstrual cycle recurs on a monthly basis, pausing only during pregnancy, until a person reaches menopause, when her ovarian function declines and she stops having menstrual periods.
The monthly menstrual cycle can vary in duration from 20 to 35 days, with an average of 28 days.
Each menstrual cycle begins on the first day of menstruation, and this is referred to as day one of the cycle.
Ovulation, or the release of the oocyte from the ovary, usually occurs 14 days before the first day of menstruation (i.e., 14 days before the next cycle begins).
So, for an average 28-day menstrual cycle, this means that there are usually 14 days leading up to ovulation (i.e., the preovulatory phase) and 14 days following ovulation (i.e., the postovulatory phase).
During these two phases, the ovaries and the endometrium each undergo their own set of changes, which are separate but related.
As a result, each phase of the menstrual cycle has two different names to describe these two different parallel processes.
Similarly, the two weeks following ovulation is referred to as the ovarian luteal phase, which also corresponds to the secretory phase of the endometrium.
So, let’s first focus on the preovulatory period, starting with the ovarian follicular phase.
This phase starts on the first day of menstruation and represents weeks one and two of a four-week cycle.
The hypothalamus is a part of the brain that secretes gonadotropin-releasing hormone, or GnRH, which causes the nearby anterior pituitary gland to release follicle stimulating hormone, or FSH, and luteinizing hormone, or LH.
Before puberty, the gonadotropin-releasing hormone is released at a steady rate, but once puberty hits, the gonadotropin-releasing hormone is released in pulses, sometimes more and sometimes less.
The frequency and magnitude of the gonadotropin-releasing hormone pulses determine how much follicle stimulating hormone and luteinizing hormone will be produced by the pituitary.
These pituitary hormones control the maturation of the ovarian follicles, each of which is initially made up of an immature sex cell, or primary oocyte, surrounded by layers of theca and granulosa cells, the hormone-secreting cells of the ovary.
Over the course of the follicular phase, these oocyte-containing groups of cells, or follicles, grow and compete for a chance at ovulation.
During the first ten days, theca cells develop receptors and bind luteinizing hormone, and in response secrete large amounts of the hormone androstenedione, an androgen hormone.
Similarly, granulosa cells develop receptors and bind follicle stimulating hormone, and in response produce the enzyme aromatase.
Aromatase converts androstenedione from the theca cells into 17β-estradiol, which is a member of the estrogen family.
During days 10 through 14 of this phase, granulosa cells also begin to develop luteinizing hormone receptors, in addition to the follicle stimulating hormone receptors they already have.
As the follicles grow and estrogen is released into the bloodstream, increased estrogen levels act as a negative feedback signal, telling the pituitary to secrete less follicle stimulating hormone.
As a result of decreased follicle stimulating hormone production, some of the developing follicles in the ovary will stop growing, regress and die off.
The follicle that has the most follicle stimulating hormone receptors, however, will continue to grow, becoming the dominant follicle that will eventually undergo ovulation.
This dominant follicle continues to secrete estrogen, and the rising estrogen levels make the pituitary more responsive to the pulsatile action of gonadotropin-releasing hormone from the hypothalamus.
As blood estrogen levels start to steadily climb higher and higher, the estrogen from the dominant follicle now becomes a positive feedback signal – that is, it makes the pituitary secrete a whole lot of follicle stimulating hormone and luteinizing hormone in response to gonadotropin-releasing hormone.
This surge of follicle stimulating hormone and luteinizing hormone usually happens a day or two before ovulation and is responsible for stimulating the rupture of the ovarian follicle and the release of the oocyte.
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