Repro 2 Menopause Flashcards
Abnormal Uterine Bleeding
What is it?
►Dysfunctional bleeding
…or…
►Structural Bleeding
• eg polyp
Dysfunctional bleeding (no structural cause)
Who gets it?
►PCOS ►Hypothalamic Hypogonadism ►Perimenopausal Pts ►Adolescents (postmenarchal) ►Hyperprolactinemia
Abnormal Uterine Bleeding
ACUTE
…vs…
CHRONIC
►ACUTE
Episode of bleeding requiring immediate intervention
►CHRONIC
>6months
does not require immediate intervention
Normal cyclical bleed
What is the basic flow of hormones?
Require a sequence of endocrine signals to characterize the cycle as ovulatory
• Estrogen first
• Followed by Progesterone
• Regression of both hormones
What do women with menorrhgia have greater endometrial levels of?
Women with menorrhgia have greater endometrial levels of PG12
How do cycles change over the span of a woman’s life?
First 5-7 yrs after menarche, cycels are longer
Become shorter over the reproduvcet years (more cycles per year)
9-10 yrs before menopausem ycles lengthen (less total per year)
Assessing amount of menses flow?
Average blood loss:
40 +/- 20 cc
Do you have accidents?
How often do you need to change pads?
Do you pass clots?
►Menorrhagia
►Metrorrhagia
►Menometrorrhagia
►Menorrhagia
– Prolonged (>7 d) or excessive (>80 cc) uterine bleeding
occurring at regular intervals
►Metrorrhagia
– uterine bleeding at irregular intervals, particularly between the expected menstrual periods
►Menometrorrhagia
– combo of the previous 2
– Prolonged uterine bleeding occuring at irregular intervals
Classification System
Structural Entities
…vs…
Non-Structural Entities
►PALM Structural Entities – Polyp – Adenomyosis – Leiomyoma – Malignant & Hyperplasia
►COEIN Non-Structural Entities – Coagulopathy – Ovulatory Dysfunction – Endometrial – Iatrogenic – Not Yet Classified
Non-Structural Entities
What to order?
Day 3 FSH Estradiol Prolactin TSH Day21 Progesterone (7 days back from menses) ß-HCG (preg test!)
CBC
Ferritin
vW factor
Coags
Renal or Liver Panel
Anovulatory Bleeding
(Dysfunction Uterine Bleeding)
DDx
►Physiological – Adolescence – Perimenopause – Lactation – Preganncy
►Pathological Hypothalmic – Anorexia nervosa – Kallman's Syndrome Pituitary – Hyperprolactinemia – Hypothyroidism – Primary pituary disease Hyperandrogenic anovulation – PCOS – Andrgoen producing tumor – CAH Ovarian – PCOS – Ovarin Failure
The likely cause of abnormal bleeding will change whether the woman is young or old
►Birth
Estrogen Withdrawal
►Birth to 10 Foreign Body Trauma Infection Ovarian Tumor Sarcoma Botryoides
►10-14 Anovulation Coagulopathies Infections Preg Complications
►14-50 Anovulation Hormonal Contraception Preg Complications Infections Endocrine Disorders Polyps & Myomas
►50+ Anovulation Polyps & Myomas Endometrial Hyperplasia Cervical / Endometrial Cancer Vaginal / endometrial Atrophy Hormone Therapy Endometrial Cancer
Hypothalamic Amenorrhea
GnRH Pulsatility
– abnormal / low
LH / FSH Release is
– low
Estrogen Levels are
– very low
End Organ Response
– thin Endometrial lining
Amenorrhea
definition
- No menses by 14yrs AND no secondary sexual characteristics
- No menses by 16 yrs WITH secondary sexual characteristics
- With previous menses, absence of 3 consecutive cycles or 6 months
Saline Infusion Sonogram
“sonohysterogram”
- U/S that uses sterile water to distend the uterine cavity to obtain more accurate info about fibroids, polyps, or the lining of the uterus.
- can determine with great accuracy how much a fibroid is pushing into the cavity of the uterus.
- useful to detect an endometrial polyp
Hysteroscopy
Scope of uterus
- requires dilation of cervix
- best done when the endometrium is relatively thin, that is after a menstruation
Polyps can cause abnormal bleeding
How?
they have a vessel going to them
Adenomyosis
(ad-uh-no-my-O-sis)
…vs…
Endometriosis
Adenomyosis
• occurs when endometrial tissue, which normally lines the uterus, exists within and grows into the muscular wall of the uterus
• ectopic endometrial tissue (the inner lining of the uterus) within the myometrium
• Thickened wall of uterus can be mistaken for fibroids
• typically disappears after menopause
Endometriosus
• endometrium grows outside the uterus
• most commonly involves the ovaries, bowel, or tissue lining your pelvis.
