Menstruation and dysmenorrhea Flashcards
Stages of puberty
Breast bud
Pubic hair
menstrual periods
Age of menarche
11-15
Age of menopause
45-55
Normal duration of single cycle
21-35 days
Feedback of oestrogen on HPG axis
Moderate oestrogen: negative feedback
High oestrogen in absence of progesterone: positive feedback
Oestrogen in presence of progesterone: negative feedback
Inhibin selectively inhibits FSH at anterior pituitary
How long is the mature oocyte viable for fertilisation for in the fallopian tube?
24 hours
After how many months of gestation can placenta take over steroid hormone production?
4 months
Follicular phase of menstrual cycle
No negative feedback Increase FSH/LH Increase Follicle growth and O O-> low FSH O-> high GnRH and LH (inhibin inhibits FSH) Day 1-14
Luteal phase of menstrual cycle
Day 14-28 LH surge Oocyte released (ovulation) Corpus luteum (O and P)-> low GnRH Regresses after 14 days
Proliferative phase of uterine cycle
Oestrogen: Fallopian tube formation thickens endometrium increased growth and motility of myometrium thins cervical mucus Alongside follocular phase
Secretory phase of uterine cycle
Progesterone: thickening of endometrium into glandular secretory form thickening of myometrium reduction in motility of myometrium thick acidic cervical mucus
Menses:
Days
Blood loss
2-7 days
10-80ml blood loss
Age of puberty in girls
8-14
Primary amenorrhea causes
Delayed puberty Imperforate hymen, transverse vaginal septum absent vagina mullerian agenesis gonadal dysgensis (Turner's) PCOS CAH
Secondary amenorrhea causes
Pregnancy PCOS premature menopause prolactinoma thyroid disease cushing's ED exercise-induced asherman's syndrome sheehan syndrome
Intermenstrual bleeding causes
Cervical ectropion, polyps or cancer endometrial polyps or cancer vaginal pathology, cancer STI hormonal contraception ovulation pregnancy SSRI, antidepressants
Dysmenorrhea causes
primary dysmenorrhea copper coil cervical/ ovarian cancer fibroids endometriosis PID
menorrhagia cause
dysfunctional uterine bleeding extremes of reproductive age fibroids endometriosis hormonal contraceptives PID anticoagulant medications, bleeding disorders endocrine disorders (DM, hypothyroidism) CT disorders endometrial hyperplasia or cancer PCOS
Post-coital bleeding causes
cervical cancer, ectropion or infection trauma atrophic vaginitis polyps endometrial cancer vaginal cancer
Pelvic pain causes
Urinary tract infection
Dysmenorrhoea (painful periods)
Irritable bowel syndrome (IBS)
Ovarian cysts
Endometriosis
Pelvic inflammatory disease (infection)
Ectopic pregnancy
Appendicitis
Mittelschmerz (cyclical pain during ovulation)
Pelvic adhesions
Ovarian torsion
Inflammatory bowel disease (IBD)
vaginal discharge causes
Bacterial vaginosis
Candidiasis (thrush)
Chlamydia
Gonorrhoea
Trichomonas vaginalis
Foreign body
Cervical ectropion
Polyps
Malignancy
Pregnancy
Ovulation (cyclical)
Hormonal contraception
pruritis vulvae causes
Irritants such as soaps, detergents and barrier contraception
Atrophic vaginitis
Infections such as candidiasis (thrush) and pubic lice
Skin conditions such as eczema
Vulval malignancy
Pregnancy-related vaginal discharge
Urinary or faecal incontinence
Stress
oligomenorrhea features
Infrequent periods
Cycle >35 days but less than 6 months in length
causes of oligomenorrhea
Constitutional:
No pathology
Cycle takes longer to complete
Anovulation: PCOS Thyroid disease Prolactinoma CAH
Primary amenorrhea definition
By 13 years when there is no other evidence of pubertal development
By 15 years of age where there are other signs of puberty, such as breast bud development
No menarche by age 16
hypogonadotropic hypogonadism
hormone levels
deficiency of LH/FSH
deficiecny of sex hormones
hypogonadotrophic hypogonadism causes
hypopituitarism damage to hypothalamus or pituitary CF/ IBD excessive exerice or dieting constitutional delay GH deficiency, hypothyoirism, Cushings, hyperprolactinaemia Kallman syndrome
hypergonadotrophic hypogonadism hormone levels
high LH/FSH
low oestrogen/ sex hormones
hypergonadotrophic hypogonadism causes
previous damage to gonads (torsion, cancer, mumps)
congenital absence of ovaries
Turner’s
Features of congenital adrenal hyperplasia
neonate: unwell shortly after birth, electrolyte disturbance, hypoglycaemia tall for age facial hair absent periods (primary amenorrhea) deep voice early puberty
androgen insensitivity syndrome pathophysiology
tissues unable to respond to androgens
male sexual characteristics dont develop
female phenotype with male genotype and internal pelvic organs
congenital adrenal hyperplasia pathophysiology
congenital deficiency of 21-hydroxylase enzyme
underproduction of cortisol and aldosterone
overproduction of androgens
autosomal recessive
androgen insensitivity syndrome features
Patients have normal female external genitalia and breast tissue.
