Polycystic Ovarian Syndrome (PCOS) - Pathophysiology, Symptoms, Treatment

The topic today is polycystic ovarian syndrome. As a quick review, gonadotropin-releasing hormone, or GnRH, is released from the hypothalamus in a normal pulsatile fashion and then travels in the blood to the cells of the anterior pituitary to cause release of luteinizing hormone, or LH, and follicle-stimulating hormone, or FSH. LH and FSH then travel in the blood to the ovary to act on the theca and granulosa cells of the follicle, causing them to work together to produce mainly estrogen before ovulation during the follicular phase and mostly progesterone after ovulation during the luteal phase. Polycystic ovarian syndrome, abbreviated PCOS, occurs when follicles do not ovulate. Remember that progesterone from the cells of the ovary has a negative feedback effect on GnRH to reduce it and keep its frequency in the normal range, which in turn keeps LH and FSH at the correct ratios. PCOS occurs due to an increase in the normal pulsatile GnRH release from the hypothalamus. The increase in GnRH pulse frequency seen in PCOS occurs due to the lack of high progesterone during a luteal phase. If a follicle does not ovulate, a corpus luteum is not created, and without a corpus luteum, there is no surge in progesterone. Progesterone is a powerful inhibitor of GnRH, so lack of it leads to a higher pulse frequency seen in PCOS. This increased pulse frequency leads to an increase in the amount of LH over FSH since LH-secreting cells are more responsive to a faster pulse frequency of GnRH release. FSH is needed to help a follicle mature to the point that it can ovulate. With PCOS, LH is relatively higher and FSH is relatively lower. This lower FSH results in follicles not maturing enough to become a full functional Graafian follicle that can ovulate. The follicles that don't ovulate are the cysts that form on the ovary. With PCOS, multiple cysts on the ovary represent past failed follicular ovulation events and are characteristic of PCOS. Also, excessive LH levels stimulate the theca cells to produce higher amounts of androgens, which leads to other symptoms characteristic of PCOS. This hyperandrogenism causes hirsutism and acne. There is also menstrual irregularity due to hormone imbalances. Infertility occurs because there is no ovulation. Insulin also plays an important role in PCOS. It is released from the pancreas and can stimulate steroidogenesis in the theca cells of the ovary to increase androgen production. Insulin also increases steroidogenesis in the adrenal cortex to further increase androgens. When insulin increases steroidogenesis in these cells, the result is even more androgen release. The androgens can have a negative feedback effect on the hypothalamus and pituitary gland, making hormone imbalances even more complicated and ovulation even more difficult. Finally, androgens cause decreased sensitivity to insulin, which creates an environment where the body must secrete more insulin in order to compensate. This situation is often called insulin resistance. With insulin resistance, more insulin is released from the pancreas. This added insulin causes even more stimulation of theca cells to produce even more androgens. The whole process is one big vicious cycle. To summarize, GnRH of the hypothalamus is released in pulses, and without a progesterone surge in the luteal phase, GnRH pulse frequency increases. LH-secreting cells of the anterior pituitary are more sensitive to the higher GnRH pulse frequency, which leads to higher relative levels of LH and lower FSH levels. This increased LH stimulates the theca cells of the ovary to make more androgens. Elevated androgens cause hirsutism, acne, and increase insulin resistance. This increased insulin resistance causes insulin levels to rise further, which in turn increases the production of androgens, resulting in a positive feedback loop. The lower FSH levels don't allow the follicle to develop into a mature Graafian follicle that is capable of ovulating, so cysts form on the ovary. Without ovulation, the corpus luteum doesn't form, so there is no progesterone surge to suppress GnRH in the luteal phase. This causes the higher GnRH pulse frequency, and we are back to the beginning of the vicious cycle. So, you see, there is a kind of chicken or the egg paradox: what comes first, insulin resistance triggering the whole thing or excessive androgen production? It's not really known what the first trigger is. It is known that increased androgens and insulin resistance are found together in women with PCOS. Women with PCOS are also at increased risk for developing endometrial cancer due to prolonged estrogen exposure without a progesterone surge in the second half of the cycle. This increased androgen can also lead to endometrial hyperplasia. Combined progesterone-estrogen oral contraceptives are useful for PCOS because progesterone inhibits the high pulse frequency of GnRH and estrogen helps with the acne and hirsutism. Other treatments include weight loss and the anti-diabetic drug metformin, both of which bring down elevated insulin levels. The potassium-sparing drug spironolactone blocks androgen receptors, limiting the action of the androgens to cause acne and hirsutism. Now for some questions. Please pause the video and think of your answers. If you answered the following, you are correct: to be true, it needs to say that hirsutism is due to elevated androgens and those with PCOS ovulate less, not more. The main hormone of the follicular phase is estrogen, not progesterone. Spironolactone is the drug that blocks androgen receptors, and the anti-diabetic drug metformin improves insulin resistance. LH and FSH are released from the anterior pituitary, not the hypothalamus, and insulin will increase androgen production. Thanks for watching.

