GYNECOLOGY

Polycystic Ovarian Syndrome (PCOS)

Lecturer: Dr. Sazon-Carlos
Date: August 28, 2018
Transcribed by: OOZMA KAPPA
OUTLINE POLYCYSTIC OVARIES
1. Polycystic Ovarian Syndrome Definition
1.1. Stein-Leventhal Syndrome (1935)
 1 or more ovaries of 10ml in volume ; 2-9mm 12
1.2. 1990 Criteria: NIH Conference follicles.
1.3. 2003 ESHRE/ASRM Consensus
1.4. Androgen Excess Society: 2008 Prevalence
2. Polycystic Ovaries
2.1. Prevalence  Affects 6%-10% of women in childbearing age (4-5 million
2.2. Difficult to Diagnose women).
2.2.1. Factors that may Change Presentation  Most common cause of anovulatory infertility (50%-60%).
2.3. When to Suspect PCOS
2.4. Diagnostic Criteria  Most common endocrine disorder in young women.
2.4.1. Anatomical Criteria  It is one of the major and unrecognized public health
2.4.2. Biochemical Criteria problems.
2.4.3. Clinical Criteria
2.5. PCOS and Pregnancy Loss
 There are so many controversies regarding the dx
2.6. Impact of PCOS  There is obese PCOS/Lean PCOS
2.6.1. Gynecological Impact
2.6.2. Cosmetic Impact Difficult to Diagnose
2.6.2.1. Hirsutism and PCOS
2.6.3. Metabolic Impact  Heterogenous symptoms
2.6.3.1. Metabolic Abnormalities in PCOS due to  Vary over time
Insulin Resistance
2.6.3.2. Metabolic Syndrome
2.7. Evaluation of Women with PCOS: General Health Issues Factors that may Change Presentation
2.8. Goal of Therapy  Ethnicity: hirsutism rarely seen in Asian population.
2.9. Surgical Therapy  Weight: worsen with weight gain; improve with weight
2.10. Team Approach to PCOS: A Coordinated Approach
3. Summary loss.
o Usually, our initial advise to the patient is weight
Black – PPT; Blue – Recording; Green – Book loss.
POLYCYSTIC OVARIAN SYNDROME DEFINITION
Stein-Leventhal Syndrome (1935) When to Suspect PCOS
 PCOS is previously known as STEIN-LEVENTHAL  Irregular or infrequent menses.
SYNDROME  Increased androgens causing hirsutism and acne.
 Amenorrhea associated with bilateral polycystic ovaries.  Polycystic ovaries by ultrasound
 Wedge Resection restored normal menses.  Exclusion of other endocrine. disorders (thyroid, adrenal,
 Many cases do not confirm to the classic description. ovary).
 The polycystic ovaries are not the primary cause but one  Additional clues:
of the manifestation of the underlying endocrine disorder o Infertility or pregnancy loss
which results in anovulaton. o Problems maintaining normal weight
o Family hx of PCOS, infertility or irregular cycles
1990 Criteria: NIH Conference o Family hx of diabetes or CVD
 Chronic anovulation o Hyper or hypoglycemia
o Hypertension
 Clinical and/or biochemical signs of hyperandrogenism.
o Dark skin patches in skin fold
o Scalp hair loss
2003 ESHRE/ASRM Consensus
o High LDL, TG, and low HDL
 Oligo- and/or anovulation. o Sleep apnea, Depression and anxiety
 Clinical and/ or biochemical signs of hyperandrogenism.
 Polycystic ovaries- Diagnostic Criteria
o Two out of 3 criteria required  Anatomical (by ultrasound)
*For the exam, we will stick to 2003 criteria o Before, it was described as having a thickened
stroma with pearl-like necklace or rosary-bead
Androgen Excess Society: 2008 pattern but not anymore. It doesn’t matter
 Hyperandrogenism - clinical and/ or biochemical. anymore where the follicles are.
 Ovarian dysfunction – reflected by oligo-anovulation and/ o It’s not usually recommended to do surgery or
or polycystic appearing ovaries. removal of ovary (containing immature follicles
 Exclusion of other androgen excess disorders. with eggs). Ovarian drilling will be the last resort
for the immature follicles to become active

