Menstrual Disorders Flashcards
What is primary amenorrhoea?
Failure to commence menses (absence of menarche):
Girls aged 16+, in the presence of secondary sexual characteristics such as pubic hair growth and breast development
Girls aged 14+, in the absence of secondary sexual characteristics
What is secondary amenorrhoea?
Cessation of periods for more than six months after the menarche (after excluding pregnancy)
What can the causes of primary amenorrhoea be divided into?
Hypothalamic - low GnRH Pituitary Ovarian Genital tract Other
What are the hypothalamic causes of amenorrhoea?
Functional disorders e.g. eating disorders or exercise, suppress GnRH = low oestradiol via ghrelin and leptin
Severe chronic conditions
Kallmann syndrome
What is Kallmann syndrome?
Genetic condition X linked recessive Failure of migration of GnRH cells Leads to hypogonadotrophic hypogonadism Failure to start puberty Absent or reduced sense of smell (anosmia)
What pituitary issues can lead to amenorrhoea?
Prolactinomas - secrete high levels of PL, inhibiting GnRH so no LH and FSH
Other pituitary tumours e.g. acromegaly or cushings, leads to mass effect
Sheehan’s - post partum pituitary necrosis following massive obstetric haemorrhage
Destruction of pituitary gland e.g. radiation, autoimmune
Post contraception can cause irregularities
What ovarian issues can cause amenorrhoea?
PCOS - causes high androgen levels
Turner’s 45 XO
Premature ovarian failure
What are adrenal causes of amenorrhoea?
Congenital adrenal hyperplasia
Androgen insensitivity syndrome - tissues unable to respond to androgen hormones e.g. testosterone
female phenotype
What is congenital adrenal hyperplasia?
Congenital deficiency of 21-hydroxylase enzyme leading to underproduction of cortisol and aldosterone, and overproduction of androgens
Autosomal recessive
Women present - early development of pubic hair, irregular or absent periods
Hirsutism and acne
What are the causes of primary amenorrhoea?
Abnormal functioning of hypothalamus or pituitary
Abnormal functioning of the gonads
Genital tract abnormalities
What genital tract abnormalities can cause amenorrhoea?
Ashermann’s - secondary to instrumentation causes adhesions
Imperforate hymen
Transverse vaginal septum
Mayer Rokitansky Kuster Hauser syndrome - agenesis of Mullerian duct system, congenital absence of uterus and upper two thirds of vagina
What is oligomenorrhoea?
Infrequent
Occurring at intervals greater than 35 days
But less than 6 months in length
What are some of the causes of oligomenorrhoea?
pcos contraception hormonal treatments perimenopause thyroid disease diabetes eating disorders excessive exercise medications e.g. anti-psychotics, anti-epileptics prolactinomas Prader-Willi
What are the investigations for primary amenorrhoea?
Focused. detailed history: when periods began, cycle length, development of secondary sexual characteristics, associated symptoms, past MH, SH, DH
FBC and ferritin - anaemia
U&Es - CKD
Anti TTG or anti EMA coeliac
FSH and LH - low in hypogonadotrophic hypogonadism, high in hypergonadotrophic hypogonadism
TFTs
Insulin like GF I screening for GH deficiency
Prolactin levels - PL raised in hyperprolactinaemia
Testosterone raised in PCOS, androgen insensitivity syndrome and congenital adrenal hyperplasia
Karyotyping if suspect genetic abnormality
Progesterone challenge test to elicit withdrawal bleed or measure serum oestradiol levels
Imaging
XRay of wrist assess bone age; constitutional delay
Pelvic USS
MRI of brain to look for pituitary pathology and assess olfactory bulbs for Kallmans
What is the progesterone challenge test?
Progesterone IM given or provera
If any bleeding more than light spotting occurs after progestin given - withdrawal bleed
Test demonstrates she has built up lining in uterus which is causing the bleed
Therefore oestradiol levels present, demonstrates lack of ovulation causing no periods
If no withdrawal bleed, either very low oestrogen or problem with outflow tract - genital abnormalities
What is the management of primary amenorrhoea?
Establish and treat underlying cause
If needed, replacement hormones
Constitutional delay - reassurance and observation
Reduce stress, CBT, healthy weight gain if due to diet, exercise etc
Optimise treatment for chronic condition e.g. thyroid
Hypogonadotrophic hypogonadism e.g. hypopituitarism or Kallman’s use of pulsatile GnRH or replacement sex hormones using COCP
Ovarian causes - use of COCP
Clomifene stimulates ovulation as a means to treat infertility
Metformin for PCOS to induce ovulation
IVF last resort
Surgery for pituitary tumours, genital tract abnormalities
Refer girls with no sexual characteristics or menstruation at 13, or if have some but no menstruation - 15.
Refer if growth retardation, galactorrhoea, genital tract malformation.
What is hypogonadotrophic hypogonadism?
Due to problems with the hypothalamus or pituitary
Deficiency in release of GnRH = hypothalamic
Deficiency in release of gonadotropins from anterior pituitary = pituitary
GnRH to hypophyseal portal system to gonadotropins in AP to LH and FSH on gonads.
Can be congenital or acquired.
What is hypergonadotropic hypogonadism?
Primary hypogonadism
Impaired response of gonads to gonadotropins FSH and LH
Due to chromosomal abnormalities e.g. Turner’s, Klinefelter’s, resistence
What is Klinefelter’s?
47 XXY
Male has additional X
Infertile, small poorly functioning testicles
Less facial, body hair
Broader hips
Breast tissue
What are the causes of secondary amenorrhoea?
Pregnancy Menopause Premature ovarian failure Hormonal contraception Hypothalamic or pituitary pathology PCOS Asherman's Thyroid pathology Hyperprolactinaemia
What are hypothalamic causes of secondary amenorrhoea?
hypothalamus reduces GnRH production, leads to hypogonadotrophic hypogonadism, amenorrhoea
Excessive exercise Low body weight EDs Chronic disease Psychological stress
What are the pituitary causes of secondary amenorrhoea?