Internally there are testes in the abdomen or inguinal canal, and an absent uterus, upper vagina, fallopian tubes and ovaries.
Structural causes of primary amenorrhea
Imperforate hymen
Transverse vaginal septae
Vaginal agenesis
Absent uterus
Female genital mutilation
cryptomenorrhea
Haematocolpos
Haematometra
USS: fluid collection at vagina/uterus
Blood cant get out
Imperforate hymen, transverse vaginal septum
All bloods normal
initial investigations for underlying medical conditions causing primary amenorrhea
Full blood count and ferritin for anaemia
U&E for chronic kidney disease
Anti-TTG or anti-EMA antibodies for coeliac disease
Hormonal blood tests assess for hormonal abnormalities in primary amenorrhea
FSH and LH will be low in hypogonadotropic hypogonadism and high in hypergonadotropic hypogonadism
Thyroid function tests
Insulin-like growth factor I is used as a screening test for GH deficiency
Prolactin is raised in hyperprolactinaemia
Testosterone is raised in polycystic ovarian syndrome, androgen insensitivity syndrome and congenital adrenal hyperplasia
genetic testing with a microarray test to assess for underlying genetic conditions in primary amenorrhea
Turner’s syndrome (XO)
imaging in primary amenorrhea
Xray of the wrist to assess bone age and inform a diagnosis of constitutional delay
Pelvic ultrasound to assess the ovaries and other pelvic organs
MRI of the brain to look for pituitary pathology and assess the olfactory bulbs in possible Kallman syndrome
management of primary amenorrhea: stress/ low body weight
Where the cause is due to stress or low body weight secondary to diet and exercise, treatment involves a reduction in stress, cognitive behavioural therapy and healthy weight gain.
Management of hypogonadotrophic hypogonadism
hypopituitarism or Kallman syndrome: treatment with pulsatile GnRH can be used to induce ovulation and menstruation. This has the potential to induce fertility.
Alternatively, where pregnancy is not wanted, replacement sex hormones in the form of the combined contraceptive pill may be used to induce regular menstruation and prevent the symptoms of oestrogen deficiency.
management of primary amenorrhea from PCOS
the combined contraceptive pill may be used to induce regular menstruation and prevent the symptoms of oestrogen deficiency.
