Tutorial 17: Menopause

Question 1

What is menopause?

Answer 1

More than 6 months of amenorrhoea, usually between 45-55 (mean 51).

Question 2

What is premature menopause?

Answer 2

Cessation of menstruation before the age of 40 (1% of women)
can be physiological or surgical menopause.

Question 3

What is the Climacteric?

Answer 3

Climateric is the transition period between ovulatory cycles and menopause during where progressive loss of ovarian function occurs.

(NB- amenorrhoea may be pregnancy)

Question 4

What is the primary function of the female reproductive system?

Answer 4

Ovum production, which is dependent on LH and FSH stimulation

Question 5

What is the role of LH in females?

Answer 5

LH stimulates the ovary (graffian follicle) to produce the major female hormone
oestradiol

Question 6

What is the role of FSH in females?

Answer 6

1. promotes follicular growth
2. induced LH receptors

Question 7

What are the functions and purpose of oestrogen?

Answer 7

1. Maintains the menstrual cycle via endometrial proliferation
2. Inhibits bone resorption
3. Decreases cholesterol and LDL and increased HDL

Question 8

What are the roles of progesterone?

Answer 8

1. Transforms oestrogen stimulated endometrium into its secretory phase
2. Protects a pregnancy by decreasing uterine contractility.
3. Changes associated with Ovarian Ageing

Question 9

What are facts/features of oocytes in woman?

Answer 9

• Females have their Maximum number of oocytes present as a fetus (about 7 months gestation)
• –> then they have 1-2 Million oocytes present in the ovaries at birth
• At puberty this falls to about 300,000
• During reproductive years this number further depletes (genetics, smoking) and there is also a decline in oocyte quality
• As a result there is a gradual change in the hormone concentrations

Question 10

What hormonal changes occur during the pre-menopausal stage/climateric?

Answer 10

• There is a slow steady decrease in cycle length due to a decrease in the follicular phase.
• There is a slight decline in oestrogen production (due to decreasing number of oocytes).
• The granulosa cells of the oocytes produce and secrete inhibin. This is polypeptide which provides negative feedback on FSH release. As the numbers of oocytes are depleted (inhibin levels are decreased) negative feedback is diminished.
• LH levels indistinguishable from younger women and Progesterone levels comparable to younger women
• Decreased responsiveness of the remaining follicles to LH and FSH

Menstrual irregularity often occurs as a result of these changes. This phase of menstrual irregularity is short or might not be present in young women presenting with premature menopause. It is then normally followed by amenorrhoea.

During mature reproductive life there is regular menses.

Question 11

What hormonal changes occur during Menopause?

Answer 11

• Marked reduction in oestrogens due to decreased ovarian function
• Most of the oestradiol present is from conversion of estrone (produced by aromatisation of the androstenedione produced by the adrenals) in the peripheral fat.
• Excessive release of LH and FSH (due to decreased oestrogen and inhibition)
• Androgens levels 50% of pre-menopausal women. Production of androgens by the ovaries and adrenals falls.
  
  • Adrenal secretion of DHEA is reduced
  • Ovaries decrease production of oestrogens, androstenedione but increased production of testosterone.

Question 12

What are some differentials for amenorrhoea?

Answer 12

• Prolactinoma
• Pituitary tumor
• Ovarian tumor
• If younger, can consider amenorrhoea due to stress, change in BMI,
• pregnancy
• Thyrotoxicosis
• Cushing Syndrome
• ?hysterectomy/oophorectomy
• Vasomotor flushes (night sweats- consider lymphoma)
• Hyperthyroidism
• Pheochromocytoma
• Pyrexia (chronic infections)

Question 13

What would you want to include in the history of a ?menopausal patient?

Answer 13

• Is this menopause? Take menstrual and past medical history then perform a physicalexamination.
• Consider differential diagnosis for amenorrhoea
• Confirmation with blood tests- elevated FSH levels are indicative of menopause. Low oestrogen levels not conclusive of the menopause.

Question 14

What are some signs and symptoms of oestrogen deficiency?

Answer 14

Hot flushes

Genitourinary atrophy

Psychological symptoms

Osteoporosis

Thin, sparse hair

Decreased breast volume

Question 15

What do the “hot flushes” of menopause involve?

