MudPhud20XX

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I am still having trouble understanding PCOS. I get that you have high estrogen due to fat cells making estrogen, then why would you still get high LH and FSH?

Also, why would using clomiphene work since it will still result in increased LH and FSH by blocking estrogen at hypothalamus.

Many thanks in advance.
 

solitarius

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Yeah, well PCOS is a situation where the LH/FSH ratio is too high.

So either FSH is high but LH is higher or FSH is low but LH high. Anyway, Sattar says that estrone operates on the pituitary to suppress FSH. And Sattar is The Man.
 
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Yeah, well PCOS is a situation where the LH/FSH ratio is too high.

So either FSH is high but LH is higher or FSH is low but LH high. Anyway, Sattar says that estrone operates on the pituitary to suppress FSH. And Sattar is The Man.
It can't be fsh is higher. To diagnose it you need LH:FSH >2 if I remember correctly
 

solitarius

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It can't be fsh is higher. To diagnose it you need LH:FSH >2 if I remember correctly
My understanding of PCOS is that it's a high LH/FSH ratio that is exacerbated (i.e., somewhat positive reinforcement) over time with more LH and less FSH.

I didn't mean to imply that FSH is shut off completely.
 
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Patau

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Biggest thing to remember about PCOS is that is a variable disease. During my step prep, I have noticed you need to be able to recognize the classic presentation, pathophysio and pharm.

PCOS is hyperandrogenism because of theca cells that over-secrete testosterone. Theca cells are the ones that secrete testosterone in the presence of LH. So why is LH is high? Shouldn't it be low because of negative feedback? The hypothalamic pituitary axis is dysfunctional in PCOS, thus the high LH.
How is the HPA dysfunctional?

Next thing you need to understand is how insulin/testosterone works on SHBG (steroid hormone-binding globulin). Insulin and testosterone decrease SHBG (for completion sake estrogen increases SHBG). We have high testosterone from the dysfunctional theca cells so we have decreased our SHBG. When SHBG is decreased we get increased testosterone which leads to hirsutism and acne. This is the reason why we give OCPs (instead of say spironolactone for antiandrogens) as a first line treatment to target hirsutism and acne because the increased estrogen causes increased SHBG decreased LH and decreased testosterone. Also the high insulin is what we believe to cause diabetes in these patients (give metformin).

Okay now what about FSH? Remember this is a variable disease so you can have high estrogen or low estrogen.
When LH is high you get increased testosterone which can be converted to estrogen through aromatase. The high extraglandular estrogens (mainly estrone) selectively supresses FSH. Elevated androgen production during the follicular phase of the menstrual cycle results in the formation of several immature cystic follicles, but with low FSH, estrogen production by the ovaries is low, and the follicles cannot continue development.

Clomiphene citrate does increase the LH, FSH by blocking estrogen at the hypothalamus like you stated OP, so because we have anovulation in PCOS the increase in FSH particularly will help mature the follicles so that they can continue to develop.
 

worldbeater

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LH and FSH are increased, due to lack of feedback inhibition of progesterone and estrogen.

Progesterone and estrogen are decreased, which causes the lack of feedback inhibition to their corresponding LH and FSH, cause those values to rise.
 
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Phloston

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I am still having trouble understanding PCOS. I get that you have high estrogen due to fat cells making estrogen, then why would you still get high LH and FSH?

Also, why would using clomiphene work since it will still result in increased LH and FSH by blocking estrogen at hypothalamus.

Many thanks in advance.
PCOS is due to GnRH dysregulation secondary to insulin resistance. That's why obesity is the biggest risk factor. When an obese woman with PCOS drops the weight, the problem often goes away.

Insulin resistance --> altered GnRH pulsation --> increased LH/FSH ratio --> LH spike occurs (high LH) before follicles are adequately matured (low FSH) --> anovulation + cysts

If you see this as an arrow-question on the USMLE, LH is up and FSH is down.

If you start getting into the specifics of how estrogen and testosterone feedback impact the LH/FSH you're overthinking it. The hormonal problem starts with GnRH dysregulation due to insulin resistance, so whilst estrogen + testosterone still exert negative feedback, the normal effect is disrupted.

From UpToDate:

"The serum concentration of follicle stimulating hormone (FSH) may be normal or low in PCOS, leading to an elevated LH/FSH ratio compared with normally cycling, early follicular phase young control women. However, neither an elevated serum LH concentration nor an increased LH/FSH ratio is part of the diagnostic criteria for PCOS. (See "Diagnosis of polycystic ovary syndrome in adults".)"