11/9- Irregularities of Menses Flashcards

1
Q

What is puberty?

A

Transition period from sexually immature to potentially fertile stage during which secondary sexual characteristics appear

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2
Q

What are the hormonal players in puberty (and throughout reproduction)?

A
  • GnRH (hypothalamus)
  • FSH (ant pit)
  • LH (ant pit)
  • Sex steroids: estrogen, testosterone (ovary)
  • Insulin like growth factor
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3
Q

What happens to hormones pre-pubertally?

A

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

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4
Q

Describe structures in the prepubertal stage

A
  • Vaginal length: 4-5 cm
  • Uterus: 2.5 cm
  • Uterine corpus to cervix ratio: < 1:1
  • Ovarian volume: around 1 cm3
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5
Q

What hormonal changes occur during puberty?

A
  • 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
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6
Q

What results from the greater sex steroid production for a given level of gondatropin in puberty (structurally)?

A
  • 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
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7
Q

What is the first sign of puberty in girls?

A
  • Thelarche (90%): breast budding
  • Pubarche (10%): pubic hair
  • The beginning of breast development usually corresponds to the onset of a growth spurt
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8
Q

When do menses typically start? Time frame between puberty and menarche?

A
  • Menses start at age 12 on average (Menarche)
  • The onset of puberty to menarche is typically 2 years
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9
Q

Describe Tanner stages for breast development? (can also rate pubic hair)

A

1- child, flat

2- prepubertal

3- early pubescent

4- late pubescent

5- adult

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10
Q

Describe the changes that occur in the menstrual cycle with:

  • Gonadotropins
  • Ovarian steroids
  • Ovarian function
  • Uterine endometrium
A

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
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11
Q

What should be taken with vital signs in all women of reproductive age?

A

Menses (consider menses as a vital sign!)

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12
Q

How is menses recorded summarily (as if a vital sign)?

A

Last menstrual period

  • Refers to FIRST day of last period
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13
Q

Describe a normal menstrual cycle

  • Warning signs of heavy flow
  • When is irregularity normal
A

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

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14
Q

What is amenorrhea?

A

Didn’t have a period in the past 6 mo

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15
Q

What is menorrhagia

A

Heavy period (100-120 mL of blood)

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16
Q

What is metrorrhagia?

A

Normal blood flow but just irregular timing

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17
Q

What is menometrorrhagia?

A

When period are irregular and heavy

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18
Q

What is DUB?

A

Dysfunctional uterine bleeding (term out of use now)

  • Irregular bleeding of unknown cause
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19
Q

What is oligomenorrhea?

A

not having regular periods, less frequent periods but within 6 month intervals

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20
Q

Instead of “DUB”, what do we use now?

  • Classification system
A

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)
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21
Q

How is amenorrhea evaluated?

A

FIRST: EXCLUDE PREGNANCY

  • Hypothalamic
  • PItuitary
  • Ovarian
  • Outflow tract
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22
Q

What can cause hypothalamic amenorrhea?

A

(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
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23
Q

When do you get worried/do a work up for primary amenorrhea?

A

Over the age of 15

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24
Q

What can cause pituitary amenorrhea?

A
  • Hyperprolactinemia
  • Thyroid disease
  • Excessive androgens such as in congenital adrenal hyperplasia/ Cushings syndrome
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25
Q

What are ovarian causes of amenorrhea?

A
  • 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
26
Q

What are outflow tract abnormalities that may lead to amenorrhea?

A
  • 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
27
Q

What is Polycystic Ovary Syndrome (PCOS)

  • Prevalence
  • Definition/cause
  • What else plays a role
A

(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)
28
Q

What are clinical features of PCOS?

A
  • Obesity
  • Hyperandrogenism: acne, hirsutism, deepened voice, clitoromegaly
  • Menstrual dysfunction: oligo/amenorrhea
  • Acanthosis nigricans
  • Hyperinsulinemia
29
Q

What is seen here?

A

Polycystic ovaries

  • Ovaries with thickened tunica and multiple small atretic follicles

(Not actually cysts, just a lot of follicles)

30
Q

What is seen here?

A

Polycystic ovary syndrome on ultrasound (Imaging is not 100% specific, but if the other symptoms are there…)

31
Q

What are biochemical/lab features of PCOS?

A
  • 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)
32
Q

How is PCOS managed?

