Climacteric, Menopause & Post-menopausal disorders Flashcards
What is Climacteric?
e.g. perimenopause
–> is where you get ovarian dysfunction ~45yrs –> diagnosis of menopause
What is the defintiion of menopause?
= amenorrhoea for 12 months
WAIT 24 months if the woman is < 50 yrs
- –> mean age of menopause in uk = 51 yrs
- < 40 yrs is premature ovarian failure / “early menopause”
What are the broad categories of symptoms of menopause?
- irregular menstural cycles
- oestrogen withdrawal symptoms e.g. hot flushes. night sweats, reduction in uterus size, vaginal atrophy
- psychological symptoms - low mood, irritability, lack of energy
- longer term effects: increased risk of coronary thrombosis, increased osteoporosis risk
Why is a symptom of menompause irregular menstrual cycles?
- declining/no ovarian follicles = decreasd response to gonadotrophins
- you get anovulatory cycles
- + less progesterone to support the endometrium –> irregular endometrial shedding
Why do women going through menopause experience:
- hot flushes/flashes
- night sweats
- changes in blood lipid profile
- uterus size reduction
- vaginal atrophy + rise in pH of vaginal fluids + reduction in lubrication
These are oestrogen withdrawal symptoms
- vaginal atrophy +
- rise in pH of vaginal fluids +
- reduction in lubrication
- can lead to dyspareunia
- & urinary incontinence
- & increased UTIs
What are the psychological symptoms of menopause and the main confounding factor for these symptoms?
- low mood
- irritability
- lack of energy
- tiredness
- impaired QoL
–> social factors are a confounding factor
What are the longer term effects of menopause and why?
increased risk of:
-
coronary thrombosis
- due to the changes in lipid profile from the oestrogen withdrawal symptoms
- & due to the redistribution of fat to visceral
-
osteoporosis
- bone resorption due to loss of oestrogen inhibition on OC differentiation
A women is going through menopause, what factors may make you more worried about her risk of osteoporosis (RFs of osteoporosis)?
- FHx of osteoporosis or hip #
- smoking!
- alcohol!
- long term steroid use
- hypogonadism and primary ovarian insufficiency (e.g. basically never had oestrogen inhibit OC’s)
- induced menopause
- disorders of thyroid or PTH
- immobility
- disorders of gut absorption, malnutrition, liver disease (OP is a skeletal complication of this)
What is the ultimate pathophysiology of menopause?
Ultimately - permanent depletion of potentially functional primordial follicles and the complete cessation of menses and fertility
What is the pathopysiology of how menopause occurs, e.g. how does the body go to permanent depletion of potentially functional primordial follicles and complete cessation of menses and fertility?
- To get there - ↓ responsiveness to gonadotrophins & declining number of ovarian follicles
- AGEING OVARY - ↓ numbers of pre-antral and early antral follicles
- –> ↓secretion of oestrogen & inhibin B declines
- –> ↑FSH consequently rises (-ve feedback removed; FSH - granulosa cells - oestrogen produced))
- (>40Iµ/L of FSH ndicates approaching menopause)
- –> temporarily salvage of small follicles
- –> maintenance of oestrogen and inhibin A levels. [inhibitns have -ve FB on HPG axis]
- CLIMACTERIC (just before menopause) - ↓↓↓ foiicles
- –> ↓secretion oestrogen & inhibin A
- –> ↑LH
- MENOPAUSE
- –> raised androgens due to high LH
- Overian theca cells produce androgens by LH stim
- (which would be required for ovarian oestrogen synthesis then transformed by the granulOsa cells - which are stim by FSH, but rememeber there is decreased responsiveness to gonadotropins)
- (hirsutism in post-menopausal women)
What happens to the hormonal changes of an ageing ovary?
- AGEING OVARY - ↓ numbers of pre-antral and early antral follicles
- –> ↓secretion of oestrogen & inhibin B declines
- –> ↑FSH consequently rises (-ve feedback removed; FSH - granulosa cells - oestrogen produced))
- (>40Iµ/L of FSH ndicates approaching menopause)
- –> temporarily salvage of small follicles
- –> maintenance of oestrogen and inhibin A levels. [inhibitns have -ve FB on HPG axis]
What happens in the hormonal changes of climacteric?
- CLIMACTERIC (just before menopause) - ↓↓↓ foiicles
- –> ↓secretion oestrogen & inhibin A
- –> ↑LH
What happens in the hormonal changes of menopause?
MENOPAUSE
- –> raised androgens due to high LH
- Overian theca cells produce androgens by LH stim
- (which would be required for ovarian oestrogen synthesis then transformed by the granulOsa cells - which are stim by FSH, but rememeber there is decreased responsiveness to gonadotropins)
- (hirsutism in post-menopausal women)
There are different changes to the homone levels in a womans body as they go ttrhough perimenopause, early post-menopause and late post-menopause/elderly.
