Gynaecology: 1ary & 2ary Amenorrhoea, PMS & Heavy Menstrual Bleeding Flashcards
At what age is 1ary amenorrhoea defined?
Defined as not starting menstruation:
1) By 13 years when there is NO other evidence of pubertal development
2) By 15 years of age where there are other signs of puberty, such as breast bud development
At what age is 1ary amenorrhoea defined when there is NO other evidence of pubertal development?
13 y/o
At what age is 1ary amenorrhoea defined where there are other signs of puberty, such as breast bud development?
15 y/o
What age does puberty start in girls?
8-14
Girls have their pubertal growth spurt earlier in puberty than boys.
What age does puberty start in boys?
9-15
How long does puberty take from start to finish?
Approx 4 years
What does puberty start with the development of in girls?
In girls, puberty starts with the development of breast buds, then pubic hair, and finally menstrual periods about two years from the start of puberty.
How many years from start of puberty do menstrual periods typically begin?
Approx 2 years
Define hypogonadism
Hypogonadism refers to a lack of the sex hormones, oestrogen and testosterone
What happens to the sex hormones before puberty?
Typically rise
How can a lack of sex hormones affect puberty?
Can cause delay
A lack of sex hormones at puberty is fundamentally due to one of what two reasons?
1) Hypogonadotropic hypogonadism –> a deficiency of LH and FSH
2) Hypergonadotropic hypogonadism –> a lack of response to LH and FSH by the gonads (the testes and ovaries)
Define hypogonadotropic hypogonadism
A form of hypogonadism that is due to a problem with the pituitary gland or hypothalamus.
This results in a deficiency of FSH or LH.
I.e. there is a problem with the PITUITARY
Define hypergonadotropic hypogonadism
Results if the gonad itself does not produce the amount of sex steroid sufficient to suppress secretion of LH and FSH at normal levels.
I.e. lack of response to LH and FSH by gonads
There is a problem with the GONADS
What is deficient in hypogonadotropic hypogonadism?
LH and FSH –> this leads to deficiency of sex hormones (oestrogen and testosterone)
What are FSH and LH?
Gonadotrophins
What are FSH and LH produced by?
Anterior pituitary
What are FSH and LH produced in response to?
GnRH (gonadotropin releasing hormone) from the hypothalamus
Result of hypogonadotropism?
Since no gonadotrophins are simulating the ovaries, they do not respond by producing sex hormones (oestrogen).
Therefore, “hypogonadotropism” causes “hypogonadism”.
A deficiency of LH and FSH is the result of abnormal functioning of the hypothalamus or pituitary gland.
Give some causes:
- Hypopituitarism (under production of pituitary hormones)
- Damage to the hypothalamus or pituitary, for example, by radiotherapy or surgery for cancer
- Significant chronic conditions can temporarily delay puberty (e.g. cystic fibrosis or inflammatory bowel disease)
- Excessive exercise or dieting can delay the onset of menstruation in girls
- Constitutional delay in growth and development is a temporary delay in growth and puberty without underlying physical pathology
- Endocrine disorders such as growth hormone deficiency, hypothyroidism, Cushing’s or hyperprolactinaemia
- Kallman syndrome
What is Kallman syndrome?
Kallmann syndrome combines an impaired sense of smell with a hormonal disorder that delays or prevents puberty.
Describe gonadotrophin levels in hypergonadotropic hypogonadism
FSH and LH are high:
1) gonads fail to respond to stimulation from the gonadotrophins (LH and FSH)
2) without negative feedback from the sex hormones (oestrogen), the anterior pituitary produces increasing amounts of LH and FSH
Consequently, you get high gonadotrophins (“hypergonadotropic”) and low sex hormones (“hypogonadism”).
Hypergonadotropic hypogonadism is the result of abnormal functioning of the gonads.
What are some causes of this?
- Previous damage to the gonads (e.g. torsion, cancer or infections such as mumps)
- Congenital absence of the ovaries
- Turner’s syndrome (XO)
Which condition is associated with hypogonadotrophic hypogonadism and anosmia?
Kallman syndrome
What is congenital adrenal hyperplasia?
A congenital deficiency of the 21-hydroxylase enzyme results in underproduction of cortisol and aldosterone, and overproduction of androgens from birth.
Inheritance of congenital adrenal hyperplasia?
Autosomal recessive
What enzyme is deficient in congenital adrenal hyperplasia?
21-hydroxylase enzyme.
Which hormones are UNDERPRODUCED in congenital adrenal hyperplasia?
Cortisol and aldosterone
Which hormones are OVERPRODUCED in congenital adrenal hyperplasia?
Androgens
In severe cases of congenital adrenal hyperplasia, how will the neonate present?
Neonate is unwell shortly after birth, with electrolyte disturbances and hypoglycaemia.
