11. The Menopause and Hormone Therapy Flashcards
What is the definition of menopause?
Menopause is the last menstrual period. It is a retrospective diagnosis made 12 months after the last period.
What is early menopause, and when does it occur?
Early menopause is the cessation of menstruation prior to age 50.
What is premature ovarian failure or primary ovarian insufficiency, and when does it occur?
Premature ovarian failure or primary ovarian insufficiency occurs when menstruation ceases before age 40. It warrants investigation to determine the cause.
What is perimenopause?
Perimenopause refers to the variable time starting a few years before and continuing for a year after menopause. It includes the climacterium.
What is the climacterium?
The climacterium refers to the time after the cessation of reproductive function, marked by changes in the menstrual cycle.
What are the main endocrine events of the climacteric?
The main endocrine events of the climacteric include:
- Loss of ovarian responsiveness to gonadotrophin stimulation.
- Gradual decline in oestradiol production.
-The precise cause of ovarian failure initiation involves oocyte depletion.
Are menopause, perimenopause, and climacterium interchangeable terms?
No, these terms are not strictly interchangeable, although they are often used that way.
What is the mean age of menopause in Western women?
The mean age of menopause in Western women is 50.8 years.
What primarily determines the age of menopause?
The age of menopause is genetically determined.
What factors may influence the timing of menopause?
Factors include:
- Smoking
- General health status and concomitant disease
- High parity
What changes occur in gonadotrophin concentrations during the menopausal transition?
Gonadotrophin concentrations rise, starting with FSH.
How might menstrual cycles change during the menopausal transition?
- Cycles may shorten, with a 7-day difference from the normal cycle length for that woman.
- Eventually, most cycles become anovulatory, leading to irregular oestradiol secretion.
- Increasing intervals of amenorrhoea may occur, with periods of up to 2 missed cycles.
What symptoms may arise due to declining and erratic oestradiol secretion?
Vasomotor symptoms may occur.
How do FSH levels change in relation to menstrual disruption?
Elevated FSH levels can precede menstrual disruption by several years and are associated with a major impairment of fertility.
When do gonadotrophin levels peak post-menopause, and what happens afterward?
Gonadotrophin secretion peaks 2-3 years post-menopause and then declines gradually over the next 2-3 decades.
What is the main steroid product of the postmenopausal ovary?
The main steroid product is androstenedione.
Is heavy, irregular bleeding a normal part of the perimenopause?
No, heavy, irregular bleeding is NOT normal during perimenopause and requires investigation.
What are the categories of symptoms and consequences of menopause related to oestrogen deficiency?
They are divided into:
- Acute (within months of hypo-oestrogenism)
- Intermediate
- Long-term (after years of hypo-oestrogenism)
What are the acute symptoms of oestrogen deficiency?
- Hot flushes
- Night sweats
- Insomnia
- Mood changes
- Anxiety and irritability
- Poor memory and poor concentration
- Loss of self-esteem
- Amenorrhoea
What are the intermediate consequences of oestrogen deficiency?
- Genital tract atrophy
- Dyspareunia and loss of libido
- Urethral syndrome
- Skin thinning
- ? Uterine vaginal prolapse
- ? Urinary incontinence
- ? Joint pains
What are the long-term consequences of oestrogen deficiency?
- Osteoporosis
- Coronary heart disease
- Cerebrovascular accidents
What are the reviewed long-term consequences of oestrogen deficiency, aside from osteoporosis?
Coronary heart disease and strokes are now being reviewed as long-term consequences of oestrogen deficiency.
Does oestrogen therapy improve outcomes for coronary heart disease and strokes in postmenopausal women?
No, studies suggest that oestrogen therapy does not improve these outcomes and may even increase the incidence of these conditions.
Do all women experience menopausal symptoms?
No, not all women complain of menopausal symptoms, and the degree of incapacitation varies considerably between individuals.
Which women are particularly at risk for osteoporosis?
Women with oestrogen deficiency due to menopause are particularly at risk for osteoporosis.
Why is judicious management of the peri-menopause important?
Judicious management of the peri-menopause is important to improve general well-being and long-term health, especially given our ageing population.
What are the indications for hormone therapy (HT)?
- Women with vasomotor symptoms and vulvovaginal symptoms.
- Premature ovarian failure
- Early menopause
- It may be used in the treatment of osteopaenia and osteoporosis in younger menopausal women but must be discontinued later when the risks of HT outweigh the benefits, especially when there are other treatment options available.
