Module 1.1 (Management of Menstrual Disorders) Flashcards
Describe the menstrual cycle, include the 4 stages and the days at which they occur
- Day 1: first day of menstruation
- Menstrual phase: lasts ~4-7 days
> shedding of endometrium
> 80mL blood loss
- Follicular phase
> endometrial proliferation (normally 6-12 mm)
> FSH -> develops follicle -> increased oestrogen
> Ends as oestrogen production peaks -> surge in LH
- Ovulation: around day 14 –> mature egg released
- Luteal phase
> Production of progesterone & less potent oestrogen by corpus luteum
> Endometrium maintained
> Upon no implantation of fertilised product, progesterone declines and menstruation occurs
Intermenstrual length: 24-35 days
What is dysmenorrhoea?
Recurrent, significant pain associated with menstruation
> Primary dysmenorrhoea (no pathology)
> Secondary dysmenorrhoea
Most common gynaecological symptom reported by women
> >70% of adolescent/young women
> 40% adult women
What are the potential causes of seconday dysmenorrhoea? How to treat?
- Endometriosis
- Endometrial polyps
- Fibroids
- Pelvic inflammatory disease (PID)
- IUD use
- Malformations of the genital tract
> The treatment of secondary dysmenorrhoea involves treating the underlying cause
When/who is secondary dymenorrhoea more likely to occur?
- Occurs in older women
- Periods are irregular
- Dyspareunia, heavy bleeding, post-coital bleeding
- Patterns in pain changes
- Poor response to treatment
What has prostaglandins have to do with dysmenorrhoea? What do they cause?
At the start of menstruation endometrial cells release prostaglandins
> prostaglandin release = progesterone withdrawal
PG causes
- Uterine contraction
- Vasoconstriction -> ischaemia
- Nerve sensitisation
> Severity of pain is proportional to PG concentration
What are the risk factors for dysmenorrhea?
- Early menarche (when period starts)
- Heavy/long duration of menstrual flow
- Family history
- Smoking
- Obesity
- Social environment (lack of support)
- Depression/mood disorders
- Nulliparity –> women who hasn’t given birth to a child
What are the symptoms of dysmenorrhea? What can worsen it?
- Cramping, suprapubic pain
May extend to lower back, thighs
- Usually begins in the first year of menstruation
- Starts several hours before start of menstruation
- May persist up to 2-3 days
- Peak pain is with maximum blood flow
- Others – diarrhoea, nausea, vomiting, light headedness, fever
- Other causes of pelvic pain (IBS, chronic PID etc) may worsen
How to assess dysmenorrhea through the following:
A) Menstrual history
B) Pain
C) Associated symptoms
D) Degree of disability
E) What to rule out
A)
- Age at menarche, when did symptoms begin, length and regularity of cycles, dates of last few periods, duration of periods, amounts of bleeding
B)
- Type, location, radiation, timing, severity, duration
C)
- diarrhoea, nausea, vomiting, light headedness, fever
D)
- Days off school/work, effect on QoL
E)
- Rule out secondary dysmenorrhoea
What is 1st line treatmet for dysmenorrhea? When to start?
(NSAID)
1st line – NSAIDs
- Reduce PG synthesis
- Effective in dysmenorrhoea in 50-70% of patients
> decrease pain, nause and diarrhoea
> all equally effective (except aspirin)
- Start at onset of symptoms and continue regularly for 2-3 days
> use loading dose to start
> can start prophylactically 24-48 hours prior to menstruation if symptoms severe
What is 1st line treatmet for dysmenorrhea? How does it work? What drug and dose to use?
(COCP)
1st line – Combined oral contraceptive pill (COCP)
- Reduced endometrium = reduced PG = reduced pain
- May take 3 months for full relief
- Less evidence compared with NSAIDs however used widely
- Use COCP containing 30microg ethinylestradiol or less
- Consider continuous use (extended cycles) if symptoms problematic
> Can combine with NSAID
What are some 2nd line treatments for dysmenorrhoea? How do they work?
2nd line – progestins – limited evidence
- Levonorgestrel IUD –> avoids systemic AE of progestins
- Local effect on endometrium
- Reduces menstrual flow, effective if heavy bleeding (relatively invasive)
- Periods may be irregular, spotting can be problematic
- Medroxyprogesterone depot –> 3 monthly injections
- Induces endometrial atrophy = less endometrium = less PGs
- Reduces BMD (not recommended in younger patients) + delayed return of menstruation
> not good option for someone looking to conceive (inhibit cycles for upto 1 year)
- Other agents (limited evidence –> CCB, vitamins, fish oil, paracetamol, montelukast)
What are non-pharmacological treatments for dysmenorrhea?
