Transcript Endometriosis Recognition

Infertility and PCOS
Erinn Myers, M4
Department of Obstetrics and Gynecology
University of Tennessee Health Science Center
January 28, 2007
Learning Objectives
Following the presentation “Infertility and PCOS”
participants should be able to:
– Diagnose PCOS.
– Understand the differences between PCO,
PCOS and PCOM.
– Decide on possible treatment.
– Exclude other problems.
DEFINITION
Inability to conceive after a year of
exposure to conception.
– Six months > 35 years old.
– A disability and a disease…
NOT an elective condition.
– Great societal and demographic impact
Factors
Male
Ovarian
Cervical
Peritoneal
Tubal
Uterine
Unexplained
Ovulation
An LH (luteinizing hormone) surge
occurs 24 to 36 hours prior to ovulation
(Follicular rupture = It is the ovary’s job
to make a cyst and rupture it.)
Progesterone is increasingly produced
after the LH surge
Secretory changes occur in the
endometrium due to progesterone.
Ovulation
Pregnancy is absolute proof of ovulation.
Serum progesterones are 99%+ proof of
ovulation. These are done:
– 8 days after a positive ovulation test
– 7 days after ovulation on a monitor
– Day 21 and 24 if ovulation day is uncertain.
Ovulation Disorders
PCOS
Hypothyroidism
Hyperprolactinemia
Weight Loss / Weight Gain
PCOS
Diagnosis
– Somatic Hyperandrogenism
– Lab Hyperandrogenism
– Oligo-anovulation
– PCOM (polycystic ovarian morphology)
1990 NIH/NICHD
PCOS diagnosis
– Ovulatory dysfunction
– Clinical hyperandrogenism and/or
hyperandrogenemia
– Exclusion of other disorders such as
Non-classical adrenal hyperplasia
Androgen secreting tumor
Hyperprolactinemia
Thyroid
2003 ESHRE/ASRM
PCOS diagnosis
– At least 2 of the following features
Oligoovulation or anovulation
Clinical and/or biochemical signs of
hyperandrogenism
Polycystic ovarian morphology (sonography)
– Exclusion of other disorders
– 2003 Rotterdam ESHRE/ASRM Consensus. Fertil Steril 81:19, 2004
PCOS
Diagnosis is more clinical than lab.
– Androgenism (hirsute, acne, central obesity)
– Oligo-anovulatory
– PCOM (polycystic ovarian morphology)
– Elevated androgens
Androgens decrease with age
– Decreased HDL and SHBG
PCOM
PCOM (polycystic ovarian morphology)
– > 12 follicles at 2 - 9 mm in at least 1 ovary
– Volume > 10cc
– Does not apply if on BCPs
– If a follicle is >10mm, repeat scan next cycle.
2003 Rotterdam ESHRE/ASRM Consensus. Fertil Steril 81:19, 2004
PCOM
PCOM (polycystic ovarian morphology)
PCOM
PCOM (polycystic ovarian morphology)
PCOM vs. Follicles
PCOM (polycystic ovarian morphology)
vs. Pre- ovulatory Follicles
Screening Tests
FSH and E2
Prolactin
TSH
17-OHP
Lipids / HDL decreased
SBHG decreased
2 hour glucose to screen for diabetes
Exclude
Non-classical 17-hydroxylase deficiency
can look like PCOS
HAIRAN - hyperandrogenic insulin
resistance and acanthosis nigricans
Adrenal tumor
Cushing’s
Prolactin
Thyroid
Pituitary insufficiency
Hypothalamic amenorrhea
Stop Using
“Inappropriate LH" as a diagnosis
LH / FSH ratio as it is not sufficiently
predictive
Fasting insulin as it is not sensitive
Dexamethasone therapy can induce insulin
resistance
Utility of LH/FSH Ratio
Study designed to understand the biological
variability of the LH/FSH ratio in women with
PCOS vs. women with normal menstruation over
one full cycle
Will assess the diagnostic utility of the LH/FAH
ratio
10 consecutive blood samples were taken at 4
day intervals in 12 PCOS patients and 11 age
and weight matched controls
– Cho, LW, et. al. Bio variation of the LH/FSH ratio in normal women and
those with PCOS. Endocrine Abstracts (2005) 9 p80
Utility of LH/FSH Ratio
7.6% of PCOS and 15.6% of controls had
LH/FSH ratio above 3
