4/10 Normal and Abnormal Menstrual Cycle

Question 1

Define dysfunctional uterine bleeding

Answer 1

Generally refers to anovulatory bleeding, or bleeding that is not from an anatomical etiology

Question 2

Define breakthrough bleeding

Answer 2

Unexpected bleeding that occurs while a woman is on exogenous hormonal meds.

Better term: unscheduled bleeding. No correlation with the ovulatory process.

Question 3

Define metrorrhagia.

Associated with anovulation or oligoovulation?

Answer 3

Irregular, frequent bleeding

Question 4

Define menorrhagia.

Associated with anovulation or oligoovulation?

Answer 4

Prolonged or excessive menstrual blood loss with regular cycles

Ovulation is occurring; etiology is not due to anovulation

Question 5

Define meno-metrorrhagia.

Associated with anovulation or oligoovulation?

Answer 5

Irregular menses with prolonged or excessive blood loss.

Question 6

Why can eating disorders, stress, excessive exercise affect levels of LH and FSH?

Answer 6

Neural transmitters (dopamine, serotonin, endorphins) affected by all of those – and are very important to GnRH release.

Question 7

Teens: we know that they bleed due to a negative feedback system between FSH and estrogen. Why don’t they also ovulate for the first few years?

Answer 7

They don’t make enough estrogen to cause ovulation

Remember we need an estrogen level around 250 for 2 days in order to induce LH surge -> egg extruding from follicle.

Question 8

Corpus luteum: what does it produce?

Answer 8

Mainly progesterone.

some estrogen

Question 9

What creates the cleavage plane between the uterine basalis and the endometrium?

Answer 9

Progesterone. both compacts down the endometrium and creates the cleavage plane.

Question 10

Cards for the normal menstrual cycle are elsewhere, but here is Ann Davis’ quick review:

Answer 10

• Estrogen low -> FSH rises
• FSH stimulates follicles that increase estrogen; dominant follicle emerges
• As estrogen reaches a peak the LH surge occurs followed by ovulation
• Cellular remains of ovulatory follicle become the corpus luteum: producing progesterone, compacts the endometrium
• If CL does not “see” hcg by day 11 it withers away. Estrogen and progesterone withdrawal creates bleed
• Low estrogen thru negative feedback causes FSH to rise

Question 11

What are the 2 phases of the menstrual cycle?

What hormone dominates each, and what effect does it have on the endometrium?

Answer 11

Proliferative/Follicular:

Estrogen dominates. Causes growth of the endometrium.

Secretory/Luteal:

Progesterone dominates. Causes compaction/stabilization of the endometrium.

Question 12

The menstrual cycle is a gonadotropin independent or dependent phase?

Answer 12

Gonadotropin dependent.

The gonadotropin-independent element of the cycle occurs before the cycle??

Question 13

During the secretory phase, what stimulates VEGF?

what consequences does this have for the corpus luteum?

Answer 13

LH stimulates VEGF - therefore it is LH that causes the CL to be so vascular.

CL is one of the most vascular structures in the body.

Occasionally a CL will bleed (especially a patient on anticoagulants or with a bleeding disorder)

Question 14

what is responsible for primary dysmenorrhea?

Answer 14

Prostaglandins: PGF2a

Women w dysmenorrhea have up to 10x higher levels of PGF2a than others.

PGF2a also stimulates uterine contractions.

Question 15

What defines a normal menstrual cycle in:

• cycle length?
• amount of flow?

Answer 15

• cycle length: Range 22-45d. Median 27d, Mean 29d
• amount of flow: 20-45 mLs

Question 16

why does cycle length decrease just prior to onset of menopause?

Answer 16

follicular reserve is in decline, so estrogen levels decline earlier.

allows FSH levels to risk more quickly/earlier.

It’s the follicular phase that will vary in length: not the luteal phase!

Question 17

How much blood loss is too much?

Answer 17

More than 80 mLs will lower hemoglobin, hematocrit and serum iron levels….

Question 18

Is a woman’s self-reported blood loss a good indication of her actual blood loss?

What correlates with increased blood loss?

Answer 18

Self-reports are not very accurate (even if based on numbers of pads/tampons)

Better indicator of increased blood loss/RBC loss is passing clots.

Question 20

What are the characteristics of normal menstruation? (5)

Answer 20

1. Structurally stable endometrium
2. Rapid withdrawal of hormonal support
3. Universal endometrial events
4. Progressive vasoconstriction and final hemostasis of coiled arterioles
5. Return of hormonal support with increasing estrogen levels to promote healing and induce regrowth of the endometrium

Question 21

Normal ovulatory cycle: what is happening with hormone levels and receptors related to endometrial growth and shedding?

