Benign gynae Flashcards
Secondary amenorrhoea
Absence of menses for >6 months in girls or women who previously had regular menstrual cycles
Or 12 months if irregular cycles / oligomenorrhoea (bleeds less frequently than 6 weekly)
Categories (WHO) of ovulatory disorders
Group 1 - 10% Hypothalamic-pituitary failure - Hypothalamic amenorrhoea - Hypogonadotrophic hypogonadism - Low oestrogen, low FSH
Group 2 - 85%
Hypothalamic-pituitary-ovarian dysfunction
- Predominantly PCOS
- Normal oestrogen, Normal FSH, Normal prolactin
Group 3 - 5% Ovarian failure - Hypergonadotrophic hypogonadism - Ovarian insufficiency - Low oestrogen, High FSH
Progestogen / gestogen challenge test
Give progesterone (e.g. provera 10mg / day for 5 days)
- Negative - nothing happens
- Positive - if period happens (usually heavy period) - Got to have oestrogen to have a positive test
More accurate way to assess oestradiol than oestradiol blood test
Positive in anovulation
Hypothalamic-pituitary amenorrhoea
causes
HYPOTHALAMIC
- Low body weight / weight change, stress or exercise-related amenorrhoea
- Craniopharyngioma or other tumours affecting the hypothalamus
- Kallmann’s syndrome
- Idiopathic
- Congenital GnRH deficiency
PITUITARY
Sheehan’s syndrome
Hyperprolactinaemia
Functioning tumours of the pituitary (prolactinoma)
Non-functioning tumours of the pituitary or affecting the pituitary
Brain radiotherapy
Post-pituitary surgery
Work up for type 1 amenorrhoea
Prolactin and TSH
Evidence of oestrogen deficiency?
GnRH challenge test
- To discriminate between hypothalamic and pituitary cause of HH
- If FSH + LH levels increase after GnRH administration, then hypothalamic cause
- Limited benefit as gonadotrophin OI is successful regardless of exact site of dysfunction
Unless apparent cause in history, MRI to exclude tumour
Correct any weight / exercise imbalance
Correction of amenorrhoea is not necessary unless conception desired
Responds very well to GnRH or gonadotrophins if conception needed
- High rate of achieving ovulation (>95%)
Interpreting prolactin results
<500 mu/l -Normal
<1000 mu/l - Consistent with stress or recent breast exam –> repeat
Threshold for imaging: >1500 mu/l on 2 occasions
- MRI or CT
Check TSH, T4, FSH/LH, testosterone, SHBG
- can be raised in hypothyroid and PCOS
Clinical features
of hyperprolactinaemia
Galactorrhoea (up to 30%)
- No correlation with prolactin levels or the presence of a tumour
Headaches
Visual field defects (5%)
- bitemporal hemoanopia due to compression of the optic nerve
Variety of menstrual cycle disturbances (e.g. anovulatory cycles, amenorrhoea)
Pathophysiology of high prolactin
Prolactin is secreted solely by the lactotroph cells of the pituitary gland
Hyperprolactinaemia can be caused:
- Decreased dopamine inhibition of prolactin release
- Increased prolactin production
- Decreased prolactin clearance
Pathological causes of high prolactin
Prolactin-secreting pituitary adenomas
- Microadenomas <10mm
- Macroadenomas >10mm
- Almost all are benign
Idiopathic Hypothyroidism - Raised TSH stimulates lactotrophs Drugs - estrogens, metoclopramide, SSRI, methyldopa, TCA, other psychotropic drugs (haloperidol, risperidone) Renal failure - decreased metabolic clearance Liver cirrhosis - Reduction in estrogen metabolism increases the estrogen concentration - depletion of dopamine
Any disease in or near the hypothalamus or pituitary that interferes with the secretion of dopamine or its delivery
- Tumours of the hypothalamus or pituitary
- Infiltrative diseases (e.g. sarcoidosis)
Physiological causes of high prolactin
Pregnancy Lactation Sleep Stress Chest wall stimulation
Treatment of prolactinomas
Don’t always treat hyperprolactinaemia
Indications for treatment:
- Anovulatory and wishing conception
- Significant tumour
- Symptomatic (e.g. galactorrhoea, headaches)
As hypo-estrogenic state, may affect bone health if untreated in the long term
Once prolactin levels <1000 IU/L, periods usually return
Surgery reserved for large marcoprolactinomas with compression-related symptoms (visual defects) which may not respond to medication
- Complication: pan-hypopituitarism
Meds: dopamine agonists
Medications for hyperprolactinaemia
Cabergoline (Dostinex)
- Initial dose 0.25mg twice weekly, up to 1mg daily.
- side effects: headaches, psych adverse effects (aggression)
- Not licensed for use in pregnancy
- Better than bromocriptine (lower side effect profile and longer acting)
Bromocriptine
- 1.25mg nocte for 5 nights, and gradually up titrate to 7.5mg daily in 2-3 divided doses over about 3 weeks
ommon adverse effects:
- N/v, headache, postural hypotension, vertigo, GI disturbance, psych changes
- 10% of patients have unacceptable adverse effects
Management of prolactinoma in sub fertility
~80% achieve pregnancy on dopamine agonist treatment
No increase in risks of pregnancy complications
- Neither cabergoline or bromocriptine has been a/w an increased risk of miscarriage, congenital malformations
Usually stop dopamine agonist once pregnant
Very low risk of tumour growth with microadenomas (<2%) in pregnancy
Risk if higher with macroadenomas (15-30% if unmedicated)
Review regularly during pregnancy - ask about headaches and changes in vision
- Microadenomas - every 3 months
- Macroadenomas - 2-3 monthly visual field check
Breastfeeding may be undertaken normally
Unless women have visual field impairment - should be treated with dopamine agonist
Incidence of PCOS
6-7% of the population
Conservative estimate - recent data suggests higher, particularly in Aboriginal population
Rotterdam criteria
Clinical and/or biochemical signs of hyperandrogenism
- Calculated free testosterone, free androgen index or calculated bioavailable testosterone
- Consider androstenedione an DHEAS if total or free testosterone are not elevated
- Reliable assessment not possible if on hormonal contraception
- Clinical - Acne, alopecia, hirsutism
Oligo and/or anovulation
- Cycle <21 or >35 days
The appearances on ultrasound of polycystic ovaries
- 20 or more follicles measuring 2-9mm in diameter
- Increased ovarian volume (>10cm3)
Other aetiologies must be excluded
Adolescents and PCOS
In adolescence women (<18y), after 2y of irregular cycles following the onset of menarche, PCOS should be considered and appropriate assessment should be undertaken
- Irregular periods are common in adolescence so don’t do anything until >2y of issues
- Need hyperandrogenism and irregular cycles to make diagnosis
PCO almost normal in this age group
- Don’t scan women <8y post menarche - 68% of women aged 19-21 will have US morphology similar to PCO
- If can’t make diagnosis but suspicious, say “at risk of PCOS”
Delay definitive diagnosis until 21y (RANZCOG revision tutorial)
Clinical features of PCOS
PSYCHOLOGICAL
Anxiety
Depression
Body image
REPRODUCTIVE Irregular cycles Hirsutism Infertility Pregnancy complications
METABOLIC (ESP IF BMI >30) Insulin resistance Metabolic syndrome Prediabetes T2DM Cardiovascular risk factors OSA
Investigations to exclude differentials in PCOS
Lab findings in PCOS
- Normal or high oestrogen
- elevated free testosterone, total and FAI
- reduced SHBG
- increased LH/FSH ratio
- prolactin - usually normal, but can be elevated
If total testosterone levels (>2x normal), virilisation Sx - consider androgen secreting tumours of adrenals or ovaries
–> imaging