Sensitivity 7.6%
Specificity 33.7%
Therefore, the biological variation of the
LG/FSH ratio is at least as wide in the
control group as in the PCOS group
– Cho, LW, et. al. Bio variation of the LH/FSH ratio in normal women and
those with PCOS. Endocrine Abstracts (2005) 9 p80
LH/FSH Ratio
Study to determine the incidence of abnormal
LH/FSH ratio in women with PCOS with
normoinsulinemia and hyperinsulinemia
Access the influence of elevated LH/FSH ratio on
selected endocrine and biochemical parameters
LH/FSH ratio119 patients with PCOS was calculated
and underwent hormonal and metabolic analysis
– Banaszewska B, et. al., Incidence of elevated LH/FSH ration in PCOS women
with normo- and hyperinsulinemia. Pocz Acad Med Bialymst. 2003;48:131-4
LH/FSH Ratio
45.4% had an LH/FSH >2, Normal
55% had normal gonadotropin ratio
Statistically significant differences between
groups with normal and elevated LH/FSH
– BMI, serum insulin, LH levels
Majority of women with elevated insulin
had a normal LH/FSH ratio
– Banaszewska B, et. al., Incidence of elevated LH/FSH ration in PCOS women
with normo- and hyperinsulinemia. Pocz Acad Med Bialymst. 2003;48:131-4
LH/FSH Ratio
LH/FSH ratio is not a characteristic attribute of
ALL PCOS women
– This study found ratio to be elevated <50%
Most of PCOS patients with normal
gonadotropin levels also had hyperinsulinemia
and obseity
Patients with hyperinsulinemia and elevated LH
had increased adrenal androgenic activity
–
Banaszewska B, et. al., Incidence of elevated LH/FSH ration in PCOS women with normoand hyperinsulinemia. Pocz Acad Med Bialymst. 2003;48:131-4
PCOS
Treatment
– Weight loss and exercise
– Clomid (clomiphene citrate) (3 months)
– Letrozole (Femara®) (aromatase inhibitor) (3
months)
– Metformin (6 months)
Note that the combination of metformin and
clomiphene are more productive at months 4-6
compared with months 1-3 .
– Gonadotropins
PCOS
Weight loss
– Poor results if BMI > 50
– Requires a dedicated program of diet and
exercise
– Use dieticians who work with diabetics
– Liposuction of cutaneous fat is not the same
as loss of visceral weight
Richard S. Legro, MD, Penn State College of Medicine, Hershey
PCOS PG Course, ASRM, New Orleans, October 2006
PCOS
Medications
– BCPs may be better with thin patients that have
normal HDL and SHBG
– Metformin causes more nausea and weight loss
than metformin-XL
– Sibutrimine (Meridia ®) – for weight loss
– Androgen receptor antagonists for hirsutism
Spironolactone (Aldactone®) and Flutemide
(Propecia®)
– Ketaconazole (Nizoral®)
– Florinithine (Vaniqa®) cream
Letrozole and Clomiphene
Birth Defects
There is no increase in birth defects for
letrozole or clomiphene if used when not
pregnant.
Letrozole associated with fewer birth
defects than clomiphene but this is not
statistically significant.
Tulandi T. Fertil Steril 85:1761, 2006
PCOS
Metformin Therapy – Long Term
–
–
–
–
–
Weight
Hyperandrogenism
Increases Fertility
Decreases Cardiac Disease
Decreases Diabetes
Monitor
– SHBG (decreased with PCO)
– HDL (decreased with PCO)
– 2 Hour Glucose
Long Term Management
BCPs may be better with a thin patient and
normal HDL and SHBG
Conclusions
PCOS Diagnosis
– Somatic or Lab Hyperandrogenism
– Oligo-anovulation
– Polycystic Ovarian Morphology
Exclude
– Non-classical 17-hydroxylase deficiency, HAIRAN, adrenal
tumor, Cushing’s, prolactinemia, thyroid disorders,
hypothalamic amenorrhea
PCOS Concepts
– Decreased HDL and SHBG
– LH/FSH ratio is not useful.
Treatment
– Weight loss, exercise, clomiphene, aromatase inhibitors,
metformin, gonadotropins
Acknowledgement
Dan C. Martin, MD, UTHSC, Memphis
ASRM PCOS Course, New Orleans, 2006