Menopause

Question 1

Menopause

Answer 1

Amenorrhoea for 12 consecutive months after the final menstrual period (FMP). Permanent end to menstrual cycle following loss of ovarian follicular activity. Menopause occurs around 45-55yrs (average 51yrs) and marks the end of natural fertility. “Exhaustion” of primordian follicles so primarily ovarian. Menopause manifests physically, it is a normal part of aging.

Question 2

Symptoms of Menopause

Answer 2

Vasomotor instability, hot flushes, night sweats, mood changes, short-term memory loss, sleep disturbances, headaches, loss of libido

Question 3

Physical Changes in Menopause

Answer 3

Atrophy of the vaginal epithelium, changes in vaginal pH, decrease in vaginal secretions, decrease in circulation to vagina and uterus, loss of vaginal tone, pelvic relaxation, cardiovascular disease, osteoporosis, alzheimer’s disease.

Question 4

What triggers menopause?

Answer 4

• Unknown what the precise trigger is.
• Oocyte depletion? - post-menopause there may be still some healthy oocytes so cannot be full picture.
• Remaining follicles may not be as sensitive to LH and FSH?
• Due to age related changes in CNS which could alter GnRH secretion?

Question 5

Physiological Hormonal Changes occurring in Menopause?

Answer 5

• Loss of functional ovarian follicles primarily responsible for menopause inprimates.
• Significant hormonal changes occur early during reproductive life.
• Gradual decline in the number of follicles, leads to decreased production of oestradiol. - So reduces negative feedback to anterior pituitary leading to increased levels of FSH. Increased levels of FSH seen as early as 35yr even though cyclic reproductive function continues. Older (but premenopausal) females have diminished oestradiol production and decreased luteal function during natural cycles compared to younger females. Decreased inhibin production by aging ovary may also contribute to sharp increase in FSH in perimenopausal period. Androstenedione is androgen precursor which causes hirsuteness and is a precursor for estrone. Estrone becomes dominant oestrogen psot menopause, beta-oestradiol dominant pre-menopause.

Question 6

Gonadotropin Levels Increase in Menopause

Answer 6

Increased levels of both FSH (especially) and LH. No monthly surges.

Question 7

Clinical Symptoms in Menopause

Answer 7

• Vasomotor dysfunction (hot flushes/flashes/night sweats) - spontaneous sensations of warmth, usually felt on chest, neck and face. Often associated with perspiration, palpitation and anxiety. LH pulses coincide with hot flushes but are not responsible for flushes. One theory is temporary disturbances of hypothalamus thermoregulatory centres (reduced oestrogen levels stimulate NA and serotonin secretion which lower the set point for body temperature) leading to inappropriate heat loss.
• Vaginal dryness - physiological responses to low concentrations of oestrogen and androgens, reduced vaginal blood flow and secretions, tissue changes. pH of vaginal fluid changes from acidic to neutral.
• Other common symptoms such as mood changes, sleep disturbances, urinary incontinence, cognitive changes, somatic complaints, sexual dysfunction, and reduced quality of life may be secondary to other symptoms, or related to other causes.

Question 8

Hormone Replacement Therapy

Answer 8

• oestrogen and progesterone
• a cochrane meta-analysis of RCTs found that symptomatic women treated with various forms of oral oestrogen had 2.6 fewer hot flushes per day than women given the placebo (equivalent to 75% reduction in frequency). Progestins given as endometrium at risk of neoplasia from unopposed action of oestrogens. Oestrogen replacement very effective against menopausal syndrome and osteoporosis (especially to symptomatic women younger than 60yrs, within 10 years of menopause, and without contraindications such as active liver disease or thromboembolic disease.
• cons - increased risk of breast and endometrial cancer? Increased risk of cardiovascular disease and venous thromboembolism.

Question 9

Selective Oestrogen Receptor Modulators (SERMs)

Answer 9

• Tamoxifen and Raloxifene - oestrogen agonist effects on bone and CVS, but oestrogen antagonist effects in reproductive tissue.
• Due to competition for oestrogen receptor (ER)?

Question 10

Non-hormonal Treatment of Menopause

Answer 10

Two trials of paroxetine, a selective serotonin reuptake inhibitor (SSRI), and two of venlafaxine, a serotonin norepinephrine reuptake inhibitor (SNRI), showed a reduction in hot flush frequency of at least one hot flush per day.

Question 11

Non-prescribed Therapies to relieve symptoms of Menopause

Answer 11

• Acupuncture - effective in treating postmenopausal symptoms such as insomnia but ineffective in relieving hot flushes.
• Black cohosh, Hypericum perforatum (St Johns Wort) and Dan Quai - effective in relieving hot flushes, irritability and insomnia.
• Still insufficient data from large systematic reviews to conclude that chinese herbal medicines are more effective than HRT or placebo.

Question 12

Menopause Diagnosis and Management (NICE guidelines)

Answer 12

• do not use FSH for diagnosis in women under 45yrs.
• offer HRT as first line treatment for vasomotor symptoms and low mood/anxiety related to menopause after discussing long and short term benefits and risks.
• consider CBT to alleviate low mood or anxiety that arise as a result of the menopause
• offer vaginal oestrogen to women with urogenital atrophy (including those on systemic HRT) and continue treatment for as long as needed to relieve symptoms.
• offer women who are stopping HRT a choice of gradually reducing or immediately stopping treatment. There is no arbritary time limit.
• women with POI should be advised to continue HRT until at least age of natural menopause.
• continue transdermal rather than oral HRT for menopausal women who are at increased risk of VTE, including those with a BMI over 30kg/m2
• HRT doesn’t increase CVD risk when started in women aged under 60 years
• any increase in the risk of breast cancer is related to treatment duration and reduces after stopping HRT.
• refer women to a healthcare professional with expertise in menopause if: treatments do not improve their menopausal symptoms, they have ongoing troublesome side effects, they have contraindications to HRT, there is uncertainity about the most suitable treatment options for their menopausal symptoms.

Question 13

Andropause

Answer 13

There is no distinct andropause in males. However as men age: gonadal sensitivity to LH decreases, androgen production decreases, serum LH and FSH increase, sperm production typically declines after age ~50yrs, many men maintain reproductive function and spermatogenesis throughout life.

Question 14

Primary Ovarian Insufficiency (POI)

Answer 14

Menopause can occur in women under 40 (idiopathic, autoimmune disorders, genetic disorders such as Fragile X, chemotherapy and radiation). Symptoms can be treated with oestrogen replacement (hormone replacement therapy).

Question 15

Stages of Normal Reproductive Ageing in Females

Answer 15

Menstrual cycle becomes irregular - may be shorter due to lack of complete follicular development, sometimes no ovulation occurs.