Abnormal Menstruation, Uterine Bleeding: Diagnosis and Management

PALM-COEIN classification system for abnormal uterine bleeding in *nongravid reproductive-age* women. *This classification refers to HeavyMenstrualBleeding in cyclic (ovulatory) menses*. This is *not classification* for women with *ovulatory dysfunction (AUB-O)*

Comprised of 4 categories defined by visually objective structural criteria (PALM) *Polyp, Adenomyosis, Leiomyoma, and Malignancy and hyperplasia*. Four categories that are unrelated to structural anomalies (COEI) *Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic* and one reserved for entities that are *not yet classified (N).* The Leiomyoma category is subdivided into pts w/ at least one submucosal myoma (LSM) and those with myomas that do not impact the endometrial cavity (LO)

High Dose Estrogen Regimens For *Unstable* Patients (Unstable: low Hgb... etc.)

Conjugated equine estrogen (Premarin) 25mg IV x1, may repeat dose at 3 and 5 hours from initial dose if bleeding continues Then once bleeding stops: Conjugated equine estrogen (Premarin) 2.5mg qid X 21-25 days; add progestin after estrogen is discontinued oral medroxyprogesterone acetate 10mg/day for 10 days OCP (containing 35 mcg ethinyl estradiol) 2 pills per day for 5 days, followed by 1 pill per day for 20 days Then will have W/D bleed

PCOS consultation pathways

Consultations An endocrinologist should be consulted for follow-up evaluations of biochemical and metabolic derangements A reproductive endocrinologist should be consulted if the patient is infertile and desires pregnancy

Systemic Causes of Abnormal Bleeding Drugs

Contraceptives Anticoagulants Antipsychotics Chemotherapy TCAs Phenothiazines

Cessation of bleeding depends, in part, on clot formation, but also on uterine factors such as

(vasoconstriction and uterine contraction - regulated by local prostaglandins) No ovulation = no progesterone = no bleeding

*Intermenstrual Bleeding* Bleeding between normal menses- Called what when on OCPs?

*"breakthrough bleeding"* stronger association with uterine pathology -Must rule out CANCER or HYPERPLASIA *if older than 30* -*Endometrial Biopsy (EMB) or hysteroscopy with D&C*

High Dose Estrogen Regimens For *Stable* Patients

**Conjugated equine estrogen (Premarin) 2.5mg qid X 21-25 days; add progestin after estrogen is discontinued oral medroxyprogesterone acetate 10mg/day for 10 days Give antiemetic such as promethazine 12.5-50 mg PR to prevent N/V More effective than combined estrogen-progestin or progestin-alone OCP (containing 35 mcg *ethinyl estradiol* BID-QID) taken in cascading regimen (5 pills on day 1, 4 pills on day 2, 3 pills on day 3, 2 pills on day 4, and 1 pill on day 5, for moderate bleeding can start with 3 pills -Give antiemetic -Treatment with 1 pill should continue for at least 1 week after bleeding stops -Then stop the 1 pill for 3-5 days to allow withdrawal bleed -Then re-start standard OCP High dose progestins alone if uterine hemorrhage is related to anovulation Others: GnRH agonists, tranexamic acid

Advantages of CombinationHormonal Therapy

*1st line therapy for abnormal uterine bleeding* -Oral Contraceptive Pills/Patches/RingsConvenient-Excellent contraceptive protection-Decreased cancer risk (endometrial / ovarian)-Best option for menorrhagia - less flow-Better control of dysmenorrhea (often not present in anovulation)

Oligomenorrhea: Menstrual periods that occur >35 days apart Secondary amenorrhea is diagnosed if no menstrual period occurs for >6 months Bleeding is typically increased or decreased when it occurs? Typically what is associated with oligomenorrhea?

*Anovulation from endocrine or systemic causes*

Polycystic Ovarian Syndrome can do what to a woman's appearance and menstrual cycle?