(ie, at the point of each of these pics)

Answer 21

Left pic: Endometrial growth. Estrogen is priming the endometrium: increase in E2 receptors, increase in progest receptors

Middle: Progesterone-stabilized endometrium. Decrease in both E2 and Progest receptors.

Right pic: Hormonal support of the endometrium is withdrawn -> shedding.

Question 22

PCOS: patients typically have amenorrhea – or menses of what length?

What is the ovulation status of PCOS patinets?

Answer 22

PCOS patients: typically have amenorrhea or irregular menses (outside the 21-45d range)

Typically have anovulation or oligoovulation

Question 23

What is one problem that occurs in PCOS as a direct result of not having progesterone?

Answer 23

Endometrium lacks well-developed structure.

There’s no cleavage plate between the basalis layer and the endometrium - lack of orderly vascular changes for shedding.

Question 24

Put these events in the correct order for normal female pubertal development:

Menarche

Pubarche

Thelarche

Ovulation

Answer 24

1 & 2. Thelarche/Pubarche (usually T first, but may be reversed)

3. Menarche
4. Ovulation

Question 25

How long between menarche and a time when 50% of cycles are ovulatory?

Answer 25

Depends on age at menarche.

If menarche is < 12y, 50% cycles will be ovulatory 1yr later.

If menarche is > 13y, 50% cycles will be ovulatory by 4.5y later.

Question 26

Do adolescents establish a normal menstrual rhythm immediately following menarche?

Answer 26

They should cycle between 21-45 days, with great cycle to cycle variation until ovulation begins.

Rhythm reflects normal feedback between FSH and E2 in the anovulatory postmenearchal teen.

Question 27

What would cause us to evaluate menstrual cycle irregularity in a teen?

Answer 27

• regular periods that become very irregular
• menses occuring more freq than 21d or less often than 45d

Question 28

What are some common causes of adolescent menorrhagia?

Answer 28

• Blood dyscrasias: von Willebrand, ITP (20%)
• Chronic anovulation (75%)

Question 29

Cycling outside 21-45 days caused by reasons that can be classified as “Ovulatory” – what are some of those reasons?

Answer 29

• Usually it is a normally-functioning HPO axis with something superimposed creating the short or long cycling.*
• Pregnancy
• Infectious (cervicitis, PID)
• Blood dyscrasias
• Anatomic (polyps, hemangiomas, malformations, myomas)
• Other: endometriosis

Question 30

Cycling outside 21-45 days caused by reasons that can be classified as “Anovulatory” – what are some of those reasons?

Answer 30

Hypothalamic: Psychogenic, stress, diet, exercise – CNS tumors – systemic disease

Endocrinopathies: PCOS, Thyroid, prolactinoma, CAH, Cushings, POF

Other: Ovarian steroid-producing tumors, endometrial cancer, menopause!

Question 31

What is one piece of patient information that can tell us if abnormal cycling is due to an abnormality of the HPO axis or due to something superimposed onto it?

Answer 31

Patient AGE, especially when combined with menstrual history.

Anatomical problems (polyps, myomas) are common in older reproductive females, may have history of normal menses

Perimenopause: will have shortening cycles, may have hot flashes, other sx

Question 32

For a patient who has cycle length outside of 21-45d range and whose cycles have never been regular, what is a likely diagnosis?

Answer 32

If menses have never been regular, PCOS is a possibility.

Question 33

In teens, the most common cause of menstrual irregularity outside of pregnancy is what?

How do we evaluate for this?

Answer 33

hypothalamic issues -> anovulation or oligoovulation

(including psychogenic stress, diet, exercise, %body fat)

Crucial to screen for eating disorders due to high mortality.

Can be a combination of factors: take a really good history.

Some patients are more “neurovulnerable” to changes in neurotransmitter levels.

Question 34

How do we evaluate for endocrinopathies related to anovulation?

• Thyroid?
• Prolactinoma?
• CAH?
• Premature ovarian insufficiency?
• Cushings?
• PCOS?

Answer 34

• Thyroid: TSH and T4 levels
• Prolactinoma: exam, level of prolactin, look for galactorrhea
• CAH: exam (hirsutism), levels of 17-OH progesterone
• Premature ovarian insufficiency: FSH levels
• Cushings: exam findings including body habitus, hypertension
• PCOS: levels of FSH, LH, testosterone, est….?