Ageing 2: Endocrine Changes with Ageing: Perimenopause & Menopause

Question 1

How do adrenocortical hormone levels change with age?

Answer 1

• DHEA/DHEAS levels decline
• Basal cortisol rises, leading to less diurnal spike (WIT?)
• Aldosterone tends to decrease (natural hTn relief????)

Question 2

How do thyroid hormone levels change with age?

Answer 2

• Negligible changes in T4
• Less T3 and more reverse T3 (does the latter work?)

(Which is more potent: 3 or 4? Which enzyme converts?)

Question 3

How do growth hormone(s) levels change with age?

Answer 3

• Decline in secretion (incl. nocturnal secretion); less GHRH and less responsiveness to it
• IGF-1 level falls in parallel

Question 4

How do calciotropic hormone levels change with age?

Answer 4

• Vitamin D levels decline due to reduced synthesis
• PTH increases after age 40-50 (compensate for decreased vitamin D)
• C cell response to hypercalcemia blunts, leading to reduced secretion of (which hormone?)

Question 5

Give some examples of reduced hormone sensitivity/action that occurs with aging

Answer 5

• Insulin resistance (↑ T2DM risk)
• Beta adrenergic desensitisation (reduced cardiovascular/respiratory reserve under stress - why? which subtype is which?)
• Vitamin D sensitivity decreases

Question 6

Define menopause/outline its diagnosis

Answer 6

• Diagnosed retrospectively; permanent loss of menstrual cycles
• Officially defined after 12 months of amenorrhoea

Question 7

Define perimenopause (+ start/finish)

Answer 7

• Stage of a woman’s life before/after menopause
• Starts when cycle length is disrupted by at least 7 days, and finishes 12 months after LMP (why does the latter make sense?)

Question 8

Outline the hormonal mechanisms behind the beginning of menopause, and why they start. Link this also to the earliest detectable lab marker in the initiation of menopause.

Answer 8

• Ovarian reserve declines with age
• As menopause approaches, there are fewer follicles left to respond to FSH and LH, meaning less inhibin and ostrogen
• Less negative feedback on the hypothalamus means more FSH (earliest lab marker), and leads to erratic and then declining production of oestrogen

Question 9

Name 2 long term physiological consequences of menopause

Answer 9

• Increased bone turnover (why?)
• Increased cardiovascular risk (why?)

Question 10

Define surgical menopause, and compare its symptoms to regular menopause. How does treatment vary?

Answer 10

• Loss of ovarian function after surgery (radical hysterectomy, bilateral oophorectomy etc)
• Symptoms typically more sudden onset; may require hormone replacement therapy

Question 11

Premature menopause is also known as…
What is a well-known cause of it?

Answer 11

• Premature/primary ovarian insufficiency (all called POI)
• Can be caused by chemo/radiotherapy in the setting of cancer (remember this from breast cancer stuff?)

Question 12

Menopause MSK effects

Answer 12

• Oestrogen is osteoprotective (transgender boxers)
• Therefore, loss of oestrogen increases risk of osteoporosis
• ↓ oestrogen can also cause muscle loss, leading to myalgia and arthralgia

Question 13

How does menopause affect the cardiovascular system?

Answer 13

• Oestrogen is thought to be cardioprotective
• Menopause is associated with increased cardiovascular risk

Question 14

Cognitive/sleep changes during menopause

Answer 14

• Reduced processing speed/memory
• Emotional instability/mood swings
• Sleep disturbance

Question 15

Genitourinary changes during menopause

Answer 15

• Vaginal dryness
• Increased UTI risk
• Vulvar itching/dysuria
• Stress/urge incontinence
• Dyspareunia (↓ lubrication, ↓ elasticity)

Question 16

Genitourinary effects of menopause at the tissue level + treatment options

Answer 16

• ↓ oestrogen causes thinner vaginal epithelium, reduced blood supply/flow, lower vaginal lubrication, loss of protective bacteria (leading to ↑ UTi risk)
• Can be treated with non-hormonal moisturisers (for mild cases) or topical oestrogen therapy

Question 17

Describe three mechanisms by which oestrogen protects bone

Answer 17

1. Induces osteoclast apoptosis
2. Reduces FSH, which otherwise ↑ bone resorption
3. Causes 1gf-1 release, which promotes osteoblast growth

Question 18

Why does menopause make you fat?

Answer 18

Reduces satiety modulation

Question 19

For which women is oestrogen only MHT indicated? What is the alternative for the others?

Answer 19

• For women who’ve ahd their uterus removed, oestrogen only is indicated
• Otherwise, E4 and P3 indicated (protects against hyperplasia)

Question 20

Routes/risks of MHT/HRT

Answer 20

• Routes: oral (but has systemic effects), patch, vaginal (good effects)
• Risks: slight breast cancer risk (remember news scandal) and increased VTE/stroke risk

Question 21

What is the use case for low-dose testosterone creams in the setting of menopause?

Answer 21

Improved libido.