Week 5 - PCOS Flashcards
What are the 3 most common symptoms seen in the clinical presentation of PCOS?
hirsutism (90%)
menstrual irregularity - with anovulation (90%)
infertility (75%)
define hirsutism
Hirsutism is the excessive hairiness on women in those parts of the body where terminal hair does not normally occur or is minimal — for example, a beard or chest hair. It refers to a male pattern of body hair (androgenic hair) and it is therefore primarily of cosmetic and psychological concern.
Clinical presentation of PCOS?
Obesity in 40-50% of women acne, oily skin clitoral hypertrophy polycystic or enlarged ovaries Glucose intolerance Acanthosis nigricans
Why is PCOS acne unique?
PCOS-related acne tends to flare in areas that are usually considered “hormonally sensitive,” especially the lower third of the face. This includes your cheeks, jawline, chin, and upper neck.
“Patients with PCOS tend to get acne that involves more tender knots under the skin, rather than fine surface bumps, and will sometimes report that lesions in that area tend to flare before their menstrual period,” Schlosser says. “They take time to go away.”
Define acanthosis nigricans
grey-brown, velvety discolouration of skin
usually at Neck, groin and axilla
associated with diabetes
prevalence of PCOS?
3-10% of reproductive age women
- one of the m/c endocrine disorders in women
- most frequent cause of anovulatory infertility
- spans menarche to menopause
Hyper secretion of which hormone is a key feature?
LH (increased LH/FSH ratio)
What is the consequence of increased LH?
- increase in LH leads to higher ovarian androgen production and arrests follicular development
- leads to multiple cysts on the ovaries (immature follicles), mostly without ovulation
Lack of ovulation exposes endometrium to unopposed ________, which can result in endometrial hyperplasia
Lack of ovulation exposes endometrium to unopposed estrogen, which can result in endometrial hyperplasia
potential sequelae / associated conditions
Type II Diabetes mellitus Obesity Dyslipidemia Endometrial hyperplasia and cancer Infertility Hypertension Sleep apnea Gestational diabetes Pregnancy induced hypertension Autoimmune thyroid conditions Raised liver enzymes (30%) Non-alcoholic liver disease Better bone density (YAY!) Cardiovascular disease ***
Etiology & Risk Factors
Cause is unknown
A genetic link likely exists
Not all women with PCOS are overweight/obese
Lean women with PCOS also have insulin resistance
What is the link between PCOS & insulin
Women with PCOS have what is called insulin resistance. This means that cells in the body are resistant to the effect of a normal level of insulin. More insulin is then produced to keep the blood sugar normal. This raised level of insulin in the bloodstream is thought to be the main underlying reason why PCOS develops. It causes the ovaries to make too much testosterone. A high level of insulin and testosterone interfere with the normal development of follicles in the ovaries. As a result, many follicles tend to develop but often do not develop fully. This causes problems with ovulation - hence, period problems and reduced fertility.
It is this increased testosterone level in the blood that causes excess hair growth on the body and thinning of the scalp hair.
Dx criteria
Diagnosis made with 2 of 3 criteria:
1. Oligo/anovulation
2. clinical and/or biochemical hyperandrogenism
3. Polycystic ovaries on transvaginal US where possible
AND exclusion of other causes (pituitary or adrenal disease)
DDXs?
Late onset congenital adrenal hyperplasia
primary or secondary amenorrhea (due to other causes)
Pregnancy
Thyroid dysfunction
Pituitary dysfunction (including hyper-prolactinemia)
Androgen-secreting tumours of ovary, adrenals
Cushings syndrome
Idiopathic hirsutism
Exogenous androgen administration
Work-up
Plasma LH/FSH ratio (ideally day 3). 3:1 ratio is indicative of the syndrome (but not diagnostic), but if negative, does not rule it out. Can fluctuate wildly.
