Abnormal Vaginal Bleeding Flashcards
Define primary amenorrhoea
- Lack of menstruation by age 16 in the presence of secondary sexual characteristics (or by age 14 in their absence)
If suspecting a physiological delay in onset of menstruation, what can you give to identify this / reassure the patient?
- Progesterone challenge
- Norethisterone for 5 days, and then a withdrawal bleed should occur
Define secondary amenorrhoea
Absence of menstruation for 6 months in the absence of pregnancy
What examination findings might ascertain a cause of amenorrhoea?
- Extremes of BMI
- Presence of secondary characteristics
- Stigmata of endocrinopathies (e.g. thyroid)
- Evidence of virilisation (deep voice, balding, clitoromegaly)
- Abdominal mass (genital tract obstruction)
- Pelvic exam - imperforate hymen, blind ending vaginal septum, absence of cervix and uterus
Name some physiological and iatrogenic causes of amenorrhoea
- Pregnancy
- Breastfeeding (high postpartum levels of prolactin suppress ovulation)
- Menopause
- Contraceptives
- Therapeutic progestogens (such as GnRH analogues)
Name some hypothalamic causes of amenorrhoea
- Stress
- Anorexia
- Excessive exercise
- Pseudocyesis (phantom pregnancy)
- SOL
- Surgery
- Radiotherapy
- Kallman’s syndrome (primary GnRH deficiency)
What anterior pituitary causes would cause amenorrhoea?
- Prolactinoma
- SOL
- Surgery
- Sheehan’s syndrome
What are some ovarian causes of amenorrhoea?
- PCOS
- POI (surgery, viral infection, cytotoxic drugs, radiotherapy)
- Ovarian dysgenesis (Turner’s syndrome 45XO)
- Menopause
What are some genital tract causes of amenorrhoea?
Genital tract outflow obstruction
- Imperforate hymen
- Transverse vaginal septum
- Cervical stenosis
- Asherman’s syndrome
What are some endocrinopathies that can cause amenorrhoea?
- Hyperprolactinaemia
- Cushing’s syndrome
- Hypo/hyperthyroidism
- CAH
Why does primary hypothyroidism cause amenorrhoea?
TSH stimulates prolactin secretion
What investigations can you do for someone with amenorrhoea?
- Pregnancy test
- FSH/LH
- Testosterone
- Prolactin level
- TFTs
- Pelvic ultrasound scan
- Karyotype (if uterus absent or Turner’s expected)
Treatment for amenorrhoea depends on what?
Desire for fertility
Those requiring ovulation usually respond well to an anti-estrogen such as clomifene
What is oligomenorrhoea?
Cycles lasting longer than 32 days (although some sources say 35 days, some say 42 days)
Name some causes of oligomenorrhoea
- PCOS most common
- Borderline low BMI
- Obesity
- Ovarian resistance leading to anovulation
- Milder degrees of hyperprolactinaemia and mild thyroid disease
Once ruled out pathology, and fertility is not desired yet, what is the treatment for oligomenorrhoea?
- CHC or cyclical progestogens
- Minimum of 3 periods a year is recommended to reduce the risk of endometrial hyperplasia due to unopposed estrogen (if not on hormones)
Define primary dysmenorrhoea
- Pain has no obvious cause
- Begins with onset of ovulatory cycles, within first 2 years of menarche
- Pain more severe on the day of menstruation or the day preceding it
- Prostaglandins are involved in the aetiology
If no physical cause is found for primary dysmenorrhoea, what can you give to diagnose?
- Ovulation suppression by tricycling COCP or GnRH analogues for 6-12 months
Name some causes of secondary dysmenorrhoea
- Endometriosis
- Adenomyosis
- PID
- Pelvic adhesions
- Fibroids
- Cervical stenosis
- Asherman’s syndrome
What medications can be given for secondary dysmenorrhoea?
- Mefenamic acid (or ibuprofen / naproxen)
- COCP
- DMPA
- LNG-IUS
What is the cause of HMB in 60% of cases?
Dysfunctional uterine bleeding
Name some benign uterine pathology that causes HMB
- Fibroids (>50% of those with HMB will have fibroids)
- Polyps
- Adenomyosis
- Pelvic infection
What investigations should be done for heavy menstrual bleeding?
