11/9- Irregularities of Menses Flashcards
What is puberty?
Transition period from sexually immature to potentially fertile stage during which secondary sexual characteristics appear
What are the hormonal players in puberty (and throughout reproduction)?
- GnRH (hypothalamus)
- FSH (ant pit)
- LH (ant pit)
- Sex steroids: estrogen, testosterone (ovary)
- Insulin like growth factor
What happens to hormones pre-pubertally?
There is a down regulation of the hypothalamic-pituitary system with reduction of the amplitude and frequency of GnRH pulses secondary to increased sensitivity to negative feedback on the hypothalamus by sex steroids
Describe structures in the prepubertal stage
- Vaginal length: 4-5 cm
- Uterus: 2.5 cm
- Uterine corpus to cervix ratio: < 1:1
- Ovarian volume: around 1 cm3
What hormonal changes occur during puberty?
- At approximately 8 years of age with no other physical changes, GnRH secretion is enhanced due to decreased negative feedback
- Increased responsiveness in pituitary leads to increase secretion of gonadotropins
- FSH increases the enzyme aromatase which produces estrogen
- As puberty progresses, a positive feedback system develops which allows for greater sex steroid production for a given level of gonadotropin
What results from the greater sex steroid production for a given level of gondatropin in puberty (structurally)?
- Vaginal length: 7- 8 cm
- The mucosa of the vagina has epithelial proliferation leading to a thicker vaginal mucosa with a lower pH
- Uterine corpus to cervix ratio: 3:1
- Endometrial stripe thickens and has a tri-laminar appearance on ultrasound
- Ovarian volume: > 1 cm3 with formation of follicular cysts
- Breasts show growth of nipples, mammary terminal ducts branch to form ductules and accumulation of fat in the breast stroma
- A pubertal growth spurt occurs because sex hormones stimulate the GH-IGF axis
- Estradiol leads to epiphyseal closure resulting in a final adult height
What is the first sign of puberty in girls?
- Thelarche (90%): breast budding
- Pubarche (10%): pubic hair
- The beginning of breast development usually corresponds to the onset of a growth spurt
When do menses typically start? Time frame between puberty and menarche?
- Menses start at age 12 on average (Menarche)
- The onset of puberty to menarche is typically 2 years
Describe Tanner stages for breast development? (can also rate pubic hair)
1- child, flat
2- prepubertal
3- early pubescent
4- late pubescent
5- adult
Describe the changes that occur in the menstrual cycle with:
- Gonadotropins
- Ovarian steroids
- Ovarian function
- Uterine endometrium
GONADOTROPINS
- GnRH is pulsatile; stimulates anterior pituitary to produce FSH
- First half of the cycle is more FSH dominated
- LH surge occurs mid-cycle and causes ovulation; following which, LH drops off
OVARIAN STEROIDS
- Estradiol produced
- LH surge stimulates progesterone rise OVARY
- Follicular phase
- Luteal cyst remains after ovulation; if pregnant it will take over ovarian hormone production (until placenta develops)
UTERUS
(day 1 of period = day 1 of menstrual cycle)
- Menstrual phase
- Proliferative phase
- Secretory phase: progesterone triggers move from proliferative to secretory phase; glands develop
What should be taken with vital signs in all women of reproductive age?
Menses (consider menses as a vital sign!)
How is menses recorded summarily (as if a vital sign)?
Last menstrual period
- Refers to FIRST day of last period
Describe a normal menstrual cycle
- Warning signs of heavy flow
- When is irregularity normal
Cycles should be:
- 21-35 days
- 7 days or less
- Typically changing 3-6 pads per day, but there is no definition of heavy menses
Warning Signs
- Changing pads/tampons every 1-2 hours
- Quarter sized or larger blood clots
- Flooding of clothes
Cycles are typically irregular during 1st 2 years after menarche
What is amenorrhea?
Didn’t have a period in the past 6 mo
What is menorrhagia
Heavy period (100-120 mL of blood)
What is metrorrhagia?
Normal blood flow but just irregular timing
What is menometrorrhagia?
When period are irregular and heavy
What is DUB?
Dysfunctional uterine bleeding (term out of use now)
- Irregular bleeding of unknown cause
What is oligomenorrhea?
not having regular periods, less frequent periods but within 6 month intervals
Instead of “DUB”, what do we use now?
