✓ 31- Menopause and Premature Ovarian Failure

Question 1

What is the average of menopause in Kuwait?

Answer 1

51

Question 2

What is the landmark for menopause?

Answer 2

Final menstrual period

Question 3

Define Perimenopause

Answer 3

Menopause transition + 1 year after FMP

Question 4

Define Early and Late Postmenopause

Answer 4

Early: 5-8 years following FMP
Late: rest of life

Question 5

What are the stages of menopausal transition?

Answer 5

Early and Late menopausal transition

Question 6

Define Early and Late Menopausal transition

Answer 6

Early: variable duration
Late: 1-3 before FMP

Question 7

What is the clinical definition of menopause?

Answer 7

menopause recognized after 12 years months of secondary amenorrhea

Question 8

Epidemiology of Menopause [Age]

Answer 8

Average age = 51

5% after 55 and 5% between 40 and 45

Question 9

What is the definition of POF/I?

Answer 9

Menopause before age of 40

Question 10

What genetic factors affect early menopause?

Answer 10

Family history
Genes that regulate immune function and DNA repair Genetic variation in the estrogen receptor gene
FMR1 permutation (fragile X mental
retardation)

Question 11

How does (fragile X mental retardation) affect menopause?

Answer 11

Associated with POF/I

Earlier menopause by up to 7 years

Question 12

What factors affect early menopause?

Answer 12

Genetics
Ethnicity 
Smoking 
Hysterectomy with ovarian consideration 
Other 
T1DM
In-utero exposure to DES

Question 13

How does smoking affect menopause?

Answer 13

Earlier menopause up to 2 years

Question 14

Ethnicity and Menopause

Answer 14

Hispanic < Caucasian < Japanese-American women

Question 15

How does a Hysterectomy with ovarian consideration cause menopause?

Answer 15

blood supply in the ovaries decreases, which accelerates the atresia that occurs in the follicles.

Question 16

What are the three main steps in ovarian development?

Answer 16

Germ cell differentiation
Continuous follicular growth
Continuous follicular atresia

Question 17

When does Germ cell differentiation occur?

Answer 17

At week 4-8 of development

Question 18

Compare the antral follicles in adults and children/fetuses

Answer 18

Antral follicles is larger in children/fetuses, these are formed in response to low levels of pulsatile FSH and LH, unlike after puberty

Question 19

What causes atresia?

Answer 19

apoptosis

Question 20

What reduces the number of oocytes before birth?

Answer 20

Atresia

Question 21

At which age does accelerated atresia occur?

Answer 21

> 37 years

Question 22

How many oocytes are found at menopause?

Answer 22

1000 oocytes, but most atresic

Question 23

At which age do females have the highest numbers of oocytes?

Answer 23

Female fetus at 20 weeks

Question 24

How many oocytes are found at puberty?

Answer 24

200,000

Question 25

What is the reproductive age?

Answer 25

15-45 years [first couple of cycles after puberty and last couple of cycle prior to menopause are anovulatory]

Question 26

At which age do we see a rapid decline in number of follicles?

Answer 26

at 37

Question 27

What is the first hormonal changes seen in early menopause and what does that correlate with?

Answer 27

Fall in Inhibit B, correlates with decrease in developing follicles

Question 28

What hormonal changes are seen in early menopause?

Answer 28

``` ↓ Inhibit B ↓ AMH ↑ FSH ↑LH ↑ Estrone ↓ Progesterone ```

Question 29

What are the late symptoms of menopause?

Answer 29

``` Bone loss Cardiovascular disease (CVD) Degenerative arthritis Body composition Skin changes Balance Pelvic organ prolapse Urinary incontinence ```

Question 30

What are the early symptoms of menopause?