A
  • 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
33
Q

Describe the subsets of heavy menstrual bleeding

A

PALMC

  • Polyp (AUB-P)
  • Adenomyosis (AUB-A)
  • Leiomyoma (AUB-L)
  • Malignancy/hyperplasia (AUB-M)
  • Coagulopathy (AUB-C)
34
Q

What are uterine fibroids?

  • Single or multiple
  • Size
  • How common
  • Age range
  • Classes/location
A

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
35
Q

What are symptoms of uterine fibroids?

A
  • Abnormal uterine bleeding
  • Pelvic pressure
  • Pain
  • Urinary symptoms
  • Abnormal reproductive function (controversial); infertility could be 2ndary to abnormal placentation
36
Q

What is seen here?

A

Uterine leiomyomata

37
Q

What is seen here?

A

Uterine fibroids on US

38
Q

Describe the cellularity of uterine fibroids

  • Stimulated by what
  • Prognosis
A
  • Unicellular in origin
  • Stimulated by estrogen/progesterone
  • Rapid growth = degeneration
  • Very unlikely to undergo malignant change (sarcomas); rare but perhaps a chance
39
Q

What is the process in evaluating abnormal uterine bleeding?

A
  • 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)
40
Q

What is seen here?

A

Saline sonohysterogram

  • Bottom left is normal
  • Bottom right has polyp
41
Q

What is menopause?

  • Mean age
A

Permanent cessation of menstruation caused by ovarian failure.

  • 12 months of amenorrhea
  • Mean age in US = 51 (unchanged for centuries)
42
Q

How dose premature ovarian failure compare to menopause (age-wise)?

A

Premature ovarian failure is ovarian failure before age 40

43
Q

Women are born with ___ oocytes

  • At menarche, ____ oocytes remain
  • Most women ovulate __ times over their reproductive lifespan
A

Women are born with 1.5 million oocytes

  • At menarche, 400,000 oocytes remain
  • Most women ovulate 400 times over their reproductive lifespan
44
Q

T/F: the age of menarche has changed in recent history

A

False! age of menarche has not changed, but age of puberty has

45
Q

As the oocytes have either ovulated or become atretic, what happens to the ovary?

A

The ovary becomes minimally responsive to pituitary gonadotropins resulting in:

  • Elevated FSH/LH
  • Decreased estrogen/progesterone
46
Q

What are menopausal lab findings?

A
  • Low estradiol
  • FSH > 40

FSH elevation in the face of low E2 is diagnostic of menopause

47
Q

What are consequences of estrogen loss (menopause): symptoms?

A
  • Hot flashes
  • Insomnia
  • Irratibility
  • Mood distrubances
48
Q

What are consequences of estrogen loss (menopause): physical changes?

A
  • Urogenital atrophy
  • Stress incontinence
  • Skill collagen loss
49
Q

What are consequences of estrogen loss (menopause): diseases?

A
  • Osteoporosis
  • Cardiovascular disease (unclear relationship)
  • Cancers (unclear relationship)
50
Q

What are treatments for menopause/symptoms?

A

Ovarian Hormone therapy

51
Q

Describe ovarian hormone therapy

A
  • 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
52
Q

What was found in the women’s health initiative for ovarian hormone therapy?

A

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

53
Q

What were criticisms of WHI?

A
  • 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
54
Q

What is the consensus regarding ovarian hormone therapy?

A
  • 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
55
Q

Describe hot flushes

A
  • 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)
56
Q

What is the etiology of hot flushes?

A
  • 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
57
Q

What are treatment options for hot flushes?

A

Treatment of choice = estrogen

  • Oral ERT
  • Transdermal ERT
  • Low dose OCP (not appropriate for smokers)
58
Q

What are contraindicates to ERT? - Absolute

A

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

59
Q

What are alternatives to estrogen?

A
  • Venlafaxine, Paroxetine
  • Gabapentin
  • Clonidine
  • Medroxyprogesterone, Megestrol
  • Phytoestrogens
  • Herbals: Black Cohosh, Evening Primrose, Dong Quai, Wild Yams
  • Vitamins: E, B6
60
Q

Describe the duration of peri-menopausal symptoms

A
  • Mean duration of climacteric: 4 years
  • Typical treatment: 1-4 years
  • Symptom control and patient desire drives decision