Plasma testosterone (or free androgen index)
Plasma prolactin
TSH
Fasting blood glucose or glucose tolerance test
Pelvic ultrasound
Diagnostic tests
DHEA-S to rule out other androgen secreting tumour
17-hydroxyprogesterone – nonclassic congenital adrenal hyperplasia
Fasting lipid panel
ALT/AST as needed to rule out hepatic steatosis if indicated
Why test 17-OH-progesterone?
17-hydroxyprogesterone (17OH-progesterone) is a useful screen for late-onset congenital adrenal hyperplasia (LOCAD).
Congenital adrenal hyperplasia, also known as CAH, is an inherited disorder affecting the hormones secreted (produced) by the adrenal glands. Approximately 1 in 12,000 infants is affected by CAH.
Any of several autosomal recessive diseases resulting from mutations of genes for enzymes mediating the biochemical steps of production of cortisol from cholesterol by the adrenal glands (steroidogenesis).
Most of these conditions involve excessive or deficient production of sex steroids and can alter development of primary or secondary sex characteristics in some affected infants, children, or adults
What are testosterone levels like in PCOS?
Free & Total T are elevated
What are levels of SHBG like in PCOS?
suppressed
Why test TSH & free T4?
to exclude hypothyroidism
Why test IGF-1? insulin-like growth factor 1
to exclude acromegaly
How do we use BBT (basal body temperature) in a naturopathic work up of PCOS?
see sustained rise between 0.2 C and 0.5 C in luteal due to thermogenic effects of a metabolite of progesterone in normal cycle
Non-invasive and relatively reliable if looking at the “big picture” vs. day to day temperatures
Involves the patient in their own care
Inexpensive but not definitive
Why is cervical mucus not an accurate picture of PCOS?
Cervical mucous may not be accurate with PCOS:
Ovulatory mucous changes may be present in the absence of ovulation
Due to surges in estrogen that may not result in ovulation
Summarize the classic PCOS presentation
Raised levels of androgens, estrogens (unopposed by progesterone), insulin and LH explain the classic PCOS presentation of anovulation or dysfunctional uterine bleeding, hirsutism, and dysfunction of glucose metabolism
Treatment strategies - if fertility not currently desired
- weight loss if obese & tx of DMII if present
- diet & exercise
IF FERTILITY NOT CURRENTLY DESIRED:
- OC to ‘tx’ anovulation, improve hirsutism, protect endometrium
- progesterone only - if combined OC contraindicated
- cyclical progesterone in luteal phase to cause menstruation
- glucocorticoids to tx hirsutism (anti-androgenic properties)
- spironolactone - antiandrogenic
Treatment strategies - if fertility is currently desired
- weight loss if obese & tx of DMII if present
- diet & exercise
IF FERTILITY IS CURRENTLY DESIRED:
- Patient is usually referred to a reproductive endocrinologist/gynecologist specializing in fertility
- Clomiphene citrate (aka Clomid) - first line treatment in PCOS to induce ovulation/conception
- FSH injections may be given with Clomid to stimulate ovulation
- Metformin to improve fertility via improving insulin resistance
- Ovarian wedge resection or ovarian drilling
What is the relevance of long-standing amenorrhea to PCOS?
- can cause unopposed estrogen
- can lead to endometrial hyperplasia
- if a woman has amenorrhea for more than 3 months she should be monitored closely
- menses should be medically induced to decrease risk of endometrial hyperplasia
How is menses induced?
progesterone-like drugs
“progesterone challenge”
If TSH and prolactin levels are normal, a progestogen challenge test can help evaluate for a patent outflow tract and detect endogenous estrogen that is affecting the endometrium. A withdrawal bleed usually occurs two to seven days after the challenge test. A negative progestogen challenge test signifies an outflow tract abnormality or inadequate estrogenization. An estrogen/progestogen challenge test can differentiate the two diagnoses.
Phytotherapy for PCOS
- cimicifuga racemosa (black cohosh)
- vitex agnus-castus
- humulus lupulus
- tribulus terrestris
- mentha spicata
- glycerrhiza glabra & peaonia lactiflora
- serenoa repens
- maitake mushroom
Herbs/foods that increase SHBG (& decrease free T)
- nettle root
- green tea
- soy
- flaxseed
Nutritional therapy for PCOS
- the “fertility diet” - for anovulation-related infertility; based on Nurses Health Study results
- low Glycemic Index diet
- hunter-gatherer diet / paleo diet
- dairy-free diet
What comprises the fertility diet?