- Classification system
Abnormal Uterine Bleeding (AUB)
Then classify with:
- Heavy menstrual bleeding
- Intermenstraul bleeding
Also divide with cause: (PALM-COEIN)
PALM
- Polyp (AUB-P): endometrial lining grows into polyps
- Adenomyosis (AUB-A): endometriosis but in lining of uterus
- Leiomyoma (AUB-L): like in PCOS
- Malignancy/Hyperplasia (AUB- M)
COEIN
- Coagulopathy (AUB-C): VWD in women (most common) or leukemia throwing of clotting factors
- Ovulatory Dysfunction (AUB-O)
- Endometrial (AUB-E)
- Iatrogenic (AUB-I)
- Not yet classified (AUB-N)
How is amenorrhea evaluated?
FIRST: EXCLUDE PREGNANCY
- Hypothalamic
- PItuitary
- Ovarian
- Outflow tract
What can cause hypothalamic amenorrhea?
(Typically refers to primary amenorrhea)
- Constitutional: runs in family; diagnosis of exclusion
- Gonadotropin releasing hormone
- Could be due to something like Kallman’s
- Anorexia/hyperathleticism
- Low body fat/weight
When do you get worried/do a work up for primary amenorrhea?
Over the age of 15
What can cause pituitary amenorrhea?
- Hyperprolactinemia
- Thyroid disease
- Excessive androgens such as in congenital adrenal hyperplasia/ Cushings syndrome
What are ovarian causes of amenorrhea?
- Gonadal dysgensis
- Eg Turner’s syndrome (have ovaries, but they didn’t develop correctly)
- Premature ovarian failure
- Basically early menopause (under age 40)
- Environmental (radiation, chemo, BMT)
- Tumors
What are outflow tract abnormalities that may lead to amenorrhea?
- Mullerian agenesis: no Mullerian structures (e.g. no uterus)
- Uterine synechiae (scarring due to abortions, TB infections, etc.)
- Cervical stenosis (could follow LEEP procedure)
- Transverse vaginal septum
- Imperforate hymen
What is Polycystic Ovary Syndrome (PCOS)
- Prevalence
- Definition/cause
- What else plays a role
(formerly “Stein-Leventhal” ovary syndrome)
- 6-10% of reproductive women
- Oligomenorrhea/amenorrhea associated with hyperandrogenism without other cause
- Role of hyperinsulinemia central to pathophysiology (many are diabetic or insulin resistant)
What are clinical features of PCOS?
- Obesity
- Hyperandrogenism: acne, hirsutism, deepened voice, clitoromegaly
- Menstrual dysfunction: oligo/amenorrhea
- Acanthosis nigricans
- Hyperinsulinemia
What is seen here?
Polycystic ovaries
- Ovaries with thickened tunica and multiple small atretic follicles
(Not actually cysts, just a lot of follicles)
What is seen here?
Polycystic ovary syndrome on ultrasound (Imaging is not 100% specific, but if the other symptoms are there…)
What are biochemical/lab features of PCOS?
- Elevated serum androgens
- Insulin resistance
- Decreased SHBG (sex hormone binding globulin)
- Low progesterone (because not ovulating; no LH surge)
- Normal estrogen! (just never get through middle part of cycle; not higher levels of estrogen, but more exposure throughout lifetime)
- Hyperlipidemia (risk factor for lifetime heart attacks)
How is PCOS managed?
- Treatment dependent on desire for pregnancy
- Pregnancy desired: ovulation induction
- No pregnancy desired: oral contraceptives (increase SHBG to drop tostosterone; helps PCOS and side effects)
- Management of androgenic side effects (e.g. laser hair removal)
- Weight loss (helps with insulin resistance)
- Insulin sensitizers: metformin
Describe the subsets of heavy menstrual bleeding
PALMC
- Polyp (AUB-P)
- Adenomyosis (AUB-A)
- Leiomyoma (AUB-L)
- Malignancy/hyperplasia (AUB-M)
- Coagulopathy (AUB-C)
What are uterine fibroids?
- Single or multiple
- Size
- How common
- Age range
- Classes/location
Leiomyomas; benign tumors of myometrial smooth muscle cells that grow inside wall of the uterus
- Single or multiple
- Range in size up to 20 cm
- Common: 45% of patients by their 40s
May be:
- Intramural (in wall)
- Submucous
- Intracavitary
What are symptoms of uterine fibroids?
- Abnormal uterine bleeding
- Pelvic pressure
- Pain
- Urinary symptoms
- Abnormal reproductive function (controversial); infertility could be 2ndary to abnormal placentation
What is seen here?
Uterine leiomyomata
What is seen here?
Uterine fibroids on US
Describe the cellularity of uterine fibroids
- Stimulated by what
- Prognosis
- Unicellular in origin
- Stimulated by estrogen/progesterone
- Rapid growth = degeneration
- Very unlikely to undergo malignant change (sarcomas); rare but perhaps a chance
What is the process in evaluating abnormal uterine bleeding?
