Menopause

Question 1

Earliest hormonal sign of peri-menopause

Answer 1

Decreasing inhibin levels

Question 2

DHEA and DHEA-S in menopause

Answer 2

Dramatic decrease (70% less DHEA, 75% less DHEA-S)

Question 3

Hormones produced by post-menopausal ovary

Answer 3

Androstenedione and testosterone

Question 4

Androstenedione in menopause

Answer 4

Approximately 50% of the pre-menopausal level (precursor for peripheral conversion is decreased)

Question 5

Testosterone in menopause

Answer 5

Changes minimally (may increase)
Production by the ovary is increased (gonadotropins driving androgen production) – however primary source of testosterone is peripheral conversion of androstenedione (which is reduced) [testosterone 25% lower]

Question 6

Estradiol in menopause

Answer 6

Circulating levels 10-20 pg/ml (derived from peripheral conversion of androgens/androstenedione)

Question 7

Insulin in menopause

Answer 7

Do not change (least likely to decrease)

Question 8

Hypothyroidism in menopause effect on cholesterol

Answer 8

Hypothyroid causes increase in cholesterol due to decrease in cell membrane LDL receptors

Question 9

T4 in menopause

Answer 9

With aging, metabolism of T4 decreases but thyroxine secretion also decreases

Question 10

T4 -> T3 and TSH production in menopause

Answer 10

Conversion of T4 to T3 inside anterior pituitary cells decreases (primary action on nuclear receptor) – reduces TRH receptors and decreases production of TSH

Question 11

Most important component of STRAW (stages of reproductive aging workshop) Criteria

Answer 11

Menstrual cycle remains most important criteria given lack of standardization of biomarker assays

Question 12

Cardioprotective effects of E2 therapy

Answer 12

o Increase in NO synthase (vasodilatory)
o Increase prostacyclin (vasodilatory)
o Inhibits oxidation of LDL
o Increase in HDL

Question 13

Atherosclerotic plaques with E2 therapy

Answer 13

o Beneficial in prevention of atherosclerotic plaques
o May be harmful in women with established atherosclerotic plaques  estrogen induces matrix metalloproteinase production or activity

Question 14

WHI intervention and population

Answer 14

• E/P (conjugated estrogens 0.625mg/MPA 2.5mg, if uterus present) vs EE (conj est 0.625mg) vs Placebo
• 27k age 50-79 (avg 63), “healthy,” 5 year f/u

Question 15

WHI findings mortality

Answer 15

No increase in E/P or EE vs placebo

Question 16

WHI findings ASCVD

Answer 16

E/P increase in 1st yr, not over entire study; Conclusion: No clear benefit of HRT for ASCVD;
Benefit for age <60 and <10 year post-menopause? (“window of opportunity” hypothesis)

Question 17

WHI findings breast cancer

Answer 17

Increased risk with E/P, EE neutral

Question 18

WHI findings colon cancer

Answer 18

Decreased risk with E/P, EE neutral

Question 19

WHI findings CVA

Answer 19

E/P and EE increase risk of CVA (age > 65)

Question 20

WHI findings VTE

Answer 20

E/P has twice the risk of EE

Question 21

WHI findings osteoporosis

Answer 21

Both E/P and EE decrease fractures

Question 22

Testosterone replacement goal

Answer 22

Use a testosterone product that can be titrated; goal total testosterone = 20-80 ng/ml

Question 23

Benefits of androgen therapy in menopause

Answer 23

• Improvement in psychological well being

- Increase in sexually motivated behavior

Question 24

SEs of testosterone administration

Answer 24

• Virilization = hirsutism, acne, alopecia
• Negative effect on lipids
• Hyperestrogenic (peripheral conversion to estrogen) + androgens do not protect endometrium = potential risk of endometrial/breast cancer
• Long term effects unknown

Question 25

Dosing/administration of testosterone

Answer 25

• Transdermal – 150-300 ug/day

- Testosterone skin gel (marketed for men) – 1 g/day (5 g/day in men)