Menopause E-book Flashcards
Menstrual cycle
Menstruation occurs as a result of cyclic hormonal variations. During the follicular phase (the first half of the menstrual cycle) the endometrium thickens under the influence of increasing levels of oestrogen, particularly estradiol, which is secreted by the developing ovarian follicles. This increase in oestrogen triggers the anterior pituitary to release a surge of luteinising hormone, this occurs through a positive feedback loop. Following this, ovulation occurs.
After ovulation and as the luteal phase progresses, the endometrium starts to further develop due to increasing levels of progesterone released by the corpus luteum. Both progesterone and oestrogen are secreted from the corpus luteum which forms from the remaining ovarian follicle after ovulation.
If conception does not occur, luteolysis occurs and steroid levels fall, which means the endometrium cannot be maintained. Stromal fluid is lost, leucocytes infiltrate and intraglandular extravasation of blood occurs. Endometrial blood flow is reduced which leads to necrosis and sloughing which is menstruation.
Aetiology of the menopause
The menopause is signalled by a woman’s last menstrual period and is defined as the permanent cessation of menstruation that results from loss of ovarian follicular activity.
There are a number of hormonal changes that occur during the menopause. This includes one part of the hypothalamic-pituitary-ovarian axis system breaking down as the ovaries become depleted of follicles which results in the lack of production of oestrogen and progesterone. Therefore the negative feedback on the hypothalamus is lost and so pituitary secretion of luteinising hormone (LH) and follicle stimulating hormone (FSH) increases resulting in high levels of these two hormones.
Menopause can be split into three stages:
- Perimenopause
- Menopause
- Postmenopause
What occurs in perimenopause
This typically begins several years before menopause as a result of the ovaries gradually making less oestrogen. It lasts up until the menopause, when the ovaries stop releasing eggs. In the latter stages of perimenopause (the last 1-2 years) the drop in oestrogen quickens which causes women to have menopausal symptoms.
What occurs in menopause
This is the point at which it has been a year since the woman last had her menstrual period. At this stage, the ovaries have stopped releasing eggs and making most of their oestrogen.
What occurs in postmenopause
These are the years that follow menopause. Menopausal symptoms such as hot flushes ease for most women however health risks related to the loss of oestrogen rise as the woman ages.
What occurs in premature menopause
This is a condition where menopause starts before the age of 40 years. It can be occurring naturally or due to the side effects of treatments.
What occurs in early menopause
This is when menopause occurs between the age of 40 to 45 years.
Menopausal symptoms
Vasomotor symptoms, commonly known as hot flushes and night sweats, are caused by dilation and constriction of blood vessels, which leads to impaired thermoregulation.
Usually this starts as a heat sensation in the chest and face but then spreads. The sensation usually only lasts a couple of minutes and is associated with sweating and skin redness. Other signs include palpitations, anxiety, and sleep disturbances.
The mechanism of these vasomotor symptoms is currently unknown however it is thought to be due to an imbalance in noradrenergic activity in the thermoregulatory centre, which is believed to be influenced by hormone level fluctuation. Increased noradrenergic activity is suspected to narrow the neutral thermoregulatory zone between sweating and shivering.
Menopause also has effects on mood. This arises via the amygdala, hippocampus and some temporal structures of the brain which are centrally involved in mood regulation and which are sensitive to fluctuating levels of sex hormones, in particular oestrogen. Oestrogen receptors (ER) are most abundant in the amygdala and hippocampus, hence during the menopause there is decreased stimulation of ER due to less circulating oestrogen thus causing low mood.
