4.27 - puberty and menopause

Question 1

Define puberty

Answer 1

transition period from sexually immature to sexually mature, reproductively fertile adult
-age varies

Question 2

Define thelarche, pubarche, axillary, and menarche. Know the order in which they occur
relative to one another and relative to the start of the growth spurt, and fertility
(ovulation and fertile ejaculate).

Answer 2

growth spurt ~ age 9
age 10: for about 3 yrs>
thelarche (Tanner stage 2) - onset of breast development
pubarche - first appearance of pubic hair
menarche - first menstruation
axillary - armpit hair
fertility - first ovulation

Question 3

Indicate the significance of Tanner Stage 2 and explain the major hallmarks for females
and males.

Answer 3

considered onset of puberty
males - scanty, long pubic hair, slight emlargement of penis, enlarged scrotum, altered texture
females -

Question 4

Explain the Gonadostat theory and how it relates to the pubertal transition and the rise
in gonadotropins and sex steroid synthesis

Question 4

Describe the major changes in LH, FSH, estradiol, and testosterone during puberty

Question 5

Describe why negative energy balance suppresses reproductive function

Question 6

Explain why Kiss1 neurons are considered central integrators regulating metabolic and
reproductive function. Explain the role of Leptin in the regulation of Kisspeptin release.

Question 7

Describe the effect of Leptin on the Kiss1 system. Indicate the significance of leptin
receptors on the ARC Kiss1 neurons

Question 8

Describe the proposed roles of mTOR and AMPK in mediating the Leptin signal. Explain
the roles of mTOR and AMPK as energy sensors

Question 9

List estrogen’s desirable and undesirable effects on the brain, breast, liver and heart,
uterus and bone

Question 10

Discuss the major symptoms associated with menopause and the average age at
menopause in the United States

Answer 10

ovaries no longer produce significant quantities of E and P
common symptoms are associated with estrogen deficiency: hot flushes, vaginal atrophy, sleep disturbances

Question 11

Explain the rationale for hormone replacement therapy. Include an explanation for
differences in estrogen, progesterone, FSH, AMH production observed pre-menopause
and post-menopause

Answer 11

b/c of estrogen’s protective effects
E and P go down, FSH increases and AMH drops to 0

Question 12

Explain what Premarin and Prempro are. Include mention of CEE and MPA

Answer 12

premarin - conjugated estrogens for hormone therapy; estrone, equilin, equilenin
isolated from mare’s urine
prempro - CEE plus medroxyprogesterone acetate (MPA synthetic progesterone)

Question 13

Describe the Women’s Health Initiative study. Include mention of the medication
administered to women in the two arms of the study (i.e., estrogen alone versus
estrogen + progesterone)

Answer 13

postmenopausal women treated daily with: 1) placebo 2) estrogen alone (CEE; premarin) or 3) estrogen and synthetic prog (CEE + MPA prempro)

Question 14

Indicate when the study started and why the estrogen + progesterone arm was stopped
in 2002. List both; a) the increased risks cited as reasons to stop the study, and b) the
benefits of estrogen + progesterone identified in the study

Answer 14

group 3 had problems - stroke, blood clots, breast cancer
group 2 stopped - stroke
–
benefits
CEE + MPA: less colectoral cancer, less hip fractures
-overall risk determined to be 15% greater than benefit (hazard ratio)

Question 15

Explain what it means if the Hazard Ratio is equal to 1, greater than 1 or less than 1. (For
our purposes, a hazard ratio is an estimate of relative risk.

Question 16

Explain how the data from the WHI 2002 paper show there is an increased risk of
cardiovascular disease (CHD) for CEE+MPA and that the increased risk is statistically
significant.

Question 17

Use the same criteria to explain how the WHI 2002 data show there is a decreased risk
of hip fracture for CEE+MPA.

Question 18

Be able to read Table 2 from the WHI 2002 paper to determine which outcomes show
risks, benefits or no difference for CEE+MPA relative to placebo.

Question 19

Explain what the global index hazard ratio is and what it represents.

Question 20

Describe how the media coverage and the public response to the WHI 2002 paper
affected sales of hormone replacement therapy.

Question 21

Explain the “therapeutic window of opportunity” or “timing”hypothesis. Explain why the
WHI study does not address this hypothesis

Answer 21

• estrogens have beneficial effects prior to menopause
  -estrogens have adverse affect when started well beyond the menopausal transition
  -maybe estrogens would have beneficial effects if initiated around entry to menopause

Question 22

Define atherosclerosis and plaque. Explain how atherosclerotic plaque formation can
cause abnormal blood flow

Question 23

Describe the proposed protective role of endogenous estrogens in women.

Answer 23

endogenous estrogens are protective
-exogenous estrogens thought to be harmful when administered well after menopausal transition

Question 24

Explain how a ruptured atherosclerotic plaque can lead to a stroke or myocardial
infarction. Include mention of the endothelium, fibrous cap and necrotic core

Question 25

Explain why exogenous estrogens can be harmful when administered post-menopause.
Include mention of the inflammatory response and matrix metalloproteinases

Answer 25

exogenous post menopause can increase inflammatory response and promote growth of atherosclerotic plaque
-increases MMP (matrix metalloproteinases) expression

Question 26

Explain how the analysis by Stevenson and co-workers (2009) supports the “therapeutic
window of opportunity” or “timing” hypothesis.

Question 27

Describe current recommendations for hormone therapy