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Premature ovarian failure

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Premature ovarian failure

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Premature ovarian failure

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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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Content Reviewers:

Rishi Desai, MD, MPH

Contributors:

In premature ovarian failure, which is also called primary ovarian insufficiency, the ovaries stop functioning normally, and this means that they stop ovulating, or releasing egg cells, and they also stop producing hormones, mainly estrogen and progesterone, and this all happens before a woman is 40 years old.

It’s considered a “primary” problem because the problem is with the ovaries themselves, rather than glands or hormones that act on the ovaries.

Normally, the hypothalamus, which is located at the base of the brain, secretes gonadotropin-releasing hormone, or GnRH.

GnRH makes the nearby pituitary gland secrete two hormones of its own, called gonadotropins.

These are follicle stimulating hormone, or FSH, and luteinizing hormone, or LH.These hormones travel to the follicles within the ovaries.

The follicles are small clusters of granulosa and theca cells that protect the developing egg cell.

FSH acts on the granulosa cells, making the follicles grow and mature, as well as secrete estrogen, while LH stimulates theca cells to secrete progesterone and small amounts of androstenedione, which is a precursor of testosterone.

All three of these hormones belong to a class of steroids, or lipid-soluble hormones.

At birth, a woman has millions of follicles, each ready and excited to do its job.

During puberty, the monthly menstrual and ovarian cycles begin, which is when the endometrium, or inner lining of the uterus, goes through cyclic changes in response to the ovarian hormones.

During the ovarian cycle, the ovarian hormones also help a handful of follicles to start growing.

Eventually, there’s ovulation which is when a single follicle fully matures and ruptures, releasing its egg cell, while the other follicles degenerate and die off.

Over time, many ovarian follicles degenerate, and the ones that remain become less and less sensitive to gonadotropin stimulation.

This goes on until menopause, when there are no remaining follicles responding to gonadotropins, and that causes menstruation and ovulation to cease entirely. In most women, this occurs between the ages of 40 and 60.

Now, in premature ovarian failure, the follicles stop responding to gonadotropin stimulation earlier than usual - that being before the age of 40.

In the majority of cases, there’s no clear cause. In some cases, it’s linked to chromosomal abnormalities like Turner syndrome, where an X chromosome is missing.

Other times it can be a gene mutations, like BRCA1, or in a syndrome like Fragile X syndrome, which is caused by the expansion of a trinucleotide repeat within a gene on the X chromosome.

In other cases, the ovaries can get harmed by chemo- or radiotherapy, or by autoimmune destruction, where the immune system goes rogue and attacks the ovaries.

There are two proposed mechanisms that could explain how premature ovarian failure develops. The first mechanism is that there are few or no remaining follicles in the ovary, and this could be because the ovary started out with only a few or because a lot of them degenerated too quickly.

Summary

Premature ovarian failure (POF) is a condition in which a woman's ovaries stop functioning before age 40. This can lead to symptoms that mimic menopause, but some women with intermittent ovarian function are still able to spontaneously get pregnant. Some cases of POF are attributed to autoimmune disorders, others to genetic disorders such as Turner syndrome and Fragile X syndrome. Symptoms of POF can include irregular or absent menstrual periods, hot flashes, night sweats, vaginal dryness, and reduced fertility. Treatment involves the replacement of the hormones that the ovaries have stopped producing, especially estrogen and progesterone. For women who struggle with infertility, in-vitro fertilization can be used.

Sources
  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "Harrison's Endocrinology, 4E" McGraw-Hill Education / Medical (2016)
  6. "Premature ovarian insufficiency (POI) and autoimmunity-an update appraisal" Journal of Assisted Reproduction and Genetics (2019)
  7. "Primary ovarian insufficiency: a more accurate term for premature ovarian failure" Clinical Endocrinology (2008)