PolyCystic Ovary Syndrome

Question 1

are PCOS and endometriosis commonly comorbid?

Answer 1

yes!

Question 2

what are common markers of PCOS?

Answer 2

amenorrhea
hirsutism
obesity
infertility
ovarian enlargement
initiated by elevated LH, androgen or estrogen, resulting in abnormal gonadotropin release by pituitary gland.

Question 3

what is dysmenorrhea

Answer 3

painful menstruation, can occur before or during period.
pain is cramping in nature, can be felt in lower abdomen, back and thighs.
other symptoms include nausea, vomiting, headache, fatigue, diarrhea
can be primary (no underlying medical condition) or secondary (caused by medical condition) such as endometriosis or uterine fibroids
treatments include over the counter pain meds, hormonal BC, and other prescriptions

Question 4

what is an ovarian cyst?

Answer 4

most common type: functional cyst. they develop during menstrual cycle.
2 types:
- follicular: usually go away on their own in 1-3 months. form when an egg doesn’t release as expected, so follicle keeps growing
- corpus luteum cysts: these also usually go away on their own. form when follicle ruptures at ovulation. the follicle resets and then fluid builds up inside. they can enlarge and cause pain, bleed, or twist the ovary.
ovarian cysts can be related to endometriosis, or formed from the outer surface of the ovary (cystadenomas), or formed with non ovarian tissue (dermoid cysts)

Question 5

PCOS prevalence

Answer 5

most common in reproductive aged people, between 5-15% of people.
familial occurrence: PCOS tends to run in families.
study of 115 sisters of 80 probands, PCOS was in 22% of reproductive aged siblings, where hyperandrogenemia was in 24%

Question 6

what is a genome wide association study

Answer 6

way to identify genes involved in human disease. searches genome for small variation called SNPs, that occur more frequently in people with a certain disease than in people without the disease.
each study can look at 100s or 1000s of SNPs at the same time, to pinpoint genes that can contribute to risk

Question 7

what has genome wide association studies said about PCOS?

Answer 7

alteration in gonadotropin secretion in european ancestry populations.

Question 8

clinical description of PCOS

Answer 8

familial heterogenous disorder of reproductive aged people, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovary morphology.
molecular basis unclear. indicates that PCOS is complex trait modulated by genetic factors, intrauterine and environmental exposures, insulin resistance, pancreatic beta cell function, steroidogenesis and steroid hormone metabolism.

Question 9

what are some markers for PCOS types?

Answer 9

oligomenorrhea
hyperandrogenism
polycystic ovaries in ultrasound
can have all of them, two of them.

Question 10

what is an ovarian cyst?

Answer 10

cyst- fluid filled sac
cysts can occur anywhere on the body
with PCOS, individuals can develop cysts due to eggs not being released over time. the follicles keep growing and form multiple “cysts”

Question 11

what might an ultrasound of PCOS look like, compared to a normal ovary?

Answer 11

lots of black holes, as opposed to 1-2.

Question 12

what happens microscopically during PCOS

Answer 12

antral follicles are arrested at mid stage of development.
thecal cell layer thickens (hyperplasia). contains disrupted and degenerative granulosa cells.

Question 13

what is hirsutism

Answer 13

can be mild or severe.
excessive hair growth, in male patterns.
correlated to serum androgen concentrations.
co-existing conditions that alter bioactivity of androgens like hypothyroidism and obesity can lead to excessive hair growth.
increase in free testosterone, with decrease in sex hormone binding globulin.

Question 14

menstrual irregularity PCOS

Answer 14

menstrual dysfunction is irregular, infrequent or absent menstrual bleeding
in some, onset of chronic an ovulation emerges beyond adolescence, but this is unusual.
20% there is absence of menses
5-10% see regular ovulatory function.
recognition of normal ovulation in PCOS is significant, in that a history of regular menstrual cycles does not exclude the diagnosis
late in reproductive life, ovulation becomes regular

Question 15

what do aging PCOS women have, with regular menstrual cycles?

Answer 15

smaller follicle cohort
higher serum FSH levels
lower androgen levels compared to age-matched PCOS with persistent anovulation

Question 16

stages of follicular development

Answer 16

germ cell cyst
primordial
primary
secondary * switch out of gonadotropin in dependency
antral *now gonadotropin dependent
pre ovulatory
ovulation
corpus luteum

Question 17

clinical description of PCOS- ovarian morphology

Answer 17

classically, those with PCOS have enlarged ovaries with numerous peripheral small antral follicles, and increased central stoma
normal ovaries have a dominant follicle, and a few (1-2) antral follicles. cystic ovaries is one big hole. polycystic is many holes and an enlarged ovary.
possible mechanism: normal follicular growth appears to occur up to midantral stage, then maturation ceases.

as follicle reaches midantral stage, the granulosa cell layer becomes degenerative, and the structure appears as a thin walled cyst.
thecal cells become hyperplasticity, and thickened compared to normal, and are responsible for increased androgen production

Question 18

an interdisciplinary look at ovarian morphology

Answer 18

histomorphometric studies have revealed a 2 or 3 fold increase in the numbers of primary, secondary and tertiary follicles compared to those of the normal ovary.
done using math to find ovary volume compared to follicle numbers
whether ovaries are endowed with greater number of follicles or whether rate of programmed cell death is slower compared to normal ovary not studied.

Question 19

ovarian morphology- pathophysiology

Answer 19

mechanism for morphogenesis of polycystic ovary has not been established
role for androgen excess on follicle growth and development has been suggested from ovarian morphology in hyperandrogenic people, with congenital adrenal hyperplasia and androgen producing ovarian tumors.
nonhuman primates treated with subcutaneous silastic capsules containing testosterone have been observed to develop enlarged ovaries and increased follicle number.

Question 20

ovarian morphology- anti mullerian hormone (AMH)

Answer 20

2 proposed functions
- AMH may serve to inhibit recruitment of primordial follicles into the pool of growing follicles to prevent early depletion
- AMH may decrease follicle sensitivity to gonadotropin stimulation to control the number of large pre antral and small antral follicles that reach the pre ovulatory stage
these proposed mechanisms are consistent with the report of decreased AMH expression in pre antral and early antral follicles of women with PCOS compared to values observed in normal women

Question 21

insulin resistance in PCOS

Answer 21

PCOS are predisposed to insulin resistance and at risk for diabetes. first degree relatives also exhibit disordered glucoses metabolism and insulin secretion.
insulin resistance may worsen the clinical manifestations of PCOS
administration of insulin lowering drugs has been shown to improve insulin sensitivity, reduce androgen levels, and restore ovulation in some, but not all patients with this disorder.

Question 22

infertility in PCOS

Answer 22

anovulation is the primary defect responsible for infertility.
some evidence that those with PCOS have higher incidence of miscarriage
small series of people, 56% of those with recurrent miscarriages had polycystic ovaries