*Can cause a decrease in menstrual periods (≤8 menstrual cycles/year, anovulatory)* *Increased facial hair, acne, and other abnormalities* *A form of insulin resistance*

Contact Bleeding AKA postcoital bleeding is considered what until proven otherwise?

*Cervical cancer until proven otherwise!!!* -More common causes - cervical eversion (ectropion), cervical polyps, cervical or vaginal infection, atrophic vaginitis

Causes of Abnormal Bleeding Common causes by population -Neonates

*Estrogen withdrawal*

Blood work as indicated *perimenopausal women have high*

*FSH*

Endometrial biopsy (women at risk of endometrial hyperplasia)

*Frequent, heavy prolonged bleeding* *History of unopposed estrogen exposure (obesity, chronic anovulation) * Failed medical management of the bleeding -High risk of endometrial cancer *tamoxifen therapy* *Lynch syndrome AKA Hereditary Nonpolyposis Colorectal Cancer*: an autosomal dominant genetic condition that has a high risk of colon cancer as well as other cancers including endometrial cancer, ovary, stomach, small intestine, hepatobiliary tract, upper urinary tract, brain, and skin)

Patterns of Abnormal Bleeding Bleeding that occurs at any time between menstrual periods

*Metrorrhagia (intermenstrual bleeding)*

Metrorrhagia Intermenstrual bleeding

*Ovulatory bleeding* Midcycle spotting - *can be documented with BasalBodyTemp.* Endometrial polyps Endometrial and cervical carcinomas *Exogenous estrogen* Becoming a more common cause

Polymenorrhea is periods that occur too frequently, what is this usually associated with

*anovulation* rarely caused by shortened luteal phase

More useful to think of DUB as

*anovulatory bleeding - the primary cause* Anovulation may be related to a systemic medical disease or a variety of factors which affect the hypothalamic pituitary axis

When you have elevated prolactin levels what test should be thought of

*brain MRI*

Dysfunctional Uterine Bleeding *Progesterone causes the enzymatic conversion of*

*estradiol to estrone, a less potent estrogen* -The changes in the endometrium remain secretory within the glands -Patients who exhibit these symptoms in the reproductive years often have ovulatory cycles or secondary reasons for altered hypothalamic function (e.g, polycystic ovary disease)

Dysfunctional Uterine Bleeding In ovulatory DUB, *prolonged progesterone secretion causes*

*irregular shedding of the endometrium* Probably related to a constant low level of estrogen that is around the bleeding threshold Causes portions of the endometrium to degenerate and *results in spotting*

Is cervical ectropion normal or abnormal?

*normal phenomenon*, especially in the *ovulatory phase* in younger women, during *pregnancy*, and in women taking *OCP*, which *increases the total estrogen level in the body*

*Oral ContraceptivesAll oral contraceptives increase SHBG and, therefore*

*reduce free testosterone*

Dysfunctional Uterine BleedingAnovulatory cycle- why does the corpus luteum fails to form what happens because of this and what is the end result

-*Failure of normal cyclical progesterone secretion resulting in unopposed production of estradiol stimulating overgrowth of the endometrium* -Endometrium proliferates and eventually *outgrows its blood supply- necrosis* -*End result is overproduction of uterine blood flow*

Simple PCOS Risk Assessment

1. Are you 40 pounds or more overweight? 2. Any family history of type 2 DM? 3. Do you have irregular periods? 4. Is there above average hair growth on your chin and upper lips? 5. Can you see a darkening of the skin around your neck or under your arms? 6. Have you had difficulty conceiving?

