BNF - Chapter 6 - Endocrine system - (Part 2) Flashcards
What are oestrogens required for the development of in females?
- Female secondary sexual characteristics
they also stimulate myometrial hypertrophy with endometrial hyperplasia.
Which have a more appropriate profile for hormone replacement therapy (HRT) - natural oestrogens or synthetic?
Natural oestrogens
List the natural and synthetic oestrogens?
Natural = Estradiol (oestradiol), estrone (oestrone) and estriol (Oestriol)
Synthetic = Ethinylestradiol and mestranol.
What activity does tibolone have?
- Oestrogenic
- Progestogenic
- and weak androgenic activity
If long term oestrogen therapy is required then women with a uterus should be given what else with oestrogen?
- A progestogen should normally be added to reduce the risk of cystic hyperplasia of the endometrium (or of endometritic foci in women who have had a hysterectomy) and possible transformation to cancer
Are oestrogens recommended for suppression of lactation?
No longer used to suppress lactation because of their association with thromboembolism
What is HRT (hormone replacement therapy) useful for?
Hormone replacement therapy (HRT) with small doses of an oestrogen (together with a progestogen in women with a uterus) is appropriate for alleviating menopausal symptoms such as vaginal atrophy or vasomotor instability.
Does oestrogen have a role in diminishing postmenopausal osteoporsis?
Yes but other drugs are preferred for osteoporosis
What may menopausal atrophic vaginitis respond to?
- A short course of a topical vaginal oestrogen preparation used for a few weeks and repeated if necessary
What does systemic therapy with an oestrogen help alleviate the symptoms of?
- The symptoms of oestrogen deficiency such as vasomotor symptoms
What activity does tibolone combine?
Tibolone combines oestrogenic and progestogenic activity with weak androgenic activity;
Is tibolone given with or without cyclical progestogen?
It is given continuously without cyclical progestogen
Which drug class is clonidine in?
- Alpha receptor agonist
What may clonidine be used for in menopausal symptoms?
Clonidine hydrochloride may be used to reduce vasomotor symptoms in women who cannot take an oestrogen, but clonidine hydrochloride may cause unacceptable side-effects.
What does HRT increase the risk of?
HRT increases the risk of venous thromboembolism, stroke, endometrial cancer (reduced by a progestogen), breast cancer, and ovarian cancer;
What is the increased risk of coronary heart disease in women who start HRT 10 years after the menopause?
there is an increased risk of coronary heart disease in women who start combined HRT more than 10 years after menopause.
Do all systemic HRT increase the risk of breast cancer?
Yes - All types of systemic (oral or transdermal) HRT treatment increase the risk of breast cancer after 1 year of use.
For which HRT preparations is the risk for breast cancer higher?
This risk is higher for combined oestrogen-progestogen HRT (particularly for continuous HRT preparations where both oestrogen and progestogen are taken throughout each month) than for oestrogen-only HRT, but is irrespective of the type of oestrogen or progestogen
Are vaginal preparations containing low dose of oestrogen to treat local symptoms thought to increase risk of breast cancer?
They are not thought to be associated with an effect on breast cancer risk.
If a decision is made to stop treatment, in the absence of contraindications, the MHRA recommends how should this be done?
- This should be done gradually to minimise recurrence of menopausal symptoms
Why may HRT use make it more difficult for radiological detection of breast cancer?
can be made more difficult as mammographic density can increase with HRT use especially oestrogen-progestogen combined treatment, but this is not thought to be the case with tibolone.
Has tibolone been associated with an increased or decreased risk of breast cancer during treatment?
Tibolone has also been associated with an increased risk of breast cancer during treatment, although the extent of risk and its persistence after stopping is currently inconclusive.
What does the risk of endometrial cancer depend on?
The dose and duration of oestrogen only HRT.
To reduce the risk of endometrial cancer with oestrogen HRT - at least how many days per 28-day cycle (in women with a uterus) should the addition of a progestogen cyclically be given?
For at least 10 days per 28-day cycle
The risk of endometrial cancer in women who have not used HRT increased with what?
Increases with body mass index (BMI)
Is the increased risk of endometrial cancer in users of oestrogen only HRT or tibolone more apparent in women who are overweight or not overweight?
More in women who are not over weight
Is there an increased risk of endometrial cancer with tibolone use?
