menopuase- QUESTIONS Flashcards
1- The only role of progesterone in HRT is endometrial protection
2 - The average age at menopause is 54 years
3 - A level of FSH of more than 30 IU/l on two separate occasions indicates ovarian failure
1 - The answer is true. Unopposed estrogen causes endometrial hyperplasia and increases the risk of endometrial cancer. Given at an adequate dosage for at least 12 days, progestogen greatly reduces the incidence of hyperplasia.
2 - The answer is false. The average age of menopause is 51 years. By the age of 54, 80% of women will be at least one year postmenopausal.
3 - The answer is true. Levels of FSH and LH increase throughout the latter stages of the climacteric and reach a peak 2 to 3 years after the menopause. A level of FSH more than 30 IU/l, measured on two separate occasions is used for diagnosing ovarian failure, especially premature menopause. However, clinical symptoms alone are enough for diagnosis in women after the age of 45.
1 - Use of bone mineral density (BMD) to assess risk of osteoporotic fractures has high sensitivity
2 - More than one third of women will suffer from osteoporotic fractures in their lifetime
3 - Testosterone is not effective for treating reduced libido in postmenopausal women
1 - The answer is false. The use of BMD alone to assess risk has a high specificity but low sensitivity. The low sensitivity (approximately 50%) means that half of all osteoporotic fractures will occur in women said not to have osteoporosis. It is, therefore, not suitable for population screening.
2 - The answer is true. Osteoporosis affects one in three women, and approximately 40% of women will suffer from fracture in their lifetime. Fractures of the wrist, hip and vertebrae, which are the main clinical manifestations of osteoporosis, have an enormous impact on quality of life, and result in significant economic burden. Fractures, particularly hip fractures, are associated with considerable excess mortality.
3 - The answer is false. Randomised double blind trials have shown that all measured domains of sexual function (sexual desire, arousal, orgasm, pleasure, responsiveness, and sexual self-image) improved significantly in women treated with testosterone patches with concomitant estrogen therapy compared to placebo. Sexual problems are common in menopausal women, with low desire being the most prevalent concern. Decreases in testosterone levels, due to either a slow decline over time with increasing age or a sudden drop after bilateral oophorectomy, may lead to sexual symptoms, including loss of libido, reduced sexual activity, and decreased arousal and orgasmic response. Testosterone patches are licensed for decreased libido along with estrogen in women with surgical menopause.
1 - This treatment is licensed for the prevention or treatment of dementia
2 - HRT reduces the risk of gall bladder disease
3 - There is a lower relative risk of coronary heart disease when HRT is commenced early in menopause
1 - The answer is false. Observational studies have shown that while estrogen may delay or reduce the risk of Alzheimer’s disease (AD), it does not seem to improve established disease. More evidence is required, especially from younger postmenopausal women taking appropriate doses and different regimens, before definitive advice can be given in relation to dementia and cognition (BMS consensus). HRT should not be prescribed for the prevention or treatment of Alzheimer’s disease.
2 - The answer is false. HRT increases the risk of gallbladder disease. Gallbladder disease increases with ageing and with obesity, and as confounder. HRT users may have silent pre-existing disease.
3 - The answer is true. Observational studies have consistently shown estrogen to help prevent coronary heart disease (CHD) in postmenopausal women. The large randomised controlled Women’s Health Initiative (WHI) trial did not confirm these observational findings. However, further analyses of the WHI study as well as the observational Nurses’ Health Study have now found that the timing of onset of hormone replacement therapy (HRT) use is important and that estrogen may have a protective role in CHD in women aged 50-59 years.
1 - Assessment of bone mineral density is essential for monitoring treatment
2 -In assessment of bone mineral density, each SD below the mean doubles the risk of osteoporosis
3 - Assessment of bone mineral density is indicated in all postmenopausal women
4 - The prediction of fracture risk is improved by the use of BMD at multiple sites
1 - The answer is false. There is insufficient evidence to determine the value of routinely monitoring bone mineral density in people taking treatment for osteoporosis.
2 - The answer is true.
3 - The answer is false. Though menopause is a risk factor for osteoporosis, measurement of bone mineral density is not routinely indicated unless associated with other risk factors.
4 - The answer is false. Some guidelines favour the concurrent use of BMD at the proximal femur and at the lumbar spine. People are defined as having osteoporosis on the basis of the lower of two T-scores. The prediction of fracture is, however, not improved by the use of multiple sites and it will increase the number of people selected. Therefore, the use of multiple sites for diagnosis is not recommended. However, where hip measurement is not possible for technical reasons or in younger postmenopausal women in whom the spine is differentially affected, spine BMD measurements may be used.