If Cushing’s features –> cortisol, DHEAS - dexamethasone suppression test
17-OH progesterone elevated in late onset CAH
Pathophysiology of PCOS
NORMAL: cholesterol converted to androgens in the theca cells under influence of LH and insulin
- Some androgens released into circulation
- Remainder are aromatised to oestrogen in the granulosa cells under the influence of FSH
- This system is regulated by circulating androgens and insulin growth factor
PCOS: Insulin resistance –> insulin augments LH-stimulated androgen production in theca cells
Low SHBG from insulin resistance –> high levels of free testosterone
Uncoupling of the normal mechanism that controls normal androgen flow onward to the granulosa cells
- Mature dominant follicles don’t develop
- Lots of small follicles develop –> Make more testosterone
- Get low progesterone as produce oestradiol only
LH thickens thecal cells in ovaries –> more testosterone
Unopposed oestradiol speeds up GnRH pulses –> make LH increase more than FSH
Implications of PCOS
Insulin resistance Metabolic syndrome Endometrial cancer Anxiety and depression Eating disorders Pregnancy risks Obstructive sleep apnoea - Remains significant even when controlling for BMI - Independent risk factor for CVD Cardiovascular disease
Insulin resistance in PCOS
Increased risk of GDM, T2DM and impaired glucose tolerance, with risk independent of, yet exacerbated by obesity
Lean women with PCOS has a 2-fold increase in incidence of T2DM compared to controls
Australian cohort with PCOS
- Impaired glucose tolerance 15%
- T2DM 4%
RANZCOG - 2h OGTT for screen
- Some authorities recommend screening all women diagnosed with PCOS
- Others recommend if fasting BSL >5.6 mmol/l, BMI >30, strong FHx of GDM, lean women >40y
By age 40, up to 40% of women with PCOS will have T2DM or impaired glucose tolerance
What is metabolic syndrome
Metabolic syndrome:
- Elevated BP >130/85 - Increased waist circumference >88cm - Elevated fasting blood glucose levels - Reduced high density lipoprotein cholesterol levels - Elevated triglyceride levels
Risk for development of CVD
Prevalence in PCOS up to 45%
Endometrial cancer
and PCOS
2-6 fold increased risk
Women with infrequent cycles (no natural period for >3 months) are at risk of endometrial hyperplasia
RANZCOG: if PCOS and oligo or amenorrhoea
- Induction of regular withdrawal bleeds (at least every 3-4 months) is advised using cyclic progestagens for at least 12 days or the COCP
- Mirena is an option
Treatment of PCOS
Lifestyle management
- 5-10% weight loss in those with excess weight yields significant clinical improvements (restore menstrual cycle and lower long term risks)
- Use of bariatric surgery should be considered where obesity is not controlled by lifestyle modifications (BMI >40, or >35 with high-risk obesity related condition)
COCP - limited evidence
- For hyperandrogenism, irregular cycles
- 35 mcg ethinyloestradiol + cyproterone acetate should not be considered first line in PCOS as per general population guidelines - due to adverse effects, including VTE
Metformin
- Routine use not recommended (RANZCOG)
- Role with increased glucose tolerance or T2DM has been diagnosed
- 20-40% get significant GI upset
Anti-androgens
- consider adding to COCP - if after >6 months failed to adequately improve hirsutism
Regular monitoring and assessment of CVD risk
Check HbA1c at diagnosis and then every 1-3y (RANZCOG - 2h OGTT)
Cushing syndrome
- causes
Results from chronic exposure to excess glucocorticoids
CAUSES
ACTH dependent
- Cushing’s disease - ACTH-producing pituitary tumour
- Ectopic ACTH syndrome - E.g. small cell lung cancer
ACTH independent
- Adrenal tumours
- Adrenal hyperplasia
Iatrogenic
- Exogenous steroids
Cushing syndrome
- Clinical presentation
Moon face Bufalo hump Wide purplish striae Proximal muscle weakness Hirsutism HTN
Diagnosis of Cushing syndrome
Exclude exogenous
High testosterone and DHEA
Diagnosis is established when 2+ different first-line tests are unequivocally abnormal
- Late night salivary cortisol - 24h urinary free cortisol excretion - Overnight 1mg dexamethasone suppression test
Effects of Cushing syndrome on pregnancy
Very high rate of pregnancy complications
- Pregnancy loss (40%)
- FGR
- Premature delivery (>50%)
- Neonatal adrenal insufficiency
Maternal morbidity high if untreated
- HTN (up to 70%)
- Diabetes (up to 25%)
- Heart failure
- Severe PET is common (15%)
- Maternal mortality is increased (2-4%)
If previous treated, or treated <20/40, then do well
Late onset adrenal hyperplasia
Unlikely classic CAH, not picked up by newborn screening
Increase in cortisol precursors, which are forced along the androgen pathway
- 17-OH progesterone
ACTH stimulation test to confirm diagnosis
- Response to ACTH is exaggerated in NCCAH
Causes of ovarian failure
Chromosomal
- Most common is Turner syndrome 45X0
- Offer karyotype if amenorrhoea before age 30
- Fragile X
Autoimmune
- Linked to other autoimmune issues, therefore screen
Resistant ovary syndrome
- On biopsy there are oocytes but they don’t respond, but not required because doesn’t change prognosis
Pure gonadal dysgenesis
Androgen-insensitivity syndrome
- Absent ovaries and uterus with a 46XY karyotype
Galactosaemia (carbohydrate metabolism, autosomal recessive)
Premature menopause
Surgical removal
Chemotherapy
Radiotherapy in proximity to the pelvic area
Idiopathic
Investigations of premature ovarian failure
Serum FSH Serum estradiol Serum free testosterone (to rule out PCOS) HCG - rule out pregnancy Serum prolactin TSH +/- thyroid antibodies Autoimmune screen Karyotype - chromosomal analysis should be performed in all women with non-iatrogenic POI - Test for Y chromosome - Fragile X
Fragile X
X-linked disorder
Decreased or absent levels of fragile X mental retardation protein (FMR 1 gene)
Full mutation
- In males causes classical FXS phenotype - developmental delay, intellectual disability, learning disabilities , ADHD, anxiety, autism, Seizures
- Full mutation in girls is much more variable
Premutation
- Spectrum of clinical findings
- Females: 1 in 250-300 in women
- Premature ovarian insufficiency
- Fragile X-associated tremor-ataxia syndrome later in life
- Neurocognitive deficits
Diagnosis
of POI
Spectrum disorder
Menstrual irregularity associated with diminishing ovarian reserve in women <40y
Characterised by menstrual disturbance (amenorrhoea or oligomenorrhoea for >4 months) with FSH levels in the post menopausal range (dependent on lab, >20 IU/l) on two occasions >4 weeks apart
Prevalence 1%
Modifiable factors to reduce POI
Gynaecological surgical practice
Lifestyle - smoking
- No causal r/ship for smoking and POI, but there is in relation to early menopause
Modified treatment regimens for malignant and chronic diseases
Sequelae of POI
Untreated POI –> reduced life expectancy, mainly due to CVD
Fertility
- Small chance of spontaneous pregnancy (5-10%), as varying and unpredictable ovarian function
- Donor oocyte and IVF if required
Reduced BMD
- Estrogen replacement is recommended - e.g. COCP
- Measure BMD at diagnosis of POI
Continue HRT until the age of natural menopause
Annual BP, weight and smoking status
Psychological wellbeing
Sexual and GU function - Topical oestrogen
Cognitive impairment
Hirsutism definition and prevalence
Presence of terminal (coarse) hairs in females in a male-like pattern
Affects 5-15% of women