After considerable debate at a 1990 National Institutes of Health Conference on PCOS, minimal criteria for diagnosing PCOS were proposed:

1. Menstrual irregularity due to oligo- or anovulation  2. Evidence of hyperandrogenism Whether clinical (hirsutism, acne, or male pattern balding) or biochemical (high serum androgen/tst concentrations)  3. Exclusion of other causes of hyperandrogenism and menstrual irregularity (congenital adrenal hyperplasia, androgen-secreting tumors, and hyperprolactinemia)

PCOS Common Risk Factors

1. Overweight/Obese 2. Insulin resistance 3. Prediabetes/Metabolic Syndrome 4. Family history of PCOS 5. Family history of diabetes or early heart disease 6. History of premature adrenarche 7. *High-risk ethnic groups (Mexican Americans)* 8. *High triglycerides, low HDL, HTN* 9. *Use of antiepileptic drugs*

Dysfunctional Uterine Bleeding Incidence

20% (adolescence) *40% > 40 years* *90% from anovulation* 10% from ovulatory cycles

Will a pap smear suffice to rule out cancer in contact bleeding?

A negative cytological smear (Pap) *DOES NOT* rule out invasive cervical cancer *Colposcopy, biopsy*, or both may be necessary to rule out cervical malignancy

PCOS Workup - Rule Out What would you be trying to rule out?

A serum hCG level should be checked to rule out pregnancy Hyperprolactinemia - fasting serum prolactin concentration 75 gram oral glucose-tolerance test (OGTT) can be performed to evaluate for diabetes The fasting lipid profile is often abnormal TSH - rule out hypothyroidism FSH level should be checked to rule out primary ovarian failure

PCOS and infertility

A subset of women with PCOS are infertile *Most women with PCOS ovulate intermittently* Conception may take longer than in other women *Women with PCOS may have fewer children than they had planned*

PCOS Medical Management who requires intervention?

ALL WOMEN WHO ARE ANOVULATORY this condition is often a precursor to more serious health issues (Unopposed estrogens can lead to endometrial hyperplasia )

PCOS *CLASSIC TRIAD*

Abnormal anovulatory cycles Hyperandrogenism Polycystic ovaries bilaterally

Patterns of Abnormal Bleeding Menorrhagia (hypermenorrhea)

Abnormally heavy, prolonged *(>2 days)* menstrual flow

AES Criteria Presence of 3 features

Androgen excess (clinical and/or biochemical hyperandrogenism) Ovarian dysfunction (oligo-anovulation and/or polycystic ovarian morphology) Exclusion of other androgen excess or ovulatory disorders

Treatment Goals for abnormal bleeding Anovulatory-Dysfunctional bleeding

Desires pregnancy = *fertility drugs/insulin sensitization* Not interested in pregnancy = hormone therapy OCPs or progestins (progesterone)

PCOS Medical Management of: Metabolic derangements:

Diet and exercise -Improves overall metabolic function *Metformin* -Improves insulin resistance and decreases hyperinsulinemia -Assess kidney, liver and cardiac function before starting -Off label use

Advantages of Progestin Therapy: "Progesterone challenge" *10 days/one time*

Dosing: *Medroxyprogesterone acetate* 10mg/10 days or *micronized progesterone* 200mg/10 days or *progesterone* 100mg IM Any bleeding more than light spotting 2 weeks after progesterone given = *estrogen* is present but the woman is not ovulating. This is a positive test for secondary amenhorrea *No progesterone from the corpus luteum = no withdrawal bleeding when progesterone stops* If no withdrawal bleeding occurs, she has very low estrogen levels or there is a problem with the outflow tract such as uterine synechiae (adhesions) or cervical stenosis (scarring).

PCOS requires the exclusion of all other disorders that can result in menstrual irregularity and hyperandrogenism lab samples should be drawn when?

Early in the morning Fasting Between days 5-9 of the menstrual cycle (if regular

Hysteroscopy is used for

direct visualization

Reasons for cycle dysfunction: Pituitary

high prolactin: tumor hypothyroid (TSH)

Progestin also used to maintain pregnancy and towards the end of the BC pack to cause withdrawal bleeding Depo is good for pregnancy because

it is such a large dose

Postmenopausal Bleeding is considered what until proven otherwise?