Recent research has also shown there to be a link between oestrogen and the serotonin system whereby:
● Oestrogen increases postsynaptic responsivity
● Oestrogen increases the number of serotonergic receptors
● Oestrogen enhances serotonergic transport and uptake
● Oestrogen also facilitates synthesis of serotonin and the levels of its metabolite
● Oestrogen upregulates 5-HT1 receptors and downregulates 5-HT2 receptors
● Oestrogen decreases monoamine oxidase (MAO) activity
These urinary changes occur for two reasons:
● Lack of oestrogen reduces the urinary tracts ability to control urination
● Advanced age, which usually coincides with menopause, has various debilitating effects on the pelvic area organs and tissues
Complications
- Osteoporosis
- Sexual dysfunction
- Insomnia
- Schizophrenia
- Bipolar disorder
- Panic disorder
- OCD
Osteoporosis
This is characterised by backache, fractures with minimal trauma, decreased height and mobility. This is caused by decreasing levels of oestrogen in the body that help to protect bone strength. Modifiable risk factors include: low dietary intake of calcium or vitamin D, smoking and a sedentary lifestyle. Osteoporosis can be a risk factor for developing: hyperthyroidism, hyperparathyroidism, CKD and diseases requiring systemic corticosteroid use. HRT is effective in treating and preventing osteoporosis, as well as the use bisphosphonates like alendronate. Selective estrogen receptor modulators lie raloxifene have also demonstrated some effectiveness in the treatment of osteoporosis
Sexual dysfunction
often results from depression or anxiety disorders and symptoms which make sexual activity uncomfortable like vaginal dryness. Treatment of the underlying depression or vaginal dryness is usually effective. In some cases treatment with androgens may be indicated
Insomnia
occurs in 40-50% of women during the menopausal transition. This may be a result of the oestrogen deficiency as it has been shown that exogenous oestrogen improves both subjective and objective sleep. HRT may help some cases of insomnia
Schizophrenia
There is a higher incidence of schizophrenia in women aged 45-50 compared to men in the same age bracket. This suggests that oestrogen may play a modulatory role in the pathophysiology of schizophrenia. Referral to a specialist is necessary in this patient population
Bipolar disorder
there is evidence to show that women with pre diagnosed bipolar disorder experience a higher amount of depressive episodes during the menopausal transition
Panic disorder
this is common during perimenopause, especially among women who experience many physical symptoms of menopause. Panic attacks in menopausal women are mostly associated with negative life events, medical comorbidity and functional impairment
OCD
The onset of OCD is more common in menopausal women than other patient populations. Hormone levels in menopause have been correlated with a worsening of
the disorder, suggesting that oestrogen may play role in the development of the disorder
Non-pharmacological management options
Many women will benefit from lifestyle changes, smoking cessation, improving diet, and regular exercise, although these factors do no necessarily reduce menopausal symptoms, they do improve overall well being and can make symptoms easier to tolerate.
- CBT
- Herbal remedies (however these are not recommended as their safety is unknown)
- Vaginal lubricant
General lifestyle modifications are also recommended to reduce menopausal symptoms. For symptoms of hot flushes and night sweats: regular exercise, weight loss, wearing light clothing, sleeping in a cooler room, reducing stress and avoiding possible triggers such as spicy foods, caffeine, smoking, and alcohol is recommended.
Non-hormonal management for vasomotor symptoms
2 week trial of: - fluoxetine 20mg OD or - Citalopram 20mg OD or Venlaflaxine 37.5mg BD
Non-hormonal management for vaginal dryness
Vaginal lubricant/ moisturiser
Non-hormonal management for psychological symptoms
- Self groups
- CBT
- Antidepressants
Pharmacological options for vasomotor symptoms
HRT with small doses of oestrogen (together we a progesterone in women with a uterus) is appropriate for alleviating vasomotor instability. Tibolone combines oestrogenic and progestogenic activity with weak androgenic activity it is given continuously without cyclical progestogen. Clonidine hydrochloride may be used to reduce vasomotor symptoms in women who cannot take an oestrogen, but may cause unacceptable side-effects. Selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs) or clonidine should not be given as first-line treatment for vasomotor symptoms alone
Pharmacological options for psychological symptoms
HRT should be considered to alleviate low mood that arises as a result of the menopause. There is no clear evidence for the use of SSRIs or SNRIs to ease low mood
in menopausal women who have not been diagnosed with depression.
Pharmacological options for altered sexual function
Testosterone supplementation for menopausal women with low sexual desire should be considered if HRT alone is not effective
Pharmacological options for urogenital therapy
HRT with small doses of an oestrogen is appropriate for alleviating urogenital atrophy.
Vaginal oestrogen may be offered to women with urogenital atrophy and treatment may be continued for as long as needed to relieve symptoms. The dose may be increased if symptoms do not resolve after seeking advice from a healthcare professional with expertise in menopause
Pharmacological options for Postmenopausal osteoporosis
Oestrogen given systemically in the perimenopausal and postmenopausal period or tibolone given in the postmenopausal period also diminish postmenopausal osteoporosis but other drugs are preferred.