Answer 30

``` Hot Flashes Sleep disturbances Depression Vaginal dryness & dyspareunia Painful intercourse Sexual dysfunction Cognitive impairment (memory & concentration) Joint pain Breast pain Migraines ```

Question 31

What are three mechanisms in which estrogen deficiency may cause bone loss?

Answer 31

Increases bone remodeling rate Increases osteoclasts and osteoblasts numbers [more osteoclasts] Increases resorption and formation [more resorption]

Question 32

How can estrogen effect bone?

Answer 32

↓ birth rate of osteoclasts ↑ osteoblasts progenitors in bone marrow ↑ pro-apoptotic effects on osteoclasts ↓ anti-apoptotic effects on mature osteoblasts & osteocytes

Question 33

What is the t-score of osteopenia, osteoporosis and severe osteoporosis?

Answer 33

Osteopenia → between -1 and -2.5 Osteoporosis → -2.5 and below Severe Osteoporosis → -2.5 and below + fragility fracture

Question 34

What changes in lipid profiles is seen in post-menopausal women?

Answer 34

Small increase in LDL | No change in HDL, but decreased protective effects

Question 35

Define POF/I

Answer 35

The development of primary hypogonadism | in females before the age of 40 years

Question 36

Epidemiology of POF/I

Answer 36

1 in 250 by age 35 years | 1 in 100 by age 40 years

Question 37

What is the pathophysiology of POI/F?

Answer 37

Unknown etiology [>75%] Accelerated follicle depletion Abnormal follicular stimulation

Question 38

What genetic defects cause accelerated follicular atresia?

Answer 38

Turner's Syndrome Fragile X Syndrome X chromosome deletions and translocation Galactosemia

Question 39

What ovarian toxins cause accelerated follicular atresia?

Answer 39

Radiation Mumps/CMV Chemotherapeutic drugs [Alkylating agents]

Question 40

What intraovarian modulators cause abnormal follicular stimulation?

Answer 40

BMP 15 [Polymorphism of Inhibit alpha subunit]

Question 41

What steroidogenic enzyme defects cause abnormal follicular stimulation?

Answer 41

CYP17 deficiency [StAR mutation] | Aromatas gene mutations

Question 42

What gonadotropin receptor function cause abnormal follicular stimulation?

Answer 42

FSH receptor mutations | Gs Alpha subunit gene mutations

Question 43

Management of Autoimmune Oophoritis

Answer 43

HRT til 50 years [normal age of menopause] Fertility IVF with oocyte donation Glucocorticoids

Question 44

Investigations of Autoimmune Oophoritis

Answer 44

21-hydroxylase or anti-adrenals antibodies | Ovarian biopsy is unnecessary

Question 45

What other condition has the same antibodies seen in autoimmune oophoritis?

Answer 45

Asymptomatic adrenal sufficiency

Question 46

What antibodies are found in autoimmune oophoritis?

Answer 46

21-hydroxylase or anti-adrenals antibodies

Question 47

Describe hot flashes

Answer 47

A sudden sensation of heat centered on the upper chest & face that rapidly becomes generalized, lasting 2-4 minutes.

Question 48

What is the frequency of hot flashes attacks?

Answer 48

Occur 1/2 per day OR 1 per hour Continues > 1 year [80%] Resolves spontaneously within 4-5 years if left untreated

Question 49

What do low serum AMH concentration indicates?

Answer 49

predictive of a poor ovarian response to exogenous gonadotropin stimulation marks a critical juncture in the timing of the menopausal transition

Question 50

What hormonal changes indicate a decline in follicular numbers?

Answer 50

Inhibit B and AMH

Question 51

What changes are seen in the Hypothalamic-Pituitary axis during the perimenopausal years?

Answer 51

Decreased sensitivity to estrogen Failure of positive feedback of E on LH normal preovulatory levels of estrogen, but no LH surge Failure of negative feedback of E on LH normal follicular phase estrogen levels do not suppress LH secretion

Question 52

What is the cause of follicular atresia in fetus and adults?

Answer 52

Fetus: apoptosis of oocyte Adult: Granulosa cell apoptosis

Question 53

Describe follicular atresia in young girls

Answer 53

most follicles that reach the pre-antral (1 mm) stage are | already atretic, with the rate of atresia is increased in larger follicle