Secondary amenorrhea definition
Absent periods for at least 3/12 if cycles previously regular
Absent periods for at least 6/12 if previously had oligomenorrhea
Causes of secondary amenorrhea
Pregnancy is the most common cause
Menopause and premature ovarian failure
Hormonal contraception (e.g. IUS or POP)
Hypothalamic or pituitary pathology
Ovarian causes such as polycystic ovarian syndrome
Uterine pathology such as Asherman’s syndrome
Thyroid pathology
Hyperprolactinaemia
The hypothalamus reduces the production of GnRH in response to significant physiological or psychological stress. This leads to hypogonadotropic hypogonadism and amenorrhoea. The hypothalamus responds this way to prevent pregnancy in situations where the body may not be fit for it, for example:
Excessive exercise (e.g. athletes)
Low body weight and eating disorders
Chronic disease
Psychological stress
Pituitary causes of secondary amenorrhea
Prolactinoma
Pituitary failure: trauma, radiotherapy, surgery, Sheehan syndrome
Investigations for secondary amenorrhea
Hormonal blood tests
Ultrasound of the pelvis to diagnose polycystic ovarian syndrome
Hormone tests for secondary amenorrhea
bHCG to rule out pregnancy High LH:FSH ratio in PCOS Prolactin TSH, T3, T4 Raised testosterone in PCOS, androgen insensitivity, CaH
Management of secondary amenorrhea (PCOS)
It is worth remembering that women with polycystic ovarian syndrome require a withdrawal bleed every 3 – 4 months to reduce the risk of endometrial hyperplasia and endometrial cancer.
Medroxyprogesterone for 14 days, or regular use of the combined oral contraceptive pill, can be used to stimulate a withdrawal bleed.
Menorrhagia features
Heavy menstrual bleeding is also called menorrhagia.
On average, women lose 40 ml of blood during menstruation.
Excessive menstrual blood loss involves more than an 80 ml loss.
The volume of blood loss is
rarely measured in practice. The diagnosis is based on symptoms, such as changing pads every 1 – 2 hours, bleeding lasting more than seven days and passing large clots.
A diagnosis can be made based on a self-report of “very heavy periods”.
Heavy menstrual periods can have a significant impact on quality of life.
causes of menorrhagia
es
Dysfunctional uterine bleeding (no identifiable cause)
Heavy menstrual bleeding with no recognizable pelvic pathology, pregnancy or general bleeding disorders
Extremes of reproductive age
Fibroids
Polyps
Endometriosis and adenomyosis
Pelvic inflammatory disease (infection)
Contraceptives, particularly the copper coil
Anticoagulant medications
Bleeding disorders (e.g. Von Willebrand disease, thrombocytopenia, platelet disorders, coagulation disorders, leukaemia)
Endocrine disorders (diabetes and hypothyroidism)
Liver disease
Connective tissue disorders
Endometrial hyperplasia or cancer
Polycystic ovarian syndrome
low risk patients for menorrhagia
Age <45, no IMB, no risk factors for endometrial cancer
History, examination, FBC
high risk patients for menorrhagia
Age >45, IMB, suspected pathology, risk factors for endometrial cancer
History, examination, FBC, USS, hysteroscopy and biopsy
outpatient hysteroscopy should be arranged if there is:
Suspected submucosal fibroids
Suspected endometrial pathology, such as endometrial hyperplasia or cancer
Persistent intermenstrual bleeding
management of menorrhagia
Tranexamic acid when no associated pain (antifibrinolytic – reduces bleeding)
Mefenamic acid when there is associated pain (NSAID – reduces bleeding and pain)
mefenamic acid mechanism of action in menorrhagia
Inhibits production of PG and inhibits the binding of PGE2 to its receptor
Reduces MBL by 20-44.5%
SE: GI usually mild (50%), dizziness and headaches (20%), deranged liver function, asthma, renal
transexamic acid mechanism for menorrhagia
Inhibits plasminogen activation (inhibit tPA, and uPA), thus reduce fibrinolysis
Reduces MBL by 50%
SE: nausea, dizziness, tinnitus, rash, abdominal cramp
Low incidence of thrombotic disorders
management of menorrhagia when contraception is wanted or acceptable
Mirena coil (first line)
Combined oral contraceptive pill
Cyclical oral progestogens, such as norethisterone 5mg three times daily from day 5 – 26 (although this is associated with progestogenic side effects and an increased risk of venous thromboembolism)
management of menorrhagia when medical management fails
Endometrial ablation involves destroying the endometrium.
The first generation of ablative techniques involved a hysteroscopy and direct destruction of the endometrium.
This has been replaced by second generation, non-hysteroscopic techniques that are safer and faster.