Endometrial cancer! Workup: -Pelvic exam (determine site of bleeding) Vaginal, cervical or uterine? -Transvaginal and transabdominal ultrasound -Endometrial biopsy -Hysteroscopy

Use ultrasonography for

Endometrial thickness Fibroids Hysterosonogram

Dysfunctional Uterine Bleeding 3 major categories

Estrogen breakthrough bleeding -Excessively thick endometrium due to unopposed estrogen (*corpus luteum failure*) Estrogen withdrawal bleeding -Sudden decrease in estrogen levels (*bilat. oophorectomy* or *cessation of estrogen therapy*) Progestin breakthrough bleeding -Progesterone/estrogen ratio is increased, *leading to atrophic and ulcerated endometrium* because of relative lack of estrogen = frequent irregular bleeding

Signs of Hyperandrogenism

Excess terminal body hair in a male distribution pattern Commonly seen on the upper lip, chin, around the nipples, and along the linea alba Acne and/or male-pattern hair loss (androgenic alopecia) Less frequently increased muscle mass, deepening voice, and/or clitoromegaly due to excessive androgens

Causes of Abnormal Bleeding Common causes by population -Pediatrics

Foreign bodies Vaginitis Urethral prolapse Trauma Precocious puberty Malignancy (sarcoma - rare)

Abnormal genital bleeding

Generic term used when the source of bleeding has not been identified

Cycle Dysfunction if anyone or more becomes elevate or suppressed the cycle is disrupted. List these components

GnRH FSH/LH Estrogen Progesterone

Treatment of Acute Menorrhagia or Ongoing Menometrorrhagia with High Dose Estrogen

Goal - to stop the bleeding *Replaces raw, denuded endometrium after prolonged bleeding* Controls acute bleeding episode; *does not treat underlying cause* Used to: Induce endometrial growth *Stimulate production of progesterone receptors in endometrium* Allow progestin to differentiate endometrium

PCOS Medical Management of: Hirsutism

Hair removal -Short and/or long-term Weight reduction -Decreases androgen production in women who are obese Oral contraception -Slows hair growth in 60-100% of women with hyperandrogenemia -OCP containing 20 mcg ethinyl estradiol combined with a progestin with minimal androgenicity (such as *norgestimate*) *Spironolactone* 50-100 mg PO bid -Antiandrogen effect (use with caution - teratogenic) *Eflornithine hydrochloride cream 13.9%5 (Vaniqa)* -Topical cream that can be used to slow hair growth -*Works by inhibiting ornithine decarboxylase*, which is essential for the rapidly dividing cells of hair follicles

Dysfunction uterine bleeding (DUB)

Has classically been used to describe *excessive noncyclic endometrial *bleeding* unrelated to anatomical lesions of the uterus or to systemic disease*

Reasons for cycle dysfunction: Endometrium

outlet obstruction and/or anatomical anomaly

Surgical Therapy would include what optons

Hysteroscopy/D&C (dilation and curettage) Endometrial ablation (typically NovaSure, ThermaChoice) Hysterectomy - *last resort*

Systemic Causes of Abnormal Bleeding Anovulation or oligoovulation

Idiopathic PCOS or endocrinopathies as above *Stress, exercise, obesity, rapid weight changes*

Reasons for cycle dysfunction: Ovary

ovarian failure (chemo) high androgens (PCOS)

Rotterdam Criteria: These criteria encompass a broader spectrum of phenotypes considered to represent PCOS

In the revised criteria, 2/3 of the following are required to make the diagnosis: Oligo- and/or anovulation Clinical and/or biochemical signs of hyperandrogenism Polycystic ovaries (by ultrasound) In addition, other etiologies (congenital adrenal hyperplasias, androgen-secreting tumors, Cushing's syndrome) must be excluded

How is Metabolic syndrome related to PCOS

In women, metabolic syndrome is characterized by abdominal obesity, dyslipidemia, elevated blood pressure, a proinflammatory state *43% prevalence of metabolic syndrome in women with PCOS*

Abnormal uterine bleeding (AUB)

Includes abnormal menstrual bleeding and bleeding due to causes such as *pregnancy, systemic disease, or cancer*

What kind of roles does insulin play in PCOS

Indirect and indrect roles in the pathogenesis of hyperandrogenemia.Insulin acts *synergistically with LH to enhance androgen production* *Insulin also inhibits hepatic synthesis of sex hormone binding globulin (SHBG)*-Key protein which binds to testosterone-Less SHBG inc the proportion of free test.-Women with PCOS often have hyperinsulinemia w/ elevated free testosterone and total testosterone at upper range of normal or only modestly elevated.