- Aerobic exercise
- High frequency transcutaneous electrical nerve stimulation (TENS)
- Acupuncture
- Heat packs (may be as effective as ibuprofen!)
- Behavioural interventions
What is summary for dysmenorrhoea?
Painful menstrual bleeding
Potentiated by PG release
First line –> NSAIDs, COC
Start therapy early and continue regularly if needed
Can use NSAID and COC together
Consider non-pharmacological treatments
How long does an average cycle last for? When does bleeding occur? What is the amount of bleeding?
Average cycle between 21-35 days
> average is 28 days
Bleeding from day 1-7
Amount should be less than 1 pad or tampon per 3 hour period
What constitutes heavy bleeding?
- Loss > 80ml
- > 7 days bleeding
- Menstruation loss considered unacceptable to woman
What are some of the characteristics of heavy menstrual bleeding? Why does it occur?
Menorrhagia = menstrual bleeding that lasts more than 7 days
- Heavy cyclical bleeding
- Occurs over several consecutive cycles
- Thought to be caused by inadequate haemostasis due to excess fibrinolytic activity (excessive breakdown of clots) and excess prostaglandin production
> most of the time caused by hormone dysfunction
Causes of heavy menstrual bleeding
A) structural
B) systemic condition
C) medication
D) complementary medicines
A)
- Endometrial polyps
- Fibroids
- Malignancy
- Trauma
B)
- Hyper- or hypothyroidism
- Coagulopathies –> inherited or acquired
- Renal/liver disease
- PCOS
- Cushing’s
C)
- Hormonal contraceptives (incl. IUD)
- Anticoagulants
- Antipsychotics
- SSRIs
- Tamoxifen
- Danazol
- Spironolactone
D)
- Ginseng
- Gingko
- Phytoestrogens
Outline the details of heavy menstrual bleeding in:
A) ovulatory (more common)
B) anovulatory
A)
- Heavy but regular periods
- Often accompanied by pelvic pain and PMS
B)
- Excessive estrogen = buildup of endometrium
- No ovulation: no progesterone to cause a withdrawal bleed
- Irregular, unpredictable heavy bleeding
- Typically occurs in <20 and >40 year olds
- Also in PCOS, low body mass, excessive exercise
How to diagnose heavy menstrual bleeding?
Through exclusion of the following
Patient menstruation history
Age of menarche, frequency and amount of menstruation, impact
Labs (rule out secondary causes)
> progesterone (day 21-23 to see if ovulation is happening), FSH/LH
> FBC and ferritin –> assess anaemia because of excessive blood loss
Pelvic ultrasound (polyps/fibroids present in 25-50% patients)
Endometrial biopsy – rule out malignancy or pre- malignant conditions
> esp in women over 40 or if at risk of endometrial cancer
> nulliparity (infertility), new onset heavy bleeding, obesity, PCOS, family hx
What are the treatment coniderations for heavy menstrual bleeding?
- Need for contraception
- Fertility considerations
- Presence of other symptoms/medical conditions
- Patient preference
- Adverse effects
> If anovulatory –> treatment must include hormonal therapy because of risk of endometrial overgrowth and cancer e.g. use COCP
Provide some information about the below drugs for heavy menstrual bleeding:
A) Tranexamic acid
B) NSAIDs
C) COCP
D) Progestin
E) Levorgestrel releasing IUD
F) Medroxyprogesterone depot
A)
- Inhibits clot breakdown
- Preferred if no dysmenorrhoea
- 1-1.5g q6-8h for 3-5 days starting at menstruation
- Can reduce blood loss by almost 50%
- Caution if risk of VTE – unlikely to be a problem
- Well tolerated besides stomach upset and nausea
B)
- NSAIDs can reduce blood loss by 20-50%
- Start before or on first day of menses and continue regularly for 3-5 days of until cessation of menses
- Required doses may be higher than OTC doses (e.g. ibuprofen up to 1600mg/day)
- Use PPI with to help with stomach adverse effect
C)
- Commonly used but limited good quality evidence (may reduce loss by 43%)
- Good option if contraception is a concern
D)
- 21 day course if ovulatory to induce withdrawal bleed
- 12 day course if anovulatory
- Reduce blood loss by 80% however poorly tolerated and short term only –> risk of hyperestrogenism
E)
- Good option if no desire to get pregnant in next few years
- Reduce blood loss by 70-90%
Levonorgestrel IUD is a first-line option. It is an effective long-term treatment but may take 6 months before its full benefit (eg light bleeding, amenorrhoea) is seen. Adverse effects such as spotting and breast tenderness may take 3–6 months to settle but systemic adverse effects are usually minimal.