Pituitary tumours e.g. prolactin secreting prolactinoma
Pituitary failure
Trauma, radiotherapy, surgery or Sheehan syndrome
What are the investigations for secondary amenorrhoea?
History and examination
Exclude physiological causes; pregnancy, menopause, lactation
Ask about contraceptives, hot flushes and vaginal dryness, headaches, acne, hirsutism, stress, symptoms of thyroid disease, any obstetric procedures
Examine for features of cushing’s, thyroid disease, excess androgens (hirsutism, acne, deep voice, clitoromegaly) visual fields
Hormonal blood tests
USS pelvis for PCOS
What hormonal tests are available for secondary amenorrhoea?
Beta HCG - pregnancy
LH and FSH:
High FSH primary ovarian failure
High LH or LH:FSH PCOS
PL - hyperprolactinaemia
MRI for pituitary tumour
Causes of raised PL - pituitary adenoma, hypothyroidism drugs e.g. SSRIs, antiemetics
Pregnancy, breast feeding, needle phobia, PCOS, renal impairment
High TSH, low T3/4 hypo
Low TSH, high - hyperthyroid
Raised testosterone in PCOS, androgen insensitivity, congenital adrenal hyperplasia
Why are those with amenorrhoea at risk of osteoporosis?
Low levels of oestrogen
Where amenorrhoea lasts more than 12 months:
Adequate Vit D and calcium
HRT or COCP
What are the causes of high FSH in primary amenorrhoea?
46 XX premature menopause, primary ovarian failure
45 XO Turner’s
What are the causes of low FSH in primary amenorrhoea?
Constitutional delay ED Exercise induced Stress induced Chronic illness
What are the causes of normal FSH in secondary amenorrhoea?
Do pelvic USS
PCOS
Uterine adhesions
What is PMS
Premenstrual syndrome
Occurs during luteal phase and resolve in menstruation
Not present before menarche, during pregnancy, after menopause.
What is the cause of PMS?
Fluctuation in oestrogen and progesterone
May be due to increased sensitivity to progesterone or interaction between sex hormones and serotonin, GABA.
What are the symptoms of PMS?
Low mood, anxiety, mood swings, irritability
Bloating, fatigue, headaches, breast pain
Reduced confidence, cognitive impairment, reduced libido
What is the management of PMS?
General healthy lifestyle Improve diet, exercise, alcohol, smoking, stress, sleep COCP SSRIs CBT
RCOG recommends COCPs containing drospirenone first line e.g. Yasmin
Continuous transdermal oestrogen patches can be used
GnRH analogues to induce menopausal state; but for severe cases, adverse effects e.g. osteoporosis.
Hysterectomy and bilateral oophorectomy if severe and medical management failed, HRT needed.
Danazole and tamoxifen for cyclical breast pain.
Spironolactone for physical symptoms e.g. breast swelling, water retention and bloating.
What is premenstrual dysphoric disorder?
A severe and disabling form of premenstrual syndrome
On average, the symptoms last six days but can start up to two weeks before menses, meaning symptoms can be felt for up to three weeks out of a cycle.
Pattern of mood symptoms (depressed mood, irritability), somatic symptoms (lethargy, joint pain, overeating), or cognitive symptoms (concentration difficulties, forgetfulness)
Treatment - SSRIs e.g. fluoxetine, CBT
If medical management ineffective; oophrectomy, hysterectomy and oestrogen patch to reduce symptoms from surgically caused menopause.
What defines HMB?
More than 80ml blood lost
e.g. changing pads every 1-2 hrs, bleeding lasting more than 7 days, passing large clots.
What are the causes of HMB?
Dysfunctional uterine bleeding (no identifiable cause) Extremes of reproductive age Fibroids, endometriosis, adenomyosis PID (infection) Contraceptives, particularly copper coil Anticoagulant medications Bleeding disorders e.g. VWD Endocrine disorders; diabetes, hypothyroidism Connective tissue disorders Endometrial hyperplasia or cancer PCOS
What should be asked in the history for HMB?
Age at menarche
Cycle length, days menstruating, variation
Intermenstrual bleeding, post coital bleeding
Contraceptive history
Sexual history
Possibility of pregnancy, plans for future pregnancies
Cervical screening history, any treatment
Migraines with or without aura - for the pill
PMH and PDH
Social history, family history
What are the investigations for HMB?
Pelvic examination with speculum and bimanual
Unless straightforward history, or young and not sexually active
FBC check for iron deficiency anaemia
Outpatient hysteroscopy if
suspected submucosal fibroids, suspected endometrial pathology e.g. endometrial hyperplasia or cancer, or persistent intermenstrual bleeding
Pelvic and transvaginal USS if
large fibroids, possible adenomyosis - associated pelvic pain or tenderness on exam, exam hard to interpret e.g. obese, hysteroscopy declined
Swabs if evidence of infection; abnormal discharge or sexual history suggestive
Coagulation screen; history of clotting disorders, VWD, periods heavy since menarche
Ferritin if clinically anaemic
Thyroid function tests if additional features of hypothyroidism
What is the management of heavy menstrual bleeding?
Exclude any underlying pathology, if identified then manage.
Could be due to copper coil, so remove coil.
If does not want contraception, tranexamic acid if no associated pain
Mefenamic acid if there is associated pain
If want contraception - mirena coil first line (IUS)
COCP
Cyclical oral progestogens e.g. norethisterone 5mg 3x daily
POP or depo injection can be tried as suppresses
Referral to specialist if treatment unsuccessful, symptoms are severe or large fibroids present
If medical management failed
Endometrial ablation e.g. balloon thermal ablation
Hysterectomy
How does tranexamic acid work?
Antifibrinolytic so reduces bleeding
Inhibits plasminogen activation
Low incidence of thrombotic disorders
How does mefenamic acid work?
NSAID so reduces bleeding and pain
What is the best way to define HMB?
