How can Cushing's disease cause both hirsutism and reduced libido?

[Polycherry]

Cushing's disease is a condition where there is increased ACTH production due to an underlying pituitary adenoma.

Hirsutism is the abnormal growth of facial hair, generally referring to the growth of facial hair in a woman. Hirsutism can happen in Cushing's disease because the increased ACTH leads to a generalized increased production of hormones from the adrenal cortex and this includes the sex corticoids.

But surprisingly and counterintuitively, there's also a decreased libido in these patients. Shouldn't an increase in sex corticoids well, increase the libido? I found an explanation online saying -

Cushing's disease (pituitary adenoma) -> inc ACTH -> increase all hormones from adrenal cortex -> increased testosterone in blood -> negative feedback inhibition to hypothalamus -> decreased synthesis and release of GNRH ->

1. decreased FSH -> deceased stimulation of sertoli cells -> no maintenence of sperm cells.
2. decreased LH --> decreased testosterone in the testis --> no gametogenesis and no libido

Well, this too makes sense. But only when seen separately. How can the cause of one symptom of the disease be due to the direct effect of increased levels the hormone while the other due to reduced levels of it due to stimulation of negative feedback?

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[navigator]

I'm confused by this as well. My understanding is that the hypercortisolemia negatively feeds back on GnRH release and causes both oligomenorrhea and reduced libido from resulting decrease in estrogen release. But if that's the case, why would we see hirsutism at all?

 

[navigator]

Nvm. I found the answer to this on UpToDate. The oligomenorrhea and reduced libido are from negative feedback of cortisol on GnRH.

Occasionally, if there are signs of hirsutism, this is from an adrenal carcinoma origin. This is bc the tumors secrete large amounts of cholesterol and are inefficient at converting cholesterol to cortisol. Also, adrenals are major source of androgens in women. Androgen excess would cause hirsutism, acne, virilization, and increased libido.

We wouldn't see hirsutism in Cushing's caused by adrenal adenomas.