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 GYNECOLOGY – Polycystic Ovarian Syndrome (PCOS)

 Biochemical
 Clinical

Anatomical Criteria
 Ultrasound
o Histologically, a polycystic ovary (PCO) displays
increases in the number of ripening and atretic
follicles, cortical stromal thickness, and number of
hilar cell nests
o Pelvic sonography is commonly used to evaluate
the ovaries in women with suspected PCOS
o In the NIH criteria or PCOS, sonographic evaluation
is not required However, sonography is particularly
important for women with PCOS seeking fertility
and in women with signs o virilization to exclude
an androgen-producing ovarian cancer Anovulation in PCOS
o A high-definition transvaginal approach is superior  Presents as:
and has a higher detection rate of PCO than the o Absence of periods
transabdominal route. o Infrequent periods (>35 day cycles)
o Transabdominal route is preferred for virginal o Dysfunctional uterine bleeding
adolescents. o Occasionally regular periods
o Sonographic criteria for polycystic ovaries rom the  Note risk of endometrial cancer
2003 Rotterdam conference include ≥ 12 small o Due to an irregular period, endometrium thickens
cysts (2 to 9 mm in diameter) or an increased and can lead to endometrial CA
ovarian volume (> 10 mL) or both  Body weight > 110% of ideal
 Surgery  However, there are LEAN PCOS
 Pathology

Hyperinsulinemia (hence also prone to DM) and

hyperandrogenism due to decreased sex hormone-binding
Biochemical Criteria
globulin production; increase ovarian androgen production;
 Altered androgens – one or more androgen levels raised disordered LH:FSH release -> feedback is disrupted ->
(testosterone, androstenedione, DHEAS)
anovulation, then ultimately leads to PCOS
 Raised LH or LH:FSH ratio

Clinical Criteria PCOS and Pregnancy Loss

 Ovulatory dysfunction  Very high incidence of pregnancy loss (30-50%)
 Insulin suppresses glycodelis (endometrial proteins),
which is important for pregnancy and implantation
o Give metformin
 Insulin sensitizers to reduce the risk of pregnancy loss
 Administration of insulin sensitizers
o Decreases circuiting androgens
o Improves ovulation and fertility

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 GYNECOLOGY – Polycystic Ovarian Syndrome (PCOS)

Impact of PCOS  Assessed by the Ferriman-Gallwey score

 Gynecological: ovulatory dysfunctioninfertility o Within this system, abnormal hair distribution is
 Cosmetic: hyperandrogenism central parts assessed in nine body areas and scored from 0 to
 Metabolic: insulin resistance and hyperandrogenism 4. Increasing numeric scores correspond to greater
 Endometrial CA hair density within a given area
o Many investigators define hirsutism as a score ≥ 8
Gynecological Impact: Ovulation Dysfunction using the modified scoring
 Predisposes women to infertility and endometrial CA  Semiobjective scoring system: Ferriman and Galwey
 Poor response to standard ovulation drugs system, between 6-12 is the lower limit
 If resistant, may do ovarian drilling  Does not always correlate with androgen levels
 Once pregnant, 1) pregnancy loss and 2) gestational
diabetes
 Give ovulation induction agents, clomiphene citrate,
aromatase inhibitors
 Initially, patients are given 3-6 cycles of oral medications.
If unresponsive, they are given gonadotropins for
ovulation induction. If still unresponsive, ovarian drilling
can be an option
o A laparoscopic surgery wherein we cauterize 4-5
drills per ovary to make it respond to our ovulation
induction agents in the future.
 Complications of ovarian induction: multiple pregnancy
and ovarian hyperstimulation
o Prone to abortion and GDM