Impact on QOL plus anaemia Impact on work and social life Bleeding through clothing Bed soiling Disrupted sleep due to heavy bleeding
Any symptoms of anaemia
Who are low risk vs high risk patients with HMB?
Low risk - <45, no IMB, no risk factors for endometrial cancer, will have history, exam and FBC with first line treatment
High risk - >45, IMB, suspected pathology, risk factors for endometrial cancer
Will have history, exam, FBC, USS, hysteroscopy and biopsy, first line treatment.
What medical management is available if fibroids are diagnosed?
GnRH analogues
Esmya - ullipristal acetate
What is the surgical management if polyps are diagnosed?
Myosure
Hysteroscopic removal of polyps
What is the surgical management if fibroids are diagnosed?
Myomectomy for fibroids
Uterine artery embolisation
What short term emergency control of HMB is available?
Norethisterone: 5mg po tds for up to 7 days. Can be used in a 3-weeks-on, 1-week-off pattern for 3-4 months to temporise, for example where patient is on waiting list for treatment.
GnRH analogues: Monthly (or quarterly, depending on preparation) injection to downregulate the cycle and induce temporary ‘medical menopause’. Often used to stop very heavy periods in the presence of fibroids, to allow for correction of anaemia and iron stores in preparation for another intervention.
What are the side effects of tranexamic acid?
nausea, dizziness, tinnitus, rash, abdominal cramps
What are the key causes of intermenstrual bleeding?
Hormonal contraception Cervical ectropion, polyps or cancer Sexually transmitted infection Endometrial polyps or cancer Vaginal pathology, including cancers Pregnancy Ovulation can cause spotting Medications e.g. SSRIs and anticoagulants
What are the causes of dysmenorrhoea?
Primary dysmenorrhoea - no underlying pathology Endometriosis or adenomyosis Fibroids Pelvic inflammatory disease Copper coil Cervical or ovarian cancer
What are the causes of post-coital bleeding?
Cervical cancer, ectropion or infection Trauma Atrophic vaginitis Polyps Endometrial cancer Vaginal cancer
What are the causes of pelvic pain?
UTI Dysmenorrhoea IBS Ovarian cysts Endometriosis Pelvic inflammatory disease Ectopic pregnancy Appendicitis Mittelschmerz Pelvic adhesions Ovarian torsion IBD
What are the causes of vaginal discharge which is abnormal?
Bacterial vaginosis Candidiasis Chlamydia Gonorrhoea Trichomonas vaginalis Foreign body Cervical ectropion Polyps Malignancy Pregnancy Ovulation - cyclical Hormonal contraception
What are the causes of pruritus vulvae?
Itching of the vulva and vagina
Irritants e.g. soaps, detergents, barrier contraception
Atrophic vaginitis
Infections e.g. candidiasis and pubic lice
Skin conditions e.g. eczema
Vulval malignancy
Pregnancy related vaginal discharge
Urinary incontinence or faecal incontinence
Stress
What are the types of dysmenorrhoea?
Primary is menstrual pain occurring with no underlying pelvic pain pathology.
Secondary is pain that occurs with associated pelvic pathology.
What is the pathology of primary dysmenorrhoea?
No fertilisation - corpus luteum regresses, so decline in oestrogen and progesterone.
Endometrial cells sensitive to decline in progesterone and release PGs.
PGs in uterus cause spiral artery vasospasm leading to ischaemic necrosis, and shedding of superficial layer.
Increased myometrial contractions.
So due to excessive release of prostaglandins.
What are the risk factors for primary dysmenorrhoea?
Early menarche Long menstrual phase Heavy periods Smoking Nullparity
What are the clinical features of dysmenorrhoea?
Lower abdominal pain
Pelvic pain, can radiate to lower back or anterior thigh
Pain is crampy, 48-72 hours
Malaise, nausea, vomiting, diarrhoea
Examinations pelvic and speculum usually unremarkable, uterine tenderness present
What are the differentials of secondary dysmenorrhoea?
Endometriosis
Adenomyosis
Pelvic inflammatory disease
Adhesions
Non gynaecological e.g. IBD, IBS
What are the investigations for dysmenorrhoea?
Work up on ruling out pathology
If at risk of STI - high vaginal swab and endocervical swab
If mass palpated, transvaginal US
What is the management of dysmenorrhoea?
Symptomatic improvement
Lifestyle changes; stop smoking
Pharmacological; analgesia with NSAIDs first line, 3-6 month trial of hormonal contraception like COCP or Mirena.
Non-pharmacological
Heat, water bottles, TENS
What are fibroids?
Uterine leiomyoma
Smooth muscle of the uterus
Oestrogen sensitive so they grow in response to oestrogen
What are the types of fibroids?
Intramural within myometrium (muscle of uterus) and distort uterus as they grow.
Subserosal are just below layer of uterus, grow outwards and fill abdominal cavity.
Submucosal below lining of utetus - endometrium.
Pendunculated - on a stalk.
What is the presentation of fibroids?
Often asymptomatic Heavy bleeding Prolonged bleeding more than 7 days Abdominal pain worse in menses Bloating Urinary or bowel symptoms due to pelvic pressure or fullness Deep dyspareunia Reduced fertility
Abdominal and bimanual examination may reveal palpable pelvic mass or enlarged firm non tender uterus.
What are the investigations of fibroids?
Hysteroscopy for submucosal fibroids with HMB.
Pelvic USS for larger fibroids.
MRI scanning before surgical options if need more info on size, shape, blood supply.
Bloods usually reserved for patients where diagnosis is unclear or as pre-operative work up if surgery needed.
What is the management of fibroids?
For those less than 3cm - medical management same as HMB.
Mirena coil first lime - must be less than 3cm and no distortion
Symptomatic management with NSAIDs and tranexamic acid
COCP
Cyclical oral progestogens
GnRH analogues can be used to reduce size prior to surgery e.g. Zolidex
What surgical management is available for smaller fibroids?