In milder cases, when will congenital adrenal hyperplasia present?
What symptoms?
Female patients can present later in childhood or at puberty with typical features:
- Tall for age
- Facial hair
- Absent periods (1ary amenorrhoea)
- Deep voice
- Early puberty
What is androgen insensitivity syndrome?
A condition where the tissues are unable to respond to androgen hormones (e.g. testosterone), so typical male sexual characteristics do not develop.
How does androgen insensitivity syndrome present?
It results in a female phenotype, other than the internal pelvic organs. 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.
Some structural pathologies may allow for menses but prevent it from escaping through the vagina.
How many this present?
There may be cyclical abdominal pain as menses build up but are unable to escape through the vagina
Structural pathology in the pelvic organs can prevent menstruation.
If the ovaries are unaffected by this pathology, what will happy?
No menstrual periods BUT typicaly 2ary sexual characteristics
Name some structural pathology that can cause 1ary amenorrhoea:
- Imperforate hymen
- Transverse vaginal septae
- Vaginal agenesis
- Absent uterus
- Female genital mutilation
What detailed history & examination should be done in cases of 1ary amenorrhoea?
History:
- General health
- Development
- FH
- Diet & lifestyle
Exam:
- Height
- Weight
- Stage of pubertal development
- Features of any underlying conditions
What is the threshold for initiating investigation for 1ary amenorrhoea?
No evidence of pubertal changes in a girl aged 13.
Investigation can also be considered when there is some evidence of puberty but no progression after two years.
Initial investigations in 1ary amenorrhoea?
1) Full blood count and ferritin –> anaemia
2) U&Es –> chronic kidney disease
3) Anti-TTG or anti-EMA antibodies –> coeliac disease
4) Hormonal blood tests –> hormonal abnormalities
What hormonal blood tests can be done in 1ary amenorrhoea?
- FSH and LH
- TFTs
- Insulin-like growth factor I
- Prolactin
- Testosterone
Describe FSH and LH levels in hypogonadotropic hypogonadism
Low
Describe FSH and LH levels in hypergonadotropic hypogonadism
High
What is Insulin-like growth factor I used as a screening test for?
Growth hormone (GH) levels –> this can affect menstruation
How can prolactin affect menstruation?
Hyperprolactinaemia can cause amenorrhoea
How may testosterone be implicated in 1ary amenorrhoea?
Testosterone is raised in polycystic ovarian syndrome, androgen insensitivity syndrome and congenital adrenal hyperplasia
What genetic condition can result in 1ary amenorrhoea?
Turner’s syndrome (XO)
What imaging may be useful in 1ary amenorrhoea?
1) Xray of the wrist to assess bone age and inform a diagnosis of constitutional delay
2) Pelvic ultrasound to assess the ovaries and other pelvic organs
3) MRI of the brain to look for pituitary pathology and assess the olfactory bulbs in possible Kallman syndrome
Imaging in possible Kallman syndrome?
MRI - assess the olfactory bulbs
Management of 1ary amenorrhoea?
Management of primary amenorrhoea involves establishing and treating the underlying cause.
Where necessary, replacement hormones can induce menstruation and improve symptoms.
Patients with constitutional delay in growth and development may only require reassurance and observation.
Where the cause is due to stress or low body weight secondary to diet and exercise, what is management for 2ary amenorrhoea?
Reduction in stress, cognitive behavioural therapy and healthy weight gain.
In patients with hypogonadotrophic hypogonadism, such as hypopituitarism or Kallman syndrome, what can be used to induce ovulation and menstruation where fertility is wanted?
Pulsatile GnRH can be used to induce ovulation and menstruation.
In patients with hypogonadotrophic hypogonadism, such as hypopituitarism or Kallman syndrome, what can be used to induce ovulation and menstruation where fertility is NOT wanted?
Replacement sex hormones in the form of the COCP may be used to induce regular menstruation and prevent the symptoms of oestrogen deficiency.
In patients with an ovarian cause of amenorrhoea (e.g. polycystic ovarian syndrome, damage to the ovaries or absence of the ovaries), what may be used to induce regular menstruation and prevent the symptoms of oestrogen deficiency?
COCP
define 2ary amenorrhoea
Secondary amenorrhea is defined as no menstruation for more than three months after previous regular menstrual periods.
When should investigations in 2ary amenorrhoea begin?
In regular periods –> Consider assessment and investigation after three to six months
In irregular periods –> After 6-12 months
What is the most common cause of 2ary amenorrhoea
Pregnancy
Give some causes of 2ary amenorrhoea
- 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
How does significant physiological or psychological stress affect periods?
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
Give 2 pituitary causes of 2ary amenorrhoea
1) Pituitary tumours e.g. prolactin-secreting prolactinoma
2) Pituitary failure e.g. due to trauma, radiotherapy, surgery, or Sheehan syndrome
How does hyperprolactinaemia affect hormones?
