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
Doc, I don’t get a period, but I do bleed occasionally.
How to help this patient?
PCOS
Estrogen → lining gets thick → can’t really maintain itself → periodic bleeding
MANAGEMENT • Weight Loss • OCP • Mirena • Metformin (if DM) • Progesterone (to shed uterine lining 10 days / 3 months)
Is it unhealthy for a super athletic female to not have periods?
YES!
Women who do NOT have periods have low estrogen
LOW BONE DENSITY
We don’t necessarily need her to ovulate, BUT, we do need her to have some estrogen around or else her bones will crumble!
May need to give estrogen …
Patient presents with Hypothalamic Hypogonadism.
Breakthrough bleeding occurs because the uterine lining is SO thin. It’s almost like it cracks and bleeds every so often.
How to manage these pts?
OCP: combo of Estrogen & Progesterone
(we must balance estrogen with progesterone. We cannot just give estrogen or the lining will get too thick and we risk cancer)
Mrs Jones comes in:
“Every month mid cycle about when I ovulate I get some spotting. What is going on?”
Totally normal
Mid-cycle spotting
It is is due to Estrogen & Progesterone dropping at that stage.
This is likely also the source of spotting in peri-menopausal women.
What are the only two possible outcomes following ovulation?
Pregnancy
…or…
Period
D&C
Dilation and curettage (D&C)
- procedure to remove tissue from inside your uterus.
- used to treat heavy bleeding or to clear the uterine lining after a miscarriage or abortion.
►Natural Menopause
…vs…
►Perimenopause
…vs…
►Premenopause
►Natural Menopause:
• permanent loss of ovarian follicular activity
• 12 consecutive months of amenorrhea
• no other obvious pathologic or physiologic cause avg age 51
►Perimenopause:
• period of time prior to the menopause and the first year after menopause
►Premenopause:
• the whole reproductive period prior to the menopause
►Induced Menopause
…vs…
►Postmenopause
…vs…
►Premature Menopause
►Induced Menopause
Cessation of menstruation due to surgical removal of the ovaries OR iatrogenic ablation (ex.chemotherapy or radiation)
►Postmenopause:
from the final menstrual period onward
►Premature Menopause
(Premature Ovarian Insuffciency)
• when menopause occurs two standard deviations below the mean
• generally accepted as age < 40
Do not say “Menopausal”
Instead, say …
Premenopausal
Perimenopausal
Postmenopausal
Menopause is NOT a disease. It is a normal physiological condition!
How does the number of eggs change over time?
7 million just before birth.
Massive reduction down to 400,000 at puberty.
Once the eggs run out, menopause arrives.
So … ovulation ceases once eggs run out.
Out of all the millions of eggs, the average woman only has 400-500 eggs that could potentially result in pregnancy.
Pathophysiology of Menopause
Depletion of ovarian follicles ↓Inhibin ↑↑Activin ↑↑↑↑ FSH & LH ↓↓Estrogen ↓↓Progesterone ↓Androgen levels reduced
Menopause Sx
- Headaches & Hot flashes
- Teeth loosen & gums recede
- Nipples become smaller & flatten
- Breasts droop & flatten
- Backache
- Abdomen loses muscle tone
- Skin becomes drier & develops a rougher texture
- Risk of CV disease
- Vaginal dryness, itching & shrinking
- Stress or urge incontinence
Said differently, what are the issues involved in Ovarian failure
- Menstrual changes
- Vasomotor Symptoms
- Urogenital changes
- Mood changes
- Sexual changes
- CV disease
- Bone Health
What are the menstrual changes that occur as woman approaches menpause?
- Cycles initially get shorter before longer
- Rapid follicular recruitment
- AUB (Abnormal Uterine Bleeding)
- Depletion in primordial follicles
- Amenorrhea eventually occurs.
Abnormal Uterine Bleeding often occurs during what stages of life?
Around menarche (age 14)
Around Menopause (age 50)
Vasomotor Sx can occur Peri-menopause.
Explain.
• Hot flashes/Night Sweats
“sudden onset of intense warmth that begins in the chest and may progress to the neck and face”
- Often associated with anxiety, palpitations, and sweating.
- Can interfere significantly with life.