Endometrial ablation
Resection of submucosal fibroids during hysteroscopy
Hysterectomy
What management is available for fibroids greater than 3cm?
Referral to gynaecology Symptomatic management with NSAIDs and tranexamic acid Mirena coil COCP Cyclical oral progestogens
What surgical management is available for larger fibroids?
Uterine artery embolisation
Myomectomy
Hysterectomy
How do GnRH analogues work?
Agonists - prolonged activation of GnRH receptors leads to desensitisation and suppressed gonadotropin secretion.
Can induce menopause like state, reduce amount of oestrogen maintaining fibroids,
For fibroids, used short term to shrink before myomectomy.
Also used in endometriosis, menorrhagia, cancer, endometrial hyperplasia.
Can be used for 6 months only, due to risk of osteoporosis.
What are the complications of fibroids?
Heavy menstrual bleeding, iron deficiency anaemia
Reduced fertility
Pregnancy complications e.g. miscarriages, premature labour, obstructive delivery
Constipation
Urinary outflow obstruction
Urinary tract infections
Red degeneration of the fibroid
Torsion of the fibroid - usually pedunculated
Malignant change to leiomyosarcoma
What is red degeneration of fibroids?
Ischaemia, infarction, necrosis of fibroid
Due to disrupted blood supply
More likely in larger fibroids above 5cm, during 2nd and 3rd trimester.
Also if fibroid rapidly enlarges during pregnancy and outgrowing blood supply.
Due to kinking in blood vessels as uterus changes shape and expands in pregnancy.
How does red degeneration of fibroids present?
Severe abdominal pain
Low grade fever
Tachycardia
Vomiting
Look out for pregnant women with history of fibroids, with severe abdominal pain and low grade fever.
What is the management of red degeneration of fibroids?
Supportive; fluids, rest and analgesia.
What are the risk factors of fibroids?
Obesity Early menarche Increasing age Family history - women with first degree affected carry 2.5x increased risk Ethnicity - African Americans 3x more
What are the differentials of fibroids?
Endometrial polyp
Ovarian tumours
Leiomyosarcoma
Adenomyosis - functional endometrial tissue within the myometrium.
What is endometriosis?
Where there is ectopic endometrial tissue outside the uterus.
A lump of endometrial tissue outside uterus is an endometrioma.
What is a “chocolate cyst”?
Endometrioma in the ovaries
Often associated with more severe forms of the disorder.
Tissue is trapped in cavity of cyst, very sticky cyst forms adhesions. Can rupture causing severe sudden abdominal pain.
What is the cause?
Exact cause unknown
One theory - during menstruation the endometrial lining flows backwards through fallopian tubes and into pelvis and peritoneum.
Endometrial tissue seeds around here.
What is the pathophysiology of endometriosis which leads to the symptoms?
Cells of endometrial tissue outside uterus respond to decrease in progesterone.
So during shedding, causes irritation and inflammation around the sites causing cyclical dull heavy or burning pain.
Deposits in endometriosis in bladder or bowel can lead to blood in urine or stools.
Localised bleeding and inflammation leads to adhesions. Leads to chronic pain.
Can lead to reduced fertility.
What is the presentation of endometriosis?
Cyclical abdominal pain, pelvic pain Deep dyspareunia Dysmenorrhoea Infertility Cyclical bleeding from other sites e.g. haematuria
Urinary and bowel symptoms
What may be seen on examination in endometriosis?
Endometrial tissue visible in vagina on speculum examination, esp post fornix
Fixed cervix on bimanual examination
Tenderness in vagina, cervix, adnexa (appendages of the uterus) tenderness in posterior fornix
What are the risk factors of endometriosis?
Early menarche Family history of endometriosis Short menstrual cycle Long duration of menstrual bleeding Heavy menstrual bleeding Defects in the uterus or fallopian tubes
What are the investigations for endometriosis?
Gold standard is laparoscopy, helps differentiate between endometriosis and chronic infection. Find chocolate cysts, adhesions, peritoneal deposits.
Biopsy, and can remove deposits.
Pelvic ultrasound scan
What is the initial management for endometriosis?
Establish diagnosis
Provide clear explanation
Listen to patient, ICE, build rapport
Analgesia - NSAIDs and paracetamol
What hormonal options are available for endometriosis?
Can be tried before definitive diagnosis with laparoscopy.
Hormones can help cyclical pain, stop ovulation and reduce endometrial thickening.
COCP, can be used back to back POP Depo Provera Nexplanon implant Mirena coil GnRH agonists - pain improves after menopause, so can create menopause like state however get menopause symptoms.
What surgical management options are available for endometriosis?
Laparoscopic to excise or ablate endometrial tissue and remove adhesions
Hysterectomy, bilateral salpingo-opherectomy induces menopause, stops ectopic tissue responding to menstrual cycle, last resort.
Consider excision rather than ablation if fertility is not a priority.
What is adenomyosis?
Endometrial tissue inside the myometrium the muscle layer of the uterus.
It is hormone dependent, resolves after menopause.
Who is adenomyosis more common in?
Those in later reproductive years
Multiparous - several pregnancies
Factors causing it include sex hormones, trauma and inflammation.
Can occur alone or alongside endometriosis or fibroids.
What is the presentation of adenomyosis?
Painful periods, heavy periods, dyspareunia
May also have fertility problems or pregnancy related complications.
Examination may demonstrate enlarged and tender uterus, feel more soft than fibroids.
What are the investigations for adenomyosis?
Transvaginal USS of pelvis
MRI and transabdominal US if TVU not available.
Gold standard to perform histological examination of uterus after hysterectomy but obviously not the most appropriate.
What is the management of adenomyosis?
Same treatment as HMB recommended.
If does not want contraception
Symptomatic relief with tranexamic acid if no pain, or mefenamic acid if in pain.
If contraception wanted: mirena coil, COCP or cyclical oral progestogens.
Can consider POP, implant, depot, GnRH analogues, endometrial ablation, uterine artery embolisation, hysterectomy.