F)
- Limited evidence
- Takes few months to work –> use NSAIDs in the meantime
> NSADs and progestin IUDs have best satisfaction
> Tranexamic acid and COCs well tolerated
> Oral progestogen lowest satisfaction
Trial therapy for 3 months, if indequate adjust dose or change agent
What are the TWO treatment options that are rarely used for heavy menstrual bleeding? Why are they not used?
Steroid hormones (danazol)
- Poorly tolerated (androgenic side effects- may be irreversible)
> Acne, oily skin, oedema, weight gain, hirsutism, voice changes, hot flushes, vaginal dryness, reduced breast size
- Must be used with non-hormonal contraception
GnRH agonists (goserelin)
- Induces amenorrhoeic state
- Non-hormonal contraception required
- A/E – hot flushes, sweating, sexual dysfunction, vaginal dryness, myalgia, oedema, mood changes
> not recommended for more than 6 months due to BMD loss
What surgery option is there for heavy menstrual bleeding?
Dilation and curettage (D&C) –> procedure to remove tissue from inside the uterus
> can also have diagnostic role if endometrial biopsy inconclusive
> endometrial ablation
> hysterectomy = last line
What is the pharmacological treatment of acute heavy menstrual bleeding?
If bleeding severe + haemodynamic instability or Hb very low
> Tranexamic acid IV 10mg q8h (or PO 1-1.5g q6-8h) until bleeding stops
If TXA not tolerated or unavailable –> use until bleeding stops for the below drugs
- COCP q6h (ethinylestradiol 30-35microg)
- Medroxyprogesterone acetate 10mg q4h
- Norethisterone 5-10mg q4h
- use antiemetic prophylactically
> High dose estrogen may be required if bleeding continues
–> COCP containing 50microg ethinylestradiol q6h until bleeding stops
> Need to taper progestin/COCP after bleeding stops
> Regular hormonal therapy required to prevent further acute events
How to monitor patients with abnormal uterine bleeding?
- Amount and frequency of flow
- Breakthrough bleeding
- Use of PRN analgesia
- QoL – number of days of school/work missed n
- Side effects
- Complications (anaemia!!!)
> Trial therapy for 3 months, if indequate adjust dose or change agent
Summary for heavy menstrual bleeding
Can have underlying pathology or be iatrogenic
> ?excessive fibrinolysis and PG synthesis
> Treat underlying cause if known
- Tranexamic acid and NSAIDs good 1st line options
- Levonorgestrel IUD or COCP if contraception required
- Anovulatory HMB should receive hormonal therapy to reduce risk of endometrial hyperplasia (cancer)
- Iron deficiency common
What is endometriosis? When does it occur? What are the concerns
Can occur anytime in reproductive life
> most commonly in 20’s or 30’s
Incidence 2-5% of reroductive age women
Endometrial tissue found outside the uterus
- Cyclical hormonal changes lead tissue to growth and breakdown -> scarring
- Cause unknown - ?retrograde menstruation ?inappropriate stem cell growth
Symptoms and pathology do not necessarily correlate
Main concerns = pain and subfertility
What are the symptoms of endometriosis?
- Abnormal bleeding
- Dysmenorrhoea
- Dyspareunia
- Subfertility
- Pelvic pain
- Painful defecation
- Bloating
What are the risk factors for endometriosis?
- Shorter cycle (<28 days)
- Longer flow length (>7 days)
- Family history
- Higher socioeconomic status
- ? maybe caffeine/alcohol intake
How to diagnose endometriosis?
Based on symptoms history
Pelvic exam, ultrasounds and MRI may assist
Definitive diagnosis can only be made with a laparoscopy
- Visualise and remove lesions/adhesions
- Biopsy
Outline what the following drugs does for endometriosis
A) NSAIDs
B) COCP
C) Progestins (levonorgestrel IUD, high dose oral or depot)
D) Danazol
E) GNRH agonists (goserelin)
A)
- Relieves pain +/- paracetamol
- Best used regularly rather than prn
- Option if trying to conceive
- Inconclusive evidence on efficacy
- first line
B)
- Usually well tolerated although not always effective
- Cyclical or continuous (if symptoms severe in “pill free” period)
- first line
MOA = inhibit ovulation, less hormones, less endometrial growth
C)
Levonorgestrel IUD = long term first line
High dose oral = short term, causes hyperestrogenism
Depot = 10mg medroxyprogesterone acetate
AE: weight gain, irregular bleeding, mood changes
D)
Use limited by androgenic A/E
Limited duration – 6-9 months
Non-hormonal contraception also required
E)
Use limited by A/E (hot flushes, vaginal dryness, reduced BMD)
“add-back” therapy – giving low dose oestrogen/progestin or tibolone – counteract BMD loss may extend treatment to 2 years
Tibolone (2.5mg daily) reduces osteoporosis and vasomotor symptoms
Non-hormonal contraception required
Why are drugs mentioned in previous question not suitable for women that is trying to conceive?