- There is no place for HT as secondary prevention. Many of the previously reported benefits of hormone therapy have not been substantiated in randomised controlled trials and the indications have accordingly been reduced.
Should hormone therapy (HT) be used for secondary prevention?
No, there is no place for HT as secondary prevention. Many previously reported benefits of HT have not been substantiated in randomised controlled trials, leading to reduced indications.
What are the principles of managing hormone therapy (HT)?
- use minimum effective dose
- adjust therapeutic regimen to achieve maximum benefit
- monitor appropriately
- length of therapy dependent on numerous factors
- discuss risk - benefits with patient thoroughly at start of treatment
What are the routes of administration for oestrogens: oral
Conjugated equine oestrogens
Esterified oestrogens
Micronized oestrogens
What are the routes of administration for oestrogens: transdermal
Patches
Cream
What are the routes of administration for oestrogens: vaginal
Cream
Oestradiol ring
Tablets
Categories for route of adminstration
oral
transdermal
vaginal
Note: Implants are no longer available.
What are the routes of administration for progestins: oral
Medroxyprogesterone acetate
Norethindrone acetate
Micronized progesterone
What are the routes of administration for progestins: vaginal
Progesterone gel
Micronized progesterone
What are the routes of administration for progestins: intrauterine
Mirena
What are the routes of administration for combination hormone therapy (oestrogen + progestin): oral
Continuous combined
Sequential
What are the routes of administration for combination hormone therapy (oestrogen + progestin): transdermal
Patch
What are the hormone therapy recommendations for women with a uterus?
- Cyclical oestrogen/progesterone therapy with regular bleeding during the perimenopausal/climacteric phase.
- Continuous combined therapy.
- Continued progestin therapy if oestrogen is contraindicated.
What is the hormone therapy recommendation for women without a uterus?
Oestrogen therapy alone is sufficient unless there is a contraindication to oestrogen therapy.
Is hormone therapy recommended after bilateral oophorectomy for endometriosis in young women? Why?
Yes, hormone therapy is recommended due to its overall health benefits. However, the ideal regimen is unclear. Adding a progestogen after hysterectomy is unnecessary but may protect against the unopposed action of oestrogens on any residual disease.
What factors should be considered when balancing the risks and benefits of combined oestrogen and progestogen therapy after bilateral oophorectomy?
The theoretical benefit of avoiding disease reactivation or malignant transformation.
The increase in breast cancer risk associated with combined therapy.
Why must risks and benefits of hormone therapy always be carefully discussed with patients?
Risks and benefits must be discussed because, for example, in the UK, mortality from stroke or ischemic heart disease far outweighs mortality from breast cancer. Adequate local studies are not always available.
What are the contra-indications to oestrogen therapy?
- Abnormal undiagnosed vaginal bleeding
- Liver disease
- Oestrogen - dependent cancer (now a subject of debate)
- Otosclerosis (scanty data suggest worsening)
- Malignant melanoma (uncertain - no conclusive data)
- Transient ischaemic attacks (?)
- Focal headaches on HT (?)
- Gallstones (prescribe with caution)
Why is the list of contra-indications to oestrogen therapy subject to change?
With current knowledge and ongoing research, the assessment of contra-indications and indications is constantly under review.
What are the common side effects of oestrogen in hormone therapy?
Heavy bleeding.
Fluid retention.
Increased appetite.
Nausea.
Mastalgia (breast pain).
What are the common side effects of progestogens in hormone therapy?
Breast pain.
Fluid retention.
Bloating.
Increased appetite.
Irritability.
Aggression.
Anxiety and depression.
Why are some symptoms of hormone therapy difficult to attribute to a specific hormone?
Symptoms such as breast pain, fluid retention, and mood changes may overlap and are not always clearly attributable to either oestrogen or progestogen.
What are the key components of monitoring and follow-up for hormone therapy?
- Check symptom control
- Enquire about side-effects
- Document bleeding pattern
- Monitor weight and blood pressure
- Endometrial sampling in selected patients
- Mammography: ideally pre-HT
- Osteodensitometry: select
Is hormone therapy (HT) contraceptive?
No, HT is not contraceptive.
What is the general rule for contraception in menopausal women?
Under 50 years: Continue contraception for 2 years post-menopause
.
Over 50 years: Continue contraception for 1 year post-menopause.
Use barrier contraception or an IUCD.
What lifestyle modifications are recommended for menopausal women?
Cessation of smoking.
Reduction of alcohol intake.
Regular exercise.
Adopting a healthy diet.
What alternative therapies can be used alongside or instead of HT?
- Clonidine: For vasomotor symptoms.