Hysterectomy
What is it?
Removal of Uterus
MANY REASONS ….
Leiomyoma
- benign smooth muscle neoplasm that is very rarely (0.1%) premalignant
- can occur in any organ, but mot commonly in the uterus, small bowel and the esophagus.
- It is essentially tissue that simply grows around a single blood supply
- can cause bleeding
- can grow inside wall or more in the submucosa
Uterine Fibroids
• benign tumours that grow in, on or outside of the wall of the uterus. They usually range in size from as small as a pea to as large as a grapefruit
• occur in 40% of women of childbearing age
Submucosal Fibroids
Sx?
- Unusually heavy or prolonged menstrual periods
- Severe abdominal cramps during menstrual periods
- Bleeding between menstrual periods
- Postmenopausal bleeding
- Infertility due to mass effect
- Pelvic pain
- Back pain
- Large submucosal fibroids can cause some discomfort in the lower abdomen
- Severe pain, if the stalk of the pedunculate submucosal fibroid twists or if the uterine fibroid outgrows its blood supplies
Malignancy & Hyperplasia
this is what we need to exclude!
Endometrial Biopsy
can be crampy, but not painful
Who should we biopsy?
Post-menopausal women …
with ANY uterine bleeding (spotting or staining)
with Endometrial thickness >4mm
Age 45 to menopause
with ANY abnormal uterine bleeding who are ovulatory
<45
Abnormal uterine bleeding that is persistant
Endometritis
&
Cervicitis
(this would be low down on our Ddx)
Gonorrhea & Chlamydia
Present with • Purulent discharge • Post-coital bleeding • Pevlic Tenderness • Fever
Ectopic Pregnancy
What is it?
• Implantation of embryo outside of the uterus.
• 98% in fallopian tube
(extrauterine pregnancy)
Sx:
• abdominal pain
• vaginal bleeding
• >50% are asymptomatic before tubal rupture
Ectopic Pregnancy
Tx?
MEDICAL EMERGENCY
Dx:
• Confirm Pregnancy (B-HCG)
• Bedside U/S
Tx:
Abort … Methotrexate
Chronic Bleeding
Hx?
Risk of preg?
Ovulatory vs non-ovulatory cycles?
(regular cycles or confusing/ random cycles?
LMP, Cycle length, days of bleeding, # of pads, flooding, clots, accidents, blood transufsions, admissions to hopsital
Intermenstrual bleeding?
Post-coital bleeding?
Had Paps?
(assess risk of Cervical Cancer)
Use of hormones, endocrine Sx …
Treatment Options for Abnormal Bleeding–
►Medical Options
– Estrogen - used for acute events only
– NSAID’s, anti-fibrinolytics - endometrial ovulatory AUB
– OCP, cyclical progesterone - anovulatory AUB
– Mirena - anovualotry or avulatory AUB
►Surgical Options (for those who have done having kids)
– Ablation
– Resection
– Hysterectomy
(burn, cut away or remove the whole lining)
Abnormal Uterine Bleeding
What is the number one thing we need to rule out?
