Role of insulin in of lean women w/ PCOS and NORMAL insulin sensitivity

KatCarney · 09-15-2007, 03:28 PM

Fertil Steril. 2007 Jun 6

Role of insulin in the hyperandrogenemia of lean women with polycystic ovary syndrome and normal insulin sensitivity.

Baillargeon JP, Carpentier A.
Department of Medicine, Division of Endocrinology, Université de Sherbrooke, Sherbrooke, Quebec, Canada.

OBJECTIVE: To determine the effect of reducing insulin secretion on hyperandrogenemia in lean normoinsulinemic women with polycystic ovary syndrome (PCOS) and normal metabolic insulin sensitivity.

CONCLUSION(S): In women with typical PCOS and normal insulin levels and metabolic insulin sensitivity, reducing insulin secretion significantly decreased androgen and increased SHBG levels. These results suggest that insulin contributes to hyperandrogenemia even in PCOS women with normal metabolic insulin sensitivity, which might be due to increased sensitivity of their androgenic insulin pathway.

DESIGN: Transversal assessment at baseline and prospective follow-up of lean PCOS group after 8 days of diazoxide, which reduces insulin secretion, and 1 month of leuprolide, which suppresses LH.

SETTING: Clinical research center of an academic hospital.

PATIENT(S): Nine lean women (body mass index </=25 kg/m(2)) with PCOS and normal insulin levels, as well as 17 lean healthy women.

INTERVENTION(S): Lean PCOS women were reassessed after 8 days of diazoxide and after 1 month of leuprolide, which suppresses LH.

MAIN OUTCOME MEASURE(S): Androgen levels and insulin-stimulated glucose disposal (metabolic insulin sensitivity), determined by euglycemic-hyperinsulinemic clamp (M-value).

RESULT(S): Mean M-value of lean PCOS women (48.5 mumol/kg.min) was similar to lean control subjects (52.9 mumol/kg.min). They also had comparable anthropometric measures, lipids, fibrinogen, and plasminogen activator inhibitor 1. The LH did not change significantly after diazoxide, but was almost suppressed after leuprolide in the PCOS group. Androstenedione decreased significantly after diazoxide and even more after leuprolide. However, free T significantly decreased only after diazoxide in lean PCOS women. Diazoxide also increased SHBG significantly in this group.

TrishainAZ · 09-15-2007, 05:37 PM

What does that mean in English?

KatCarney · 09-15-2007, 08:22 PM

This part sums it up: These results suggest that insulin contributes to hyperandrogenemia even in PCOS women with normal metabolic insulin sensitivity, which might be due to increased sensitivity of their androgenic insulin pathway.

hsuter · 09-15-2007, 08:33 PM

I'm still confused...

TrishainAZ · 09-15-2007, 08:43 PM

I know... the sad part is that I actually have my degree in physiology and I still don't get much of it!

KatCarney · 09-15-2007, 09:48 PM

Androgen: A male sex hormone that promotes the development and maintenance of the male sex characteristics. The major androgen is testosterone.

Androgenic: Pertaining to the development of male characteristics, including body hair, the genital organs and muscle mass. "Androgenic" is the adjective form of the noun "androgen," a word referring to any of the male hormones, including testosterone and androsterone.

Hyperandrogenemia = Androgen Excess

PCOS is the most common cause of androgen excess(or hyperandrogemia) in women. (see source below)

To restate the conclusion from the study above: These results suggest that insulin contributes to ANDROGEN EXCESS even in PCOS women with normal metabolic insulin sensitivity, which might be due to increased sensitivity of their androgenic insulin pathway.

So even though some women with PCOS have normal insulin sensitivity, the insulin they DO have - even at normal levels - might STILL contribute to androgen excess possibly because the androgenic insulin pathways are more sensitive (for some reason).

Quote:

Source: http://www.emedicine.com/med/topic3489.htm

In polycystic ovarian syndrome (PCOS), the most common cause of androgen excess and hirsutism, the ovarian theca cells increase their ovarian androgen production under the stimulatory activity of the raised LH levels.

Hyperinsulinemia due to peripheral insulin resistance is often present in those women and it promotes hyperandrogenemia through the binding of insulin to the IGF-1 receptor. Insulin mimics the action of IGF-1, which augments androgen production by the theca cell in response to LH. Since insulin decreases levels of SHBG, the circulating levels of free testosterone are also increased. Most of those patients are infertile due to anovulation as the increased LH activity causes a defective granulosa cells' aromatization of androgens to estrogens and results in reduced estrogen levels. Spontaneous miscarriages also increase.

Obesity and hyperinsulinemia often present in patients with PCOS can cause abnormal lipid metabolism that can lead to atherosclerosis and a predisposition to coronary artery disease.

refrain02 · 09-15-2007, 09:59 PM

Basically...
There are two groups:
1) Thin PCOS women that don't have insulin resistance
2) Thin "normal" women, also without insulin resistance

They gave them two drugs in combination.
The first drug Diazoxide, reduces insulin secretion
The second drug Leuprolide, decreases LH and FSH levels

Conclusion
Mean M-value of lean PCOS women (48.5 mumol/kg.min) was similar to lean control subjects (52.9 mumol/kg.min).
M-value is the deviation from normal glucose in the blood. So they are saying that the drugs did not change the blood glucose levels of the women

They also had comparable anthropometric measures, lipids, fibrinogen, and plasminogen activator inhibitor 1.
Both groups did not have a change in Body Fat, liver function was good and equal, and no problems with inflammation

The LH did not change significantly after diazoxide, but was almost suppressed after leuprolide in the PCOS group.
In the thin-PCOS women group. The LH levels did not change with the insulin decreasing drug, but insulin levels were almost nothing after the LH/FSH inhibitor was used

Androstenedione decreased significantly after diazoxide and even more after leuprolide.
Androstenedione (the precursor to Testosterone) levels also decreased after the insulin drug, but decreased even more with the LH/FSH drug (which I think would be expected because without FSH, you aren't getting follicle production...and therefore no cysts...and therefore not androgen increase from the cysts)

However, free T significantly decreased only after diazoxide in lean PCOS women. Diazoxide also increased SHBG significantly in this group.
Free testeosterone (not bound to proteins and able to bind to androgen receptors on cells) also decreased after the insulin decreasing drug was given to the PCOS women.
Also SHBG (a protein that binds almost all testosterone (leaving the unbound as free T) increased...which is a good thing because when testosterone is bound to SHBG, it can't enter cells. Therefore your "male characteristics" should decrease because the SHBG is binding up the left over testosterone.

Conclusion...by giving thin PCOS women that are not insulin resistant this combo of drugs, it reduces their PCOS symptoms even though one of the drugs decreases insulin. Because it decreases FSH, it should also reduce cyst formation etc....
But, these drugs are definitely not for women who are TTC. We need that FSH!!!!!

Hope that helped

KatCarney · 09-15-2007, 10:06 PM

Quote:

Originally Posted by refrain02

Hope that helped

Whoo, hooo! that was GOOOOOOOD!

hsuter · 09-15-2007, 10:55 PM

That did help...thanks!

refrain02 · 09-16-2007, 12:58 AM

Ha thanks...its basically my job to read research articles all day to understand them and apply them to my own research. It's just nice to read something that is not about cancer sometimes

sheepiegirl · 09-17-2007, 01:11 PM

Thanks refrain, that was awesome.

Thanks Kat for the article.