A typical example of one of these techniques involves passing a specially designed balloon into the endometrial cavity and filling it with high-temperature fluid that burns the endometrial lining. This is called balloon thermal ablation.
short-term emergency control of heavy menstrual bleeding
norethisterone
GnRH analogues
short-term emergency control of heavy menstrual bleeding:
norethisterone
5mg PO TDS for up to 7 days
Can be used in a 3 weeks on, 1 week off pattern for 3-4months to temporise
When patient is on waiting list on treatment
short-term emergency control of heavy menstrual bleeding:
GnRH
Monthly 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
Pre-menstrual dysphoric syndrome
Psychological, emotional and physical symptoms that occur during the luteal phase of the menstrual cycle
causes of PMS
Premenstrual syndrome is though to the caused by fluctuation in oestrogen and progesterone hormones during the menstrual cycle.
The exact mechanism is not known, but it may be due to increased sensitivity to progesterone or an interaction between the sex hormones and the neurotransmitters serotonin and GABA.
PMS symptoms
Low mood
Anxiety
Mood swings
Irritability
Bloating
Fatigue
Headaches
Breast pain
Reduced confidence
Cognitive impairment
Clumsiness
Reduced libido
Diagnosis of PMS
Symptom diary spanning two menstrual cycles
cyclical symptoms that occur just before, and resolve after, the onset of menstruation
GnRH analogue to see if symptoms resolve
management of PMS
General healthy lifestyle changes, such as improving diet, exercise, alcohol, smoking, stress and sleep
Combined contraceptive pill (COCP)
SSRI antidepressants
Cognitive behavioural therapy (CBT)
RCOG recommends COCPs containing drospirenone first line (i.e. Yasmin). Drospironone as some antimineralocortioid effects, similar to spironolactone. Continuous use of the pill, as opposed to cyclical use, may be more effective
Severe cases of PMS management
continuous transdermal oestrogen (patches)
norithisterone, Mirena coil
GnRH analogues
Hysterectomy and bilateral oopherectomy to induce menopause
Danazole and tamoxifen for cyclical breast pain
spironolactone for physical symptoms
Progesterone in PMS management
progestogens for endometrial protection against endometrial hyperplasia when using oestrogen
trigger withdrawla bleed
Physiology of menopause
Inside the ovaries, the process of primordial follicles maturing into primary and secondary follicles is always occurring, independent of the menstrual cycle.
At the start of the menstrual cycle, FSH stimulates further development of the secondary follicles.
As the follicles grow, the granulosa cells that surround them secrete increasing amounts of oestrogen.
The process of the menopause begins with a decline in the development of the ovarian follicles. Without the growth of follicles, there is reduced production of oestrogen.
Oestrogen has a negative feedback effect on the pituitary gland, suppressing the quantity of LH and FSH produced.
As the level of oestrogen falls in the perimenopausal period, there is an absence of negative feedback on the pituitary gland, and increasing levels of LH and FSH.
The failing follicular development means ovulation does not occur (anovulation), resulting in irregular menstrual cycles.
Without oestrogen, the endometrium does not develop, leading to a lack of menstruation (amenorrhoea). Lower levels of oestrogen also cause the perimenopausal symptoms.
Symptoms of menopause
Hot flushes
Emotional lability or low mood
Premenstrual syndrome
Irregular periods
Joint pains
Heavier or lighter periods
Vaginal dryness and atrophy
Reduced libido
Night sweats
Anxiety
Some women get spaced, irregular or erratic bleeding before their final period which should be investigated
risk factors for menopause
Cardiovascular disease and stroke
Osteoporosis
Pelvic organ prolapse
Urinary incontinence
diagnosis of menopause
A diagnosis of perimenopause and menopause can be made in women over 45 years with typical symptoms, without performing any investigations.