Vasomotor Sx
Who gets it?
• 75-80% of women experience them
• Generally from 6 months to 5 years but can
last as long as 15 years
• Can occur in the perimenopause
Vasomotor Sx
What causes it?
Etiology:
Estrogen withdrawal leads to …
- Dysregulation of the firing rate of the thermosensitive neurons in the preoptic hypothalamus
- Decreased alpha 2 adrenergic activity
- Significantly smaller thermoneutral zone
Vasomotor Symptoms
How to manage?
►Lifestyle
• Cool rooms
• regular exercise
• stop smoking
►Hormone Therapy • Estrogen alone or with progestin: lowest dose for the shortest duration • Estrogen and SERM (Bazedoxifene) • Progestin • Tibolone
►Non-Hormonal Therapies
• Clonidin alpha 2 agonist
• Gabapentin GABA analogue
• SSRI paraoxetine
►Stellate Ganglion block
►Non-Prescription Therapies
• Controversial for Black Cohosh & Red Clover
• Vit E
• No evidence for acupuncture
In the Hormone-Deprived State:
- Atrophy of urogenital epithelium and subepithelial tissues
- Degeneration of collagen, elastin, smooth muscle
- Decreased blood-flow to tissues
What are the S/S consequences?
- Vaginal Atrophy
- UTI’s
- Incontinence
- Pelvic Prolapse
Vaginal Atrophy occurs in the Hormone-Deprived State.
This is because ... • thinning of the epithelium • less blood flow • vaginal length and diameter shrinks • nerve endings are exposed increased trauma
What are the S/S consequences?
- dyspareunia
- vaginal dryness
- itching
- irritation
Dewscribe the the cahnges in the vaginal mucosa that occur/
►Pre-menopause
…vs…
►Post-menopause
►Pre-menopause • Thick • lush • rugae • moist
►Post-menopause • thin • pale • dry • flat
Why are there more UTIs in post-menopausal women?
- Mucosa is thinner
- Glycogen production declines
- Decreasing levels of lactobacilli
- Reduced lactic acid production
Urinary Incontinence occurs
Why?
Reduction in mean urethral closure pressure
Thinning of bladder mucosa and increased irritation
How does mood change in menopause?
►Some evidence for increased irritability, tearfulness, anxiety, and poor concentration
►Secondary to??
• Fluctuating estrogen levels in the peri-menopause
• Sleep disturbance
Depression is relatively common with menopause?
►Women at risk include: • History of depressive disorders • Poor physical health • Life stressors • Hx of surgical menopause • Long transition
►Why?
• Estrogen – positive effects on serotonin activity
• could be be used in some severe cases of post-menopausal depression
• Up-regulation of 5-HT1 receptors
• Decreased MOA activity
What is the effect of menopause on sex?
• Female sexuality is complex
►What we do know about menopause and sex:
• Lack of estrogen → dyspareunia, decreased vaginal blood flow, altered sensation
• Reduction in ovarian testosterone
• AUB is problematic
• Depressive symptoms affect sexual function
How can all these Sx be managed?
►Address interpersonal and contextual components of relationship/sexuality
►Address biologic factors
– AUB
– Treat vaginal atrophy
– Treat Depression/Anxiety/Stress/Meds
►Routine evaluation of hormone levels has limited value
►Testosterone therapy by physicians experienced in sexual health
CV risk increases drastically post-menopause
Why?
- Less favorable lipid profiles
- Increased insulin resistance
- Increased likelihood of thrombosis
Do we use estrogen?
Current statistics show that hormonal estrogen therapy increases the risk of breast cancer and CV disease.
Is there a Fam Hx of breast cancer?
We can use it, but MUST individualize the treatment and MUST discuss with patient.
IF we use it, use lowest dose for the shortest amount of time to control their Sx.
What is the effect of Menopause on Bone?
Loss of estrogen → accelerated decline in bone density
T-Score
Normal
T> -1
Osteopenia
-1 to -2.5
Osteoporosis
<-2.5
Sum it up … issues with menopause:
►Menstrual problems ►Vasomotor ►Urogenital ►Mood changes ►Sexual Dysfunction
►Long-term health issues:
• CVS Disease
• Bone Health
We only use the term :”Hormone Replacement Therapy (HRT) for younger women being treated for Premature ovarian insufficiency (POI)
For older women (post-menopause) what do we say?