- healthy oils
- complex carbs (whole grains, rice, quinoa, fruits & veggies)
- beans
- nuts
- moderate amount full fat dairy
- foods high in iron
- lots of vegetables - should make up half the plate
- protein from plant sources vs animal sources
AVOID:
- caffeine
- alcohol
- simple carbs (potatoes, bread, sugars)
- low fat dairy foods
- fish that contains mercury
- avoid low carb/high protein diets (focus on high plant foods)
- trans-fatty acids
- consume moderate amounts of beef, chicken, turkey
Optimal BMI of 21
Describe the glycemic index diet
Glycemic index (GI) describes how quickly sugar from a particular food enters the bloodstream i.e., it refers to its quality. The higher the GI, the faster the rate of sugar’s entry into the blood. Why is this important? Large rises in blood sugar increase the demand for insulin. If we can decrease the amount of high GI foods in the diet, we can help manage the insulin response and therefore decrease its demand in addition to managing blood sugar levels.
The aim is to keep total glycemic load for the day under 150 and fibre at 35 g/day
GI: low=1-55 mid=56-69 High=70-100
Foods to avoid entirely:
Refined white flour products: pastas, cakes, muffins, pretzels etc…
Refined sugar loaded cereals, candies, baked goods etc….
Processed foods packed with empty calories (sugar and fat) or salt (soups, microwave/theater popcorn, chips etc…)
Margarine, butter and shortening
Smoked or cured meats: bacon, hot dogs, smoked luncheon meats, sausages, ham, SPAM etc…
Heavily sweetened or artificially sweetened soft drinks, kool-aid, juice flavored drinks etc…
Fried foods, including French fries, potato chips, corn chips, doughnuts etc….
Various foods assigned a value.
Lifestyle modification for PCOS?
Exercise!
Increase BMR & lean muscle mass
Considered first-line treatment in PCOS!
Recommend both aerobic, high intensity & weight-bearing, but mostly something enjoyable that the patient is willing to do.
Weight loss of even 5-10% can restore ovulation.
Why almonds & walnuts in PCOS?
- almonds: MUFA-rich
- walnuts: PUFA-rich
Randomized (n=31) 31 g fat/d X 6 weeks – either walnuts (~1/3 cup) or almonds (~1/2 cup)
Walnut intake resulted in - Reduced androgen levels by increasing SHBG
- Improved insulin sensitivity and decreased HbA1C
- Reduced LDL and apoprotein B
- Increased n-3/n-6 PUFA ratio
Almond intake resulted in - Reduced free androgen index
Eur J Clin Nutr. 2011 Mar;65(3):386-93. doi: 10.1038/ejcn.2010.266. Epub 2010 Dec 15.
Why fish oil in PCOS?
- Several studies have shown beneficial effects of fish oil in women with PCOS
- Decrease in BMI and hirsutism score, and insulin sensitivity increased, improved lipid profile, decreased androgen levels
- Doses ranged from 1000mg - 1500mg
Why resveratrol in PCOS?
- early stages of research in PCOS
- rat studies show that ovarian tissue less prone to effects of insulin on the tissue
- allows normal apoptosis of tissue to occur
- resveratrol needs to be in liquid/encapsulated format to be adequately absorbed
Why chromium in PCOS?
improve insulin resistance patterns though not ovulation in women with PCOS
Why vitamin D in PCOS?
- may improve insulin secretion & lipid parameters in obese women with PCOS
- in women with PCOS –> low serum 25-OH-Vit-D levels are associated with obesity, metabolic and endocrine disturbances, & supplementation may improve menstrual frequency
Why N-acetylcysteine (NAC) in PCOS?
- been shown to increase circulating insulin levels
- increases SHBG
- improves menstrual regularity
- 600 mg tid