Answer 15

• present in 70% of perimenopausal women
• sensation of intense warmth and heat of the upper body followed by profuse sweating.
• Typically lasts for 4 mins (30secs-5mins). Frequency varies from 1-2/hr to 1-2/week.
• Symptoms may persist for 1 year (about 82%) or even >5 years (25%)
• Treatment- HRT is effective but not all women are relieved of their symptoms by HRT.

Question 16

What does the “genitourinary atrophy” of menopause involve?

Answer 16

Atrophic vaginitis- vaginal rugae flattens, vaginal dermis becomes thinner, increase in vaginal pH, vaginal dryness.

• Itching, discomfort, burning, dyspareunia (pain during intercourse), vaginal bleeding due to above, but also due to decreased cervical secretions
• Treatment- local oestrogen cream (minimally absorbed)

Atrophic distal urethritis- UTI’s, ascending infection, dysuria, urinary frequency

• Can have atrophic cystitis- urgency, incontinence without dysuris or pyuria

Question 17

What do the psychological symptoms of pregnancy involve?

Answer 17

• Depression, anxiety, fatigue, irritability, headaches and dizziness
• ?attributable to poor sleep quality and pattern

Question 18

What does the osteoporosis of menopause involve?

Answer 18

• ?oestrogen increases bone turnover without increased urinary or intestinal excretion of calcium. Mechanism unclear.
• Fracture and complications are a major cause of morbidity and mortality

Question 19

When do you prescribe Hormone Replacement Therapy?

Answer 19

1. Use HRT short term for severe symptoms of flushes and night sweats. Screen first. 6 monthly review and after 1-2yrs of use try and wean patients off HRT.
2. In premature menopause HRT should be used unless there are contraindications. HRT in these women will decrease the risk of osteoporosis.

Question 20

What are some contraindications for HRt/Eostrogen therapy?

Answer 20

1. Undiagnosed vaginal bleeding
2. Previous breast cancer
3. Previous VTE
4. Previous heart attack
5. Previous stroke
6. High risk of CVD

Question 21

What are the absolute changes in outcomes with Hormone Replacement Therapy (HRT)?

Answer 21

** image

HRT increases risk of Alzheimers in women older than 65 years of age.

New research however has found that HRT is associated with decreased rates of Alzheimers in women carrying the Alzheimer’s ApoE4 gene.

Question 22

What should Hormonal Replacement Therapy not be used for?

Answer 22

• Prevention of CVD
• Prevention or treatment of osteoporosis- other agents available
• Vaginal atrophy- need to try local therapy first. Only if local oestrogen creams and moisturisers have failed and this is a serious problem for the patient.
• Mood symptoms.

Question 23

What hormonal preparations are available for use during menopause?

Answer 23

1. Oestrogens- oral, transdermal (bypasses first pass), implant, tablets.
2. Progestogens- Oral, intrauterine (mirena), vaginal pessaries.

Question 24

What are the 3x main different regimes available for HRT treatment during menopause?

Answer 24

1. Continuous oestrogen & sequential progestogen:
   
   • used in perimenopausal women who are still menstruating or had a period within the last 12 months.
   • Continuous oestrogen + 10-14 days of progestogen monthly.
   • NB: 5 fold increase in incidence of endometrial cancer with unopposed oestrogen therapy, therefore he addition of progestogen removes this risk. All women with an intact uterus receiving oestrogen therapy require progestogen.
2. Continuous oestrogen and progestogen:
   
   • ​used in women more than 1 year post menopausal.
   • Results in endometrial atrophy. Breakthrough bleeding might occur in 1st six months but eventually amenorrhoea results.
3. Oestrogen alone:
   
   • only for women who have had hysterectomies (as no risk of endometrial cancer)

Question 25

What Withdrawl symptoms can be experienced if HRT was used for menopausal symptoms?

Answer 25

* try to avoid rebound flushes * gradual decrease over **6-12 weeks or even longer** * gradual decrease of oestrogen but **continue progestogen** _until oestrogen is stopped_ * may still experience hot flushes but _normally less intense and do not last for as long_

Question 26

What stratergies can be used to reduced HRT withdrawl symptoms?

Answer 26

* using a **lower dose** of HRT * cutting the pills in half * using **patches** with decreasing dose * alternative- **clomidine** α-blocker, can relieve flushes.