Usually associated with an underlying endocrine disorder
Three types of hair
Lanugo - soft hair densely covering fetus, shed in first 4/12 PP
- Can be seen in women with disorders that include anorexia nervosa
Vellus hair - soft, longer than lanugo hair (<2cm), non-pigmented, covers the body
Terminal hair - longest, pigmented, makes up hair of eyebrows, scalp, axillary and pubic areas
Phases of hair growth
Impact of hormones
Three phases of hair growth
○ Anagen - active growing phase
○ Catagen - involuting phase
○ Telogen - resting phase, hair is shed
Androgens are the most important hormones regulating hair type, growth and distribution
Causes of hirsutism
Androgen excess
- PCOS (70-80% of women with hirsutism )
- Androgen-secreting tumours
- Late onset CAH
- Cushing’s syndrome
- Drugs - Testosterone, danazol, anabolic steroids
Drugs - Non-androgen factors
- Phenytoin
- Minoxidil - for baldness
- High-dose corticosteroids
Idiopathic hirsutism (6-7%)
Ferriman and Gallwey score
0 = absence of terminal hair 4 = extensive terminal hair growth
Modified score (current one) uses 9 sites - Upper lip, chin, chest, arm, upper abdomen, upper back, lower back, thighs
- Mild 8-15
- 16-25 moderate
- > 25 severe
Issues with Ferriman and Gallwey score
Impact for women doesn’t correlate with scores
- Scoring systems used for research rather than clinical settings typically
Ethnic variation - derived from population study of white women
Most women have been using cosmetic measures by the time they see a clinician, so scores may not be accurate
Intra-observer agreement appears to be relatively good, but inter-observer agreement appears poor
Management of hirsutism
COCP
- reduces free plasma testosterone levels
Cyproterone acetate - strong progestogen, reduces LH
- Wide variation, but expect to lower Ferriman-Gallwey score by 15-40% within 6 months
Spironolactone (androgen inhibitor)
- When used with COCP overall effectiveness improved
- Cochrane review: superior to finasteride and low dose cyproterone acetate for up to 12 months after end of treatment
Finasteride - inhibitor of 5 alpha-reductase enzyme
Definition of PMS
When symptoms cause impairment of daily activities and interpersonal relationships in cyclical fashion usually following ovulation and resolved by menstruation
- Must demonstrate during the luteal phase of the menstrual cycle
Symptoms are not an exacerbation of an underlying psychological or physical disorder
PMS vs. PMDD
The affective and/or somatic symptoms in physiological PMS are bothersome but are not disabling to the woman, whereas they would cause significant impairment of occupational or social function in PMDD
Premenstrual dysphoric disorder (PMDD) diagnosis
Most severe form
Must have 5 / 11 symptoms, one of which must include mood
- Mood swings
- Anger, irritability
Sense of hopelessness,
- Tension, anxiety
- Difficulty concentrating
- Change in appetite
- Diminished interest in usual activities
- decreased energy
- Feeling overwhelmed
- Breast tenderness, bloating, weight gain, joint / muscle aches
- Sleeping too much or not sleeping enough
Luteal phase symptoms
By definition, affective symptoms predominate but most women also have physical symptoms
Must disrupt daily functioning
Pathophysiology of PMS
Revolves around the ovarian hormone cycle
- Reinforced by absence prior to puberty, in pregnancy and after menopause
Two theories
1. Some women are ‘sensitive’ to progesterone
- Abnormalities in neurotransmitters (serotonin and GABA) –> progesterone hypersensitivity
○ Serotonin receptors are responsive to oestrogen and progesterone
No evidence of hormone imbalance
Diagnosis of PMS
Symptoms should be recorded prospectively, over two cycles, using a symptom diary
- Useful comparison for effectiveness of treatment in future
Symptom diary should be completed prior to commencing treatment
GnRH analogues may be used for 3 months for a definitive diagnosis if the completed symptom diary alone is inconclusive
Complementary treatments for PMS
CBT
- Consider routinely
- Better maintenance of treatment effects compared with fluoxetine in one study
- May avoid pharmacotherapy and potential adverse effects
Benefit in trials for
- Calcium, vitamin D
- Vitex agnus castus (herbal supplement)
Some benefit
- Exercise
- Evening primrose
- Acupuncture
Mixed results
- vitamin B6
- Mg
- St John’s wort
Medications for PMS
SSRI - consider 1st line - luteal or continuous dosing - fluoxetine works within 24h Spironolactone - Can treat physical Sx
COCP
- Drospirenone-containing COCP (Yasmin)
- Caution about type of progestogen in pill
- Continuous rather than cyclical use recommended
Hormonal medical management
- Percutaneous estradiol + cyclical progesterone has been shown to be effective
- Consider LNG-IUS for endometrial protection
Danazol
- is effective in luteal phase for breast symptoms
- Potential irreversible virilising effects
- effect on lipid profile
- must be on contraception
Progesterone - good evidence that it is not appropriate
- No evidence to support LNG-IUS use alone
Hysterectomy + BSO
- Trial GnRH analogues pre-op as a test of cure and to ensure HRT is tolerated
- Use HRT post-op, especially if <45y
Menstrual cycle
- Follicular phase
First half = follicular phase (of ovary)
- Menstrual phase at the start, then proliferative phase of endometrium
With menses, progesterone from previous luteal phase falls (as CL involutes), lifting the negative feedback on hypothalamic GnRH
Rise in FSH –> maturation of follicles
Increasing oestrogen produced by the follicles - at low levels cause negative feedback suppressing FSH
Smaller follicles undergo atresia as they rely on FSH for development
larger follicle continues to grow independently of FSH
Dominant follicle makes large amount of oestradiol
When certain oestrogen threshold is reached, leads to LH (and smaller FSH) surge (positive feedback)
LH surge –> ovulation
- Ovulation occurs approx 36h from the onset of surge
Define menopause
The permanent cessation of menstruation
Defined retrospectively, 12 months after the final menstrual period
Average age 51.5y
Define
- Early menopause
- Premature menopause
Early menopause
-Before age 45, but after the age of 40
Premature menopause
- Before age 40
- Primary ovarian insufficiency
- POI affects ~1% of women
Perimenopause or menopause transition
Time from the onset of menstrual cycle changes until one year after the final menstrual period
Early menopause transition - marked by persistent difference of 7+ days in length of consecutive cycles
Late - periods of amenorrhoea of 60 days or more, frequent anovulation, onset of perimenopausal symptoms
Usually starts ~47y
Can last 4-8y
factors a/w early and late menopause
Factors a/w earlier menopause
- Hysterectomy
- Smoking
- Lower level of education
- Living at an altitude >2000m
- Being single
Factors a/w later menopause:
- Parity
- Higher BMI
- Oral contraceptive use
Numbers of vasomotor symptoms of menopause
70-80% of women
Most common reason for women to seek advice / treatment
Usually start during the menopause transition
Average duration = 4-5y
10% have symptoms for >10y
Midlife women health assessment
- Smear
- Mammogram
- Lipids
- FBC
- TSH
- Renal and liver function
- Ferritin
- HbA1c
- Vit D in at risk women
Screen for anxiety and depression
Offer lifestyle advice
Dual x-ray Absorptiometry (DXA) - if high risk
- Used to measure bone density in those with increased fracture risk