Cause amenorrhoea
What are non pharmacological options for endometriosis?
Symptoms often re-occur following cessation of medical treatment – surgery warranted
Surgery is often necessary for large lesions
- Laparoscopic ablation/removal of adhesions to total abdominal hysterectomy with bilateral salpingo-oophorectomy (uterus, fallopian tubes and ovaries)
- Most women have at least 3 laprascopies prior to major surgery
- Medication may be used to delay surgery
Symptoms can also re-occur following surgery
Endometriosis summary
- Pain and subfertility due to endometrial tissue growing outside of uterus
- Hormonal treatments can reduce severity of pain –> with or without surgery
- Fertility issues – discussed in later lecture, surgery most effective n
- 1st line medical treatments
COCs +/- NSAID
Progestins incl. levonorgestrel IUD
- Side effects limit use of other agents
Why does Polycystic Ovarian Syndrome (PCOS) occur?
> most common endocrine disorder in reproductive age women (6-8%)
Inappropriate gonadotrophin secretion (too much LH = follicles cant develop properly and ovulation cant occur)
- Anovulation
- Increased androgen production
- Insulin resistance + hyperinsulinaemia
> no luteal phase = reduced progesterone = unopposed oestrogen = risk of endometrial hyperplasia
What are the clinical characteristics of PCOS?
Hyperandrogenism (excesive testoterone in women)
- Hirsutism
- Acne
- Alopecia
Oligomenorrhea (infrequent menstrual periods) or amenorrhoea
- <9 menses per year
Central/abdominal obesity (30-60% of POCS sufferers)
- Related to hyperandrogenism and hyperinsulinaemia
What are some complications associated with PCOS?
Impaired glucose tolerance & T2DM, metabolic syndrome & CV risk, OSA
How to diagnose PCOS?
Hyperandrogenism
Menstrual irregularity
Polycystic ovaries
What are the treatment goals for PCOS?
Reduce hirsutism, maintain cycle regularity, decrease insulin resistance
Prevent long term complications
What COCP is used in PCOS? Why is it used?
COCP – low dose estrogen and consider anti-androgen progestogen (cyproterone/drospirenone)
- Regulate cycle and reduce androgenism
- Reduce risk endometrial cancer
What to use if COCP contraindicated for PCOS?
Cyclical progestin
> 12 day cycle (e.g. MPA 10mg or norethisterone 5mg daily)
When is levonogestrel IUD used in PCOS?
minimise endometrial overgrowth ONLY.
Wont regulate cycle and minimal affect on androgenism
Why are the following medications used in PCOS:
A) Metformin
B) Spironolactone
C) Metformin, clomiphene etc - in later lecture
A)
- Helps to improve cycle regularity (less than hormonal treatments)
- Improves insulin resistance
- Minimal benefit to hirsutism c/w COCP
B)
- Hyperandrogenism symptoms only
C)
- Fertility management
Non-pharmacological options for PCOS?
Reduce weight – 1st line treatment
- 5% weight loss helps to restore regular menstrual cycle
- Possibly reduces risk of endometrial cancer
Diet and exercise
- Helps maintain weight
- Reducing risk of T2DM and CV disease
Summary of PCOS
Complex pathophysiology
Troublesome symptoms include hyperandrogenism and irregular menstruation
Long term complications due to insulin resistance and endometrial hyperplasia
Ensure risk factors monitored and modified where able
> diet/exercise play important role
COCP can aid in major issues (regularity, androgenism, risk reduction)
> target insulin resistance with metformin
> target hyperandrogenism with spironolactone
What is premenstrual syndrome?
Cyclical recurrence of symptoms during luteal phase (before menstruation) of menstrual cycle
- Often symptoms dissipate with onset of menses
- Mixture of mood, physical and cognitive symptoms’
> Symptoms usually begin 25-35 years of age
> Can exacerbate other chronic conditions (epilepsy, migraine, asthma)
What is premenstrual dysphoric disorder (PMDD)
Severe PMS
Why are some theories of why PMS occurs?