luteinizing hormone or LH and follicle stimulating hormone or FSH LH and FSH then travel in the blood to the ovary to act on the theal and granulosis cells of the follicle causing them to work together to produce mainly estrogen

before ovulation during the folicular phase and mostly progesterone after ovulation during the ludal phase polycystic ovarian syndrome abbreviated peos occurs when follicles do not ovulate remember that progesterone from the cells of the ovary has a negative Fe back effect on GnRH to reduce it and

keep its frequency in normal range which in turn keeps LH and FSH at the correct ratios PCOS occurs due to an increase in the normal pulsatile GNR release from the hypothalamus the increase in GNR pulse frequency seen in posos occurs due to

the lack of high progesterone during a ludal phase if a follicle does not ovulate a corpus ludum is not created and without a corpus ludum there is no surge in progesterone progesterone is a powerful inhibitor of GNR so lack of it leads to

a higher pulse frequency seen in peos this increased pulse frequency leads to an increase in the amount of LH over FSH since LH secreting cells are more responsive to a faster pulse frequency of GNR release FSH is needed to help a follicle

mature to the point that it can ovulate with posos LH is relatively higher and FSH is relatively lower this lower FSH results in follicles not maturing enough to become a full functional graphion follicle that can ovulate the follicles that don't ovulate are the

cysts that form on the ovary with posos multiple cysts on the ovary represent past failed folicular ovulation events and are characteristic of posos also excessive LH levels stimulate the theal cells to produce higher amounts of androgens which leads

to other symptoms characteristic of peos this hyperandrogenism causes heroism and acne there is also menstrual irregularity due to hormone imbalances infertility occurs because there is no ovulation insulin also plays an important role in posos it is released from the pancreas and can stimulate

steroidogenesis in the theal cells of the ovary to increase antigen production insulin also increases steroidogenesis in the adrenal cortex to further increased androgens when insulin increases steroidogenesis in these cells the result is even more Androgen release the androgens can have a negative

feedback effect on the hypothalamus in pituitary gland making hormone imbalances even more complicated and ovulation even more difficult finally androgens cause decreased sensitivity to insulin which creates an environment where the body must secrete more insulin in order to compensate this situation is

often called insulin resistance with insulin resistance more insulin is released from the pancreas this added insulin causes even more stimulation of theal cells to produce even more androgens the whole process is one big vicious cycle to summarize GNR of the

hypothalamus is released in pulses and without a progesterone surge in the ludal phase GNR pulse frequency increases LH secreting cells of the anterior pituitary are more sensitive to the higher GNR pulse frequency which leads to higher relative levels of LH

and lower FSH levels this increased LH stimulates the theal cells of the ovary to make more androgens elevated androgens cause hutis acne and increase insulin resistance this increased insulin resistance causes insulin levels to rise further which in turn increases the production of

antigens resulting in a positive feedback loop the lower FSH levels don't allow the follicle to develop into a mature graphine follicle that is capable of ovulating so cysts form on the ovary without ovulation the Corpus ludum doesn't form so there is no progesterone

surge to suppress GNR in the ludal phase this causes the higher GNR pulse frequency and we are back to the beginning of the Vicious Cycle so you see there is a kind of chicken or the egg Paradox what comes first insulin

resistance triggering the whole thing or excessive Androgen production it's not really known what the first trigger is it is known that increased androgens and insulin resistance are found together in women with posos women with Pacos are also at

increased risk for developing endometrial cancer due to prolonged estrogen exposure without progesterone surge in the second half of the cycle this increased antigen can also lead to endometrial hyperplasia combined progesterone estrogen oral contraceptives are useful for peos because progesterone inhibits

the high pulse frequency of GNR and estrogen helps with the acne in heroism other treatments include weight loss and the anti-diabetic drug metformin both of which bring down elevated insulin levels the potassium sparing drug spyon lactone blocks Androgen receptors

limiting the action of the androgens to cause acne in heroism now for some questions please pause the video and think of your answers if you answered the following you are correct to be true it need to say that

heroism is due to elevated androgens and those with peos ovulate less not more the main hormone of the folicular phase is estrogen not progesterone spironolactone is the drug that blocks Androgen receptors and the anti-diabetic drug me Forin improves

insulin resistance LH and FSH are released from the anterior pituitary not the hypothalamus and Insulin will increase Androgen production thanks for watching