1) High prolactin levels act on the hypothalamus to PREVENT the release of GnRH.
2) Without GnRH, there is no release of LH and FSH.
3) This causes hypogonadotropic hypogonadism.
Only 30% of women with a high prolactin level will have galactorrhea (breast milk production and secretion).
What is the most common cause of hyperprolactinaemia?
Pituitary adenoma secreting prolactin
In patients with high prolactin levels, what investigation should be done?
CT or MRI scan of brain to assess for pituitary tumour
Often there is a microadenoma that will not appear on the initial scan, and follow up scans are required to identify tumours that may develop later.
Treatment for hyperprolactinaemia?
Often no treatment.
Dopamine agonists such as bromocriptine or cabergoline can be used to reduce prolactin production.
What does assessment of 2ary amenorrhoea involve?
1) Detailed history and examination to assess for potential causes
2) Hormonal blood tests
3) US of pelvis to diagnose PCOS
What hormone tests can be done in 2ary amenorrhoea?
1) hCG –> rule out pregnancy
2) LH and FSH
3) Prolactin (potentially followed by MRI)
4) TSH
5) Testosterone
What does high FSH in 2ary amenorrhoea indicate?
1ary ovarian failure
What does high LH or high LH:FSH ration in 2ary amenorrhoea indicate?
PCOS
In amenorrhoea, what does a raised TSH but low T3/T4 indicate?
Hypothyroidism
In amenorrhoea, what does a low TSH but raised T3/T4 indicate?
Hyperthyroidism
What does a raised testosterone in amenorhoea indicate?
1) PCOS
2) Androgen insensitivity syndrome
3) Congenital adrenal hyperplasia
Management of 2ary amenorrhoea?
1) Establish and treat underlying cause
2) Where necessary, replacement hormones can induce menstruation and improve symptoms.
Management of amenorrhoea in PCOS?
Women with PCOS require a withdrawal bleed every 3-4 months to reduce risk of endometrial hyperplasia and endometrial cancer.
What can be used to stimulate a withdrawal bleed in women with PCOS?
1) Medroxyprogesterone for 14 days
OR
2) Regular use of the COCP
Patients with amenorrhoea associated with low oestrogen levels are at risk of which condition?
Osteoporosis
When do women with amenorrhoea require management to reduce risk of osteoporosis?
> 12 months
What can be given in women with amenorrhoea to reduce risk of osteoporosis?
1) Ensure adequate vitamin D and calcium intake
2) Hormone replacement therapy or the combined oral contraceptive pill
What is premenstrual syndrome (PMS)?
Premenstrual syndrome (PMS) describes the psychological, emotional and physical symptoms that occur during the luteal phase of the menstrual cycle, particularly in the days prior to the onset of menstruation.
What phase of the menstrual cycle does PMS occur?
Luteal phase
When does the luteal phase occur?
From moment of ovulation to start of menstruation (final 14 days)
When do symptoms of PMS resolve?
Once menstruation begins
Symptoms are not present:
a) before menarche
b) during pregnancy
c) after menopause
Cause of PMS?
Fluctuation in oestrogen and progesterone during cycle
Common symptoms of PMS?
- Low mood
- Anxiety
- Mood swings
- Irritability
- Bloating
- Fatigue
- Headaches
- Breast pain
- Reduced confidence
- Cognitive impairment
- Clumsiness
- Reduced libido
Does PMS occur in the absence of menstruation after a hysterectomy, endometrial ablation or on the Mirena coil?
Yes can do as the ovaries continue to function and the hormonal cycle continues.
Can PMS occur in response to the combined contraceptive pill or cyclical hormone replacement therapy containing progesterone?
Yes - described as progesterone-induced premenstrual disorder.
What is premenstrual dysphoric disorder
When features of PMS are severe and have a significant effect on quality of life
How is diagnosis of PMS made?
1) Diagnosis is made based on a symptom diary spannin) WO menstrual cycles.
2) Definitive diagnosis may be made (under specialist) by administering a GnRH analogues to halt the menstrual cycle and temporarily induce menopause, to see if the symptoms resolve.
Management of PMS?
1) General healthy lifestyle changes, such as improving diet, exercise, alcohol, smoking, stress and sleep
2) COCP
3) SSRI antidepressants
4) CBT
5) Symptom management e.g. continuous transdermal oestrogen (patches) –> BUT progesterone also required for endometrial protection (e.g. Mirena coil, cyclical progestogen to trigger withdrawal bleed)
6) GnRH analogues –> induce menopausal state (but only reserved for severe cases e.g. risk of osteoporosis)
7) Hysterectomy and bilateral oophorectomy –> induce menopause where symptoms are severe
COCPs containing what are recommended 1st line in PMS?
