PCOS Flashcards
1
Q
PCOS intro
A
- arguably the most prevalent medical condition in women
- PCOs are present in 32% pts with amen. & 87% of pts with hirsutism & regular cycles
- Presents in 22% of population with self-defined ‘normal’cycles
- Prevalence = approx 5-10%
- most common cause of anovulatory infertility (~73%)
2
Q
Explain symptomology & diagnosis of PCOS
A
- Pts with PCOS have multiple symptomatology; endocrinology, gynaecological, T2D, dermatological, eating disorder psychiatry
- Prev. diagnosed by post-mortems, c-section & abdominal surgery
- Presents as a spectrum diagnosed by elimination (e.g. CAH = excess androgens, thyroid disease=disrupted HPG, hyperprolactinaemia)
- Rotterdam Criteria now used to diagnose, requires the following:
- PCOs= either 12 or more folllicles measuring 2-9mm diameter and/or incr ovarian volume >10ml in either ovary & no DF >10mm -> diagnosed by US through all planes to ensure accurate follicle count (TVUS not always appropriate for cultural reasons/adolescents)
- Hyperandrogenism - clinical & biochemical evidence > assays not standardised across labs, normative data not clearly defined
- Ovulatory dysfunction - oligomenorrhoea or anovulation (confirm ovulation by measureing serum P4 levels at mid-luteal phase of cycle
3
Q
Difference between ovulatory/anvulatory follicles with regards to DF/IR
A
- Ovulatory PCOs still get DFs which developn and released irregularly
- Anovulatory PCOs remain in early follicular phase and higher insulin resistance than ovulatory PCOS
4
Q
PCOS genetics?
A
- PCOS thought to be a polygenic condition associated with a no. of gene mutations identified via GWAS (first identified in a group of Hans chinese women all with PCOS)
- Mutations in DENND1A & THADA1 linked to T2D & FSHR LHCGR and insulin receptor genes
- Familial aggregation > sisters more likely to be affected & 1st degree relatives have higher rates of metabolic abnormalities
- MZ twins are twice as likely to both have PCOS than DZ
- All obvious candidates ruled out but there is 2 hit hypothesis for PCOS. 1st hit = PCO, 2nd hit = PCOS
- IR is also familial -caused by a post-receptor binding defect, not a receptor gene mutation
5
Q
Consistant feature of gonadotrophin secretion in PCOS
A
- Big FSH:LH ratio (high mean LH/low mean FSH)
- Rapid GnRH freq from impared neg FB on the pulse generator - caused by reduced sensitivity to inhibitory action of P4 in the presence of oestradiol
- PCO causes very variable LH levels but the mean lies above the normal range > LH hypersecretion amplifies androgen prod by theca
6
Q
Insulin in nature/cause of PCOS symptoms
hyperandrogenism
Metabolic defet
A
-Insulin is a co-gonadotrop with LH in the theca so stimulates androgen prod - resukts in hyperandrogenemia
-Metabolic defects –> IR aka prediabetes –> more insulin req to control glucose levels as glucose uptake is ineffective
-Hyperinsulinemia is an important factor in maintaining hyperandrogenemia actind directly to induce excess androgen prod by theca cells
-Also as a co-gonadotroph, augmenting effect of incr LH stimulus seen in majority of women with PCOS
-
7
Q
Does elevated insulin exert other actions ?
A
- The elevated insulin is implicated in central actiond of androgens in impairing P4 inhibition of the GnRH pulse generator
- In vitro, insulin increased mRNAs for adrenal steroidogenic enzymes and acutely enhanced adrenal secretory responses to ACTH
8
Q
Mechanisms behind IR?
explain Insulin defect
A
- Mechanisms underlying IR are not completely understood but seem to be different than other IR states e.g. DM2 & are considered to be unique & intrinsic features of PCOS
- Defect in insulin actions in PCOs women appears to be selective, affecting metabolic but not mitogenic actions incl glucose metabolism but not cell growth
9
Q
Explain what happens to Insulin under physiological conditions (receptor etc)
A
- In normal physiological conditions the binding of insulin to the cell surface receptors give rise to a long cascade of molecular alterations that lead to signal transduction & result in initiation of its actions in target tissues
- Insulin action is mediated through a protein tyrosine kinase receptor
- B subunit of insulin receptor contains a tyrosine kinase whose activity is enhanced via auto-phosphorykation of the tyrosine residues and inhibited by serine phosphorylation
10
Q
IR and future prognosis?
A
- IR likely to have a lifelong impact on the patient
- Pts become more insulin resistant as weight increases (linear); insulin sensitivity declines at a faster rate with PCOS women (exponential)
11
Q
IR and what symptoms does it cause
A
- IR linked to anovulation
- Incr insulinaemia from IR acts at dermis to induce acanthosis nigricans (dark, thick skin patches/skin tags on face/neck/underarms/thighs)
- PCOS= central adiposity linked to IR
12
Q
PCOS link with weight & energy expenditure
A
- 30-35% pts with PCOS are overweight or obese
- Normal weight PCOS pts have a reduced calorie diet
- PCO associated with reduced energy expenditure; equivalent to 1.9kg fat per year (17,000 calories)- survival advantage because fewer calories are required
- Reduced energy use is due to reduced post-prandial thermogenesis after eating: amplified in obesity
- results in incr incidence of GDM (maternal incr in glucose crosses placenta and incr foetal insulin levels ) > large for gestational age foetus
13
Q
PCOS & T2D
lipid profile
A
- PCOS pts have incr risk of T2D - 15% post-menopausal women with PCOS has T2D;
- 30-40% with PCOS have altered lipid profile > high cholesterol regardless of BMI; elevated triglycerides and low HDL
- High cortisol intermedia layer = predictor of stroke & MI
14
Q
SHBG basics
A
SHBG is reduce, most of T is bound to SHBG therefore in PCOS there is more free T
15
Q
IR treatment
A
- treat with diet and exercise to conceive; very calorie restricted diet - requires support & exercise
- Weight reduction = incr chance of spontaneous ovulation, reduced chance of miscarriage, doesnt req. drugs, reduced incidence of GDM, improves baby & long term pt outcome
- Orlistat > reduces uptake of fat from bowel to assist with weight loss
- Bariatric surgery - gastric band/bypass/sleeve
- Metformin