PREGNANCY
Always get a preg test
ß-HCG
Primary Amenorrhea
def
No menses by 14 yrs AND absence of secondary sexual characteristics
… or …
No menses by 16 yrs WITH presence of secondary sexual characteristcs
Secondary Amenorrhea
def
Previous history of menstruation
… & …
No menses for 3 cycles or 6 months
Amenorrhea – Systems Approach
- Hypothalamus
- Pituitary
- Thyroid
- Adrenal
- Ovary
- Uterus
- Cervix
- Vagina
- Hymen
Amenorrhea
Hx
►Outlet – cyclic abdominal pain, unsuccessful tampon/sexual intercourse
►Uterus/Cx – Pregnancy, STI, previous D&C
►Ovary – Moliminal, menopausal, androgen,
mass
►Pituitary – Thyroid, PRL, adrenal
►Hypothalamus – chronic illness, previous radiation, trauma, diet, exercise, stress, eating disorders
● Mass symptoms – headache, vision changes
● Kallman’s syndrome – anosmia
Amenorrhea
Phx Exam
►Record of growth, Tanner stages, Ht/wt %
►Vitals - BP
►Head to Toe ● Neuro exam – Thyroid ● Tanner Breast – Abdominal ● Genital - External genitalia, virilization, estrogenization ● Skin - Acne, hirsutism, Café Au Lait
Primary Amenorrhea - Investigations
►bHCG ►FSH, LH, E2 ►PRL, TSH ►Progesterone challenge test – If negaEve, consider Head imaging ►Androgens (if Sx) – testosterone – androstenodione, DHEAS, – 17 OH Progesterone (congential adrenal hyperaplasia) ►Pelvic U/S ►Karyotype ►MRI Head
Gonadotropic Classification of Amenorrhea
►Hypergonadotropic hypogonadism – Ovaries are “failing” – FSH high – LH high – Estradiol low
►Hypogonadotropic hypogonadism – CNS is “Failing” – FSH low – LH low – Estradiol low
►Eugonadotropic eugonadism – Gonads are working just fine ... look elsewhere – FSH normal – LH normal – Estradiol normal
►Hypergonadotropic hypogonadism
Investigation?
Once we rule out
– excessive exercise
– anorexia
MRI Head
MRI - better at looking at pituitary than CT
Hypogonadotropic Hypogonadism
```
CNS Etiology
structural
~~~
►Adenoma, Prolactinoma, craniopharyngioma, other CNS lesions
►Sheehan’s syndrome
►Kallman’s Syndrome
• Isolated GnRH deficiency caused by disrupted GnRH neuron migration
• Anosmia, +/- midline facial defects
• Possible KAL1 gene mutaEon
►Idiopathic hypogonadotropic hypogonadism
►FSH β mutation
Hypogonadotropic Hypogonadism
Non-CNS
non-structural
►Anorexia (thin pt) ►strenuous exercise ►Stress ►Primary hypothyroidism ►Hyperprolactinemia ►Physiological delay
(the brain is essentially saying … “this is NOT a good time to have a baby!”)
Eugonadotropic Eugonadism
►Endocrinological etiology
– PCOS
– Hyperprolactinemia
►Structural
– Reproductive tract
Special Tests: – Physical exam – TSH, PRL, androgens (if symptomatic) – Progestion challenge test – U/S
Progesterone Challenge Test
►Provides an estimate of the estrogen concentration and confirms the presence of an estrogen-primed uterus
• Medroxy-progesterone 5-10 mg q daily for 5-10 days
• Micronized progesterone 200-300 mg q daily for 5-10 days
►Positive response = normal withdrawal bleeding (3-5 d of menses) usually occurring 2-3 days after the end of progestion, but up to 10 days tells us there is progesterone on board
• Will be positive in 90% of women with E2> 50 pg/mL
Hyperprolactinemia
Elevated Prolactin,
Low/normal gonadotropin levels
Causes:
– prolactin-inducing medications
– hypothyroidism
– pituitary tumor (prolactinoma)
Outflow Tract Abnormalities
►Congenital
• Imperforate hymen
• Vaginal septum (Transverse, longitudinal)
• Cervical agenesis – Mullerian agenesis - MRKH
►Acquired
• Asherman’s
Mullerian Agenesis - MRKH
►Defect in Anti-Mullerian Hormone (AMH) gene
►Normal Breasts, Normal pubic hair, Normal ovaries
• No uterus/cervix/upper vagina (missing gene = no uterus!)
►10-40% have renal abnormality
►10-15% skeletal abnormality
►Tx
• Psych Support, Sexual activity, Fertlity
• First Line - Vaginal Dilators
• Second Line – Surgical neovagina
Hypergonadotropic Hypogonadism
►Primary ovarian Insufficiency
– Previously termed premature ovarian failure
►Normal Karyotype
►Abnormal Karyotype
Hypergonadotropic Hypogonadism
Investigations
SPECIAL TESTS
►Karyotype
►Auto-immune work-up – thyroid, pancreas, adrenals, ovaries • AnE-TPO ab, • anti-thyroglobulin ab • anti-adrenal ab • anti-ovarian Ab • HbA1C • am cortisol • calcium • phosphate
Hypergonadotropic Hypogonadism
Normal Karyotype
►Previous ovarian surgery
►Chemotherapy, RadiaEon therapy
►Gonadal dysgenesis
►Autoimmune • Addison’s Disease • Thyroid disease • Type 1 DM, • Myasthenia Gravis • SLE
►Receptor mutations – RARE!