What is thought to be the cause of adenomyosis?
When the endometrial stroma is allowed to communicate with the underlying myometrium after uterine damage.
Pregnancy and childbirth
C section
Uterine surgery e.g. endometrial curettage
Surgical management of miscarriage or termination
Most commonly in posterior wall
What are the risk factors for adenomyosis?
High parity
Uterine surgery e.g. any endometrial curettage or ablation
Previous caesarean section
Hereditary occurrence has been reported
How can adenomyosis affect pregnancy?
Infertility Miscarriage Preterm birth Small for gestational age Preterm premature rupture of membranes Malpresentation Need for c section Post partum haemorrhage
What is endometrial hyperplasia?
Abnormal proliferation of endometrium
Risk factor for development of endometrial carcinoma.
What are the types of endometrial hyperplasia?
Hyperplasia without atypia - cytological change
Atypical hyperplasia - considered a premalignant condition, requires histological examination
What are the risk factors of endometrial hyperplasia?
Oestrogen unopposed by progesterone stimulates endometrial cell growth, so any risk factors which cause raised oestrogen levels.
Obesity - androgens converted to oestrogen Exogenous oestrogen Oestrogen secreting ovarian tumour Tamoxifen use PCOS due to anovulation Nulliparity Hereditary non polyposis colorectal carcinoma. Diabetes
Use of combined oral contraceptive decreases risk.
What is the presentation in endometrial hyperplasia?
Abnormal vaginal bleeding
Intermenstrual bleeding, irregular bleeding, menorrhagia or post menopausal bleeding.
There may be vaginal discharge.
What are the investigations for endometrial hyperplasia?
Urgent referral if physical exam identifies ascites or pelvic/abdominal mass not obviously fibroids.
USS suggests ovarian cancer.
Endometrial biopsy using pipelle biopsy
Hysteroscopy and biopsy - curretage
Transvaginal ultrasound but if suspicion high still want to do a biopsy.
2 week wait for women over 55 with postmenopausal bleeding.
What is the management of hyperplasia without atypia?
Reassurance - unlikely to progress to cancer, will return to normal with or without tx.
Address any risk factors, watchful waiting
Progestogen treatment
Follow up
Hysterectomy if change, relapse, patient preference.
What is the management of atypical hyperplasia?
Total hysterectomy advisable due to risk of malignant progression.
Additional salpingo-oophrectomy for post menopausal women.
Women who want to preserve fertility, can use progestogen options with regular monitoring by three monthly endometrial biopsy and advice for hysterectomy when possible.
What is endometritis?
Infection or inflammation of the endometrium - inner lining of uterus.
Acute or chronic, obstetric or non-obstetric making up PID.
What causes endometritis?
Usually 2-3 organisms involved.
Staph or Strep
E Coli, chlamydia trachomatis, gardnerella vaginalis, neisseria
What are the risk factors of obstetric endometritis?
C section, further increased if HIV positive. Prolonged rupture of membranes Severe meconium staining Long labour and multiple examinations Manual removal of placenta Retained products of conception Obesity, diabetes
What are the symptoms of endometritis?
Fever, abdo pain, offensive smelling lochia Abnormal vaginal bleeding PPH Dyspareunia Dysuria General malaise
Temp, pain and uterine tenderness
Tachycardia
What are the investigations for endometritis?
Blood cultures FBC white cell count raised Check midstream urine High vaginal swab Endometrial biopsy rarely appropriate
What is the management of obstetric endometritis?
Antibiotics
If suspect sepsis give piperacillin and tazobactam.
If less severe first line clindamycin and gent.
What is the menopause?
Have not had periods for 12 months
What is postmenopause?
Period from 12 months after the final menstrual period onwards
What is the perimenopause?
Time around the menopause, where the woman may be experiencing vasomotor symptoms and irregular periods
What is the physiology of the menopause?
Decline in development of ovarian follicles
Usually FSH allows growth to secondary follicles, and granulosa cells secrete oestrogen.
Without growth of follicles, there is reduced oestrogen. Has negative feedback on pituitary so less LH and FSH.
In perimenopausal period, there is no negative feedback so FSH and LH are rising.
Anovulation due to failing follicular development means irregular periods, and no oestrogen so no endometrial lining to amenorrhoea.
What are the perimenopausal symptoms?
Hot flushes Emotional lability or low mood Premenstrual syndrome Irregular periods Joint pains Heavier or lighter periods Vaginal dryness and atrophy Reduced libido
What are the risks of a lack of oestrogen?
Cardiovascular disease and stroke
Osteoporosis
Pelvic organ prolapse
Urinary incontinence
When can a diagnosis of menopause be made?
Over 45 years with typical symptoms with investigations.
Consider an FSH blood test in
women under 40 with suspected premature menopause
Women 40-45 with menopausal symptoms or change in menstrual cycle
What contraception should be advised in menopausal women?
Needed 2 years after last menstrual period in under 50s, one year after LMP in over 50s
Use of barrier methods, mirena or copper coil, POP, progesterone implant, depot, sterilisation
These are UKMEC1 no restrictions
COCP UKMEC2 - advantages outweigh risks
Consider norethisterone or levonorgestrel
Can be given up to 50 if no contraindications
Why is the depot provera unsuitable beyond 45 years old?
weight gain and osteoporosis
Due to reduced bone mineral density
How can perimenopausal symptoms be treated?
Vasomotor symptoms likely to resolve 2-5 years without any treatment.
HRT
Tibolone synthetic steroid hormone acts as continuous combined HRT
Clonidine acts as alpha adrenergic agonist and imidazoline agonist - for vasomotor symptoms, flushes
CBT
SSRIs e.g. fluoxetine or citalopram
Testosterone as gel or cream for libido
Vaginal gel or cream for dryness and atrophy
Vaginal moisturisers e.g. Sylk
What is premature ovarian insufficiency?
Menopause before the age of 40
Due to decline of ovaries at an early age
What is the presentation of premature ovarian insufficiency?