1 - All patients should have a dietary assessment and calcium and vitamin D should be prescribed unless contraindicated
2- Raloxifene relieves hot flushes
3 - HRT is of most benefit for the prophylaxis of postmenopausal osteoporosis if started early in menopause and continued for up to five years
4 - Activities like swimming reduce further bone loss
1 - The answer is true. Provision of adequate dietary or supplemental calcium and vitamin D is an essential part of osteoporosis management. In northern latitudes, cutaneous synthesis of vitamin D occurs only in the summer, and many diets lack sufficient amounts of this vitamin for adequate intake in the absence of solar exposure. Most studies show that about 1.5 g of elemental calcium is necessary to preserve bone health in postmenopausal women and elderly women who are not taking HRT. Everyone over 65 years should aim to take 400 IU of vitamin D daily. For the majority of people over 65 this can only be achieved by vitamin D supplementation.
2 - The answer is false. One of the side effects of Raloxifene is hot flushes.
3 - The answer is true.
4 - The answer is false. Low-impact, weight-bearing exercise, such as walking, and high-intensity strength training that targets the muscle groups around the hip, spine, and wrists decrease the risk of osteoporosis.
1 - Tibolone increases bone mineral density
2 - Tibolone is more effective than estrogens plus progestogens in improving sexual function
3 - Tibolone can be used safely in people with a history of thromboembolism
1 - The answer is true. 2.5 mg tibolone prevents bone loss in postmenopausal women with and without osteoporosis, and its effect on bone mineral density (BMD) is similar to conventional combined HRT in healthy women. At this dose, tibolone significantly reduces the incidence of fractures in postmenopausal women without osteoporosisan effect that is comparable to both estrogen-only and combined HRT. 1.25 mg tibolone also consistently and significantly increases BMD. The LIFT (Long-term Intervention on Fractures with Tibolone) study found that 1.25 mg tibolone reduces the incidence of new osteoporotic fractures by 50% in older women with osteoporosis relative to placebo. Tibolone is currently a second-line option for the prevention of osteoporosis, and so only women who are unable to use other medicines should be prescribed tibolone for osteoporosis.
2 - The answer is true. Tibolone, because of its combined estrogenic, androgenic, and SHBG-lowering activity, is associated with improvement in sexual desire. In some studies, women on tibolone expressed a greater improvement in overall sexuality and sexual function when compared with women on combined continuous HRT (E2 2 mg; NETA 1 mg) or estrogen alone (transdermal 17beta E2 50 microgram).
3 - The answer is false. The few data available do not suggest that tibolone increases risk of venous thromboembolism (VTE) compared with combined HRT users or with non-users. However, on the basis of the increased risk of VTE in association with conventional HRT, tibolone is contraindicated in women with previous idiopathic or current VTE. In addition, it is recommended that women with a history of, or risk factors for, thromboembolic disorders are supervised closely during treatment. (UK Public Assessment Report.)
Regarding tibolone…
1 - The efficacy for relief of hot flushes is comparable to conventional HRT
2 - The risk of breast cancer is lower compared with combined HRT
3 - Tibolone increases risk of stroke in elderly people
1 - The answer is true. 2.5 mg tibolone is the optimum daily dose for relief of menopausal symptoms, with comparable efficacy to conventional combined HRT. 1.25 mg tibolone is the minimum effective daily dose, and likely provides sufficient relief for some women, depending on the severity of their symptoms.
2 - The answer is true. The Million Women Study identified a significantly increased risk of having breast cancer diagnosed in tibolone users (relative risk [RR] 1·5 [95% CI 1·3-1·7]), which is comparable with that for estrogen-only HRT (1·3 [1·2-1·4]) and significantly lower than that for combined HRT (2·0 [1·9-2·1]). Risk increased with longer duration of use and returned to baseline within a few years of stopping treatment. A study using the General Practice Research Database found no significant increase in risk. Unlike conventional HRT, tibolone has a limited effect on mammographic density.