- Pregnancy test
- FBC
- Ferritin, TFTs, clotting if clinically indicated
- STI screen
- If under 45, can consider treating first before further investigations
- If over 45, TV USS, pipelle biopsy, hysteroscopy and biopsy
Name some medical treatments for HMB
- LNG IUD (reduction in blood loss by 90%)
- Antifibrinolytics (TXA 1g TDS for 4 days)
- NSAIDs
- COCP
- Oral progestogens are of limited benefit
- DMPA
- GnRH analogues
Describe endometrial ablation
- Destruction of endometrium down to basalis layer
- Microwave (MEA), thermal balloon (thermachoice), novasure (electrical impedance)
- 90% will be significantly improved
- 30% will be amenorrhoeic
- 20% will need a second procedure by 5 years
- Small risk of bleeding, infection, uterine perforation, failed procedure
How does PCOS lead to insulin resistance / hyperinsulinaemia?
- Reduced production of SHBG in the liver
- Testosterone therefore unbound
- Increased androgens stop follicular development and causes anovulation and menstrual disturbance
- Weight gain = insulin resistance and more insulin production
What happens to LH levels in PCOS?
- Elevated due to increased production from anterior pituitary
- Theca cells from ovary produce excess androgens due to hyperinsulinaemia and increased serum levels of LH
- When more LH than FSH, ovaries synthesise androgens rather than estrogens
- Theca cells therefore produce more testosterone
Why do women with PCOS have more estrogen?
- Follicular development stops just short of full maturation
- No ovulation but continued estrogen production
- Continued estrogen unopposed by progestogen causes the endometriuim to become hyperplastic
- Testosterone is also converted to estrogen in peripheral fat tissue
What metabolic problems arise from PCOS?
- Insulin resistance in up to 80% of women
- Independent of obesity but exacerbated by weight gain
- 40% of obese women with PCOS have glucose intolerance of T2DM by end of their 4th decade
- Limited evidence to suggest higher risk of CVD
What pregnancy complications occur from PCOS?
- Infertility
- Gestational diabetes
- 3-4x increased risk of PIH, PET, GDM
- 2x increased risk of premature delivery
- Children of women with PCOS are at increased risk of metabolic and reproductive dysfunction
What are the diagnostic criteria for PCOS?
If two or three of the following features are present
- Infrequent or no ovulation (i.e. menstrual disturbance)
- Clinical and/or biochemical signs of hyperandrogenism (i.e. hirsutism, acne, raised testo levels)
- Polycystic ovaries seen on USS (presence of 12 or more follicles) or increased volume >10mm3
In adolescents, the first two HAVE to be present
Who with PCOS should be offered a glucose tolerance test?
- When planning a pregnancy
- When pregnant
- If BMI >25
- Ethnicities at higher risk of DM
Who might receive insulin-sensitising drugs in PCOS (in a non-fertility setting)?
- Severe oligomenorrhoea or amenorrhoea
- Impaired glucose tolerance
- Low SHBG
Usually not done in primary care
How can you manage the menstrual irregularities of PCOS if fertility is not desired?
- Cyclical progestogens
- COCP
- LNG IUS
A woman with PCOS presents with <1 period every 3 months and has a BMI of 38. What investigation will you do?
- Prescribe a cyclical progestogen (MPA) to induce a withdrawal bleed
- Refer for TV USS to check endometrial thickness
- If >10mm, may need endometrial sample (certainly if <7mm it is unlikely to be hyperplasia)
Who would you refer with hirsutism?
- 2WW if possibility of underlying adrenal/ovarian neoplasm (i.e. rapid new hair growth, signs of virilisation, pelvic or abdominal mass)
- Refer to secondary care if raised testo >4 or elevated 17-hydroxyprogesterone (CAH)
What treatments can be given for hirsutism?
- Topical vaniqua (topical eflornithine)
- CHC containing EE (off-label)
- CHC containing cyproterone acetate (Dianette) is licensed for moderate hirsutism
How do COCs manage hirsutism?
- Reduce hyperandrogenism by suppressing LH secretion
- Reduces ovarian androgen secretion
- Increases production of SHBG
- Reduces free androgen levels
- Cyproterone acetate and drospirenone act as a weak androgen receptor antagonist
Which hormones are more androgenic?
- COCs containing levonorgestrel and norethisterone are more androgenic, but these have less VTE risk
- Progestogens with low androgenicity are norgestimate, desogestrel and gestodene
Describe the treatment of hirsutism with Dianette
- Co-cyprindiol (ethinylestradiol with cyproterone acetate)
- Licensed for severe acne that has not responded to antibacterials
- Licensed for moderate-severe hirsutism
- Risk of VTE is higher
- Shouldn’t be used as a sole contraceptive, but will provide contraceptive cover
- Advise patient of signs/symptoms of VTE
- Discontinue 3 months after acne has been controlled
What happens to LH and FSH throughout the menstrual cycle (and how does it change in PCOS)?
