Menopause Flashcards
Earliest hormonal sign of peri-menopause
Decreasing inhibin levels
DHEA and DHEA-S in menopause
Dramatic decrease (70% less DHEA, 75% less DHEA-S)
Hormones produced by post-menopausal ovary
Androstenedione and testosterone
Androstenedione in menopause
Approximately 50% of the pre-menopausal level (precursor for peripheral conversion is decreased)
Testosterone in menopause
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]
Estradiol in menopause
Circulating levels 10-20 pg/ml (derived from peripheral conversion of androgens/androstenedione)
Insulin in menopause
increases (or least likely to decrease)
Hypothyroidism in menopause effect on cholesterol
Hypothyroid causes increase in cholesterol due to decrease in cell membrane LDL receptors
T4 in menopause
With aging, metabolism of T4 decreases but thyroxine secretion also decreases
T4 -> T3 and TSH production in menopause
Conversion of T4 to T3 inside anterior pituitary cells decreases (primary action on nuclear receptor) – reduces TRH receptors and decreases production of TSH
Most important component of STRAW (stages of reproductive aging workshop) Criteria
Menstrual cycle remains most important criteria given lack of standardization of biomarker assays
Cardioprotective effects of E2 therapy (or before menopause)
o Increase in NO synthase (vasodilatory)
o Increase prostacyclin (vasodilatory)
o Inhibits oxidation of LDL
o Increase in HDL
Atherosclerotic plaques with E2 therapy
o Beneficial in prevention of atherosclerotic plaques
o May be harmful in women with established atherosclerotic plaques estrogen induces matrix metalloproteinase production or activity
WHI intervention and population
- 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
WHI findings mortality
No increase in E/P or EE vs placebo
WHI findings ASCVD
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)
WHI findings breast cancer
Increased risk with E/P, EE neutral
WHI findings colon cancer
Decreased risk with E/P, EE neutral
WHI findings CVA
E/P and EE increase risk of CVA (age > 65)
WHI findings VTE
E/P has twice the risk of EE
WHI findings osteoporosis
Both E/P and EE decrease fractures
Testosterone replacement goal
Use a testosterone product that can be titrated; goal total testosterone = 20-80 ng/ml
Benefits of androgen therapy in menopause
- Improvement in psychological well being
- Increase in sexually motivated behavior
SEs of testosterone administration
- 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
Dosing/administration of testosterone
- Transdermal – 150-300 ug/day
- Testosterone skin gel (marketed for men) – 1 g/day (5 g/day in men)
Leptin in menopause
decreases
Which hormones INCREASE most with age?
- Cortisol
- Norepinephrine
- Insulin
GH in menopause
decreased
Why does E2 increase thrombosis?
Decreased fibrinogen, Factor VII, Antithrombin III
Estrogen’s % reduction in colon ca
30%
Overall Benefits (5) vs Risks (5) of HRT
(not shown - reduction in T2DM)