What happens to
- GnRH
- LH & FSH
- Oestrogen
- Progesterone
- Inhibin
- Testosterone
in PERIMENOPAUSE?
- GnRH
- increased pulsatility
- LH & FSH
- increased
- (>40ul/L of FSH indicates approaching menopause e.g. TRYING to stimulate follicles that arent there)
- increased
- Oestrogen
- slight decline
- Progesterone
- moderate falls
- Inhibin
- slight decline
- Testosterone
- progressive decline
There are different changes to the homone levels in a womans body as they go ttrhough perimenopause, early post-menopause and late post-menopause/elderly.
What happens to
- GnRH
- LH & FSH
- Oestrogen
- Progesterone
- Inhibin
- Testosterone
in EARLY POST-MENOPAUSE?
- GnRH
- progressive decrease in pulsitility (vs increase in peri)
- LH & FSH
- increased
- Oestrogen
- rapid decline in levels (vs slight in peri)
- Progesterone
- unpredictable
- Inhibin
- significant decline (as opposed to slight in peri) [inhibin normally suppresses FSH]
- Testosterone
- progressive decline
There are different changes to the homone levels in a womans body as they go ttrhough perimenopause, early post-menopause and late post-menopause/elderly.
What happens to
- GnRH
- LH & FSH
- Oestrogen
- Progesterone
- Inhibin
- Testosterone
in LATE POST-MENOPAUSE?
- GnRH
- reduction in overall levels
- LH & FSH
- progressive decline (vs increased for past 20
- Oestrogen
- sustained very low levels (not declining now, just low)
- Progesterone
- undetectable
- Inhibin
- undetectable
- Testosterone
- sustained low
Diet and lifestyle management of menopause is a possibility.
What lifestyle change for menopause has the following positive effect?
- Prevention of lung cancer
- Reduction of CVD
- Beneficial effects on bone loss
Stopping smoking!
Diet and lifestyle management of menopause is a possibility.
What lifestyle change for menopause has the following positive effect?
- Reduction of calorie intake
- Fewer, less severe vasomotor symptoms
- Beneficial effects on bone loss
- Prevention of alcohol-related liver damage
- Reduction in incidence of breast cancer
- Reduction of CVD
Reducing alcohol consumption
Diet and lifestyle management of menopause is a possibility.
What lifestyle change for menopause has the following positive effect?
- Reduction of calorie intake
- Fewer, less severe vasomotor symptoms
- Beneficial effects on bone loss
- Reduction in incidence of breast cancer
- Reduction in incidence of endometrial cancer
- Reduction of CVD
normal BMI
non-hormonal prescriptions can help reduce menopausal symptoms such as vaginal dryness, osteoporosis and vasomotor symptoms.
What can be used for vaginal dryness?
vaginal moisturisers & lubricants
non-hormonal prescriptions can help reduce menopausal symptoms such as vaginal dryness, osteoporosis and vasomotor symptoms.
What can be used for osteoporosis?
- bisphosphonates
- raloxifene, denusumab [RANKL inhibitors preventing OC surface receptors]
- teriparatide [PTH hormone analogue]
non-hormonal prescriptions can help reduce menopausal symptoms such as vaginal dryness, osteoporosis and vasomotor symptoms.
What can be used for vasomotor symptoms?
- Alpha-adrenergic agonists
- (clonidine) - induces SM contraction and vasoconstriction
- Beta-blockers
- (propranolol)
- Neuromodulators
- (Fluoxetine (SSRI), Paroxetine, Citalopram, Gabapentin, Venlafaxine)
What are these examples of?
- Acupuncture
- Reflexology
- Magnetism
- Reiki
- Hypnotism
complementary drug free therapies for menopause
What are these examples of?
- Black cohosh (Actea racemosa)
- Dong quai (Angelica sinensis)
- Evening primrose oil (Oenothera biennis)
- Gingki (Gingko biloba)
- Ginseng (Panax ginseng)
- Kava kava (Piper methysticum)
- St John’s Wart (Hypericum perforatum)
herbal/natural preparations for menopause syx help
What are these examples of?
- Phytoestrogens such as isoflavones and red clover
- Natural progesterone gel
- Dehydroepiandrosterone (DHEA)
“natural” hormones for menopause
designed to be ingested or applied to the skin
Hormone replacement therapy can be used to reduce syx of menopause e.g. vasomotor, urogenital (incontinence, urgency, dryness & dyaparenunia) and neuropsychiatric (headaches, dizziness, anxiety, poor memory, depressive mood, irritability, mood swings, loss of libido).