3 - The answer is true. The LIFT (Long-term Intervention on Fractures with Tibolone) study identified a significantly (2.2-times) increased risk of stroke, mostly ischaemic, in tibolone users; risk increased from the first year of treatment. Baseline risk of stroke is strongly age-dependent, and so the absolute risk with tibolone increases with older age. Randomised controlled trials have identified an approximate 1.3-times increase in stroke risk for combined HRT. For women older than about 60 years, the risks associated with tibolone start to outweigh the benefits because of the increased risk of stroke.
1 - Transdermal HRT is preferred if the woman has lactose sensitivity
2 - Transdermal HRT is preferred if the woman prefers more natural therapy
3 - Transdermal HRT is preferred if the only symptom is vaginal dryness
1 - The answer is true. All tablets contain lactose.
2 - The answer is false. With transdermal preparations, breakdown in the gut and liver is avoided, so a lower dose can be used and higher estradiol levels are achieved in the systemic circulation. The estradiol:estrone ratio is closer to that of the premenopausal woman. Making it more physiologically ‘normal’. However it is still ‘hormone replacement’ and therefore is not natural.
3 - The answer is false. Vaginal estrogens are preferred if the only symptom is vaginal dryness.
1 - Transdermal HRT is preferred if the woman has a history of migraine
2 - Transdermal HRT is preferred if the woman is taking a hepatic enzyme-inducing drug
3 - Transdermal HRT is preferred if the woman has inflammatory bowel disorder
1 - The answer is true. Migraine is often triggered by fluctuating hormone levels during the menstrual cycle. Transdermal administration produces more stable circulating levels and may be less likely to provoke or exacerbate migraine.
2 - The answer is true. This avoids hepatic first pass and therefore the effect of increased hepatic enzyme activity.
3 - The answer is true. Because bowel disorder may affect absorption of oral HRT.
1 - Long-term use of estrogen-only or combined HRT may be associated with a small increased risk of ovarian cancer, which returns to baseline a few years after stopping treatment
2 - HRT is indicated for reducing the risk of colorectal cancer in women with a strong family history of colorectal cancer
3 - HRT reduces the fracture risk of both hip and vertebrae
1 - The answer is true. The randomised Women’s Health Initiative found no significant increase with combined estrogen-progestogen HRT. The increased risk found in the Million Women Study for ovarian cancer is not high in statistical terms and certainly not higher than that found in other studies. There is currently insufficient evidence to recommend alterations in HRT prescribing practice. (BMS Consensus statement (link is external).)
2 - The answer is false. Though HRT reduces the risk of colorectal cancer by about a third, little is known about colorectal cancer risk when treatment is stopped. There is no information about HRT in high risk populations and current data do not allow prevention as a recommendation. (BMS Consensus statement. (link is external))
3 - The answer is true. There is evidence from randomised controlled trials, including the Women’s Health Initiative (WHI), that HRT reduces the risk of both spine and hip as well as other osteoporotic fractures even in women at low risk. The ‘standard’ bone conserving doses of estrogen were considered to be estradiol 2 mg, conjugated equine estrogens 0.625 mg and transdermal 50 microgram patch. However, it is now evident that half these doses or even lower also conserve bone mass.
1 - Early menarche is a recognised risk factor for osteoporosis
2 - Smoking is a recognised risk factor for osteoporosis
3 - Low dietary calcium intake is a recognised risk factor for osteoporosis
4 - Sedentary lifestyle is a recognised risk factor for osteoporosis
5 - Slender body habitus is a recognised risk factor for osteoporosis
1 - The answer is false. Hypo-estrogenic conditions like premature hypogonadism, menopause and secondary amenorrhoea of more than one year, are associated with osteoporosis but not early menarche.
2 - The answer is true. Smoking increases risk of osteoporosis.
3 - The answer is true. Low calcium intake, low vitamin D levels (lack of sunlight and/or low dietary intake) increase risk of osteoporosis.
4 - The answer is true. Sedentary lifestyle (particularly during adolescence) or conditions associated with prolonged immobility increases risk of osteoporosis.
5 - The answer is true. Low body mass index (less than 19 kg/m²) increases risk of osteoporosis.
Which of the following statements regarding HRT and breast cancer is true?
Continuous combined HRT accounts for three extra cases in every 1000 women who use it for 2 years between the ages of 50 and 59
Continuous combined HRT accounts for five extra cases in every 1000 women who use it for 2 years between the ages of 50 and 59
Continuous combined HRT accounts for three extra cases in every 1000 women who use it for 5 years between the ages of 50 and 59
The use of estrogen-only HRT is associated with a higher risk compared with combined HRT
The use of tibolone is associated with the highest risk
Continuous combined HRT accounts for three extra cases in every 1000 women who use it for 5 years between the ages of 50 and 59
The correct answer is that continuous combined HRT accounts for 3 extra cases in every 1000 women who use it for 5 years between ages of 50 and 59. See the British Menopause Society’s fact sheet on HRT and breast cancer (link is external).