Menometrorrhagia Bleeding that occurs at irregular intervals the amount and duration vary. Any condition that can cause what type of bleeding can lead to menometrorrhagia?

Intermenstrual bleeding! **If you have a condition that can cause intermenstrual bleeding it can lead to menometrorrhagia

Questions to ask about bleeding:

Is there a pattern to the bleeding? Calendar? How often do you change a pad (8/day) or tampon? Are you soiling sheets at night? Getting up? How many days are heavy? How long does the bleeding last? Do you have bleeding or spotting in between periods or after intercourse? Do you have pain? Describe. Has your menstrual pattern changed? Over what time period? Is patient having symptoms of early pregnancy? History of unprotected intercourse? Dates/outcomes of any pregnancies/infertility? (GPFPAL) Describe any premenstrual symptoms? What medications is the patient taking? Any signs of hirsutism (hair, deep voice) or virilization? Recent weight changes, stress, excessive exercise? Any nipple discharge? Any easy bruising or bleeding/clotting problems?

Reasons for cycle dysfunction Usually inadequate progesterone due to lack of

LH surge at midcycle *caused by alteration in GNRH release*

Advantages of Progestin Therapy: Who can use this to their advantage?

Management of dysfunctional uterine bleeding*Can be used in women who cannot take OCPsHypercoaguability, PE/DVT, estrogen-dependent tumor HX/FHx**Treatment of endometrial hyperplasia - prevent "unopposed estrogen"* effect*Inexpensive Depo MPA for contraception or menorrhagia*Very convenient 3-12 months to work

PCOS Medical Management of: Anovulation

Metformin -Frequently (but not universally) improves ovulation rates -Bleeding precautions with start of medication - consider OCP -Pretreatment with metformin has been shown to enhance the efficacy of *clomiphene (Clomid)* for inducing ovulation Management of infertility - can be referred to reproductive endocrinology

PCOS pathogenesis

Multiple genetic variants and environmental factors interact Inherited basis established by twin studies: Inc prevalence of PCOS in female first degree relatives -monozygotic correlation 71% -dizygotic correlation of 38% -1st degree female relatives 20-40%

In cycle dysfunction, what do OCPs manipulate? The hypothalamus, ovaries?

OCP manipulates the *hypothalamus/brain*, not the ovary. The ovaries are being "tricked" but not affected directly

Hypomenorrhea aka cryptomenorrhea Causes

Obstruction - *hymenal or cervical stenosis* *Uterine synechia* (*Asherman's syndrome* - intrauterine adhesions) Diagnosed by *hysterogram or hysteroscopy* Oral contraceptives - can have little to no flow Reassurance Endometrial ablation

PCOS Medical Management of Mestrual irregularities

Oral contraceptive -Daily exposure to progestin, antagonizes endometrial proliferation -Prevents unwanted pregnancy -Inhibits ovarian androgen production -Increases SHBG (sex hormone binding globulin) production -Pregnancy should be excluded before therapy with oral contraceptives is started - DUH!