How long does guidance say to use HRT for and in practice how long is this?
- current guidance recommends use for as short-a-time as possible
- often needed 2-5 years in practice
How can HRT be given?
- daily tablets
- transdermal patched
- oestrogen vaginal ring
- mirena coil
The types of HRT are oestrogen, 2x types of oest + progest and testosterone
when should oestrogen only HRT be used?
only for women post hysterectomy
risk of endometrial and ovarian cancer!!
The types of HRT are oestrogen, 2x types of oest + progest combined and testosterone
when is testosterone given?
to women with disorders of sexual desire and energy levels failing to respond to normal HRT
The types of HRT are oestrogen, 2x types of oest + progest combined and testosterone.
What are the 2x types of combined oestrogen and progesterone HRT and when are they used?
CYCLICAL HRT
- 28d cycle,
- 16-18d oestrogen alone,
- 10-12d combo (cyclical HRT)
- perimenopause [perimenopause, ovarian dysfunction ~45y/o] or
- early postmenopausal year
CONTINUOUS HRT
- Oestrogen & progesterone continuously (continuous combined HRT)
- use in known postmenopausal or >54yrs
- [e.g. amenorrhoea for >12 months or 24 months if woman<50yrs]
What are the benefits of HRT?
- Symptomatic relief
- Protective against:
- osteoporosis,
- Alzheimer’s,
- colon cancer,
- gum disease,
- macular degeneration
What are the risks of HRT?
- modest increase in the risk of breast (combined),
- & endometrial and ovarian cancers (oestrogen only)
- Risk breast cancer (smaller than the extra risk from moderate alcohol use),
- Risk returns to normal soon after stopping
- & endometrial and ovarian cancers (oestrogen only)
- increased risk of venous thromboembolism (pro-thrombotic effect of oestrogen)
- increased risk of ischaemic stroke, especially in women aged over 60 years. (why use as little hrt ~2-5yrs and if avg start is 51 will stop by 60; oestrogen prothrombotic effect)
What side effeccts does oestrogen give?
- Breast tenderness or swelling (E)
- Nausea (E)
- Leg cramps (E)
- Headaches (E)
- cancer risks from oestrogen only: endometrial and ovarian cancer
what side effects does progesterone give?
- Fluid retention (P)
- Breast tenderness (P) [oestrogen also gives breast tenderness/swelling]
- Headaches (P)
- Mood swings (P)
- Depression (P)
- Acne (P)
- e.g. as CL produces progesterone and these effects are from progesterone could explain PMS weeks before mensturation (after luteal phase)
What are the CIs for HRT?
- Suspected pregnancy
- Breast cancer (topical oestrogens okay)
- Endometrial cancer
- Active liver disease
- Uncontrolled hypertension
- Known current VTE (FHx = relative)
- Known thrombophilia
- Otosclerosis
- Relative - abn bleeding, large fibroids, hx benign breast disease, FHx VTE, chronic liver disease, migraine with aura (like COCP)
When is something classified as post-menopausal bleeding?
What is this until proven otherwise?
PMB = >1 year after the last period
= endometrial carcinoma until proven otherwise
what causes may there be of PMB?
-
ENDOMETRIAL CARCINOMA UNTIL PROVEN OTHERWISE
- (inc risk of endo cancer w/oestrogen only HRT and so it is a CI for HRT)
- other cancers = vulval, vaginal, cervical
-
Other causes than cancer:
- Endometrial or cervical polyps
- Atrophy
- Foreign bodies e.g. pessaries
- HRT related e.g. oestrogen withdrawal (can bleed from oestrogen build up/bleed)
- e.g. remember cyclical hrt gives a period
- (could also be ovarian tumour)
- e.g. remember cyclical hrt gives a period
- NB: PMB maybe confused with URETHRAL, VAGINAL and RECTAL bleeds –> check where its coming from!
How do you investigate for postmenopausal bleeding or unschedules bleeding on HRT?
- first do hx and exam (bimanual - see where blood is and speculum)
- if you see suspicous cervical, vaginal or vulval lesion –> urgent gynae oncology referral
- –> TVUSS = pipelle biopsy (goes into uterus for biopsy) ; looking for endometrial thickening e.g. if >10mm or suspected polyp
- –> adnexal mass = ovarian cyst guidance
- if E.T. <4mm and no other biopsy maybe atrophic vaginits, consider vaginal oestrogen
- If unable to pass pipelle:
- hysteroscopy
What are the indications for endometrial biopsy?
- Post-menopausal bleeding (PMB) & endometrial thickness on TVUSS >4mm
- Heavy menstrual bleeding (HMB) >45yrs
- HMB associated with IMB
- Treatment failure
- Prior to ablative techniques