There is a small increase in the risk of developing breast cancer with HRT and it depends on the type of HRT used. Combined HRT (estrogen + progestogens) probably accounts for 3 extra cases in every 1000 women who use it for 5 years between the ages of 50 and 59 years. There appears to be no increase in the risk for shorter term use of less than 3 years. The use of estrogen-only HRT has a lower risk than combined HRT. The risk with tibolone appears to be similar to that of estrogen only.
Final assessment 11
A 45-year-old woman approaches you in the menopause clinic. Her mother died at the age of 48 from acute myocardial infarction.
She wants more information on the use of HRT and other medications to prevent coronary heart disease (CHD).
Which of the following statements is correct?
Aspirin should be taken regularly after the age of 50 years to prevent CHD
Estrogen does not reduce the risk of CHD in women with premature menopause
Estrogen may have a protective role in CHD prevention in women aged 50–59 years
New evidence is available regarding the use of lipid lowering agents to prevent CHD in menopausal women
Pharmacotherapy is as good as the combination of lifestyle measures and pharmacotherapy in the prevention of CHD in menopausal diabetic women
- Estrogen may have a protective role in CHD prevention in women aged 50–59 years.
- Women with a premature menopause should take estrogen to reduce the risk of CHD.
- The role of lipid-lowering agents is uncertain.
- Aspirin cannot be recommended for primary prevention of CHD, but may protect against stroke.
- Treating hypertension reduces the risk of CHD.
In diabetics, prevention of CHD is based on management of established cardiovascular risk factors through both lifestyle measures and pharmacotherapy.
In metabolic syndrome, prevention of CHD is based on management of established cardiovascular risk factors through both lifestyle measures and pharmacotherapy. Stopping smoking, reducing obesity, improving diet and undertaking regular exercise are key lifestyle measures.
Which of the following statements regarding osteoperosis management in menopausal women is true?
Bisphosphonates should be taken daily
Denosuab (den OH sue mab). is now licensed for use in postmenopausal women with osteoporosis
Raloxifene is associated with an increased risk of uterine but not breast cancer
Raloxifene use is associated with a reduced risk of coronary heart disease as it reduces cholesterol levels
Strontium should be taken with calcium supplements for best effect
The correct answer is denosuab is now licensed for use in postmenopausal women with osteoporosis. See the British Menopause Society’s Consensus Statement on Prevention and treatment of osteoporosis in women (link is external).
Bisphosphonates should be taken in the morning on an empty stomach with plain water. Most of them are taken as once a week preparations. Ibandronate is once a monthly preparation.
Raloxifene does not affect the uterus but reduces the risk of breast cancer. Even though it reduces the cholesterol level, the significance of that reduction on the risk of developing coronary heart disease is still unclear.
Strontium is taken as once daily bedtime dose, ideally 2 hours after eating and 2 hours after calcium supplements.
Denosuab is now licensed to be given as 6-monthly injections in postmenopausal women with osteoporosis. Denosumab is a human monoclonal antibody that blocks rank ligand. Rank ligand stimulates osteoclats that encourage bone resorption.
A 49-year-old woman approaches you in the clinic as she has been having regular, troublesome hot flushes for past 6 months. Her last period was 2 weeks ago and they are regular.
Which is the most suitable type of HRT to start her on?
Continuous combined HRT Estrogen only HRT - oral tablets Estrogen only HRT - patches Sequential combined HRT Tibolone
The correct answer is sequential combined HRT. See the British Menopause Society’s fact sheet on HRT and breast cancer (link is external).
If a woman is having menopausal symptoms and are still having menstrual bleeds, then she will be suitable for sequential combined HRT (i.e. daily estrogen with the addition of progestogens for 10 or 12 days in the 28 day cycle). This method usually gives a monthly bleed.
If the woman is amenorrhoeic for at least 12 months then she should be given continuous combined HRT (estrogen and progestogens together daily). This method may be associated with a few episodes of spotting or light bleeding in the early months of use. Tibolone is another drug used to treat symptoms without causing return of monthly bleeds.
Following a hysterectomy estrogen only HRT is needed.