- Bisphosphonates: For osteoporosis.
- SERMs (Selective Estrogen Receptor Modulators): For osteoporosis.
- Psychotherapy: For selected patients.
What is the pathophysiology of vasomotor instability (hot flushes) in menopause?
The precise pathophysiology is unknown, but it is thought to be related to low or fluctuating levels of circulating oestrogen, which affects hypothalamic thermoregulation.
When is the peak incidence of hot flushes in menopausal women?
The peak incidence occurs just after menses cease, affecting 50-80% of women. Up to 20% of women continue experiencing hot flushes for 5 years or more.
What are the characteristics of hot flushes?
Hot flushes are unpredictable and can occur during the day or night. They are characterized by a sudden, transient increase in heat lasting from a few seconds to 5 minutes, followed by a feeling of cold as the body cools.
What are genitourinary symptoms associated with oestrogen deficiency in menopause?
Symptoms include vaginal atrophy, senile vaginitis (itching, burning, discomfort, dyspareunia, and bleeding), frequency, nocturia, dysuria, urge incontinence, and increased risk of urinary tract infections.
How can vaginal atrophy be treated in menopausal women?
Local oestrogen preparations can be used for up to 6 months to treat vaginal atrophy. As the vagina becomes oestrogenised, the absorption of local oestrogen decreases.
How does oestrogen deficiency affect the bladder and urethra in menopausal women?
Oestrogen deficiency can cause atrophic changes in the bladder trigone and urethra, leading to symptoms like frequency, nocturia, dysuria, and urge incontinence. It can also lead to increased susceptibility to urinary tract infections due to shortening of the urethra.
What is the role of local versus systemic oestrogen therapy for urinary symptoms in menopause?
Local oestrogen therapy may benefit some women with overactive bladder, but systemic therapy may worsen stress incontinence. Ultralow transdermal therapy has no effect on urinary symptoms.
How does oestrogen deficiency affect collagen production and ligaments in menopause?
Oestrogen deficiency leads to decreased collagen production, weakening of ligaments and fascia, and an increased risk of prolapse.
Is hormone therapy recommended for the treatment of sexual dysfunction in menopause?
No, hormone therapy is not recommended for the sole treatment of sexual dysfunction, including low libido.
How does oestrogen deficiency affect cardiovascular health in menopause?
Oestrogen deficiency leads to metabolic changes that impact the development of atherosclerosis and thrombosis. It causes adverse effects on lipoproteins and lipids, increasing LDL and triglycerides (elevating cholesterol) and decreasing HDL. Central body fat distribution also increases the risk of cardiovascular events.
What changes occur in the coagulation cascade during menopause?
Menopause is associated with an increase in serum fibrinogen, antithrombin, and plasminogen activator inhibitor 1, which are highly predictive of coronary heart disease. There is a reduction in fibrinolysis, along with a slight increase in coagulation.
What is the risk of coronary heart disease (CHD) after menopause
Heart disease is uncommon in premenopausal women, but the rate of myocardial infarctions increases after the age of 50, with women experiencing a greater rate of increase than men. Observational studies suggested hormone therapy (HT) could prevent CHD, but randomized controlled trials (RCTs) showed an increased risk.
What did the Women’s Health Initiative (WHI) reveal about the relationship between hormone therapy and coronary heart disease?
The WHI showed an increase of 8 cases of coronary heart disease per 100,000 women per year with oestrogen-progesterone therapy. The study also suggested that the timing of initiation of therapy is important, with fewer events in women who started therapy near menopause.
What was the effect of hormone therapy on stroke risk in the WHI?
The WHI showed an increased risk of thrombotic strokes: 8 per 10,000 women per year with oestrogen-progesterone therapy and 11 per 10,000 women per year with oestrogen therapy alone. However, in younger women aged 50-59, there was no significant effect on stroke risk.
What did the Heart and Estrogen/progestin Replacement Study and the Women’s Estrogen for Stroke Trial find regarding stroke risk?
These studies showed no increase in stroke rate, even in secondary prevention trials.
What did the Nurses Health Study reveal about stroke risk with hormone therapy?
The Nurses Health Study, the largest and longest prospective cohort study, indicated an increased risk of ischaemic stroke, which was consistent with findings from the WHI.
How does hormone therapy affect the risk of venous thromboembolism (VTE)?
Both observational and RCT data show an increased risk of VTE in the first 1-2 years after starting HT. The risk is lower in women who start treatment before the age of 60. A body mass index (BMI) greater than 30 is associated with a threefold increase in the risk of VTE.