Cosmetic Impact
 Hyperandrogenism
o Hirsutism
o Acne

Hirsutism and PCOS

 Central
 In a female, hirsutism is defined as coarse terminal hair
(sexual hair) in a male pattern distribution
 PCOS accounts or 70 to 80 percent of cases of hirsutism,
which typically begins in late adolescence or the early 20s.
 Idiopathic hirsutism is the second most frequent cause
 Elevated androgen levels play a major role in determining
the type and distribution of hair. Within a hair follicle,
testosterone is converted by the enzyme 5α-reductase to
dihydrotestosterone (DHT)
 Although both testosterone and DH convert short, soft
vellus hair to coarse terminal hair, DH is markedly more
effective than testosterone.
 Conversion is irreversible, and only hairs in androgen-
sensitive areas are changed in this manner to terminal
hairs.
 As a result the most common areas affected with excess
hair growth include the upper lip, chin, sideburns, chest,
and linea alba of the lower abdomen.
 Specifically, escutcheon is the term used to describe the
hair pattern of the lower abdomen.
 In women, this pattern is triangular and overlies the mons
pubis, whereas in men it extends up the linea alba to form
a diamond shape.

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 GYNECOLOGY – Polycystic Ovarian Syndrome (PCOS)

o Metformin
 Being given if the patient is at risk of
DM

Effect of Lifestyle in Hirsute PCOS

 Weight gain causes an increase in insulin resistance and
androgen production in PCOS women
 Modest weight loss and increase on exercise
o e.g. 50-10% weight loss will often improve
hirsutism by reducing androgen production
 This weight loss can help the patient get
pregnant already

OCP and Hirsutism

 First line treatment for hirsutes (manages endometrium
and contraception also)
 Synthetic E2 suppresses gonadotropin driven androgen
production
 Increase in SHBG (Sex hormone binding globulin)
decreases bioavailable testosterone to hair follicle
 Addition of low dose CPA (Cyproterone Acetate –
Diane35) provides anti-androgenic progesterone
o Also effective in the treatment of hirsutism
 OCP Treatment of Hyperandrogenism
o Inhibit ovarian/adrenal androgen production
o Block androgen receptor
o Block 5 alpha reductase in the hair follicle
especially the CPA

Metforming and Hirsutism

 Useful alternative to OCP in women with hirsutism who
also desires fertility
 Common to have gut side effects
 Commence slowly, work up to 1500mg/day
o Given with meals
 Monitor with liver and renal function (occasional
hepatotoxicity, theoretical risk of lactic acidosis)
 In both lean and overweight women with PCO
o Improves insulin sensitivity and lipids
o Decreases hyperandrogenism
o Increases frequency of ovulation (40-70%)
compared to placebo

Combination Anti-Androgen Therapy

 Use in conjunction with OCP
 Specialist prescription
 Require monitoring (liver function)
 Used in more severe hirsutism or unresponsive women
 Require contraception
 6 months before effect but may improve up to 2 years
after initiating therapy (50% reduction in FG score)
Management of Androgen Excess Symptoms in PCOS
 First line treatment Treatment of Skin Manifestations of PCOS
o Weight loss and exercise  Drug Therapy
 First line is always weight loss especially  Cosmetic Therapy
in overweight or obese patients o Skin care
o Oral contraception o Hair removal
 First line, if the patient just wants to
regulate the cycles

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 GYNECOLOGY – Polycystic Ovarian Syndrome (PCOS)