Contraceptive needs for perimenopause
Use for 2y after the LMP in women <50y
Use for 1y after LMP in women >50y
Lifestyle changes for menopause to recommend
Stress reduction Regular exercise Optimal weight management Appropriate diet Smoking cessation Weight bearing exercise Calcium / vitamin D intake Avoid excessive alcohol and caffeine
Lifestyle changes for menopause to recommend
Stress reduction Regular exercise Optimal weight management Appropriate diet Smoking cessation Weight bearing exercise Calcium / vitamin D intake Avoid excessive alcohol and caffeine
Non-pharmacological methods that have evidence for Rx of menopausal Sx
Shown to reduce troublesome VMS
- Hypnosis
- Cognitive behaviour therapy
No evidence for herbal supplements, acupuncture, chiropractic or homeopathy Methods not shown to reduce VMS - Yoga - Exercise - Diet - Supplements - Weight loss - Black cohosh and phytoestrogens - OTC / CAM - have not consistently been shown to be effective for VMS
Non-HRT pharmacological methods for Rx of menopause
Shown to be superior to placebo in some RCTs for management of VMS
SSRIs
- Paroxetine and fluoxetine should not be used in women taking tamoxifen
SNRI
Trial SSRI / SNRI for 4 weeks - should be sufficient to establish whether Rx if effective
- Use at low to moderate doses for VMS
- ADR: nausea, drowsiness, sexual dysfunction
Centrally acting medications - gabapentin, clonidine
Gabapentin
- Only non-hormonal agent with equivalent efficacy to MHT for treating VMS
- Side effects: drowsiness, headaches, GI upset
Clonidine
- ADR: dry mouth, drowsiness, visual disturbance
Silicone-based lubricant more effective than water-based at reducing pain during sex in patients with breast cancer
Symptoms that may improve with oestrogen (however not primary indication for MHT):
Sexual dysfunction Sleep disturbance Mood swings Joint or muscle pains Quality of life
Contraindications for MHT
Personal Hx of breast cancer / estrogen-dependent cancer
Undiagnosed vaginal bleeding
RELATIVE: High risk of VTE or thrombophilia Previous VTE (oral MHT contraindication) Personal wish not to use hormones Severe active liver disease Untreated HTN
Commencement after age 60y, or >10y after menopause, is generally not recommended
Risks outweigh benefits
Perimenopause MHT options
COCP provides:
- Cycle control
- Contraception
- Relief from vasomotor symptoms and other symptoms
Prevents bone loss
Can be used in non-smoking women without CV or thrombotic risk factors until the age of 50y
Skip placebo tablets to prevent VMS in the pill free week
Oral E + LNG-IUS
- Provides contraception
- Reduces uterine bleeding
- Can provide endometrial protection from systemic oestrogen
Cyclical MHT
- Will not provide contraception or regulate cycles
Advantages and disadvantages of oral and transdermal oestrogen
Oral estrogen PROS Convenience Reliable absorption for most users CONS Increased risk of VTE, cholelithiasis Increased SHBG and therefore decreased free testosterone Increased TBG - may need to adjust thyroxine dose Administration of higher total dose
Transdermal preparations PROS Avoidance of gut and first-pass hepatic metabolism - No change in SHBG or TBG Little / no increase in VTE Lower total dose Convenient for some women
CONS Patches can cause skin irritation Gel can be 'sticky' and inconvenient Occasionally poorly absorbed Women may forgot to change
Tibolone
Synthetic steroid with oestrogenic, progestogenic and weak androgenic effects
Effective for vasomotor and urogenital symptoms
Only use in women >12 months since menopause as may cause irregular bleeding in younger women
Benefits in RCT
- Alleviate VMS
- Improve BMD
- Reduce fracture risk
- Modest effect on some domains of female sexual function
- Stimulates the breasts less than combined MHT
Side effects:
- Headache, Acne, Increased hair growth, Occasionally, irregular bleeding
Does not increase the risk of endometrial hyperplasia / cancer, VTE, breast cancer, or CVD risk
Less bleeding in the first 3/12 of treatment
Increased risk of stroke in women >65y, breast cancer recurrence
Monitoring MHT
Start with low dose therapy
May take up to 6-8 weeks before adequate symptom relief
Aim for lowest dose, for shortest duration
Initially review 6/12, then annual follow up
Unscheduled bleeding in the first 6/12, but after that needs to be investigated
Review general health status, update PMHx and FHx, and need for continued MHT
No set min or max duration of therapy
Most guidelines recommend use for up to 4-5y
Cessation may lead to surgent symptoms in around 50% of women
No optimum method for discontinuing
MHT and cardiovascular disease
Not used for primary prevention of CHD
In women within 10y of menopause, MHT does not increase the risk of coronary heart disease
WHI RCT
- CHD was not significantly differ during the intervention or post intervention phase for either estrogen only or combined therapy, c.f. placebo
- In those 50-59y
○ Significantly reduced for users of estrogen only therapy
○ Not increased for users of combined MHT
Cochrane review of MHT
Recent systematic review supports ‘window of opportunity’ for initiation of MHT in women within 10y of their last period for maximum benefit and minimal risk
- Overall MHT conferred no protective effect on all-cause mortality, CV death, non-fatal infarction, angina or revascularisation
○ But did increase stroke and VTE risk
- In women who start MHT <10y after the menopause, there was lower mortality and lower incidence of CHD
○ No increased risk of stroke in this group
Benefits of MHT
Reduced fracture risk
- MHT increased bone density
Reduced colon cancer risk
- Conferred by both combined MHT and tibolone use
Reduced Alzheimer’s disease
- In MHT initiated around the time of menopause
Breast cancer and MHT
Risk of breast cancer appears greater with:
- Combined MHT c.f. estrogen alone
- Greater exposure to progesterone (continuous > intermittent)
- micronized (“natural”) progesterone may be safer
- Duration of use
Breast cancer risk may persist after discontinuation of MHT
- Risk decreases
Uncertain if oestrogen alone increases breast cancer risk
- Large RCTs suggest no increase in risk (may decrease risk)
~1 extra case per 1000 women using MHT for 1y
Avoid MHT after breast cancer
- May be safe if high inherited risk of breast cancer but no PMHx, but limited data
Thromboembolic risk and MHT
Risk greatest in first year of MHT use
Combined MHT - increased VTE risk (2-fold)
Oral estrogen also increased risk
In absence of PMHx or FHx, screening for thrombophilia is not indicated before starting MHT
Transdermal MHT does not appear to increase VTE risk in low VTE-risk women
Stroke and MHT
Gallbladder disease
Increased risk of stroke reported in women >60y or >10y from menopause using either oral oestrogen or combined MHT
No increase with <50mcg transdermal dose used
Increased risk of cholecystitis with oral MHT use
- 12 extra cases per 1000 women per 5y
Ovarian cancer and MHT
Large meta-analysis of observational studies
- Increased risk of ovarian cancer - serous and endometrioid subtypes
- Absolute increase in risk of uncertain clinical significance
Reduced risk of clear cell and mucinous subtypes
1 large RCT
MHT after breast cancer
Non-hormonal options
- Bisphosphonates or SERMs for osteoporosis
- Statin and aspirin for CVD
- SSRI, SNRI, clonidine, gabapentin - vasomotor symptoms