Hypergonadotrophic hypogonadism
Underactivity of gonads means lack of negative feedback so excess of gonadotropins, so raised FSH and LH
Low oestradiol
Irregular menstrual periods
Secondary amenorrhoea
Low oestrogen levels - hot flushes, night sweats, vaginal dryness
What are the causes of premature ovarian failure?
Idiopathic
Iatrogenic - chemo, radio, surgery e.g. oophorectomy
Autoimmune - coeliac, adrenal insufficiency, T1DM, thyroid disease
Genetic - FH, Turner’s
Infections - mumps, TB, CMV
How can premature ovarian failure be diagnosed?
Women younger than 40 years with typical menopausal symptoms and elevated FSH.
FSH level needs to be persistently raised >25 IU/I on two consecutive samples separated by more than 4 weeks.
What diseases are associated with premature ovarian failure?
Cardiovascular disease Stroke Osteoporosis Cognitive impairment Dementia Parkinsonism
What is the management of premature ovarian failure?
HRT until at least age when typically go through menopause.
Still risk of pregnancy, need contraception.
Traditional HRT
COCP
HRT before age of 50 will not increase breast cancer, however may be increased risk of VTE which can be reduced with transdermal methods e.g. pathces
What is HRT?
Exogenous oestrogen given to alleviate symptoms
Those that have a uterus need progesterone; prevents endometrial hyperplasia and endometrial cancer secondary to unopposed oestrogen.
Women that still have periods should go on cyclical HRT with cyclical progesterone and breakthrough bleeds.
Postmenopausal women with a uterus, and >12m no periods can have continuous combined HRT.
What non hormonal menopause treatments are there?
Lifestyle changes, improve diet, exercise, weight loss, smoking, reduce alcohol, reduce caffeine, reduce stress.
CBT
Clonidine
SSRIs
Venlafaxine selective serotonin norepinephrine reuptake inhibitor
Gabapentin
What are the common side effects of clomidine?
Dry mouth, headaches, dizziness, fatigue
Sudden withdrawal can result in rapid increases in BP and agitation
What alternative remedies are often used instead of HRT?
Black cohosh - liver damage
Dong quai - bleeding disorders
Red clover - oestrogen effects, oestrogen sensitive cancers
Evening primrose oil - drug interactions, clotting disorders, seizures
Ginseng for mood and sleep benefits
What are the indications for HRT?
Replacing hormones in premature ovarian insufficiency
Reducing vasomotor symptoms e.g. hot flushes, night sweats
Improving symptoms e.g. low mood, decreased libido, poor sleep, joint pain
Reduce risk of osteoporosis in <60
What are the benefits of HRT?
Improved vasomotor and other symptoms
Improved quality of life
Reduced risk of osteoporosis and fractures
What are the risks of HRT?
Only applies to those over 50
No risk of endometrial cancer if no uterus
No increased risk of breast cancer if oestrogen only
No increased CVD risk with oestrogen only
In those under 60, benefits outweigh risks
Increased risk of breast and endometrial cancer
Increased risk of VTE
Increased risk of stroke and coronary artery disease in long term use in older women
Evidence inconclusive for ovarian cancer, risk minimal
How can the risk of endometrial cancer with HRT be reduced?
Adding progesterone if has a uterus
How can the risk of VTE with HRT be reduced?
Patches rather than pills
How can the risk of breast cancer with HRT be reduced?
Use of local progestogens e.g. Mirena than systemic
Same for risk of cardiovascular disease
What are the contraindications to HRT?
Undiagnosed abnormal bleeding Endometrial hyperplasia or cancer Breast cancer Uncontrolled hypertension VTE Liver disease Active angina or MI Pregnancy
What is the assessment before HRT?
Full history ensure no contraindications
Family history to assess risk of oestrogen dependent cancers and VTE
Check BMI and BP
Ensure cervical and breast screening up to date
Encourage lifestyle changes to improve symptoms and reduce risk
How do you choose the HRT formulation?
- local or systemic symptoms
local - topical treatments e.g. cream or tablets
systemic - systemic treatment, step 2 - do they have a uterus
no - oestrogen only HRT
yes - add progesterone - combind HRT - have they had a period in past 12 months
Yes - cyclical combined
postmenopausal - continuous combined HRT
How can oestrogen be delivered in HRT?
Oral
Transdermal - patches or gels
patches more suitable if poor control on oral treatment, higher risk of VTE, CVD and headaches
How can progesterone be delivered in HRT?
Cyclical - 10-14 days per month and then have breakthrough bleed during oestrogen only part.
Continuous for postmenopausal
if not had period in past 24 months if under 50
no period in past 12 months if over 50
can switch from cyclical to continuous after 12 months if over 50, 24 months if under 50, switch during withdrawal bleed.
continuous has better endometrial protection.
Delivery of progesterone for endometrial protection:
Oral as tablets
Transdermal patches
Intrauterine system - mirena coil
What are the types of progesterone in HRT?
Progestogens which are chemicals that target and stimulate progesterone receptors
Progestins are synthetic progestogens
C19 and C21 prescribed in HRT, progestogens.
C19 derived from testosterone, more male in their effects. Helps reduced libido, e.g. norethisterone, levonorgestrel
C21 derived from progesterone, helpful for side effects e.g. low mood, acne
What is an example HRT regimen for someone with no uterus?
Oestrogen only pills e.g. Elleste Solo
Oestrogen only patches e.g. Estradot
What is an example HRT regimen for someone perimenopausal still with periods?
Cyclical combined tablets or patches
Mirena coil plus oestrogen only pills or patches
What is an example of a regimen for a postmenopausal woman with a uterus for HRT?
Continuous combined tablets, continuous combined patches
Mirena coil and oestrogen only pills or patches
What is tibolone?
Synthetic steroid stimulates oestrogen and progesterone receptors, also weakly stimulates androgen receptors.
Helps with reduced libido.
Can be used for continuous combined HRT
How long does it take for HRT to take full effect?