OLDER WOMEN (post-menopause)
“Postmenopausal Hormone Therapy (HT)”
Postmenopausal Hormone Therapy (HT)
What are the goals?
- Reduce estrogen deficiency symptoms (hot flashes, sleep disturbance, cognitive change, vaginal Sx)
- Treat urogenital atrophy
- Prevent osteoporosis
Premature ovarian insufficiency
Definition from North American Menopause Society
“Premature menopause and premature ovarian insufficiency are conditions associated with a lower risk of breast cancer and earlier onset of osteoporosis and CHD, but there are no clear data as to whether ET or EPT will affect morbidity or mortality from these conditions. Despite this, it is logical and considered safe to recommend HT for these younger women, at least until the median age of natural menopause.”
HT & Breast Cancer
HT does not cause cancer. Rather it accelerates the risk of cancer already present.
No increased risk if used less than 5 yrs. After 5 yrs of use there was an added risk. Once discontinued, the risk goes back.
What is the “bad” thing for breast cancer?
Family Hx of Breast Cancer is the biggest player
Obesity, young menarche, HT all PALE in comparison to the power of genes.
Protective Factors
• Exercise
• Early-menopause
What is the analogy for the action of Estrogen & Progesterone?
Estrogen is the fertilizer
Progesterone is the lawn mower
What is the affect of HT on blood?
Estrogen promotes coagulopathy
Risk increases with increased age & increased BMI
Women at risk for venous thrombosis should be cautioned about the added risk from HT
What do we think now of the effect of Estrogen HT on CV risk?
Estrogen therapy does NOT increase the risk of CV disease in the early postmenopausal years, but increases it if begun some time after menopause.
Estrogen-Progesterone Hormone Therapy
(E+P)
This is for women with an intact uterus
Benefits & Risks
►Risks • Venous thromboembolism • Stroke (inconsistent data) • Breast cancer (use beyond 5 years) • Ovarian cancer • Gallbladder disease
►Benefits
• Quality of life
• Bone density
• Colon Cancer Reduction
Estrogen Hormone Therapy
This is for those WITHOUT an intact uterus
(hysterectomy pts)
Benefits & Risks
►Risks • Venous thromboembolism • Stroke (inconsistent data) • Ovarian cancer • Gallbladder disease
►Benefits
• Quality of life
• Bone density
HT ► Sum it up:
We only use HT for during the first 10 yrs post-menopause (CV risk gets too high after that).
Intact Uterus?
• E+P
• Reduced risk of colon cancer
Hysterectomy Pt?
• E only
• no risk of breast cancer with proper Tx
Anatomy of Uterus
►Fundus
(top portion)
►Body
►Cervix
(bottom)
Round Ligament of Uterus
travels through the inguinal canal to Labia majora
Which ligaments secures the ovary?
►Suspensory Ligament of Ovary
– secures it laterally
►Ligament of the ovary
– secures it medially
– attaches to the lateral wall of the uterus
– remnant of the gubernaculum
Where does metastasis spread?
Ovary
..vs…
Uterus
Ovary - lymphatic drainage on posterior side
Uterus - regional lymph nodes
Cardinal Ligament
(=transverse cervical ligament)
Muscles of Female Deep Pouch
►Deep transverse perineal M.

►Sphincter urethrovaginalis
►External urethral sphincter
►Compressor urethrae
Muscles of Female Superficial Pouch
►Superficial Transverse Perineal M.
►Bulbospongiosus M.
(covers Bulb of Vestibule)
►Ischiocavernosus M.
covers Corpus Cavernosus M.
Pudendal Nerve
What are the 3 branches?
Dorsal Nerve of Clitoris
Perineal
Inferior Rectal
19 year old university student
- She has known her current boy friend, a fellow university student, for 6 months and they have been sexually active for 4 months.
- has been using condoms
- regular menses, home preg test positive 1 week after missed LMP
- She presents with her boy friend, very upset and help
OPTIONS?