- Vaginal lubricants for superficial dyspareunia
- Anticholinergics for urinary urgency
RANZCOG - reasonable therapeutic option for control of GU symptoms
- discuss risk of small amount of systemic absorption
Current data does not support MHT in these women
- Cessation of tamoxifen may improve VMS
Define osteoporosis
Pathophysiology
Bone density >2.5 standard deviations below the young normal mean
Peak bone mass usually reached during a woman’s 20s to 30s
Oestrogen plays an important role in maintaining bone strength
Osteoporosis occurs when resorption occurs more quickly than formation
Low oestrogen levels –> increases in osteoclast numbers and activity –> sustained excess of bone resorption over bone formation
Average woman loses up to 10% of her bone mass in the first 5y after menopause
More than 50% of post-menopausal women have a fracture of some sort between menopause and death
Osteoporosis risk factors
Ethnicity - Polynesian or African descent - higher bone density and lower fracture risk than European or Asian Weight PMHx and FHx of fractures Smoking Glucocorticoid use - Also phenytoin and carbamazepine Falls Early menopause Thyroid or parathyroid disease Coeliac disease Rheumatoid arthritis Chronic kidney or liver disease
Non-pharmacological interventions
to prevent osteoporosis
Underweight avoidance
- Hip fracture risk increases steeply when BMI is <20
Smoking cessation
Moderating alcohol intake
Remaining physically active
Falls prevention
Dietary calcium
- 1300mg/day for women >50y
Vitamin D - ~5-15 mins of sunlight / day
Pharmacological interventions
for osteoporosis
Calcium supplements
- minimal evidence influences fracture risk
- increases BMD by 1%
Vitamin D
- can be helpful in frail elderly
- caution as high amounts may cause bone resorption
Bisphosphonates - bind to bone surfaces where they inhibit the activity of osteoclasts
- IV 1-2 years or PO weekly
- Can precipitate symptomatic hypocalcaemia if given to patients with severe vitamin D deficiency. Therefore give with vitamin D
- Rare ADR: osteoporosis of the jaw, atypical femur fractures in long term use
MHT
SERM
- Reduces vertebral fracture risk but not hip
Denosumab 6 monthly sc injection
- Monoclonal antibody, inhibits bone resorption
Endometriosis definition and incidence
Presence of endometrial-like tissue outside the uterus which induces a chronic, inflammatory reaction
Australia: 11.4%
Up to 50% of infertile women
Pathophysiology of endometriosis
Uncertain - likely multifactorial
Retrograde menstruation - widely accept theory, initiating step
- Other factors, e.g. genetics, hormones, immune dysfunction, may be required to create favourable environment to promote endometriotic implant formation, proliferation and development
Coelomic metaplasia - Transformation of peritoneal tissue into endometrial tissue through hormonal / immunological factors
Genetic - lteration of cellular function that increases attachment of endometrial cells and evasion of these cells from immune clearance
7x increased risk of endometriosis if FHx
Hormones
- stromal cell defect associated with increased estrogen and prostaglandins
- Growing evidence of progesterone resistance and therefore progesterone-mediated control of endometrial proliferation
Oxidative stress and inflammation
Apoptosis suppression
Infertility and endometriosis - pathophysiology
Inflammatory state –> toxic effect on gametes, embryos and impairing tubal motility, impairs implantation
Peritoneal macrophages –> phagocytose sperm
Pelvic adhesions and endometriomas –> anatomical distortion
Reduced ovarian reserve
Dyspareunia and chronic pelvic pain - impair normal sexual function
Endometriosis medical treatment - while on prevents conception
Diagnosis of endometriosis
Laparoscopy + histological verification = gold standard
- Sensitivity 94%, specificity 79%
Histological features (2/4 for diagnosis)
- Endometrial stroma
- Endometrial epithelium
- New haemorrhage
- Old haemorrhage (hemosiderin)
Factors contributing to delay in diagnosis
Delays form symptom onset to diagnosis ranging from 4 to 11 years - Australia - average 7y
Menstruation-related myths and cultural misperceptions
The assumption that dysmenorrhoea is a normal
System - limits resources –> delays
Patients may conceal severity due to embarrassment
Healthcare professionals normalising or dismissing Sx
USS characteristics of endometrioma in premenopausal women
Ground glass echogenicity
1-4 compartments
No papillary structures with detectable flow
Obstetric outcomes for endometriosis
Miscarriage Ectopic APH Abruption Placenta praevia MROP PTB PET NND
Endometriosis Action Plan - Australia
- Develop the concept of an endometriosis network of expertise
- Raise public awareness of endometriosis
- Treatment and management of endometriosis
- Understand endometriosis through research
Staging for endometriosis
Revised American Society for Reproductive Medicine classification (rASRM)
Stage I = Minimal
1-5 points
Superficial lesions
No significant adhesions
Stage II = Mild
6-15 points
Some deep lesions, no significant adhesions
Stage III = Moderate 16-40 points Multiple implants Includes endometrioma Includes minor adhesions
Stage IV = Severe
>40 points
Severe adhesions with bowel and/or bladder involvement
Severe damage to the pouch of Douglas
Issues with staging for endo
- May not correlate with symptoms experienced / quality of life, reproductive outcome, recurrence risk
- Poor prognostic information and predictive accuracy with respect to treatment outcomes
But has been used for a long time, widespread use in research
Stage classification helps to determine how to optimally deal with the disease surgically
Alternative treatments for endo
Acupuncture appears to be moderately effective and safe but requires repeated treatments
TENS - some effectiveness in the short term
Cannabis has been shown to be moderately effective for relieving chronic pain
- Benefits far outweighed by potentially serious side effects
- No studies in women with endometriosis
Inconclusive evidence
- Exercise
NSAIDs for endometriosis
Virtually no evidence for endo
NSAIDs have a favourable effect on primary dysmenorrhoea and are widely used as first-line treatment
- Can be useful in up to 50% of women with dysmenorrhoea
Advantages:
- Readily available
- Inexpensive
Disadvantages:
- GI side effects
- Around 50% of women will not find benefit
Hormonal therapy for endometriosis
Most hormonal contraceptives have been shown to be equally effective
Reduces endometriosis-associated dyspareunia, dysmenorrhoea, non-menstrual pain
Theoretical benefits of progesterone > combined
COCP
- may reduce recurrence after surgery
Progestagens
- Inhibit growth of lesions by inducing decidualisation followed by atrophy of uterine-type tissues
- Adverse effects: weight gain, fluid retention, depression, BTB
- Medroxyprogesterone acetate, norethisterone
- LNG-IUS - effective in reducing pain
- Between 1/4 and 1/3 of women do not respond to treatment
Danazol - don’t use, high burden androgenic side effects
GnRH agonists –> produces hypogonadotrophic-hypogonadal state through downregulation of pituitary gland
As effective as other medical therapies in relieving pain
- May reduce progression
- No improvement in fertility
Can be associated with severe side effects (hot flushes, urogenital atrophy, depression, loss of BMD)
Surgery for endometriosis
