Physiology/Pathophysiology of the Menopause Transition

Question 1

What is the definition of Menopause?

Answer 1

1)A normal, natural event, defined by the final menstrual period (FMP) and confirmed after 1 year of no menstrual bleeding
2)Represents the permanent cessation of menses resulting from loss of ovarian follicular function, usually because of aging
3)Normally occurs between the ages of 40 and 58 years.

Question 2

What percentage of a women’s life will be spent in menopause?

Answer 2

40%

Question 3

What is meant by natural menopause?

Answer 3

Permanent cessation of menses for 12 months from loss of ovarian follicular activity.

Question 4

What is meant by induced menopause?

Answer 4

Surgical or iatrogenic loss of ovarian function (eg, bilateral oophorectomy, chemotherapy, pelvic radiation, other forms of ovarian toxicity).

Question 5

What is primary ovarian insufficiency?

Answer 5

Loss of normal ovarian function before age 40 y, resulting in irregular menstrual cycles and reduced fertility. (Can be transient)

Question 6

When is premature menopause?

Answer 6

FMP before age 40 y.

Question 7

When is early menopause?

Answer 7

FMP before age 45 y. Occurs between the ages of 40 and 45 years in approximately 3% of the population.

Question 8

When is late menopause?

Answer 8

FMP after the age 55 y.

Question 9

Define perimenopause/menopause transition/climacteric.

Answer 9

The time frame “around menopause” marked by intermenstrual cycle irregularities or other menopause-related symptoms (hot flashes, sleep problems, vaginal dryness); ends after 1 y of amenorrhea.

Question 10

What is meant by Postmenopause?

Answer 10

Stage of life after FMP.

Question 11

What is the most common Etiology of POI, premature menopause, and early menopause

Answer 11

Most common is Idiopathic, but other etiologies include genetic, autoimmune, iatrogenic, infectious, and metabolic.

Question 12

Primary Ovarian Insufficiency (POI)

Answer 12

Characterized by hypergonadotropic hypogonadism(LH, FSH high and sex hormones low) that can be transient.
Affects 1% of women aged younger than 40 years.

Question 13

What is premature menopause?

Answer 13

Permanent ovarian failure.

Question 14

What percent of population goes into early menopause?

Answer 14

3%

Question 15

What is normal physiologic aging?

Answer 15

Natural process of physiologic deterioration that is genetically determined and environmentally modifiable.

Question 16

What is reproductive aging?

Answer 16

Progressive loss of oocytes by ovulation and atresia.
Not correlated with chronologic aging.

Question 17

Describe how the number of oocytes decrease over time in terms of #of ovarian follicles from gestation onward.

Answer 17

At 20 weeks’ gestation: 6 to 7 million oocytes.
At birth: 1 to 2 million oocytes.
At puberty: 300,000 to 500,000 oocytes.
At menopause: 300 to 400 oocytes, most of which are incompetent

Question 18

What is Straw?

Answer 18

In 2001, the Stages of Reproductive Aging Workshop (STRAW) established a nomenclature for reproductive aging based on menstrual cycle.
STRAW+10 updated and modified the model in 2011. Considered the gold standard for categorizing reproductive aging. Divides the reproductive lifespan into three broad phases, further broken down into seven stages centered on the FMP

Question 19

What are the stages of Straw?

Answer 19

Reproductive Phase: Early (Stage −5), Peak (Stage −4), and Late (Stage –3).
The Menopause Transition (MT): Early (Stage –2) and Late (Stage –1). FMP(Stage 0)
Postmenopause Phase: Early (Stage +1) and Late (Stage +2).

Question 20

Who can you apply Straw staging to?

Answer 20

Applies to menstruating women regardless of demographics, age, body mass index (BMI), and lifestyle characteristics.

Question 21

Most common for measuring ovarian reserve.

Answer 21

Follicle-stimulating hormone (FSH) in conjunction with estradiol (days 2-5 of menstrual cycle, not taking hormones)
FSH >10 IU/L + estradiol < 60 pg/mL.
FSH <10 IU/L + estradiol >100 pg/mL.

Question 22

Where is AMH produced?

Answer 22

Produced by the granulosa cells of preantral and small antral follicles.
Measure any day of the cycle or while taking hormones.
Not recommended as a screening tool in general population.
<1 ng/mL.

Question 23

When should you measure AMH?

Answer 23

Any day of the cycle or while taking hormones. Not recommended as a screening tool.