Metabolic Impact Team Approach to PCOS: A Coordinated Approach

 Metabolic: Insulin resistance and hyperandrogenism  Fertility
o Type 2 Diabetes  Risk of endometrial cancer
o Dyslipidemia o Monitor the endometrial thickness regularly with
 Check the lipid profile the Transvaginal ultrasound
o Cardiovascular Disease  Metabolic disorder
o Hypertension  Hirsutism and Acne
 Inform the patient about the lifetime disease entities that  Drug therapy/surgery
are consequences of PCOS. Prevention by lifestyle  Nutritional counselling
modification – diet, exercise, and weight loss  Exercise
 Cosmetic therapy
Metabolic Abnormalities in PCOS due to Insulin Resistance  Psychological counselling
 Impaired GTT (40%)
 Diabetes – 5x more likely than weight matched controls
 Gestational diabetes increased risk SUMMARY
 Dyslipidemia  A combination of drug therapy, counselling and cosmetic
o ↓HDL, ↑LDL, ↑TG procedures is needed
o Potential cardiovascular risk  Dramatic lifestyle change are needed
 A team approach to PCOS will maximize results
Metabolic Syndrome  PCOS is a life-long disease. Even if the patient have no
 Three of five needed for diagnosis longer polycystic ovaries on UTZ they can still be a PCOS
o Increased waist circumference (>36 in) patient
o Elevated TGs (>149 mg/dl)
o Decreased HDL cholesterol (<50 mg/dl)
o High blood pressure >130/85 ---------------------------------------------------------------------------
o Fasting glucose >100 mg/dl TREATMENT (William’s Gynecology, 3rd Edition)
 The treatment choice for each symptom of PCOS depends
Evaluation of Women with PCOS: General Health Issues on a woman’s goals and the severity of endocrine
 Glucose Tolerance Test (2 hour OGTT) dysfunction.
 Monitor BP: Hypertension  Thus, anovulatory women desiring pregnancy will
 Check Lipid Profile: Dyslipidemia undergo significantly different treatment than
 Assess risk factors for heart disease adolescents with menstrual irregularity and acne.

Goal of Therapy Conservative Treatment

 Gynecological  Women with PCOS who have fairly regular cycle intervals
o Improve reproductive function (8 to 12 menses per year) and mild hyperandrogenism
o Reduce risk of endometrial cancer by making may choose not to be treated. In these women, however,
your patient menstruate regularly periodic screening or dyslipidemia, diabetes mellitus, and
 Cosmetic: Reduce serum androgens metabolic syndrome is prudent.
 Metabolic: Ameliorate complications due to IR  For obese patient – lifestyle changes focus on diet and
o Glucose intolerance exercise
o Dyslipidemia o Modest weight loss (5% of BW) can restore the
o Atherogenesis normal ovulatory cycle. This improvement
o Hypertension results from reductions in insulin and androgen
levels, the latter mediated through increases in
Surgical Therapy SHBG levels
 Wedge Resection  The optimal diet that best improves insulin sensitivity is
o No longer advocate not known
 Ovarian drilling o Diets high in carbohydrates increase insulin
o One of the last resorts secretion rates, whereas diets high in protein
 Bariatric surgery and at lower those rates
o For severely obese patients but is not being o However, very-high-protein diets are concerning
advised due to its complications like going back with respect to stresses on kidney function.
to the previous weight o Moreover, they afford only short-term weight
 Ovulation induction is usually being done for infertile loss initially with lesser benefits over time
patients o Thus, it appears that a well-balanced hypocaloric
diet offers the most benefit in treating obese
women with PCOS.

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 GYNECOLOGY – Polycystic Ovarian Syndrome (PCOS)

