Gynae: POI, Menopause and HRT Flashcards
what is premature ovarian insufficiency?
defined as menopause before the age of 40 years. results in the decline of normal activity of the ovaries at an early age leading to typical symptoms of menopause
explain how premature ovarian insufficiency is characterised by hypergonadotropic hypogonadism
Under-activity of the gonads (hypogonadism) means there is a lack of negative feedback on the pituitary gland, resulting in an excess of the gonadotropins (hypergonadotropism). Hormonal analysis will show:
- Raised LH and FSH levels (gonadotropins)
- Low oestradiol levels
what are some causes of primary ovarian insufficiency?
- Idiopathic - the cause is unknown in more than 50% of cases
- Iatrogenic - interventions such as chemotherapy, radiotherapy or surgery (i.e. oophorectomy)
- Autoimmune - possibly associated with coeliac disease, adrenal insufficiency, type 1 diabetes or thyroid disease
- Genetic - positive family history or conditions such as Turner’s syndrome
- Infections such as mumps, tuberculosis or cytomegalovirus
how does primary ovarian insufficiency present?
irregular menstrual periods
lack of menstrual periods
Symptoms of low oestrogen - hot flushes, night sweats, vaginal dryness
how is primary ovarian insufficiency diagnosed?
can be diagnosed in women younger than 40 with typical menopausal symptoms plus elevated FSH (needs to be persistently raised above 25 IU/l on 2 consecutive samples separated by more than 4 weeks)
what conditions associated with lack of oestrogen are women with primary ovarian insufficiency at risk of?
- Cardiovascular disease
- Stroke
- Osteoporosis
- Cognitive impairment
- Dementia
- Parkinsonism
how is primary ovarian insufficiency managed?
HRT until at least the age which women typically go through menopause - this reduces cardiovascular, osteoporosis, cognitive and psychological risk
Contraception is still required
what are the 2 options for HRT in women with premature ovarian insufficiency?
traditional hormone replacement therapy - associated with lower blood pressure
COCP - more socially acceptable/less stigma for younger women and also acts as contraceptive
is there an increased risk of breast cancer with HRT before the age of 50?
no considered to be increased risk of breast cancer compared with general population as woman would ordinarily produce the same hormones at this age
is there an increased VTE risk?
may be increased VTE risk with HRT in women under 50 years old
risk reduced by using transdermal methods
what is menopause?
retrospective diagnosis made after a woman has had no periods for 12 months
defined as a permanent end to menstruation
experienced on average around age of 51
what is postmenopause?
describes the period from 12 months after the final menstrual period onwards
what is perimenopause?
refers to the time around the menopause where a woman may be experiencing vasomotor symptoms and irregular periods. includes the time leading up to the last menstrual period, and the 12 months afterwards. This is typically in women older than 45 years.
what is menopause caused by?
lack of ovarian follicular function resulting in changes in sex hormones associated with menstrual cycle
O & P are low
LH and FSH are high in response to an absence of negative feedback from oestrogen
physiology of menopause
Inside the ovaries, the process of primordial follicles maturing into primary and secondary follicles is always occurring, independent of the menstrual cycle. At the start of the menstrual cycle, FSH stimulates further development of the secondary follicles. As the follicles grow, the granulosa cells that surround them secrete increasing amounts of oestrogen.
The process of the menopause begins with a decline in the development of the ovarian follicles. Without the growth of follicles, there is reduced production of oestrogen. Oestrogen has a negative feedback effect on the pituitary gland, suppressing the quantity of LH and FSH produced. As the level of oestrogen falls in the perimenopausal period, there is an absence of negative feedback on the pituitary gland, and increasing levels of LH and FSH.
The failing follicular development means ovulation does not occur (anovulation), resulting in irregular menstrual cycles. Without oestrogen, the endometrium does not develop, leading to a lack of menstruation (amenorrhoea). Lower levels of oestrogen also cause the perimenopausal symptoms.
what the perimenopausal symptoms?
- Hot flushes
- Emotional lability or low mood
- Premenstrual syndrome
- Irregular periods
- Joint pains
- Heavier or lighter periods
- Vaginal dryness and atrophy
- Reduced libido
caused by a lack of oestrogen
what does a lack of oestrogen increase the risk of?
- Cardiovascular disease and stroke
- Osteoporosis
- Pelvic organ prolapse
- Urinary incontinence
how is menopause diagnosed?
diagnosis of perimenopause and menopause can be made in women over 45 years with typical symptoms, without performing any investigations
when is an FSH blood test required to help with diagnosis of menopause
- Women under 40 years with suspected premature menopause
- Women aged 40 – 45 years with menopausal symptoms or a change in the menstrual cycle
what are the rules regarding contraception around the menopause??