The first definitive surgical intervention has been shown to deliver the greatest benefit
- Pain improvements at 6 months ~83% vs. ~53% for second procedure
Excision > ablative - better at 12 months, less dysmenorrhoea, dyschezia
- No change to dyspareunia
Surgery for deep endometriosis possible and effective
- Incomplete resection may reduce symptomatic outcomes, but radical interventions increase the risk of major complications
Consider hysterectomy + BSO + removal of all visible endometriosis if completed family and failed to respond to more conservative treatments
- BSO reduces the risk of reoperation due to recurrent pelvic pain by 6x
Counsel that may be only one form of chronic pelvic pain
Surgical interruption of pelvic nerve pathways
- Presacral neurectomy is effective as an additional procedure to conservative surgery to reduce endometriosis-associated midline pain
Post-op endo management
Secondary prevention = interventions to prevent the recurrence of pain symptoms or the recurrence of disease in the long-term defined as >6 months after surgery
After cystectomy for endometrioma, recommend COCP for secondary prevention - effective at minimising recurrence rates after cystectomy
Mirena or COCP for at least 18-24 months recommended for secondary prevention of endometriosis-associated dysmenorrhoea (but not for non-menstrual pelvic pain or dyspareunia)
Recurrence rates of endo
Recurrence rate of symptoms and endometriotic lesions varies from 10-55% within 12 months
Risk of requirement for repeat surgery is higher in women <30y at the time of surgery
Also in those with deep / advanced endo, adhesions, those with high BMI
time dependent
- time dependent - 20% at 2y, 40% at 5y
Risk factors for recurrence of endo
At time of surgery:
- Stage of disease
- Hx of previous surgery
- Presence of DIE and adhesions, how much residual disease remained
- Presence and means of removal of endometrioma (drainage vs. excision)
Following hysterectomy - 15% have persisting pain, 3-5% may have worsening pain post-op:
- Chronic pain unrelated
- Residual or microscopic disease
- Preservation of ovaries, use of HRT where there is residual disease
Risk factors for recurrence following surgery:
- Not applying ongoing medication immediately following surgery
- Not following up with patients regularly and in the long term
Menopause and endo
97% of women become painfree after menopause
Combined HRT recommended over oestrogen only
- unopposed oestrogen could theoretically could reactivate disease
Options for natural menopause
- Mirena and low dose oestrogen patch
- Mirena appears to have the highest success rate for reducing endometriosis recurrence
ENDOMETRIOSIS AND CANCER
There is no evidence that endometriosis causes cancer
No increase in overall incidence of cancer in women with endometriosis
Some cancers are slightly more common in women with endometriosis
Ovarian cancer - clear cell, low-grade serous, endometrioid
- Overall risk is low
- lifetime risk is increased from ~1 in 100 to 2 in 100
- No evidence for screening
Risk of ovarian cancer appears particularly increased in women with a long-standing history of untreated ovarian endometriosis
Chronic pelvic pain definition
Intermittent or constant pain in the lower abdomen or pelvis of a woman of >6 months in duration, not occurring exclusively with menstruation or intercourse, and not associated with pregnancy
symptom not a diagnosis
Pathophysiology of chronic pain
2 neurophysiological mechanisms implicated
Nociceptive
- Injury to a pain sensitive structure
- Somatic, visceral
Non-nociceptive
- Neuropathic - Pain as a result of changes in the nerve itself
- Psychogenic
Central sensitisation - altered pain sensory processing and impaired central pain modulation - reduced ability of the CNS to diminish responses to peripheral stimuli
Definition of Allodynia and hyperalgesia
hyperalgesia - exaggerated response to noxious substances / pain triggers, through general increase in responsiveness of the tissues to pain
Allodynia - Pain response from stimuli which do not normally provoke pain
Viscero-visceral hyperalgesia
IBS, painful bladder syndrome may develop due to shared neural pathways in the pelvis
Viscero-muscular / somatic hyperalgesia
These can lead to myofascial pain or “trigger points” in the abdominal wall (or pelvic floor) which shares the same spinal segment as the sensitised viscera
Often described as severe, sharp, stabbing pains, sometimes perceived to be in the ovary, which can occur without pattern, or after exercise or prolonged time in one position
Pathology involved in CPP
GYNAE Endometriosis Adenomyosis Adhesions Ovarian remnant syndrome Pelvic congestion syndrome
UROLOGIC
Interstitial cystitis
GIT
IBS
IBD
Chronic constipation
MSK Pelvic floor dysfunction Myofascial pain syndromes Fibromyalgia Adhesions
NEURO Postherpetic neuralgia Incisional neuroma Visceral hyperalgesia Pudendal neuralgia
Management of CPP - Non-invasive therapy
Exercise programs
CBT has a strong evidence base for managing chronic pain, can also improve sleep and stress
Physical therapy
- Internal manual therapy - Up to 70% of patients will have moderate to significant improvement in pain and voiding symptoms
Nutrition
Massage
Acupuncture (poor quality evidence)
Management of CPP - Analgesia
Paracetamol, NSAIDs
Opioids should be avoided in the community
- Risks are likely to outweigh benefits and may worsen her pain in the long-term via nerve pathway sensitisation
Tricyclic antidepressants
- Pain responds faster than depression to TCAs
- Side effects: sedation and anticholinergic effects
- Tend to use for short period of time (approx 8 weeks)
Venlafaxine - Useful in pain and depression
Gabapentin particularly useful for burning, lancinating pain, interstitial cystitis
- Little evidence with pelvic pain
Injections
- trigger point injections
- Botox
- Nerve blocks
Surgical procedures for CPP
Sacral nerve stimulation
- Reduces pain and improves voiding dysfunction in patients with interstitial cystitis and pelvic floor dysfunction
- Not first line
Neuroablative procedures, E.g. LUNA, presacral neurectomy
- Insufficient evidence to recommend use in management of painful periods
- Significant difference in midline abdominal pain after PSN
Hysterectomy
- 10% of hysterectomies for CPP
- Success rates 60-95%
Failure of hysterectomy to relieve CPP is associated with:
- Lack of pelvic pathology
- Age <30y
- Lack of commercial insurance
- Psychological problems
Almost 40% of patients with no pelvic pathology with have persistent pain post-hysterectomy
Definition of adenomyosis
deep endometrial tissue (non-neoplastic endometrial glands and stroma) surrounded by smooth muscle hyperplasia within the myometrium
Focal or diffuse
Traditionally a histological diagnosis post-hysterectomy, therefore true prevalence is not known
Imaging features of adenomyosis
TV US + MRI - 80-90% accuracy
- Similar diagnostic accuracy
- Better quality USS = now similar sen + spec to MRI
USS less predictive for adenomyosis if co-existing fibroids
TVS features
- Bulky, globular
- Heterogeneous, venetian blind effect
- Asymmetrical wall thickness (particularly fundal or posterior wall)
- focal areas have indistinct borders compared to fibroids
MRI features
- Thickened endo-myometrial junction
Compare USS and MRI as diagnostic modalities
- for adenomyosis
USS
- readily accessible