Imaging: Polycystic ovaries are defined as

Ovarian ultrasonography - transvaginal approach Polycystic ovaries are defined as *12 or more follicles in at least 1 ovary* measuring *2-9 mm in diameter* or a *total ovarian volume of >10 cm3* *Classic "String of Pearls" Appearance on Sonogram*

Insulin Resistance and the Ovaries

Ovaries - source of both male and female hormoneInsulin resistance → increased insulin → *hyperinsulinemia + other complex and different change → directly effect ovaries → formation of cysts on the ovaries* (filled with fluid - do not cause ovarian cancer)

MOA of OCPs

Ovulation suppression - suppression of GnRH and pituitary gonadotropin secretion Inhibits mid-cycle LH surge, so no ovulation Suppression of ovarian folliculogenesis, by suppressing pituitary FSH secretion Progestin-related mechanism -Endometrial regression - steady state of reproductive hormones, less proliferation, less secretion -Alteration in cervical mucus -Impairment of normal tubal mobility and peristalsis

In evaluating abnormal bleeding, differentiate between ovulatory and anovulatory

Ovulatory -Regular cycles q 21-36 days (Day 1 is ? ) -Premenstrual sx (bloating, breast pain, irritability) -Dysmenorrhea (first/second day) -BasalBodyTemp - biphasic -Cervical mucus changes Anovulatory is absence of the above

In the history ask about sleep apnea and check for acanthosis nigricans and DM for what syndrome

PCOS

Polymenorrhea Menometrorrhagia Oligomenorrhea Postcoital bleeding (contact bleeding)

Periods that occur too frequently Bleeding that occurs at *irregular intervals*, amount and duration vary Menstrual periods that occur *>35 days apart* Bleeding with cervical contact (intercourse, pap...)

In PCOS what findings really amplifies the degree of the disorder

Peripheral insulin resistance with hyperinsulinemia and obesity amplifies the degree the disorder

Causes of Abnormal Bleeding Common causes by population -Adolescents

Persistent anovulation (PCOS, contraception) pregnancy coagulopathies Infection

For abnormal bleeding what *needs to be done* on your physical exam

Physical examination of the external and internal anatomy of the female genital tract  *A diagnosis cannot be established without speculum and pelvic examination!*

*Most common* cause of infertility in the US

Polycystic Ovarian Syndrome

Causes of Abnormal Bleeding Common causes by population -Third and fourth decades of life

Pregnancy *Structural lesions (polyps, leiomyoma)* Anovulation (PCOS, contraception and endometrial hyperplasia) Infection Thyroid dysfunction

Metformin (Glucophage) - reduces insulin resistance; insulin sensitizer, hepatic glucose output decreased, peripheral insulin-stimulated uptake increased adverse rx?

Pregnancy category B Commonly encountered adverse reactions include anorexia, nausea, vomiting, diarrhea, epigastric fullness, constipation, and heartburn - requires monitoring not to exceed 2500 mg/d

Spironolactone (Aldactone) - potassium-sparing diuretic that can be used to treat hirsutism 50-200 mg/d PO qd or divided bid adverse rx?

Pregnancy category D - Fetal risk shown in humans Hyperkalemia may occur but generally not encountered in patients with normal renal function; GI discomfort, irregular menstrual bleeding

Treatment Goals for abnormal bleeding

Prevent endometrial hyperplasia/cancer -Unopposed estrogen *(<3 month rule)* Prevent/treat anemia -IronDefAnemia secondary to AUB - common Restore quality of life

Hormonal Management

Progestins (progesterone) Uterine lining becomes atrophic Estrogen/progestin combination OCP Patch Ring

NIH Evidence-based Methodology Workshop on PCOS in December 2012 concluded that the ____________________ should be adopted for now because it is most inclusive

Rotterdam criteria

Diagram showing: Normal nutrition Under nutrition Over weight/PCOS

Sex steroids DECREASED in starvation or malnutrition, think anorexia

Systemic Causes of Abnormal Bleeding Trauma

Sexual intercourse (esp. while pregnant) Sexual abuse Foreign bodies Pelvic trauma

PCOS Surgical Care

Surgical management is aimed mainly at restoring ovulation Ovarian wedge resection -Has fallen out of favor because of the efficacy of clomiphene and postoperative adhesion formation Laparoscopic surgery - including electrocautery, laser drilling, and multiple biopsy -Potential complications include formation of adhesions and *diminished ovarian reserve* -No increase in multiple pregnancy (like Clomid)

what is an anovulatory cycle

The anovulatory cycle is a menstrual cycle characterized by varying degrees of menstrual intervals and the *absence of ovulation and a luteal phase*