3-6 months
When should oestrogen containing contraceptives or HRT be stopped before surgery?
4 weeks before major surgery
What are the oestrogen side effects of HRT?
Nausea and bloating Breast swelling Breast tenderness Headaches Leg cramps
What are the progesterone side effects of HRT?
Mood swings Bloating Fluid retention Weight gain Acne and greasy skin
What are the characteristic features of PCOS?
Multiple ovarian cysts, infertility
Oligomenorrhoea, hyperandrogenism and insulin resistance
What is the Rotterdam criteria?
Need at least 2 of 3 features
Oligoovulation or anovulation, irregular or absent periods
Hyperandrogenism - hirsutism and acne
Polycystic ovaries on ultrasound, or ovarian volume more than 10cm3
What is the presentation of PCOS?
Oligomenorrhoea or amenorrhoea Infertility Obesity Hirsutism Acne Hair loss in a male pattern
Insulin resistance and diabetes Acanthosis nigricans CVD Hypercholesterolaemia Endometrial hyperplasia and cancer Obstructive sleep apnoea Depression and anxiety Sexual problems
What are the differentials for hirsutism?
Medications e.g. phenytoin, ciclosporin, anabolic steroids
Ovarian or adrenal tumours that secrete androgens
Cushing’s
Congenital adrenal hyperplasia
Why is there insulin resistance in PCOS?
Believed it may play a part in causing PCOS
Pancreas has to produce more insulin, insulin promotes release of androgens from ovaries and adrenal glands.
More insulin means more androgens e.g. testosterone, and suppresses sex hormone binding globulin produced in the liver.
Reduced SHBG leads to hyperandrogenism, as normally it binds to androgens and suppresses their function.
High insulin contributes to halting development of follicles leading to anovulation.
What blood tests are recommended for PCOS?
Testosterone Sex hormone binding globulin Luteinizing hormone FSH Prolactin - may be mildly elevated Thyroid stimulating hormone
What do hormonal blood tests typically show in PCOS?
Raised LH, raised LH:FSH ratio, high LH to FSH
Raised testosterone, raised insulin
Normal or raised oestrogen levels
What imaging is required for PCOS?
Pelvic ultrasound - not reliable in adolescents
Transvaginal ultrasound to visualise the ovaries; follicles arranged around the periphery as string of pearls.
What is the diagnostic criteria to diagnose PCOS from imaging?
12 or more developing follicles in one ovary
Ovarian volume more than 10cm3
What is the screening test for diabetes in PCOS?
2 hour 75g oral glucose tolerance test
Performed in the morning before breakfast
Baseline fasting plasma glucose, 75g glucose drink then measuring plasma glucose 2 hours later.
What is seen in the screening test for diabetes in PCOS?
Impaired fasting glucose of 6.1-6.9mmol before drink
Impaired glucose tolerance - glucose at 7.8-11.1 mmol/l
Diabetes - plasma glucose at 2 hours is above 11.1
What is the general management of PCOS?
Weight loss, calorie-controlled diet low glycaemic index exercise smoking cessation antihypertensive medications where required statins where indicated QRISK >10%
check for endometrial hyperplasia and cancer
infertility
hirsutism, acne, obstructive sleep apnoea
depression and anxiety
orlistat can help with weight loss it is a lipase inhibitor
Why do those with PCOS have an increased risk of endometrial cancer?
Obesity, Diabetes, Insulin resistance, Amenorrhoea are risk factors
Normally corpus luteum releases progesterone after ovulation, but with PCOS do not ovulate. So like unopposed oestrogen, endometrial lining continues to thicken but does not shed - endometrial hyperplasia and risk of cancer.
When do those showing signs of PCOS need to be further investigated?
Extended periods between periods >3 months or abnormal bleeding need pelvic ultrasound.
Cyclical progestogens given to induce a bleed prior to scan. If thickness is then greater than 10mm need biopsy.
What can reduce the risk of endometrial hyperplasia and cancer in PCOS?
Mirena coil for continuous endometrial protection
Inducing withdrawal bleed every 3-4 months with cyclical progestogens or COCP
How can infertility in PCOS be managed?
Weight loss Clomifene Laparoscopic ovarian drilling - diathermy and laser drilling IVF Metformin and letrozole
Need screening with oral glucose tolerance test at 24-28 weeks for gestational diabetes.
How can hirsutism in PCOS be managed?
Weight loss
Hair removal; waxing, shaving, plucking
Laser hair removal
Co-cyprindiol COCP for hirsutism and acne due to anti-androgenic effect, but does increase VTE so usually stopped after 3 months.
Topical eflornithine for facial hirsutism, takes 6-8 weeks
Will return within 2 months if use is stopped
Spironolactone, finasteride, flutamide
How can acne in PCOS be managed?
COCP first line
Co-cyprindiol may be best option
Topical adapalene
Topical antibiotics e.g. clindamycin with benzoyl peroxide
Topical azelaic acid
Oral tetracycline antibiotics
What are endometrial polyps?
Localised outgrowths from surface of endometrium. They appear at any age from the early reproductive years through to the postmenopausal period.
Usually benign lesions but have been implicated in subfertility, as removal of these lesions may improve rates of pregnancy and/or reduce pregnancy loss.
What are the symptoms of endometrial polyps?
Usually asymptomatic
May contribute to abnormal uterine bleeding, manifesting as either intermenstrual bleeding (IMB), HMB or postmenopausal bleeding.
Occasionally, protrusion of the polyp through the cervix may result in PCB.
Attempts by the uterus to expel the polyp may cause colicky, dysmenorrhoeic pain.
How can endometrial polyps be investigated?
Visualised on transvaginal ultrasound
Investigations for abnormal bleeding and infertility
Most easily detected in secretory phase of menstrual cycle when the non-progestational type of glands in the polyp stand out in contrast to the normal surrounding secretory endometrium.
If their presence is suspected either clinically or on transvaginal ultrasound, then can perform a transvaginal sonohysterography or hysteroscopy, with or without directed excisional biopsy.