Yes
Does the risk of ovarian cancer disappear after discontinuing combined HRT or oestrogen only HRT?
yes it does - within few years after stopping
Does combined or oestrogen only HRT increase risk of VTE?
Yes - especially in the first year of use
Is risk of VTE with non-oral HRT greater or lower?
Although the level of risk of thromboembolism associated with non-oral routes of administration of HRT has not been established, it may be lower for the transdermal route.
Does combined HRT or oestrogen only HRT increase the risk of stroke?
Slightly increases the risk of stroke
Which HRT does a o women with a uterus usually require?
A woman with a uterus normally requires oestrogen with cyclical progestogen for the last 12 to 14 days of the cycle or a preparation which involves continuous administration of an oestrogen and a progestogen (or one which provides both oestrogenic and progestogenic activity in a single preparation).
When are continuous combined preparation or tibolone not suitable?
are not suitable for use in the perimenopause or within 12 months of the last menstrual period;
In other words - can only be used in post-menopausal women
What may women using continuous combined preparations of HRT or tibolone experience?
- May bleed irregularly in the early stages of treatment = of bleeding continues endometrial abnormality should be ruled out and consideration given to changing to cyclical HRT
Can oestrogen alone be used in women without a uterus
Yes
What circumstances in women without a uterus may progestogen still be considered?
n endometriosis, endometrial foci may remain despite hysterectomy and the addition of a progestogen should be considered in these circumstances.
Does transdermal administration avoid first-pass metabolism?
yes
For patients on HRT - how many weeks may it need to be stopped before surgery?
Major surgery under general anaesthesia, including orthopaedic and vascular leg surgery, is a predisposing factor for venous thromboembolism and it may be prudent to stop HRT 4–6 weeks before surgery;
it should be restarted only after full mobilisation.
What about if HRT is continued or if discontinuation is not possible (e.g. in non-elective surgery)?
prophylaxis with unfractionated or low molecular weight heparin and graduated compression hosiery is advised.
Hormone replacement therapy should be stopped (pending investigation and treatment), if any of the following occur?
sudden severe chest pain (even if not radiating to left arm);
sudden breathlessness (or cough with blood-stained sputum);
unexplained swelling or severe pain in calf of one leg;
severe stomach pain;
serious neurological effects including unusual severe, prolonged headache especially if first time or getting progressively worse or sudden partial or complete loss of vision or sudden disturbance of hearing or other perceptual disorders or dysphasia or bad fainting attack or collapse or first unexplained epileptic seizure or weakness, motor disturbances, very marked numbness suddenly affecting one side or one part of body;
hepatitis, jaundice, liver enlargement;
blood pressure above systolic 160 mmHg or diastolic 95 mmHg;
prolonged immobility after surgery or leg injury;
detection of a risk factor which contra-indicates treatment.
What is ethnylestradiol licensed for?
Ethinylestradiol (ethinyloestradiol) is licensed for short-term treatment of symptoms of oestrogen deficiency, for osteoporosis prophylaxis if other drugs cannot be used and for the treatment of female hypogonadism and menstrual disorders.
It is also used licensed for the palliative treatment of prostate cancer.
What role does raloxifene have postmenopause?
Raloxifene hydrochloride is licensed for the treatment and prevention of postmenopausal osteoporosis; unlike hormone replacement therapy, raloxifene hydrochloride does not reduce menopausal vasomotor symptoms.
What drug treatment may endometriosis respond to?
t may respond to a progestogen, e.g. norethisterone, administered on a continuous basis. Danazol and gonadorelin analogues are also licensed for endometriosis.
Oral progestogens have also been used for severe dysmenorrhoea - what if contraception is also required e.g. younger women?
The the best choice is a combined oral contraceptive
What progesterone effect does Ulipristal acetate have?
Ulipristal acetate is a progesterone receptor modulator with a partial progesterone antagonist effect
What are the use of ulipristal acetate?
Intermittent ulipristal acetate can be used to treat moderate to severe symptoms of uterine fibroids in premenopausal women where surgery and uterine artery embolisation are unsuitable, or have failed. Ulipristal acetate is also used as a hormonal emergency contraceptive.
What is vaginal atrophy?
Thinning + Drying of the vaginal walls due to less oestrogen
What is endometriosis?