►BEFORE 14 WEEKS
● Surgical: Suction Aspiration
● Medical: Medical Abortion
►AFTER 14 WEEKS
● Surgical: Dilation and Evacuation
● Medical: Induction Abortion
37 y/o
• happily married for two years
• delighted to find herself pregnant for the first time.
• She and her husband had requested genetic testing. At 16 weeks gestation she had an amniocentesis.
• The genetics laboratory has just phoned you, cytogenetic testing confirms an Trisomy 18
• Now 18 weeks pregnant
OPTIONS?
►BEFORE 14 WEEKS
● Surgical: Suction Aspiration
● Medical: Medical Abortion
►AFTER 14 WEEKS
● Surgical: Dilation and Evacuation
● Medical: Induction Abortion
32 y/o woman presents at gestation
• Homeless
• Substance addiction with use throughout pregnancy
• Abusive relationship
• Three previous children living in Ministry care
• Two previous abortions
• halfway through current pregnancy
OPTIONS?
►BEFORE 14 WEEKS
● Surgical: Suction Aspiration
● Medical: Medical Abortion
►AFTER 14 WEEKS
● Surgical: Dilation and Evacuation
● Medical: Induction Abortion
What is the difference between a maternal indication vs a female indication?
Maternal Indication
• mother’s health
Fetal Indication?
• physical anomaly (e.g. anencephaly)
US Pregnancies
►51% Intended
►49% unintended
22% → birth
20% → abortion
7% → fetal loss
Making abortion legal is the best way to contribute to maternal health.
Countries where abortion is illegal do NOT have less abortion rates. Abortions still happen, they just happen unsafely.
(eg) Abortion is illegal in Africa. They still happen … unsafely, and women die.
IUDs
How long can they be used?
5 yrs in Canada which is very conservative.
Copper IUD has even higher effectiveness as the T arms contain copper which stimulates a local inflammatory response. Sperm cannot travel through this zone.
What % of pregnancies are unintended?
Half!
Therefore, when a woman presents, as “Was this an intended pregnancy?”
What is the average age of first birth in Canada?
30
(women spend the first half of their lives trying to AVOID getting pregnant)
NOTE: More than HALF of all abortions occur in women in their 20s
Are you planning to get pregnant within the next year?
YES?
Let’s help prepare you for that. Folate …
NO?
Let’s make sure you are protected …
Abortion Techniques
►BEFORE 14 WEEKS
● Surgical: Suction Aspiration
● Medical: Medical Abortion
►AFTER 14 WEEKS
● Surgical: Dilation and Evacuation
● Medical: Induction Abortion
Medical Abortion:
►Methotrexate – teratogenic – up to 7 wks LMP only ►Mifepristone – cause "demise" of baby – not yet available in Canada
►Misoprostol
– synthetic PGE1
– causes uterine contractions and the ripening (effacement or thinning) of the cervix → expulsion of pregnancy
- A 15 year old girl consults you worried about her periods. Her parents are patients of your practice.
- Your history and examination reveals an 8 week pregnancy.
- While discussing the pregnancy it is clear she and her same age boyfriend suspected this before seeing you, and that she adamantly wants an abortion…
Ensure there is no delay in the patient receiving the care that they desire
Help them find the care they are seeking
Is she able to understand the choices before her and the consequences before her?
Obligation to not tell parents. This is her private info.
►BEFORE 14 WEEKS
● Surgical: Suction Aspiration
● Medical: Medical Abortion
What if female is 12 y/o and has been assaulted?
Report to Ministry of Children and Family Development
(I am required to report due to the Child, Family and Community Services Act)
By the law, a female who is less than 18 with a partner who >2 years older must be reported (consensual or not)
►BEFORE 14 WEEKS
● Surgical: Suction Aspiration
● Medical: Medical Abortion
POI
What is the controversy?
It is very clear that we NEED to treat.
The controversy is HOW we treat?
HT is sufficient. However, there is still a chance that spontaneous ovulation can occur. Pts may prefer to take OCP as that is what their friends are thinking.
Why does she need Tx?