What is the treatment for endometrial polyps?
Small 1cm or less may resolve asymptomatically
Watchful waiting can be treatment of choice
Surgical removal if women suffering with bleeding or infertility.
Hysterscopic guidance and curettage with or without local anaesthetic.
What are the causes of abnormal uterine bleeding?
Structural lesions (‘PALM’) P olyps (endometrial, endocervical) A denomyosis L eiomyoma (uterine fibroids) M alignancy and hyperplasia
Non-structural causes (‘COEIN’) C oagulopathies Von Willebrand disease Platelet dysfunctions Rare clotting factor deficiencies Thrombocytopenia (low platelets)
O vulatory dysfunction
Anovulatory or disturbed ovulatory cycles (disturbance of oestrogen positive feedback or other ovarian mechanisms)
Polycystic ovary syndrome
Thyroid disease
E ndometrial primary causes
Errors of endometrial molecular pathways affecting local vascular function
I atrogenic
A category including all causes from therapeutic or human interference. This includes AUB side effects of medicinal therapies, drugs or use of devices, e.g. IUCDs.
N ot yet classified
Rare or novel causes which do not immediately or obviously fit into any of the other categories at this time. These may change with new research.
Two examples of such conditions are uterine arteriovenous malformations, which can cause very heavy menstrual bleeding, or the novel diagnosis of ‘isthmocoele’ (the lower segment ‘niche’ frequently found following caesarean section).
What are cervical polyps?
Benign growths protruding from the inner surface of the cervix.
Usually asymptomatic, but some can undergo malignant change.
What causes cervical polyps?
Develop due to focal hyperplasia of the columnar epithelium of the endocervix.
Due to chronic inflammation
Abnormal response to oestrogen - often associated with endometrial hyperplasia
Localised congestion of the cervical vasculature
Most common in multigravidae
Peak incidence between 50 and 60.
What are the clinical features of cervical polyps?
Often asymptomatic, only identified via routine cervical screening.
If symptomatic, usually abnormal vaginal bleeding - menorrhagia, intermenstrual, post-coital or post-menopausal.
Can cause increased vaginal discharge.
Can rarely grow large enough to block cervical canal and cause infertility.
What are the differentials for cervical polyps?
Any causes for abnormal vaginal bleeding including cervical ectropion, cancer, STIs, fibroids, endometritis or pregnancy related bleeding.
In the post-menopausal population exclude endometrial carcinoma.
Could also be an endometrial polyp projecting through the cervical canal.
What are the investigations for a cervical polyp?
Histological examination following removal
other investigations are to exclude alternative causes
Triple swabs if any suggestion of infection e.g. purulent discharge - take endocervical and high vaginal swabs.
Cervical smear to rule out CIN
If bleeding persists after removal, USS to assess endometrial cavity as could be associated endometrial polyps.
What is the management of cervical polyps?
Remove whenever identified as risk of malignant transformation
Small polyps in primary care with polypectomy forceps and polyp is avulsed as it is twisted, should not be pulled off
Larger polyps removed by diathermy loop excision in colposcopy.
All sent for histological examination.
What are the complications of polyp removal?
Infection
Haemorrhage
Uterine perforation
What surgical management is available for HMB?
Endometrial ablation if uterus normal size, fibroids <3
Uterus with large fibroids may need uterine artery embolisation, myomectomy or hysterectomy
What are the techniques for endometrial ablation?
Hysteroscopy performed prior to assess suitability
Transcervical resection of endometrium, wire loop shaves of endometrium
Balloon ablation; balloon filled with heated fluid sits inside uterus for pre-specified length of time to destroy endometrium, cervix dilatation needed
Microwave energy delivered into the endometrial cavity to destroy the endometrium
Bipolar mesh e.g. Novasure
Inserted into uterus, expanded, energy delivered to endometrium
When is endometrial ablation contraindicated?
Those who would like to retain their fertility, or have a diagnosis of endometrial hyperplasia or malignancy
Considered to be less effective in women under 35, where pain is major associated symptom, or uterus is enlarged
What are the complications of endometrial ablation?
Fluid overload Electrolyte disturbances Intraoperative injury Cervical laceration Uterine perforation Bowel or bladder injury Inflammatory response may lead to intrauterine scarring and tissue contraction
What are the types of hysterectomy?
Total - removal of uterus and cervix
Sub-total - removal of body of uterus, leaving cervix behind
Total hysterectomy and bilateral salpingo-oophorectomy - removal of uterus, cervix, fallopian tubes and ovaries.
Radical hysterectomy - removal of uterus and cervix, parametrium, vaginal cuff and part or whole of fallopian tube
What are the indications for a hysterectomy?
Heavy menstrual bleeding
Pelvic pain
Uterine prolapse
Gynaecological malignancy usually ovarian, uterine or cervical
Risk reducing surgery e.g. BRCA1 or BRCA2 or Lynch syndrome
Life saving procedure in management of major PPH
What are the complications of hysterectomy?
Damage to bladder or ureter and long term disturbance to bladder function
Damage to bowel
Haemorrhage requiring blood transfusion
Return to theatre due to bleeding or wound dehiscence
Pelvic abscess or infection
Venous thrombosis or pulmonary embolism
Risk of death within 6 weeks, main causes of death are pulmonary embolism and cardiac disease
What are the causes of a retroverted uterus?
Orientated posteriorly rather than anteverted towards the bladder
Normal variation present from birth Pelvic surgery Pelvic adhesions Endometriosis Fibroids Pelvic inflammatory disease Labour of childbirth
What are the investigations for abnormal uterine bleeding?
Pregnancy test
FBC - check for anaemia
Coagulation profile
Serum TSH - hyperthyroidism or hypothyroidism
Transvaginal ultrasound scan to rule out structural abnormalities e.g. fibroids or adenomyosis
Hysteroscopy - endometrial cavity pathology e.g. polyps, or risk of hyperplasia or malignancy, so also take a biopsy.