- cheap
- first line imaging for menorrhagia and dysmenorrhoea
- user dependent
- limited in obesity
- TVS with 3D images - similar sen + spec to MRI
- can look at other pathology
MRI
- expensive
- ordered by specialist
- less user dependent
- limited is claustrophobia or metal wear
- easily able to identify and measure transition zone
Pathophysiology of adenomyosis
Unknown
Endometrial invasion with alteration in the junctional zone
- E.g. Disruption of the junction such as after pregnancy (especially with complications, e.g. prolonged labour, CS) and abdominal trauma, tissue injury
Chronic myometrial contractions –> micro trauma
Changes to myometrium mean that the uterus is not able to optimally contract and constrict vessels –> heavy periods
Misplaced pluripotent Mullerian remnants
May be a genetic component
Coexists with endometriosis in 12% of women
Risk factors:
- Increasing parity
- TOP
- Uterine curettage
- CS
Appears to be an association with oestrogen exposure
Histopathology of adenomyosis
Pathognomonic feature = presence of endometrial tissue within the myometrium
- The ectopic endometrium usually has an immature proliferative pattern
Diffuse adenomyosis – on gross inspection uterus is uniformly large and boggy
Focal adenomyosis – on gross inspection can resemble a fibroid but without the pseudo-capsule so cannot be easily shelled out
Management of adenomyosis
Non-hormonal - NSAID, TXA
COCP, with withdrawal bleed every 4-6 months
LNG-IUD
- Mirena –> reduction of junctional zone on MRI
- Mirena equal to hysterectomy in bleeding improvements at 1y
GnRHa agonist
Hysterectomy +/- BSO
- Consider trial of GnRH analogue prior to ensure pain is relieved completely with chemical suppression of the ovaries, especially in younger women
Embolisation has been used to treat focal adenomyomas, but results are not encouraging
Discrete adenomyomas can be excised laparoscopically and good success rates for pain relief have been reported
Endometrial ablation
- good results with superficial adenomyosis <2.5mm, but high failure rate with deep adenomyosis
Limitations of imaging to diagnose adenomyosis
Imaging to diagnose adenomyosis is becoming more advanced
However, the clinical diagnosis of adenomyosis prior to hysterectomy is often inaccurate
This is due to:
- Variability and non-specific nature of symptoms, which tends to mimic any combination of uterine fibroids, endometriosis and HMB due to ovulatory or endometrial dysregulation
- Variability of the sensitivity and specificity of pelvic ultrasound to diagnose adenomyosis
- No standardized way to diagnose or classify adenomyosis on imaging and no diagnostic threshold
FIGO definition of normal bleeding patterns
Frequency of menses = 24-38 days
Duration <8 days
Regularity (shortest to longest cycle variation)
Regular <7-9 days*
<9 days - 18-25y and 42-45y
<7 days for 26-41y
Irregular >8-10 days
Flow volume - patient determined
ALWAYS ABORMAL
- Intermenstrual bleeding - either random or cyclic
- Unscheduled bleeding on progestin +/- oestrogen
PALM COEIN
- what is it?
FIGO approved classification system for the causes of non-gestational AUB
PALM - generally discrete / structural entities
COEIN - non-structural
P = Polyp A = Adenomyosis L = Leiomyoma M = Malignancy and hyperplasia
C = Coagulopathy O = Ovulatory dysfunction E = Endometrial disorders I = Iatrogenic N = Not otherwise classified
Features suggestive of coagulopathy on Hx in women presenting with HMB
HMB since menarche
PPH, surgical-related bleeding, bleeding associated with dental work
Bruising 1-2 times / month, epistaxis 1-2x/month, frequent gum bleeding, FHx of bleeding symptoms
90% sensitive for presence of coagulopathy in women with HMB
Tests may include assays for von Willebrand factor, Ristocetin cofactor, partial thromboplastin time (PTT)
vWD is most common
When to do a pipelle biopsy
Required if ET >4mm or >16mm
OR
Persistent IMB
>45y with treatment failure
Irregular bleeding while on HRT or tamoxifen
Von Willebrand’s disease treatment
COCP - Effective treatment as increase fibrinogen, prothrombin, FVII, FVIII and/or vWF
LNG-IUS - Effective management of HMB
Endometrial ablation
- Effective
- One study found 3/7 women needed hysterectomy
Desmopression acetate and vWF replacement may be needed to control HMB
Surgery - hysterectomy
- Get advice from haematology
- Timing and need for infusion determined by factor vWF and factor VII levels pre- and post-op
Key points about ablation for HMB
General anaesthetics with associated risks
Not appropriate if distorted endometrial cavity (fibroids, septum)
Mirena:
- 90% reduction in menstrual flow
- 85% patient satisfaction
Ablation
- 80% effective
- 20% women go on to have hysterectomy in the future
Device failure Pain, bleeding, infection Cervical trauma Perforation +/- organ injury Chronic pain, especially in previous tubal ligation Haemtometra
Not recommended if future pregnancy desired – increased risk of miscarriage, ectopic pregnancy, abnormal placentation
Reliable contraception required
Causes of PMB
Atrophy - up to 60%
Hormonal effect
Polyps
Hyperplasia
Endometrial carcinoma
Ovarian, tubal, cervical malignancy
Causes of IMB
Ovarian causes
- 1-2% of women will spot at ovulation
- Oestrogen secretin tumours can cause IMB
Uterine causes
- Iatrogenic
- Hormonal contraceptives and implants
- SSRIs, anticoagulants
- Infective - Endometritis
- Structural - benign, Polyps, fibroids, adenomyosis
- Structural - malignant, Endometrial cancer
Cervical causes
- Iatrogenic - Following exam, smear
- Cervicitis secondary to infection (chlamydia, gonorrhoea)
- Cervical ectropion
- Cervical polyps - largely benign (malignancy 0.1%, dysplasia 0.5%)
- Cervical cancer - 3-18% prevalence in PCB
Vaginal causes
- Atrophic vaginitis
- Trauma, foreign bodies, sexual abuse
- Vulvovaginitis secondary to Trichomonas vaginalis or Candida albicans if severe oedema or excoriation
- Vaginal cancer
Vulval causes
- Herpes simplex, Genital warts
- cancer
AVM
- USS findings
- Cause
- Treatment
Rare
Largely acquired lesions - usually following pregnancy event
Usually present with AUB
- Often episodic, torrential, can result in significant anaemia or even shock
USS
- Subtle myometrial heterogeneity and multiple tubular or spongy anechoic or hypoechoic areas within the myometrium
- Colour Doppler
- intense vascularity with turbulent, multidirectional flow
Resuscitation
- Could use foley catheter to stem bleeding
Medical
- COCP
- Danazol - Thought it decreases blood flow to the AVM, allowing the lesion to thrombose
Uterine artery embolisation- Consider if life threatening bleeding
Hysterectomy - Definitive treatment
What are endometrial polyps
and pathophy
Localised hyperplastic overgrowths of endometrial glands and stroma which form projections over the endometrial surface
Proposed that polyps lose their apoptotic cell regulation and overexpress oestrogen and progesterone receptors causing them to grow
Risk factors for polyps
Age - Incidence increases with age, peaks in 5th decade of life, then declining at menopause Tamoxifen Obesity MHT FHx - Lynch syndrome
Clinical course of polyps
> 1cm less likely to regress
6-10% can potentially regress
Risk of malignancy
- 95% benign
- Risk of malignancy / hyperplasia more in post-menopausal and those who are symptomatic
- Size not associated with risk of malignancy
Fibroid
- what are they?