Question 24

What is a normal level of AMH?

Answer 24

1-2 ng/mL.

Question 25

What level of AMH can indicate poor reserves?

Answer 25

<1 ng/mL.

Question 26

What is AFC(antral follicle count)?

Answer 26

Number of ultrasound-detected follicles 2 mm to 10 mm in both ovaries.

Question 27

Which are Useful markers of ovarian response to controlled ovarian stimulation?

Answer 27

AMH and AFC

Question 28

What is the AFC in low ovarian reserve?

Answer 28

<7

Question 29

How many women will be over 50 yo in 2020 and how will that change by 2060?

Answer 29

64 million, will rise to 90 million

Question 30

What is the overall life expectancy of woman?

Answer 30

81.2 and 67.2% of women age 50 and over are expected to live this long in 2013.

Question 31

In 2016, how many canadian women were over age 50?

Answer 31

39% and will increase to 43% in 2038.

Question 32

What happens in early menopause transition phase?

Answer 32

1)Persistent cycle irregularity >=7 days 2)Decline in inhibin B and AMH because of reduction in follicles (low AFC). 3)Diminished ovarian reserve. Lower AMH and inhibin B promotes growth of remaining follicular pool, accelerating follicular atresia(Low AMH and inhibin B = signs of low egg count → the body tries to stimulate the last few follicles → this speeds up their loss → ovarian reserve declines even faster.) 4)Early follicular FSH is variable. 5)Luteal out-of-phase (LOOP) events occur in about one in four cycles. 5)May or may not have mild vasomotor symptoms (VMS). 6)May have pronounced premenstrual syndrome.

Question 33

What happens in late menopausal transition phase?

Answer 33

1)Amenorrhea > 60 d. 2)Menstrual cycles have variable cycle length. 3)Variable estradiol levels with increased prevalence of anovulation. 4)FSH levels are ≥25 IU/L because of few remaining oocytes. 5)Negligible AMH and AFC. 6)LOOP cycles occur in a third of women; 7)VMS and other signs of menopause likely.

Question 34

What is LOOP?

Answer 34

When there is a surge of estrogen in the luteal phase

Question 35

What are some symptoms of LOOP?

Answer 35

Mastalgia Migraines Menorrhagia Fibroids Endometrial Hyperplasia

Question 36

What can LOOP put at risk for?

Answer 36

Reproductive cancers(esp with longer MT) Increased risk of Twins with pregnancy

Question 37

Why does obesity cause higher estradiol levels?

Answer 37

Because of aromatization of androgens to estrogens

Question 38

What does the adrenal cortex produce?

Answer 38

Cortisol, Aldosterone, Androgens(DHEA and Androstenedione)

Question 39

What does the adrenal medulla produce?

Answer 39

Norepinephrine, epinephrine and dopamine

Question 40

Adrenal androgens are enzymatically converted to estrogens in the ______.

Answer 40

peripheral tissues.

Question 41

Does cortisol increase or decrease as we age?

Answer 41

Increases

Question 42

Do androgens increase or decrease as we age?

Answer 42

Decreases

Question 43

Is the drop in androgens correlated with menopausal symptoms?

Answer 43

No

Question 44

Should you check androgen levels? Why or Why not?

Answer 44

No, because there are no serum androgen concentrations that define female androgen insufficiency.

Question 45

Explain what happens to Cortisol levels in late perimenopause and early menopause.

Answer 45

85% will experience marked rise in DHEA and androstenediol. Moderate rise in DHEAS, testosterone, and androstenedione.

Question 46

When do adrenal androgen levels return to premenopause levels?

Answer 46

Adrenal androgen levels return to premenopause level within 1 to 2 years after FMP.

Question 47

Why does cortisol go up in late perimenopause?

Answer 47

Marked rise in cortisol is associated with rise in FSH in late perimenopause.

Question 48

What is changes in cortisol patterns associated with?

Answer 48

Changes in cortisol patterns associated with mood, sleep, and vasomotor symptoms (VMS).

Question 49

What does Swan stand for?

Answer 49

Study of women's health across the nation

Question 50

What did SWAN study show in regards to DHEA?

Answer 50

Confirmed well-established age-related fall in circulating DHEAS levels. Systematic review and meta-analysis of DHEA use in postmenopausal women with normal adrenal function found no evidence of improvement in sexual symptoms, serum lipids, serum glucose, weight, or bone mineral density (BMD). DHEA supplementation for postmenopausal women is not routinely recommended.