Increased CV Morbidity & mortality with untreated POI
loss of bone mineral density
Increased risk of Alzheimers
Urogential Sx
QOL
OCP
…vs…
HRT
►OCP
– is like a super physiological dosage; much higher than simple replacement dose
– overrides HPO axis
►HRT
– will not override system
– these women can still ovulate
– women CAN get pregnant!
The action is very different because of the amount of Estrogen that is given. There are many “recipes” for HT. Often requires fine-tuning based on Sx.
38 y/o pt with Amenorrhea
51 y/o with Amenorrhea
►38 y/o pt with Amenorrhea
– POI
– check hormones. FSH will be elevated in POI as the hypothalamus is trying to “wake up” the ovaries which are acting insufficiently.
►51 y/o with Amenorrhea
– Natural menopause
– Therefore, do not check hormones. Hormones are a roller coaster through menopause. Results will be meaningless
My friend swears by progesterone cream. She does’t take Estrogen. Can I just use that?
►Progesterone cream – Unregulated – People are trying to use it as a replacement for systemic Progesterone. – Studies have shown no benefit. – No secretory change in endometrium
What is Black Cohesh?
Actaea racemosa
– native NA herb
– we don’t suggest it, but people may ask
– may be helpful in the short term (six months or less) for women with symptoms of menopause
– Weil says it may be helpful to some women experiencing menopausal symptoms, but is not effective for all women.
Who is HT for?
ONLY indicated for Sx control & improved QOL within the first 10 yrs of post-menopause.
Asherman’s Syndrome
- genetic condition
- intrauterine adhesions/scarring or synechiae
- acquired uterine condition, characterized by the formation of adhesions (scar tissue) inside the uterus and/or the cervix
Sheehan’s Syndrome
• aka “postpartum hypopituitarism”
- During pregnancy, the pituitary expands due to hormonal demands.
- Severe hemorrhage during delivery can drop BP so low that the O2-greedy pituitary infarcts.
RESULT: causes the permanent underproduction of essential pituitary hormones
• relatively common before modern medicine
Kallman Syndrome
- genetic condition
- failure to start or complete puberty
- affects males & females
- hypogonadism & infertility
- altered sense of smell
- hypothalamic neurons that are responsible for releasing GnRH fail to migrate into the hypothalamus during embryonic development
Menopause Effects
Short Term
…vs…
Long Term
Short-Term • menstrual problems • vasomotor • urogenital • mood changes • sexual dysfunction
Long-Term
• CV disease
• Bone Health
POI
What are the causes?
- Turner’s
- Fragile X Premutation Carriers
- Radiation
- Drugs
- Auto-immune
Post-menopausal women can be treated with up to 5 yrs of HT for severe Sx.
HOWEVER, this is contra-indicated in those with a positive family Hx of breast cancer.
How then to manage vasomotor Sx?
SSRI
Paroxetine (Paxil)
SNRI
• Venlafaxine (Effexor)
Where do women get their testosterone?
- Most is from the Kidney Zona Reticularis via LH & FSH
- 60% bound to SHBG (sex hormone binding globulin)
- 35& bound to Albumin
- 1-2% free (ACTIVE FORM)
What are S/E of taking Estrogen?
- decreased libido
- weight gain
- moodiness
- nausea
- breast tenderness
Estrogen increases SHBG → ⬇︎Free form → less Active Testosterone → ⬇︎Libido
What’s the deal with smoking and taking the pill?
We always want people to stop smoking. Studies have demonstrated an association of increased CV risk when smoking is combined with the pill.
Once a woman reaches age 35 it is “loosely” contra-indicated. We can use this as motivation for the patient. We need to kick the habit in order to stay on the pill.
Estrogen Dosage
HT►0.625 mg
What did Angelina Jolie have done?
Oophorectomy & Mastectomy
She had a strong family Hx of Breast Cancer & ovarian cancer. Some doctors in the states have advocated removing the breasts & ovaries & fallopian tubes in women with such risk factors once they are done having kids. There is a move towards this in the US. We have been told to simply wait till their normal physiological menopause and let their hormones discontinue naturally.
How do we screen for Ovarian Cancer?
We don’t. There is no screen. It often can go undetected until advanced.
What is the effect of removing the ovaries?
Menopause! It’s kind of like POI but without ANY risk of getting pregnant.