Pathophysiology not entirely known
> Potentially mediated by progesterone or changes in PG
> Hormonal and central neurotransmitters (esp. serotonin)
> Genetic and family history
How to diagnose PMS/PMDD?
To establish diagnosis, symptoms must be:
- Characteristic of PMS/PMDD
- Limited to luteal phase (often worse few day before menses)
- Impact daily life
- Present for 2 consecutive cycles
- Not explained by other diagnosis
> DSM-5
> Can use GnRH therapy for 3 months diagnostically
Diagnosis of PMS by affective and somatic symptoms
see attahed image
PMS: Sx relieved within 4 days of menses and do not re-occur until day 13 of cycle
PMDD: Sx interfere with daily life and end a few days after menses
How to assess PMS/PMDD?
- Daily symptom diary for 2-3 months
- If symptoms are not cyclical or not in luteal phase consider alternate diagnosis
- If symptoms do not interfere with daily living -> mild PMS
- If symptoms do interfere with daily living -> PMS
What have they tried in the past?
> Anything worked? How long tried for? Including complementary therapies
Any other medical conditions?
> Rule out potential causes – anaemia, hypothyroidism etc
Should there be changes in period in PMS/PMDD?
Should not see any changes in period in PMS/PMDD
What is 1st line treatment for PMS and PMDD?
COCP
- Mixed result – 50% no change, 25% better, 25% worse
- Use continuously – evidence for 168 day cycle
- Consider anti-androgen progestogen if significant fluid retention
- Only COCP to be studied in RCT was ethinylestradiol with drospirenone
SSRI –> fluoxetine and sertraline most commonly used
- Any SSRI can be tried
- Intermittent (2 weeks before menses until day 1-3 of period) just as effective as continuous
- If intermittent not effective switch to continuous
- Drug of choice for PMDD
What is a second line treatment for PMS and PMDD?
Transdermal oestrogen and cyclical progesterone
- estradiol 100microg patch and micronised progesterone 100-200mg PV on day 17-28 of cycle
- may supress ovulation (not guaranteed)
> Non-hormonal contraception required
Higher dose SSRI
When are progestogens used in PMS/PMDD?
Historically used but no evidence to support use
IUD – only to reduce endometrial proliferation
Outline what the following drugs do for PMS/PMDD
A) GnRH agonists
B) Diuretics - spironolactone
C) NSAIDs
D) Complementary therapies
A)
- Effective but not routinely recommended
- Use limited by adverse effects –> BMD loss = 6 months recommended
- Use “add-back” therapy (50-100microg estradiol patch and 100mg micronised progesterone, or tibolone)
> patch less AE than oral route
> add back therapy to help with vasomotor symptoms and BMD
> micronised progesterone = natural, less long term AE
B)
- 25-100mg/day during luteal phase
- Most helpful for fluid retention, bloating, breast tenderness
> monitor electrolyte levels, don’t take potassium
> use effective contraception while taking this drug, can cause feminisation of the male offspring
C)
- Naproxen, mefenamic acid most studied although likely class effect
- May help with physical symptoms
D)
- Chasteberry, vitamin B6
- Ensure adequate calcium intake (1200-1500mg/day)
Non-pharmacological treatment for PMS/PMDD?
> first line
Cognitive behavioural therapy – considered first line
Patient education and symptom diary
> Knowledge can be empowering
Exercise
> Regular aerobic exercise reduces severity of symptoms
Diet
> Sodium restriction if bloating, caffeine reduction if irritable or insomnia
Hysterectomy and bilateral oophorectomy (remove uterus and ovaries) = last line for severe symptoms
> Should trial GnRH agonist first for 3 months
> HRT required if patient <45 years old
> Progesterone makes symptoms worse
Monitoring for PMS and PMDD?
What to follow up
- Symptoms – mood and physical
- Comparison to start of therapy
- Side effects
- Additional therapies
> non-pharmacological
> support from friends/family
Try one agent for 2-4 cycles before switching to alternate therapy
Summary for PMS and PMDD?
Cyclical emotional and physical symptoms corresponding with luteal phase of menstrual cycle
Non-pharmacological treatments should be considered
Mild-moderate PMS treatment
> COCP (consider continuous)
Severe PMS/PMDD if mood symptoms most troublesome
> SSRIs
> Ovulation suppression if nothing else effective
Most optimal period for fertilisation?
5 days before ovulation and 12-24 hours after ovulation