Need to use effective contraception:
- Two years after the last menstrual period in women under 50
- One year after the last menstrual period in women over 50
do hormonal contraceptives have any affect on the menopause?
no affect on when it occurs or when it occurs
may suppress and mask symptoms - hard to diagnose in women on hormonal contraceptives
what are some good contraceptive options for women approaching the menopause?
- Barrier methods
- Mirena or copper coil
- Progesterone only pill
- Progesterone implant
- Progesterone depot injection (under 45 years)
- Sterilisation
what is the deal with the COCP?
UKMEC 2 (advantages generally outweigh risks) after aged 40, can be used up to age of 50 if there are no other contraindications
use cocp with norethisterone or levonorgestrel in women over 40 due to relatively lower risk of VTE
how can perimenopausal symptoms be managed?
- No treatment
- Hormone replacement therapy (HRT)
- Tibolone, a synthetic steroid hormone that acts as continuous combined HRT (only after 12 months of amenorrhoea)
- Clonidine, which act as agonists of alpha-adrenergic and imidazoline receptors
- Cognitive behavioural therapy (CBT)
- SSRI antidepressants, such as fluoxetine or citalopram
- Testosterone can be used to treat reduced libido (usually as a gel or cream)
- Vaginal oestrogen cream or tablets, to help with vaginal dryness and atrophy (can be used alongside systemic HRT)
- Vaginal moisturisers, such as Sylk, Replens and YES
what is HRT used for?
used in perimenopausal and post menopausal women to alleviate symptoms associated with menopause
symptoms caused by low oestrogen levels so have to replace oestrogen
need progesterone in women with a uterus to prevent endometrial hyperplasia and endometrial cancer secondary to unopposed oestrogen
not all women will require HRT, what are some non-hormonal treatments for menopausal symptoms?
- Lifestyle changes such as improving the diet, exercise, weight loss, smoking cessation, reducing alcohol, reducing caffeine and reducing stress
- Cognitive behavioural therapy (CBT)
- Clonidine, which is an agonist of alpha-adrenergic and imidazoline receptors
- SSRI antidepressants (e.g. fluoxetine)
- Venlafaxine, which is a selective serotonin-norepinephrine reuptake inhibitor (SNRI)
- Gabapentin
what is clonidine?
act as an agonist of alpha-2 adrenergic receptors and imidazoline receptors in the brain
lowers blood pressure and reduces heart rate - also used as as antihypertensive
can be helpful for vasomotor symptoms and hot flushes, particularly where there are contraindications to using HRT
what are some side effects of clonidine?
dry mouth
headaches
dizziness and fatigue
withdrawal can result in rapid increase in blood pressure and agitation
name some alternative remedies that can be used to help menopause symptoms?
- Black cohosh, which may be a cause of liver damage
- Dong quai, which may cause bleeding disorders
- Red clover, which may have oestrogenic effects that would be concerning with oestrogen sensitive cancers
- Evening primrose oil, which has significant drug interactions and is linked with clotting disorders and seizures
- Ginseng may be used for mood and sleep benefits
what are some indications for HRT
- Replacing hormones in premature ovarian insufficiency, even without symptoms
- Reducing vasomotor symptoms such as hot flushes and night sweats
- Improving symptoms such as low mood, decreased libido, poor sleep and joint pain
- Reducing risk of osteoporosis in women under 60 years
what are the benefits of taking HRT?
women < 60 years - benefits generally outweigh risks
- Improved vasomotor and other symptoms of menopause (including mood, urogenital and joint symptoms)
- Improved quality of life
- Reduced the risk of osteoporosis and fractures
what are the risks of HRT?
- Increased risk of breast cancer (particularly combined HRT – oestrogen-only HRT has a lower risk)
- Increased risk of endometrial cancer
- Increased risk of venous thromboembolism (2 – 3 times the background risk)
- Increased risk of stroke and coronary artery disease with long term use in older women
- The evidence is inconclusive about ovarian cancer, and if there is an increase in risk, it is minimal
These risks do not apply to all women:
- The risks are not increased in women under 50 years compared with other women their age
- There is no risk of endometrial cancer in women without a uterus
- There is no increased risk of coronary artery disease with oestrogen-only HRT (the risk may even be lower with HRT)
how can the risks of HRT be reduced?
risk of endometrial cancer reduced by taking progesterone in women with a uterus
VTE reduced by using patches rather than pills
what are some contraindications to HRT?