Without ovaries, there is no risk of ovarian cancer! Jolie also has breasts removed due to her BRCA risk.
She has lost her hormone source. HRT can be delivered via estrogen patch and a progesterone intrauterine device.
How could supply HRT to Jolie?
►Estrogen Patch – "Estradot Patch" – "OrthoEvra®" – via transdermal – worn for 3 consecutive weeks (changed every week) then 1 week off for menstruation – applied to lower abdomen or buttocks.
►Progesterone IUD
(eg) Mirena
Depo-provera®
Depot medroxyprogesterone acetate
(DMPA)
- long acting reversible hormonal contraceptive birth control drug
- Injected every three months
- progestin-only contraceptive
OC
MOA?
Progestogen negative feedback decreases the pulse frequency of GnRH release by the hypothalamus, which decreases the secretion of FSH and greatly decreases the secretion of LH by the anterior pituitary. No LH surge
Decreased levels of FSH inhibit follicular development, preventing an increase in estradiol levels.
Progestogen negative feedback and the lack of estrogen positive feedback → NO LH SURGE!
Causes inhibition of follicular development and the absence of a LH surge prevent ovulation.
OC: “the pill”
How does it work?
►To prevent ovulation.
►To thicken cervical fluid, impeding the progress of sperm.
►To weaken the uterine lining (keeps thin)
For the 28-pill packet, 21 pills are taken, followed by a week of placebo to maintain schedule
placebo pill also contains iron
pill suppresses the normal cycle, and the withdrawal bleeding occurs while the placebo pills are taken.
withdrawal bleed sometime during the placebo week, and is still protected from pregnancy during this week
“beads on a string”
What is this referring to?
Ovarian “cysts” which are actually astral follicles
visible on transvaginal U/S
Dx: PCOS
A 44-year-old gravida-1, para-1 woman has continuous vaginal bleeding for 21 days. She is hemodynamically stable. She normally has menses occurring every 28 days and lasting 5 days. Physical examination, including pelvic exam, is normal. A pregnancy test is negative. The most appropriate next step in management is:
Endometrial Sampling
We MUST rule out an anatomical cause for her bleeding (endometrial hyperplasia or cancer) before assuming that it is dysfunctional uterine bleeding and beginning treatment especially in the non-urgent clinical scenario.
A 35-year-old woman presents with secondary amenorrhea. She relates that she has not been sexually active for over one year. She denies any hyperandrogen symptoms.
She has noticed fatigue and weight gain over the past year.
What lab work?
Pregnancy test (always!) FSH TSH PRL E2
What is E2?
estrone (E1)
estradiol (E2)
estriol (E3).
Which are / are not Sx of Amenorrhea?
►hot flushes ►insomnia ►galactorrhea ►visual disturbances ►superficial dysparunea ►lack of energy ►urinary frequency ►nausea ►hirsuitism
ARE Sx ... ►hot flushes ►insomnia ►superficial dysparunea ►lack of energy ►urinary frequency
NOT Sx ... ►galactorrhea ►visual disturbances ►nausea ►hirsuitism
What is the most common FIRST sign of menopause?
change in menstrual pattern.
- 48 y/o woman
- had a hysterectomy at 45 for dysfunctional uterine bleeding
- now suffering from severe hot flushes and wishes to discuss HT
What HT should we give?
Estrogen only
NOTE: A Women who has had a hysterectomy is not at risk for Endometrial Cancer and therefore can safely take only estrogen.
Estrogen
…vs…
Progesterone
What are common S/E?
►Estrogen
– breast tenderness
– nipple sensitivity
– vaginal discharge (increased physiological discharge).
►Progesterone
– breast tenderness
– bloating
– increased appetite
The risk of HT includes which of the following?
►increased risk of venous thromboembolism
►increased risk of gallbladder disease
►increased risk of Alzheimer’s disease
►increased risk of unscheduled vaginal bleeding
►increased risk of mastalgia
Is a risk of HT:
►increased risk of venous thromboembolism
►increased risk of gallbladder disease
►increased risk of unscheduled vaginal bleeding
►increased risk of mastalgi
NOT a risk of HT:
►increased risk of Alzheimer’s disease