- At beginning of cycle, LH and FSH are usually 5-20mlU/ml
- At LH surge, LH increases to 25-40
- In PCOS, LH will be 2-3x higher than FSH (i.e. LH may be 18 when FSH is 6)
- This will disrupt ovulation
What happens to DHEA-S in PCOS?
- DHEA-S (dehydroepiandrosterone) is another male hormone found in all women
- An androgen secreted by the adrenal gland
- Normal range between 35-430 ug/dl
- PCOS levels will be >200
What happens to prolactin in PCOS?
- It’s usually normal, but is important to check to rule out other causes
- Some PCOS do have a slightly higher prolactin though, between 25-40
How is SHBG difference in PCOS?
- Normal range is 18-144 nmol/L
- May be reduced in PCOS (resulting in more free testo)
What is free androgen index and how are these levels different in PCOS?
- FAI estimates the amount of free testosterone
- Divide total testosterone level by the SHBG = FAI
- Normal levels are 0.18-7% (higher in women >50)
- FAI may be elevated in PCOS
What is the subjective and objective measurement of HMB?
- Subjective: interferes with physical, emotional, social and material quality of life
- Objective: >80ml or prolonged bleeding (>7/7)
What is the FIGO classification of abnormal uterine bleeding?
PALM - COEIN
Structural
- Polyps
- Adenomyosis
- Leiomyoma
- Malignancy and hyperplasia
Nonstructural causes
- Coagulopathy
- Ovulatory dysfunction
- Endometrial
- Iatrogenic
- Not yet classified
What lab tests are recommended by NICE for investigation of HMB?
- FBC for all
- Coagulation if HMB since periods started and personal / family history suggesting coag disorder
- Do not routinely test for ferritin, hormone profile, TFTs (unless other symptoms)
Who does NICE recommend should have an outpatient hysteroscopy?
- Symptoms such as persistent IMB or
- Risk factors for endometrial pathology
(recommended for women with HMB if uterine cavity abnormalities or endometrial pathologies are suspected because it is more accurate than USS and has a low risk of complications)
Who does NICE recommend should have an endometrial biopsy?
- High risk of endometrial pathology
– Persistent IMB or irregular bleeding
– Infrequent HMB who are obese or PCOS
– Tamoxifen
– HMB treatment failure
States endometrial biopsy should only be done in the context of hysteroscopy
What considerations are there for management of HMB?
- Desire for fertility
- Severity of symptoms
- Potential underlying cause
- Acceptability of treatments
- Potential contraindications to treatment
When can LNG IUD be used first line for management of HMB (NICE)
- No identified pathology
- Fibroids <3cm
- Suspected / diagnosed adenomyosis
What pharmacological treatment is there for fibroids >3cm?
Non-hormonal
- TXA
- NSAIDs
Hormonal
- LNG IUD (if no cavity distortion)
- COCP
- Cyclical oral progestogens
- UPA
What are the surgical options for fibroids >3cm?
- Uterine artery embolisation
- Myomectomy
- Hysterectomy
- Can consider endometrial ablation if no distortion of the cavity
When can UPA be used in management of fibroids?
- Intermittent tx of mod-severe symptoms of fibroids (>3cm) in premenopausal women
Only if
- Surgical options not suitable / have tried and failed / declined
- No underlying liver disease
What risks are there with UPA used for fibroid treatment?
- Serious liver injury / failure
- LFTs will need to be done prior to starting, monthly for first 2 courses, and once before each new treatment
What is endometrial hyperplasia?
- Irregular proliferation of endometrial glands with increase in gland:stroma ratio
- Precursor to endometerial cancer
What causes endometrial hyperplasia?
- Unopposed estrogen stimulated endometrial cell growth by binding to estrogen receptors in nuclei of endometrial cells
Name some risk factors for endometrial hyperplasia
- Increased BMI (peripheral conversion of androgens in adipose tissue to estrogen)
- Anovulation
- Estrogen-secreting tumours (e.g. granulosa cell tumours have 40% prevalence of endometrial hyperplasia)
- Drug-induced (estrogen-only HRT without endometrial protection)
- Tamoxifen (long-term)
What is the 2014 WHO classification of endometrial hyperplasia?