PCOS ultrasound for rotterdam has to show

The presence of 12+ follicles in each ovary measuring 2-9 mm in diameter and/or increased ovarian volume (>10 mL) One ovary fitting this definition is sufficient to define PCOS

Systemic Causes of Abnormal Bleeding Endocrinopathies

Thyroid disease *Hyperprolactinemia* PCOS Cushing's syndrome

Causes of Abnormal Bleeding Common causes by population -Menopausal women

Thyroid dysfunction *Endometrial atrophy* Endometrial hyperplasia Structural lesions Malignancy

Treatment Goals for abnormal bleeding Correct other endocrine problems such as

Thyroid dz (hypo hyper) Pituitary Ovarian

Patterns of Abnormal Bleeding Hypomenorrhea (cryptomenorrhea)

Unusually light menstrual flow *Can occur with OCP - no tx, reassurance*

Disadvantages of Progestin Therapy

Variable compliance *No protection against ovarian cancer vs OCPs* *No contraceptive protection with progesterone challenge dosing* Cyclic dosing does not provide contraception

Systemic Causes of Abnormal Bleeding Coagulation disorders

Von Willebrand's disease Thrombocytopenia Acute leukemia Advanced liver disease

Insulin resistance and elevated insulin levels disrupt the balancing of hormones in what way

Wrong proportions of female hormone (estrogen) and male hormone (testosterone) Too much free testosterone leads to: Increase in facial and chest hair Losing hair on their heads Increased muscle mass in upper arms and chest Acne Deepening voice Abnormal hormone levels - also *inhibit normal ovulation due to low progesterone*

DUB is diagnosed when?

after exclusion of the pathologic causes of AUB and the terms are NOT interchangeable

PCOS Pathophsyiology deals with abnormalities in the metabolism of

androgens and estrogen and in the control of androgen production. High serum concentrations of androgenic hormones (testosterone, andostenedione, and dehydroepiandrosterone sulfate DHEA-S) *may* be present.

Menorrhagia causes

Causes: submucosal myomas (fibroids), complications of pregnancy, adenomyosis (ectopic glandular tissue), IUDs (copper), endometrial hyperplasias, malignant tumors and dysfunctional bleeding

PCOS possible menstrual abnormalities

Chronic anovulation Oligomenorrhea Secondary amenorrhea Dysfunctional uterine bleeding

Menorrhagia what is considered normal or abnormal

Clots may not be abnormal it may signify excessive bleeding Gushing open faucet bleeding is always abnormal

PCOS what else to consider dealing with diet

Comprehensive program of diet and exercise to reduce the risk of developing DM A diet patterned after the type 2 DM diet emphasizing fiber; decreased refined carbohydrates, trans fats, and saturated fats; and increased omega-3 and omega-9 fatty acids Women with abnormal lipid profile need to be counseled on management *No statins for women planning childbearing* Accumulating evidence suggests that vitamin D deficiency may contribute to metabolic syndrome

Reasons for cycle dysfunction: Hypothalamus

stress weight losstumor*CNS meds**puberty*peri menopause

Approximately 50% of women with PCOS have abdominal obesity characterized by a waist circumference of greater Blood pressure Patients with signs and symptoms of metabolic syndrome may have elevated blood pressure >

than 35 in (>88 cm) 130/85 mmHg

Androgen excess can be tested by measuring

total and free testosterone levels An elevated free testosterone level is a *sensitive* indicator of androgen excess Other androgens, such as DHEA-S may be normal or slightly above the normal range  Levels of sex hormone-binding globulin (SHBG) are usually low (not commonly done)

How many woman with PCOS are obese?

present in nearly half of all women

Medroxyprogesterone (Cycrin, Provera) No effect on androgen production -

progestins stop proliferation of endometrial cells, allowing organized sloughing of cells after withdrawal Often used cyclically