- Rule out pregnancy
- Endometrial biopsy if > 35 yo (determine based on risk factors)
- Saline-infusion sonography (to look at abnormalities of uterine lining/cavity): can ID polyps, fibroids, etc.
- Hysteroscopy/D&C: can do initially if suspect cancer (D/C: dilation and curretage?; scrape off whole uterine lining and send to pathology)
What is seen here?
Saline sonohysterogram
- Bottom left is normal
- Bottom right has polyp
What is menopause?
- Mean age
Permanent cessation of menstruation caused by ovarian failure.
- 12 months of amenorrhea
- Mean age in US = 51 (unchanged for centuries)
How dose premature ovarian failure compare to menopause (age-wise)?
Premature ovarian failure is ovarian failure before age 40
Women are born with ___ oocytes
- At menarche, ____ oocytes remain
- Most women ovulate __ times over their reproductive lifespan
Women are born with 1.5 million oocytes
- At menarche, 400,000 oocytes remain
- Most women ovulate 400 times over their reproductive lifespan
T/F: the age of menarche has changed in recent history
False! age of menarche has not changed, but age of puberty has
As the oocytes have either ovulated or become atretic, what happens to the ovary?
The ovary becomes minimally responsive to pituitary gonadotropins resulting in:
- Elevated FSH/LH
- Decreased estrogen/progesterone
What are menopausal lab findings?
- Low estradiol
- FSH > 40
FSH elevation in the face of low E2 is diagnostic of menopause
What are consequences of estrogen loss (menopause): symptoms?
- Hot flashes
- Insomnia
- Irratibility
- Mood distrubances
What are consequences of estrogen loss (menopause): physical changes?
- Urogenital atrophy
- Stress incontinence
- Skill collagen loss
What are consequences of estrogen loss (menopause): diseases?
- Osteoporosis
- Cardiovascular disease (unclear relationship)
- Cancers (unclear relationship)
What are treatments for menopause/symptoms?
Ovarian Hormone therapy
Describe ovarian hormone therapy
- For 40 years, ovarian hormone therapy (estrogen or estrogen/progesterone) was advocated for prophylactic indications
- Estrogen: women without a uterus
- Estrogen and progesterone: women with a uterus
- Given for hot flushes, osteoporosis
- A # of large observation cohort and case-controlled studies suggested benefit of ovarian hormone therapy to prevent/delay heart disease and Alzheimer’s disease
- No longer given prophylactically due to risks
What was found in the women’s health initiative for ovarian hormone therapy?
Randomized controlled study
Results:
- Protection from osteoporosis
- Reduction in colorectal cancer (37%)
- Increased risk of heart disease (29%)
- Increased risk of stroke (41%)
- Increased risk of thrombosis (100%)
- Increased risk of breast cancer (26%)
Perhaps, therapy would help in early menopause
What were criticisms of WHI?
- Mean participant age >60 years
- Is this data comparable to a woman who recently underwent menopause?
- When the data for women 50-59 was pooled and analyzed separately, there was a trend toward reduced total mortality
- Further studies are pending
What is the consensus regarding ovarian hormone therapy?
- Ovarian hormone therapy is indicated primarily for relief of significant menopausal symptoms such as hot flashes
- Length of treatment should be minimized depending on patient’s clinical course and preference
Describe hot flushes
- Pressure in head, increased warmth to head and trunk
- Last 30 seconds to 5 minutes
- Frequently occur at night
- 80% women experience at menopause and 25-50% have them up to 5 years
- Often resolve without treatment in 2-5 years
- Not pathognomonic of menopause
- (30% of women seek medical attention)
What is the etiology of hot flushes?
- Decrease in circulating estrogen levels causes thermoregulatory center in hypothalamus
- Severity relating to rapidity of change
- Obesity is protective due to increased peripheral conversion of androgens and decrease SHBG
What are treatment options for hot flushes?
Treatment of choice = estrogen
- Oral ERT
- Transdermal ERT
- Low dose OCP (not appropriate for smokers)
What are contraindicates to ERT? - Absolute
Absolute C/I to ERT
- Undiagnosed vaginal bleeding
- Breast cancer: H/O, suspected, current
- Endometrial cancer: under 5 years
- Active venous clot
- Active liver disease
With a uterus, combination therapy is indicated
What are alternatives to estrogen?
- Venlafaxine, Paroxetine
- Gabapentin
- Clonidine
- Medroxyprogesterone, Megestrol
- Phytoestrogens
- Herbals: Black Cohosh, Evening Primrose, Dong Quai, Wild Yams
- Vitamins: E, B6
Describe the duration of peri-menopausal symptoms
- Mean duration of climacteric: 4 years
- Typical treatment: 1-4 years
- Symptom control and patient desire drives decision