Pharmacological options for hot flushes
Strong evidence suggested that transdermal oestradiol plus progestogen greatly reduces the frequency of hot flushes in women with a uterus
Benefits and Risks of HRT
The benefits of HRT include reduction of vasomotor symptoms; improved sleep, joint pain and quality of life; improved psychological symptoms; relief of vaginal dryness and improved sexual function; improved bone mineral density and reduced fracture risk; reduced risk of colon cancer, dementia, prevention of diabetes, macular degeneration and cataract formation, improved skin healing.
The risk of VTE associated with HRT is greater for oral than transdermal preparations.
The risk associated with transdermal HRT given at standard therapeutic doses is no greater than baseline risk. HRT with oestrogen alone is associated with no, or reduced, risk of CHD; HRT with oestrogen and progestogen is associated with little or no increase in the risk of CHD. Oral oestrogen is associated with a small increase in the risk of stroke and HRT with oestrogen and progestogen can be associated with an increase in the risk of breast cancer.
Side effects of HRT include
● Breast tenderness ● Headaches ● Nausea ● Indigestion ● Abdominal pain ● Vaginal bleeding ● Some types of HRT can also cause a small increase in your risk of certain serious problems, such as blood clots and breast cancer
Cautions and contraindications for HRT
For women at increased risk of VTE, avoid oral HRT and consider transdermal HRT. For women with cardiovascular risk factors, HRT can be considered, however cardiovascular risk factors should be managed. For women with hypothyroidism, monitor thyroid function regularly to ensure that thyroid hormone levels remain in the acceptable range.
Premature menopause HRT
In premature menopause, there is an increased risk of osteoporosis and ischaemic heart disease due to early loss of oestrogens. In premature menopause HRT should be taken at least until the age of normal menopause and for 5-10 years after the age of 50.
It should be taken until the age of 52 and for 5-10 years after this age in surgically-induced menopause
Perimenopause HRT
Perimenopausal women may still need contraception. Contraception should continue to be used until 1 year after the last period if over the age of 50, and for 2 years if under the age of 50
Tibolone
Side effects
● Breast abnormalities ● Cervical dysplasia ● Endometrial thickening ● Gastrointestinal discomfort ● Genital abnormalities ● Abnormal hair growth ● Increased risk of infection ● Pelvic pain ● Postmenopausal haemorrhage ● Vaginal discharge ● Vaginal haemorrhage ● Increased weight
Contraindications - Tibolone
Contraindications include active or recent thromboembolic disease, history of breast cancer, liver disease, and history of thromboembolism
Cautions - Tibolone
Tibolone should be used with caution in: diabetes, history of endometrial hyperplasia, history of fibrocystic disease, history of liver disease, and risk of stroke
Interactions - Tibolone
Bleomycin, cyclophosphamide, lenalidomide, methotrexate, and raloxifene all interact with tibolone
Clonidine
Side effects
● Constipation ● Depression ● Dizziness ● Dry mouth ● Fatigue ● Headache ● Nausea ● Postural hypotension ● Salivary gland pain ● Sedation ● Sexual dysfunction ● Sleep disorders ● Vomiting
Clonidine - CI
Contraindications include severe bradyarrhythmia secondary to second- or third-degree AV block or sick sinus syndrome
Clonidine - Interactions
acebutolol, amlodipine, bendroflumethiazide, and chlorpromazine
Clonidine - cautions
Caution should be taken when using clonidine in: cerebrovascular disease, constipation, heart failure, history of depression, mild to moderate bradyarrhythmia, polyneuropathy, Raynaud’s syndrome, or other occlusive peripheral vascular disease
Antidepressants
Side effects
SSRIs and SNRIs: ● Feeling agitated, shaky or anxious ● Feeling and being sick ● Indigestion and stomach aches ● Diarrhoea or constipation ● Loss of appetite ● Dizziness ● Insomnia or feeling very sleepy ● Headaches ● Low sex drive
Antidepressants - cautions
SSRIs may not be suitable if you have: bipolar disorder, a bleeding disorder or if you’re taking medicines that can increase bleeding risk, type 1 diabetes and type 2 diabetes, epilepsy, and kidney disease.
Antidepressants - CI
Poorly controlled epilepsy, mania
Antidepressants - interactions
St John’s wort, monoamine oxidase inhibitors, and other serotonergic drugs, NSAIDs, anticoagulants, drugs that prolong QT interval