• Savage syndrome: Mutations in FSH receptor
►Idiopathic
Hypergonadotropic Hypogonadism
Normal Karyotype
Fragile X (FMR1) Premutations
– Increased CGG repeats in FMR1 gene (Xq27.3)
– Most common inherited cause of mental retardation and autism
– Family history of autism, mental retardation, developmental delay, POI
– 14% in familial POI, 1-7% in sporadic
Hypergonadotropic Hypogonadism
Abnormal Karyotype
►Turner Syndrome
– 45XO
– Mosaics – 45X0/46XX, 45X0/46XY
►46XY
– Androgen Insensitivity Syndrome
– Swyer syndrome – Non-functioning SRY mutation (body does not recognize SRY)
Turner Syndrome
►Short stature, webbed neck, low set ears/ hairline, wide spaced nipples/shield chest, short 4th metacarpal, wide carrying angle, absent sexual development
►Mosaic 50%, 5% XY
►15% begin puberty, 5% menstruate
►Treatment
– Pubertal Induction
– Hormone Replacement
– Fertility, Contraception
Disorders of Androgen Action(AIS)
►X linked recessive
►Mutation in gene coding for androgen receptor resulting in insensitivity to androgens
►Inguinal testes (no spermatogenesis), breast development, no pubic hair, blind vagina, no uterus
• Breast development – peripheral conversion of testosterone to estrogen
►Complete – gonadectomy at puberty
►Incomplete – may be virilized, gonadectomy at dx
Androgen Synthesis Disorder•
• 5alpha reductase deficiency (T—error—DHT) – Autosomal recessive
– Internal male, external female
– Virilize at puberty
Hypogondatotropic Hypogonadism
Tx
“The weight at which you last had regular menstrual cycles is the weight you need to be to get them back”
(Anorexia, strenuous exercise)
- Reduce stress
- Pregnancy → Ovulation induction with gonadotropins
Eugonadotropic Eugonadism
Tx?
►Hypothyroidism – synthroid
►HyperprolacEnemia – correct underlying cause, Bromocriptine, cabergoline
►PCOS – healthy weight
• Treat the concerning symptom – acne, hirsutism, regular progestin withdrawal to prevent endometrial hyperplasia
►Pregnancy
• Ovulation induction – clomiphene citrate, mesormin, laparoscopic ovarian drilling, gonadotropins
Hypergonadotropic hypgonadism
►Psychological support
►Hormone Replacement until age of menopause
• If delayed puberty – may require pubertal induction
• Hormone Replacement
– Estrogen and cyclic progestion
– Combined Oral Contraceptive
►15% can resume ovulation, 5-10% may become pregnant
• Counsel on contraception
►Fertility
• Oocyte donation, Adoption
What medication could we use to promote folliculogenesis?
Clomiphene Citrate!
Breast - NO
Uterus - YES
- POI
- Gonadal dysgenesis – Turner, Swyer
- Autoimmune oophori5s
- Fragile X premutation
- Iatrogenic – RT, chemo
- Galactossemia
Hypo – ED, stress, chronic, Kallman, craniopharyngioma, infection
Breast - NO
Uterus - NO
- XY karyotype
- agonadism – vanishing testes
- Enzyme def
Breast - YES
Uterus - YES
- Outflow tract obstruction
- Anovulation
- high PRL
- Hypothyroid
- PCOS
- Hypothalamic
Breast - YES
Uterus - NO
- AIS
* MRKH
Endometrial Cancers
What are most derived from?
Most are Carcinomas
arise from epithelium that lines endometrium and forms the glands
What happens to the Transitional Zone of the cervix as a woman ages?
It retreats into the internal os.
In other words, in a younger woman, there is lots of pink that is visible. However, we will need a brush to reach that same area in an older woman because it moves up.
Umbilical Vein
What does it carry?
carries oxygenated blood from the placenta to the growing fetus
20 mmHg
Within a week of birth, it is completely obliterated and is replaced by a fibrous cord:
“round ligament of the liver”
“ligamentum teres”
Umbilical Artery
What does it carry?
carries de-oxygenated blood from the placenta to the growing fetus
50 mmHg
There are TWO … one for each side of the body
Who has a thin lining?
- Pre-pubescent
- Just after menses (day 3)
- women on OC
- Post-menopause
Anytime Estrogen is not around!
Who has a thick lining?
- Right before menstruation
- PCOS
Anyone with unopposed Estrogen