- incidence
Smooth muscle tumours of the uterus with a monoclonal origin
77% of uterine histology specimens
12-25% of reproductive age women
Risk factors for fibroids
Ethnicity - Black 2-3x increase > white Early menarche (<10y) Age (advancing age) Parity - >1 pregnancy beyond 20/40 reduces risk Hereditary - Familial predisposition in some families DES exposure
Physiology for why get symptoms of fibroids
AUB
- Abnormal vasculature, impaired endometrial haemostasis, increased endometrial surface area, altered contractility
Pain
- Altered contractility, increased bleeding and clots, degeneration, deep dyspareunia
Pressure if large
Infertility / obstetric complications
- Distortion of uterine cavity –> increased miscarriage, altered endometrium overlying fibroid, changes in uterine contractility
Complications of fibroids
Hyaline degeneration - Relatively common
- Presents as painful enlarged fibroids due to hyaline / cystic degeneration pathological process
Red degeneration - typically occurs due to infarction at mid-pregnancy
Calcification - Typically in postmenopausal women
Sarcomatous change - 0.2% risk
Infection - Relatively rare
Torsion of pedunculated fibroids
Impact of fibroids on fertility
Subserosal - Do not appear to have a significant effect
Intramural
- May be associated with reduced fertility and increased miscarriage rate
- insufficient evidence to determine whether myomectomy improves fertility outcomes
>8cm associated with infertility, <5cm not major role
Submucosal
- Associated with reduced fertility and an increased miscarriage rate
- Hysteroscopic myomectomy is likely to improve fertility outcomes, but only poor quality studies
- > 2cm may have space effect
FIGO staging of fibroids
0-2 = submucosal
0 = pedunculated
1 <50% intramural
2 >50% intramural
3 =. contacts endometrium but 100% intramural
4-5 intramural
6 subserous
7 subserous pedunculated
8 - other, e.g. cervical
Hormonal therapy for fibroids
Depo provera - Reduced menstrual loss and fibroid volume after 6/12
Mirena - Fibroids <3cm and not distorting uterine cavity
- Reduces blood loss, increases Hb and relieves symptoms
GnRH agonists - Zoladex
- Works for 12-13 weeks
- Low oestrogen state with menopausal side effects
- Limit to 6 months
- Usually used pre-op
- Can make surgical planes difficult, but may need can change approach (e.g. pfannenstiel vs. midline)
Uterine artery embolisation for fibroids
- description
- outcomes
Ensure appropriate imaging assessment prior to UAE (Doppler USS and ideally MRI) to exclude malignancy
Conscious sedation and LA
Involves angiographic catheter into the uterine arteries via the common femoral artery, followed by injection of embolic particles until the flow becomes sluggish
Reduced pressure symptoms in ~60%
Reduced AUB (heavy) in 70-90%
Reduced pain in ~80%
25% chance of requiring hysterectomy within 5y
Contraindications to UAE
ABSOLUTE Asymptomatic fibroids Pregnancy PID (recurrent or current) Suspected or known uterine malignancy Anaphylaxis to contrast
RELATIVE
Desire to conceive - High quality data lacking
Postmenopausal status
Fibroid location
- Submucosal or subserosal with narrow stalk - sterile peritonitis or intrauterine infection
Number / size of fibroids
Risks with UAE
Risk of minor adverse outcome 30-45%
Risk of major complications - 5%
Early:
- ‘Embolisation syndrome’ - Pain, nausea, malaise, fever
- Vaginal discharge
- Pelvic infection - including pyomyoma
- Expulsion of necrotic submucosal fibroid (5-8%)
- Sepsis requiring urgent hysterectomy - 1%
Late:
- Ovarian failure / insufficiency
- Recurrence
- Failure of response
- Fibroid expulsion and impaction
- Fistula
- Bladder / vaginal injury
- VTE (0.3%)
- Sepsis
- Delayed diagnosis of cancer
Cochrane review (2014) - UAE vs. surgery (myomectomy, hysterectomy) for symptomatic fibroids
Increased:
- Minor complications (short and long-term)
- Number of unplanned reviews and re-admissions after discharge
- Surgical reintervention rate
Decreased:
- Length of hospitalisation
- Procedure duration
- Resumption of ADL
No significant difference in:
- Intra procedural complications
- Short or long term major complications
- Patient satisfaction at 2 and 5y
- No difference in long-term ovarian failure rates
Fertility and UAE
due to lack of good quality evidence, caution should be employed to avoid routine use of UAE in young patients wishing to conceive
Concerning outcomes that could affect reproductive potential:
- Non-target embolisation –> ovarian embolisation and impaired ovarian reserve
- Decrease in endometrial volume due to an inadequate blood supply
1 RCT comparing UAE to myomectomy - Pregnancy rates were significantly higher, with lower miscarriage rates in myomectomy group
MR guided focused ultrasound (MRgFUS)
Thermoblative technique causing tissue destruction
High frequency ultrasound waves produced heat to denature proteins –> cell death and shrinkage of proteins
For premenopausal women with fibroids
Limited data
Myomectomy
Hysterectomy associated with lower surgical risks than abdominal myomectomy and will achieve definitive symptoms cure, therefore reserve for those wanting to preserve fertility
Improves spontaneous fertility if <41y
Retreatment rate 20% over 2-5y
Bleeding –> hysterectomy in 1%
Deliver by CS
Hysteroscopic myomectomy
Type 0 and 1 submucosal fibroid
Lower chance in size >5cm
Reduces intracavity fibroid size by 90-100%
Decrease HMB >80%
Improve fertility (40-60%)
Secondary treatment required in 2y in 10%
Complication rate 1-2%
Menstrual cycle physiology
- luteal phase
Second half = luteal phase (of ovary)
Fixed at 14 days (the life span of the corpus luteum)
Secretory of endometrium
Corpus luteum is formed from the remnant of the ovarian follicle - Luteinized theca and granulosa cells
CL is maintained by LH Initially - If pregnant, HCG maintains CL CL secretes - Progesterone - at high levels suppresses GnRH. Makes endometrium receptive to implantation of fertilised gamete - Oestrogen - Inhibin - negative feedback on FSH
If no pregnancy, CL involutes
Concentrations of oestradiol and progesterone drop –> level of FSH starts to rise as negative feedback disappears
Endometrial changes during the menstrual cycle
In the first half of the cycle, when oestradiol present, lining proliferates
With rising progesterone, the endometrium goes through staged series of development
- Spiral arteries continue to grow
- Uterine glands secrete more mucous
- After day 15, window for fertilisation closes as cervical mucus thickens and is less hospitable for sperm
- Window of implantation approx half way through the luteal phase where the endometrium is receptive to an embryo
RANZCOG 2019 statement on vaginal rejuvenation
strongly discourages the performance of any surgical or laser procedure that lacks current peer reviewed scientific evidence other than in the context of an appropriately constructed clinical trial
At present, no evidence they are effective, enhance sexual function, or improve self-imageRefers to devices that deliver thermal energy to the vaginal mucosa
Marketed for the treatment of vaginal menopausal symptoms, sexual dysfunction, urinary incontinence
What is vaginal rejuvenation?
Refers to devices that deliver thermal energy to the vaginal mucosa
Marketed for the treatment of vaginal menopausal symptoms, sexual dysfunction, urinary incontinence