NICE guidelines (2015) recommend considering an FSH blood test to help with the diagnosis in:
Women under 40 years with suspected premature menopause
Women aged 40 – 45 years with menopausal symptoms or a change in the menstrual cycle
Serum FSH levels are more than 40MIU/ML at least twice 4-6weeks apart
contraception in menopause
Fertility gradually declines after 40 years of age. However, women should still consider themselves fertile. Pregnancy after 40 is associated with increased risks and complications. Women need to use effective contraception for:
Two years after the last menstrual period in women under 50
One year after the last menstrual period in women over 50
Hormonal contraceptives do not affect the menopause, when it occurs or how long it lasts, although they may suppress and mask the symptoms. This can make diagnosing menopause in women on hormonal contraception more difficult.
managemet of perimenopausal symptoms
vasomotor symptoms are likely to resolve after 2-5 years
No treatment
Hormone replacement therapy (HRT)
Tibolone, a synthetic steroid hormone that acts as continuous combined HRT (only after 12 months of amenorrhoea)
Clonidine, which act as agonists of alpha-adrenergic and imidazoline receptors
Cognitive behavioural therapy (CBT)
SSRI antidepressants, such as fluoxetine or citalopram
Testosterone can be used to treat reduced libido (usually as a gel or cream)
Vaginal oestrogen cream or tablets, to help with vaginal dryness and atrophy (can be used alongside systemic HRT)
Vaginal moisturisers, such as Sylk, Replens and YES
natural management of menopause
Exercises
Running, swimming, yoga are highly recommended
Smoking cessation
Reduced alcohol and coffee intake also helps with symptoms of hit flushes and night sweats
Mediterranean style diet
benefits of HRT menopause
Symptomatic women <60 years or <10 years from their menopause
HRT is the most effective treatment for hot flushes and low mood
Decline in sexual function: due to lack of oestrogen and HRT can improve sexual desire and also it reduces vaginal dryness and pain with sex
It prevent osteoporosis, thereby reducing risk of falls and associated fractures
HRT reduces some urinary symptoms and risk of uterine infections particularly when used topical vaginal preparations
side effects of HRT in menopause
Headaches
Breast tenderness
Bloating
Muscle cramps
Irregular bleeding
CVD risk
IHD risk:
stroke
breast cancer
VTE
types of HRT in menopause
Sequential HRT:
Starting within 12 months of the last period to minimise the risk of irregular bleeding patterns
Continuous combined HRT:
Not had a period for 12 months
Women can experience some irregular bleeding in the first 3 months of treatment
Tibolone:
Own class of HRT
Vaginal oestrogen:
Vaginal pessaries or creams can help with vaginal and urinary symptoms
starting HRT in menopause
Transdermal oestrogen including patches and gel (estrador, sandrena)
Micronised progesterone or dydrogesterone or mirena
Transdermal combined HRT like evorel conti
Oral ERT estradiol valerate (zumenon), hormonin (estradiol, estriol, esterone), or conjugated equine esterogen (premarin)
Oral combined HRT including femostan, indiving depends on progestogen component
Non-hormonal treatment options
Bio-identical hormones:
Derived from soy and plant extracts
Modified to be structurally identical to natural body hormones
Not regulated or licensed in the UK
Herbal medicines:
Not regulated by medicine authority
These can react with drugs used for treatment of breast cancer, epilepsy, asthma and heart disease
Some reduce the symptoms of hot flushes and night sweats like St John’s wort, black cohosh, iso-flavones (contained in soya beans)
Vaginal lubricants and moisturiser:
Symptoms of vaginal discomforts can be treated with lubricants such as yes WB
Alternative therapy:
Acuepressure
Acupuncture
Reflexology or homeopathy is limited in managing menopausal symptoms of hot flushes
Likewise, role of aromatherapy is not proven to be beneficial
Psychological treatments:
CBT has proven to elevate the low mood or anxiety related to menopause
medical treatments in menopause
Other medical treatment:
Available on prescription includes clinidine, gabapentin and SSRI for hot flushes
Androgen (testosterone) therapy:
Known reduction in rates of testosterone production from ovary leading to low blood testosterone levels might be associated with a fall in libido or sex drive
Also loss of energy and concentration
Currently this hormone is not available on NHS or treatment for menopausal symptoms