 Exercise is known to have a beneficial effect in treating o Blocks the conversion of testosterone to DHT
patients with type 2 DM and also improve cardiovascular o Finasteride
capacity  5mg – for prostate CA (Proscar) and
hirsutism
Treatment of Oligo- and Anovulation  1mg – tx of male alopecia (Propecia)
Hormonal Agents  S/E: decreased libido
 Combination oral contraceptive pills (COCs)
o First line treatment for menstrual irregularities Eflornithine Hydrochloride
o Induces regular menstrual cycles  Antimetabolite topical cream
o Lower androgen levels  Irreversible inhibitor of ornithine decarboxylase
o Thin the endometrium o Enzyme necessary for hair follicle cell division
o Suppresses gonadotropin release → ↓ ovarian and function
androgen production
o Estrogen component increases levels of SHBG, Androgen-receptor Antagonists
which binds free androgen  Competitive inhibitors of androgen binding to the
o Progestin component antagonizes the androgen receptor
endometrial proliferative effect of unopposed  S/E: Metrorrhagia (Intermenstrual Bleeding – IMB),
estrogen from PCOS, thus reducing the interferes with external genitalia development in male
endometrial hyperplasia risk foetuses during early pregnancy
o Pregnancy test is indicated if the last menstrual  Used in conjunction with OCPs – for regular menstruation
period was more than 4 weeks prior COC and provide effective contraception
initiation  None of the antiandrogen agents are FDA-approved or
o Progesterone withdrawal every 1 to 3 months treatment of hyperandrogenism and thus are used off-
for patients who are not candidates for label
combination hormonal conception  Spironolactone (Aldactone) is the primary antiandrogen
used currently in the US
Insulin Sensitizing Agents  Cyproterone acetate – SE: liver injury
 Metformin  Flutamide
o Most commonly prescribed in women with o Nonsteroidal antiandrogen
impaired glucose tolerance and insulin resistance o Tx of prostate CA
o 1500 to 2000 mg in divided doses daily with o Hepatotoxic
meals
o S/E: GI upset Hair Removal
o Decreases androgen levels in both lean an obese  Depilation
PCOS patients → increased rates of spontaneous o Hair removal above the skin surface
ovulation o Shaving is the most common form
o Category B and safe to use as an ovulatory o Topical agents containing calcium thioglycolate
induction agent as monotherapy or with which breaks disulfide bonds
clomiphene citrate  Epilation
 Clomiphene citrate – first line o Removes the entire hair shaft and roots
treatment for ovulation induction o Plucking, waxing, threading (khite), electrolysis,
 Thiazolidinediones – used in patients with DM and laser treatment
o Rosiglitazone and pioglitazone improve ovulation
rate however, the glitazones are class C drugs Acne Treatment
and should be discontinued if pregnancy is  Lowering of androgen levels
achieved  COC pills, antiandrogen such as spironolactone, 5α
reductase inhibitors
Hirsutism Treatment
 Primary goal is to lower androgen level to halt further Topical Retinoids
conversion of vellus hairs to terminal ones  Regulate the follicular keratinocyte and normalize its
desquamation
Lowered Effective Androgen Levels  Direct anti-inflammatory properties
 COCs - ↓ ovarian androgen production  Topical Retinoid monotherapy
 GnRH agonists lower gonadotropin level over time, and in o Mild noninflammatory comedonal acne
turn subsequently lower androgen levels  Topical Retinoid + topical antimicrobial/ benzoyl peroxide
o Long term administration is not ideal due to o Mild inflammatory pustules
associated bone loss, high cost, and menopausal  Triple Therapy or oral retinoid or oral antibiotics
side effects o Moderate to severe acne
 5α-reductase inhibitors

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 GYNECOLOGY – Polycystic Ovarian Syndrome (PCOS)

 Tretinoin may cause transient worsening o acne during

the first weeks of treatment
 Tretinoin and adapalene are category C thus are not
recommended during pregnancy or breast feeding
 Tazarotene is category X

Topical Benzyl Peroxide

 Bactericidal to P. acnes by generating ROS within the
follicle
 Weak comedolytic and anti-inflammatory
 Combined with topical clindamycin or erythromycin

Topical Antibiotics
 Erythromycin and clindamycin
 Oral – doxycycline, minocycline, erythromycin
o S/E: sun sensitivity and GI upset

Oral Isotretinoin (Accutane)

 Treatment of severe recalcitrant acne
 Teratogenic during first trimester of pregnancy
o Malformations of cranium, face, heart, CNS, and
thymus

Acanthosis Nigricans
 Optimal treatment or acanthosis nigricans is directed
toward decreasing insulin resistance and
hyperinsulinemia
 Other methods, including topical antibiotics, topical and
systemic retinoids, keratolytics, and topical
corticosteroids

Surgical Therapy
 Ovarian wedge resection is now rarely performed,
 Laparoscopic ovarian drilling restores ovulation in many
women with PCOS that is resistant to clomiphene citrate
 Oophorectomy is a viable option or women not seeking
fertility who exhibit signs and symptoms of ovarian
hyperthecosis and accompanying severe
hyperandrogenism.

– End –