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Amenorrhea: Pathology Review

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Pathology

Reproductive system

Male and female reproductive system disorders
Male reproductive system disorders
Female reproductive system disorders
Reproductive system pathology review

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Amenorrhea: Pathology Review

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USMLE® Step 1 style questions USMLE

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A 35-year-old woman comes to the office with complaints of irregular menstruation. She has had only two periods in the last year. Menarche was at age 12, and she had a regular menstrual cycle until 12 months ago. The patient also reports feeling flushed at night without provocation and experiencing occasional dyspareunia with post-coital spotting. Past medical history is noncontributory. Temperature is 36.9°C (98.5°F), pulse is 70/min, respirations are 13/min, and blood pressure is 118/76 mmHg. Cardiopulmonary and abdominal exams are unremarkable. The patient has Tanner stage V breasts and pubic hair. Pelvic examination reveals a small anteverted uterus and minimal vaginal rugations. Abdominal examination is within normal limits. Urine pregnancy test is negative. Serum TSH is 3.2 µU/mL. Which of the following set of hormonal changes will most likely be observed in this patient?

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Transcript

Content Reviewers:

Antonella Melani, MD

Two people come to the clinic one day. First you see Ana, a 17 year old teenage girl. Ana comes with her mother, who’s worried because Ana hasn’t had her first period yet.

Upon physical examination, you notice that Ana is quite short for her age. In addition, she has a wide neck, broad chest, and poorly developed breasts with widely spaced nipples. You decide to perform a blood test, which reveals low estrogen levels and high FSH and LH.

Next, comes María, a 25 year old female who’s concerned because she hasn’t had her period for nine months now.

She’s sexually active, so the first thing you do is ask for a pregnancy test, which comes up negative.

When asked about physical activities, she refers to going for a 2-hour run every single day, plus swimming and then tennis on weekdays.

Regarding her diet, she’s very strict when it comes to avoiding fatty foods. On physical examination, you realize that María is underweight, and a blood test reveals low levels of estrogen, LH, and FSH.

Okay, now both Ana and María have amenorrhea, which is generally defined as the absence of menstruation in females of reproductive age.

Now, for menstruation to happen, an individual must have a regular female reproductive anatomy and sexual development, which is normally under control of the hypothalamic-pituitary-gonadal axis.

First, the hypothalamus secretes gonadotropin-releasing hormone, or GnRH for short, which goes to the anterior pituitary to stimulate the release of gonadotropic hormones, which are luteinizing hormone or LH, and follicle-stimulating hormone or FSH.

LH and FSH then stimulate the gonads to produce sex hormones; in females, LH and FSH stimulate the ovaries to secrete estrogen and progesterone, which are responsible for the female primary sexual characteristics.

These are the changes necessary for reproduction, including menstruation, ovulation, and uterine development.

LH and FSH are also responsible for the development of secondary sex characteristics that aren’t required for reproduction, like breast development, hip widening, and hair growth mainly on the axillae and genital areas.

Now, once sex hormones have done their job, they signal the hypothalamus and pituitary to turn off the secretion of GnRH, FSH, and LH.

Menarche, which refers to the first menstrual period, occurs during early adolescence or puberty, usually by the age of 15.

Following menarche, the menstrual cycle recurs on a monthly basis until a person reaches menopause, pausing only during pregnancy.

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.

During the menstrual cycle, the ovaries and the endometrium each undergo their own set of changes, which are separate but related.

Now, the first two weeks of the menstrual cycle is called the preovulatory or follicular phase, and this corresponds to the menstrual and proliferative phases of the endometrium.

During this phase, the pituitary mainly secretes FSH, which stimulates follicles scattered throughout the ovaries to start developing and secreting estrogen.

The increased estrogen levels act as a negative feedback signal, telling the pituitary to secrete less FSH. As a result, some of the developing follicles in the ovary will regress and die off.

However, the follicle that has the most follicle stimulating hormone receptors, will continue to grow, becoming the dominant follicle that will eventually undergo ovulation.

Now, 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 FSH and especially LH.

This surge stimulates ovulation, which is the rupture of the dominant follicle to release the oocyte, so the secretion of estrogen decreases.

Meanwhile, the uterus is preparing the endometrium for implantation and maintenance of pregnancy.

This process begins with the menstrual phase, which is when the old endometrial lining from the previous cycle is shed and eliminated through the vagina, producing the bleeding pattern known as the menstrual period.

The menstrual phase is followed by the proliferative phase, during which high estrogen levels stimulate thickening of the endometrium, as well as emergence of spiral arteries to feed the growing functional endometrium.

Following ovulation, the remnant of the ovarian follicle becomes the corpus luteum. So the two weeks following ovulation is referred to as the postovulatory or luteal phase.

This corresponds to the secretory phase of the endometrium, where the uterine glands begin to secrete more mucus.

Now, the corpus luteum secretes estrogen, which rises again, as well as lots of progesterone, which acts as a negative feedback signal on the pituitary, decreasing release of FSH and LH.

Over time, the corpus luteum gradually degenerates into the nonfunctional corpus albicans.

The corpus albicans doesn’t make hormones, so estrogen and progesterone levels slowly decrease.

When progesterone reaches its lowest level, the spiral arteries collapse, and the endometrium prepares to shed through menstruation.

This shedding marks the beginning of a new menstrual cycle and another opportunity for fertilization. Okay now, amenorrhea can be classified as primary or secondary.

Primary amenorrhea is when a female over the age of 15 hasn’t had her first menstruation, or menarche, despite normal growth and development of secondary sexual characteristics; or when a female over the age of 13 has neither had her menarche nor developed any secondary sexual characteristics.

For your exams, some high yield causes of primary amenorrhea include Turner syndrome, müllerian agenesis, and imperforate hymen.

On the other hand, secondary amenorrhea is when a female who used to have regular menstrual cycles stops having them for at least three consecutive months, or for six months in a female who used to have irregular menstrual cycles.

Most often, secondary amenorrhea is caused by natural processes, such as pregnancy, menopause, and breastfeeding.

However, in some cases, secondary amenorrhea can be caused by an underlying disorder.

For your exams, the most important is a hormonal imbalance at any level of the hypothalamic-pituitary-ovarian axis, such as functional hypothalamic amenorrhea; hyperprolactinemia; and polycystic ovarian syndrome or premature ovarian failure.

Other less frequently tested hormonal disorders that may cause secondary amenorrhea include Cushing syndrome, which is an endocrine disorder that involves high levels of cortisol; as well as thyroid disorders like hyperthyroidism, where the thyroid gland produces too much thyroid hormones, or