Endometriosis is the growth of endometrial-like tissue outside the uterus.
Which age does endometriosis affect?
Women of reproductive age, although the exact cause is unknown, it is an oestrogen dependent condition and is associated with menstruation
What symptoms is associated with endometriosis?
- pelvic pain, painful periods and subfertility
Women with endometriosis report pain, which can be frequent, chronic and severe, as well as tiredness, more sick days, and a significant physical, sexual, psychological and social impact
Endometriosis is an important cause of what?
Endometriosis is an important cause of subfertility and this can also have a significant effect on quality of life.
Do every women with endometriosis show symptoms?
No - so it is is difficult to know how common the disease is in the population
How do most drug treatments for endometriosis work?
By suppressing ovarian function and are contraceptive
What does surgical treatment aim to remove?
Aims to remove or destroy endometriotic lesions
What is the first-line management of endometriosis-related pain?
A short trial (such as 3 months) of paracetamol or an NSAID alone or in combination
Which hormonal treatment should be offered to women with suspected, confirmed or recurrent endometriosis?
Combined oral contraceptive or progestogen
What can hormonal treatment for endometriosis reduce?
Reduce pain and has no permanent negative effect on subsequent fertility
For endometriosis what should women be asked about to guide surgical decision making?
Women with suspected or confirmed endometriosis should be asked about their symptoms, preferences and priorities with respect to pain and fertility, to guide surgical decision-making.
When should gonadotropin-releasing hormones be given?
For deep endometriosis involving the bowel, bladder or ureter, gonadotropin-releasing hormones given for 3 months before surgery should be considered
Can women with endometriosis who are trying to conceive be offered hormonal treatment?
No - should not be offered hormonal treatment, because it does not improve spontaneous pregnancy rates.
What is heavy menstrual bleeding also known as?
- Menorrhagia
how much blood loss or more is considered as menorrhagia?
Excessive menstrual blood loss of 80ml or more, and/or for a duration of more than 7 days, which results in the need to change menstrual products every 1-2 hours.
Heavy menstrual bleeding occurs regularly every 24-35 days
For menorrhagia what should the choice of drug be guided by?
By the presence or absence of fibroids (including size, number and location), polyps, endometrial pathology or adenomyosis, other symptoms (such as pressure or pain), co-morbidities and patient preference
In females with heavy menstrual bleeding and unidentified pathology, fibroids less than 3 cm in diameter causing no distortion of the uterine cavity, or suspected or diagnosed adenomyosis, what is first line treatment option?
- A levonorgestrel-releasing intrauterine system
What should patients be advised when going on a levonorgestrel intrauterine device?
irregular menstrual bleeding can occur particularly during the first months of use and that the full benefit of treatment may take at least 6 months.
What are the other options for menorrhagia is levonorgestrel releasing intrauterine system is unsuitable?
either tranexamic acid, an NSAID, a combined hormonal contraceptive, or a cyclical oral progestogen should be considered
Why may progestogen only contraceptives be helpful in menorrhagia?
They may supress menstruation and be beneficial to females with heavy menstrual bleeding
What type of treatment is recommended in patients actively trying to conceive?
A non-hormonal treatment
What about females with fibroids of 3cm or more in diameter?
- Referral to a specialist should be considered
What are the treatment options for females with menorrhagia and fibroids of 3cm or more in diameter after specialist referral?
Treatment options include tranexamic acid, an NSAID, a levonorgestrel-releasing intrauterine system, a combined hormonal contraceptive, a cyclical oral progestogen, ulipristal acetate, uterine artery embolisation, or surgery.
When can intermittent ulipristal acetate be given?
Intermittent ulipristal acetate can be offered to treat moderate to severe symptoms of uterine fibroids in premenopausal women where surgery and uterine artery embolisation are unsuitable, or have failed.
Which treatment should be considered if uterine fibroids are causing an enlarged or distorted uterus?
Treatment with a gonadotrophin-releasing hormone analogue before hysterectomy and myomectomy should be considered
What are the indications of raloxefine?
60mg once daily for treatment and prevention of postmenopausal osteoporosis
60mg once daily for 5 years for breast cancer (chemotherapy) in postmenopausal women at moderate to high risk
Is raloxifene use for chemoprevention of breast cancer a licence use in UK?
Not licensed in the UK but it is for chemoprevention in the USA