- Undiagnosed abnormal bleeding
- Endometrial hyperplasia or cancer
- Breast cancer
- Uncontrolled hypertension
- Venous thromboembolism
- Liver disease
- Active angina or myocardial infarction
- Pregnancy
what needs to be dome before anyone can start HRT?
- Take a full history to ensure no contraindications
- Take a FHx to assess the risk of oestrogen dependent cancers (e.g. breast cancer) and VTE
- Check the BMI and blood pressure
- Ensure cervical and breast screening is up to date
- Encourage lifestyle changes that are likely to improve symptoms and reduce risks
how to chose the right HRT
Step 1: local or systemic symptoms?
- Local symptoms: use topical treatments such as topical oestrogen cream or tablets
- Systemic symptoms: use systemic treatment – go to step 2
Step 2: uterus?
- No uterus: use continuous oestrogen-only HRT
- Has uterus: add progesterone (combined HRT) – go to step 3
Step 3: period in the past 12 months?
- Perimenopausal: give cyclical combined HRT
- Postmenopausal (more than 12 months since last period): give continuous combined HRT
what are the two options for delivering systemic oestrogen?
oral
transdermal - more suitable with poor control on oral treatment or higher risk of VTE, cardiovascular disease and headaches
what are the 2 regimes for giving progesterone?
cyclical progesterone - given 10-14 days per month, used for women that have had a period within the past 12 months, cycling allows pt to have a monthly breakthrough bleed during the oestrogen-only part of the cycle similar to a period
Continuous progesterone - used when woman has not had period in past 24 months if under 50, 12 months if over 50
Using continuous combined HRT before postmenopause can lead to irregular breakthrough bleeding and investigation for other underlying causes of bleeding.
You can switch from cyclical to continuous HRT after at least 12 months of treatment in women over 50, and 24 months in women under 50. Switch from cyclical to continuous HRT during the withdrawal bleed. Continuous HRT has better endometrial protection than cyclical HRT.
what are the 3 options for delivering progesterone for endometrial protection?
oral
transdermal
IUS - 4 years for endometrial protection then needs replacing
define PROGESTOGENS, PROGESTERONE & PROGESTINS
- Progestogens refer to any chemicals that target and stimulate progesterone receptors
- Progesterone is the hormone produced naturally in the body
- Progestins are synthetic progestogens
what are the 2 classes of progestogens?
C19 & C21
refer to chemical structure and number of carbon atoms in the molecule
C19 - derived from testosterone examples = norethisterone, levonorgestrel, desogestrel
C21 derived from progesterones examples = dydrogesterone and medroxyprogesterone
what is tibolone?
synthetic steroid that stimulates oestrogen and progesterone receptors
weakly stimulates androgen receptors
effects on androgen receptors mean tibolone can be helpful for patients with reduced libido
used as a form of continuous combined HRT, women need to be more than 12 months without a period
can cause irregular bleeding
what is testosterone?
male sex hormone
naturally present in low levels in women
menopause may be associated with reduced testosterone resulting in low energy and reduced sex drive
treatment with testosterone is usually initiated and monitored by a specialist
transdermal administration
additional points to remember
- Follow up three months after initiating HRT to review symptom and side effects
- Side effects often settle with time, so it is worth persisting for at least three months with each regime
- It takes 3 – 6 months of treatment to gain the full effects
- Problematic or irregular bleeding is an indication for referral to a specialist
- Ensure the woman has appropriate contraception
- Stop oestrogen-containing contraceptives or HRT 4 weeks before major surgery (NICE guidelines 2018 – NG89)
- Consider other causes of symptoms where they persist despite HRT (e.g. thyroid, liver disease and diabetes)
what are some common options for contraception with HRT?
mirena coil
progesterone only pill
what are some oestrogenic side effects?
- Nausea and bloating
- Breast swelling
- Breast tenderness
- Headaches
- Leg cramps
what are some progestogenic side effects?
- Mood swings
- Bloating
- Fluid retention
- Weight gain
- Acne and greasy skin
can switch to an HRT with a different type of progesterone
what can be done when someone suffers from side effects of HRT?
change the route of administration
how should HRT be stopped?
no specific regime for stopping HRT
can be stopped gradually or abruptly depending on the preference of the woman
does not affect long term symptoms
gradually reducing may reduce risks of symptoms recurring suddenly