- Hyperplasia without atypia
- Atypical hyperplasia
What is the cancer progression risk of hyperplasia without atypia?
-5% risk over 20 years
What is the cancer progression risk of atypical hyperplasia?
- 27.5% after 19 years
- Concomittant cancer in up to 43% undergoing hysterectomy for atypical hyperplasia
If endometrial thickness is 3mm on TVUSS in someone with PMB, what is the probability of cancer?
<1%
What are the pharmacological treatment options for hyperplasia without atypia?
1st line LNG IUD
- Higher regression rate, more favourable bleeding profile, less side effects
Continuous oral progestogen 2nd line
- Medroxyprogesterone 10-20mg/day
- Norethisterone 10-15mg/day
Treat for minimum of 6 months
What is the surveillance schedule for hyperplasia without atypia?
- 6 monthly intervals until 2x consecutive negative biopsies
- If higher risk e.g. BMI >35 or treated with oral progestogens, long-term FU with annual biopsies
When would someone with hyperplasia without atypia require a hysterectomy?
- Progresses to atypical hyperplasia
- No regression after 12 months of treatment
- Relapse / persistent symptoms
- Woman declines endometrial surveillance or medical treatment
What is the management for atypical hyperplasia in someone who is not concerned re. fertility?
- Total hysterectomy due to risk of underlying malignancy or progression to cancer
- +BSO if peri- or post-menopausal
- Consider salpingectomies in pre-menopausal as this may reduce ovarian malignancy risk
What is the management of atypical hyperplasia in someone wishing to preserve fertility?
- MDT discussion with histology, imagine (TVUSS +/- MRI) and tumour markers (Ca 125)
- LNG IUD first line, oral progestogens 2nd line
- 25% live birth rate - refer to fertility specialist, consider assisted reproduction
- Endometrial biopsy every 3 months until 2x negatives, then 6-12 monthly
- Hysterectomy once fertility no longer required
How should you manage someone with endometrial hyperplasia on tamoxifen?
- Routine use of LNG IUD cannot be recommended as uncertain risk of breast cancer recurrence
- Reassess need for tamoxifen if endometrial hyperplasia diagnosed
- MDT with breast team / oncologist
What is Kallmann Syndrome?
- GnRH deficiency with anosmia
- Would present with primary amenorrhoea
- Also low FSH, LH and estradiol
What are streak ovaries?
- Seen with abnormalities / absence of X chromosome (i.e. Turner’s 45XO or triple XXX syndrome)
- ‘streak’ of fibrous tissue where ovaries should be
- Form of aplasia
- Usually removed due to malignant transformation risk
A pregnant woman has a pituitary adenoma, which dopamine agonist can she take?
Bromocriptine
Name some causes of PMB
- Atrophic vaginitis
- Trauma (e.g. pessary)
- HRT
- Endometrial polyp
- Endometrial hyperplasia
- Endometrial carcinoma
- Rarely estrogen secreting tumours (theca and granulosa cell tumours)
What are 75% of endometrial cancers?
Endometrioid adenocarcinoma
Name some complications of having fibroids
- Calcification
- Hyaline degradation
- Red degradation
- Sarcoma change
- Torsion of pedunculated fibroids
- Prolapse of cervical fibroids
What treatment options are there for fibroids in women who wish to conceive?
- UAE
- Myomectomy
What happens during the follicular phase of the menstrual cycle?
- Formation of dominant follicles
- Secrete estrogen ++ which in turn stimulates LH/FSH, until rupture of dominant follicle from the LH surge
What happens during the luteal phase of the menstrual cycle?
- Remnant of ruptured dominant follicle (corpus luteum) produces progesterone
- Negatively inhibits LH
- Makes the endometrium go through secretory phase and growth of spiral arteries
- When estrogen and progesterone fall, the endometrium collapses
How does anorexia, excessive exercise and stress cause amenorrhoea?
- Reduction in GnRH
- Reduction in LH and FSH
Why does breastfeeding cause amenorrhoea?
- Raised prolactin inhibits GnRH production, thereby inhibiting LH and FSH
Why does Asherman syndrome cause amenorrhoea?
- No functional endometrium left
- Scar tissue makes endometrium refractory to hormonal stimulation
What is a submucosal fibroid?
- Extends into the uterine cavity
What is a submural fibroid?
- Within the myometrium / muscular uterine wall
What is a subserosal fibroid?
- Project outside the uterus