What is the rate of bone loss during menopause?
Bone loss accelerates in the 2-3 years before menopause, occurring at a rate of 5% per year. After menopause, it decreases to 1-2% per year, typically 3-4 years post-menopause. Bone loss is faster in trabecular bone (spine) than in cortical bone (femur).
What defines osteoporosis?
Osteoporosis is a skeletal disorder characterized by compromised bone strength, which increases the risk of fractures. Bone mineral density (BMD) is measured to diagnose osteoporosis, with results expressed as a T-score.
How is osteoporosis diagnosed using bone mineral density (BMD)?
Osteoporosis is diagnosed when the T-score is greater than or equal to -2.5 standard deviations (SD) from the mean, comparing the patient’s bone density to that of a young adult population. The T-score is used in postmenopausal women, and results are expressed in standard deviations.
What is the FRAX tool and how does it assess fracture risk?
The FRAX tool is a computer-generated score that assesses the probability of a fracture over a 10-year period. It uses various variables, including BMD, ethnicity, age, gender, family history of fragility fractures, history of fractures, BMI, and medications, to estimate fracture risk.
When is hormone therapy used for osteoporosis, and what are the risks?
Hormone therapy may be used early in menopause, but osteoporosis is most common later in life. The risks of hormone therapy typically outweigh the benefits for osteoporosis in postmenopausal women.
What are some medications used in the treatment of osteoporosis?
Medications include:
- Calcium (1000mg daily)
- Vitamin D (800 IU daily)
- Bisphosphonates (the treatment of choice for osteoporosis and fractures)
- Selective Estrogen Receptor Modulators (SERMs) such as Raloxifene
- Strontium ranelate and teriparatide (recombinant human PTH1-34).
What lifestyle changes can help manage osteoporosis?
Lifestyle changes include:
- Discontinuing smoking and excessive alcohol consumption
- Consuming a nutritious diet with adequate calcium, including dairy products
How does oestrogen/progestin therapy impact breast cancer risk?
Oestrogen/progestin therapy is associated with an increased incidence of breast cancer. The risk increases with the duration of use. After stopping therapy, the risk declines and returns to baseline within approximately 5 years. However, despite the increased risk, there is little evidence suggesting an increase in breast cancer mortality.
Is hormone therapy safe for breast cancer survivors?
Currently, there is no hormone therapy that is considered safe for breast cancer survivors, as all evidence suggests an increase in recurrence rates
What is the relationship between unopposed oestrogen and endometrial cancer?
Unopposed oestrogen is contraindicated due to the risk of endometrial cancer. In women with an intact endometrium, a progestin component must be added to hormone therapy, which can be delivered through continuous combined or sequential EPT. An alternative method for endometrial protection is the Mirena intrauterine system.
How does hormone therapy affect ovarian cancer risk?
Studies on ovarian cancer and hormone therapy show conflicting results. Some epidemiological studies suggest no association, while others show a modest increase in risk.
How does hormone therapy affect colon cancer risk?
Most studies indicate that oestrogen/progestin therapy significantly reduces the risk of colorectal cancer in women.
What are the potential benefits of hormone therapy (HT)?
The potential benefits of HT include:
- Therapeutic: Improvement of acute and intermediate menopausal symptoms.
- Preventative: Role in the prevention of osteoporosis.
What are the therapeutic benefits of hormone therapy (HT)?
HT can help improve acute and intermediate menopausal symptoms, such as hot flashes, night sweats, and vaginal dryness, providing relief for women experiencing these issues.
What are the preventative benefits of hormone therapy (HT)?
HT plays a role in the prevention of osteoporosis by helping to maintain bone mineral density and reduce the risk of fractures in postmenopausal women.
What is the significance of menopause in a woman’s life?
Menopause occurs during a time of significant life changes, such as caring for aging parents and children becoming independent. It is a natural part of aging and can affect a woman’s sense of mortality.
How should patients going through menopause be treated?
Patients should be treated with sympathy, considering the emotional and physical challenges of menopause. As women may spend many years in the postmenopausal phase, timely and adequate therapy is important to improve quality of life and reduce long-term morbidity.
What is the role of hormonal therapy in menopause management?
Hormonal therapy remains a controversial treatment option. While it offers benefits, such as symptom relief, it carries associated risks. Women should be fully informed and make decisions on whether to pursue therapy.
How should hormone therapy (HT) be managed?
Women receiving HT should be re-evaluated annually to assess their continued need for therapy and to screen for any conditions linked to HT. The goal is to use the lowest effective dose for the shortest period.