Drospirenone (i.e. Yasmin)
Has some antimineralocortioid effects, similar to spironolactone.
What can be given for cyclical breast pain in PMS?
1) Danazole
2) Tamoxifen
What can be used to treat the physical symptoms of PMS, such as breast swelling, water retention and bloating?
Spironolactone
What is menorrhagia?
Heavy menstrual bleeding
How much blood do women lose (on average) during menstruation?
40ml
What ml is defined as exessive menstrual blood loss?
> 80 ml
However, 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
Causes of menorrhagia?
- Dysfunctional uterine bleeding (no identifiable cause)
- Extremes of reproductive age
- Fibroids
- Endometriosis and adenomyosis
- Pelvic inflammatory disease (infection)
- Contraceptives, particularly the copper coil
- Anticoagulant medications
- Bleeding disorders (e.g. Von Willebrand disease)
- Endocrine disorders (diabetes and hypothyroidism)
- Connective tissue disorders
- Endometrial hyperplasia or cancer
- Polycystic ovarian syndrome
Key things to ask about in any presentation with a gynaecological problem?
- Age at menarche
- Cycle length, days menstruating and variation
- Intermenstrual bleeding and post coital bleeding
- Contraceptive history
- Sexual history
- Possibility of pregnancy
- Plans for future pregnancies
- Cervical screening history
- Migraines with or without aura (for the pill)
- Past medical history and past drug history
- Smoking and alcohol history
- Family history
Investigations in menorrhogia?
1) Pelvic examination with a speculum and bimanual should be performed –> to assess for fibroids, ascites and cancers.
2) FBC –> look for iron deficiency anaemia
When should a pelvic exam with speculum and bimanual NOT be performed in menorrhagia?
- Straightforward history heavy menstrual bleeding without other risk factors or symptoms
- Young and not sexually active
When should a hysteroscopy be arranged in menorrhagia?
- Suspected submucosal fibroids
- Suspected endometrial pathology, such as endometrial hyperplasia or cancer
- Persistent intermenstrual bleeding
If large fibroids are thought to possibly be the cause of menorrhagia (i.e. palpable pelvic mass), what investigation can be done?
Pelvic and transvaginal US
What would indicate the need for a a coagulation screenin menorrhagia?
- FH of clotting disorders e.g. vWd
- Periods have been heavy since menarche
If patients are clinically anaemic, what investigaion can be done?
Ferritin
How can the thyroid affect periods?
Hypothyroidism can cause menorrhagia –> consider TFTs
Management of menorrhagia?
1) Exclude or manage underlying pathology e.g. fibroids, anaemia, bleeding disorders, cancer, copper coil
2) Establish whether contraception is required/acceptable
3) Treat accordingly
For women who DONT want contraception, treatment can be used during menstruation for symptomatic relief of menorrhagia.
In menorrhagia with no associated pain, what can be given?
Tranexamic acid
What is tranexamic acid?
Antifibrinolytic - reduces bleeding
For women who DONT want contraception, treatment can be used during menstruation for symptomatic relief of menorrhagia.
In menorrhagia WITH associated pain, what can be given?
Mefenamic acid
What is mefenamic acid?
NSAID - reduces bleeding and pain
1st line management of menorrhagia where contraception IS wanted?
Mirena coil
Management options of menorrhagia when contraception is wanted?
1) Mirena coil (first line)
2) COCP
3) 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)
Final options –> endometrial ablation, hysterectomy
What is endometrial ablation?
Involves destroying the endometrium
Give some causes of abnormal uterine bleeding
Bleeding either coming from: endometrium, cervix, vagina or vulva.
Structural:
- polyps
- adenomyosis
- fibroids
- malignancy & hyperplasia
Non-structural causes:
- infection/inflammation e.g. endometritis
- endometriosis
- coagulopathy e.g. vWd, anticoagulants
- ovulatory dysfunction e.g. PCOS, hypothyroidism
- obesity
- exogenous oestrogen
How may patients with heavy menstrual periods (HMB) present?
- Flooding
- Passage of clots
- Prolonged periods
- Fatigue and shortness of breath (if resulting anaemia)
May have symptoms linked to underlying causes:
- Fibroids: painful periods
- Polyps: IMB, PCB
- Malignancy (e.g. endometrial cancer): IMB, PCB, PMB
- Endometriosis and adenomyosis: pelvic pain
Important areas to cover in history in heavy menstrual bleeding
1) Cycle regularity and establishing if there is any IMB, PCB and PMB
2) PMH: gynaecological history (including smears), co-morbidities, clotting disorders
3) Drug history: anticoagulants, antiplatelets, tamoxifen (a risk factor for endometrial hyperplasia)
4) Contraception: method and plans for future pregnancies as this may influence management
What clincial exams may be relevant in the context of menorrhagia?
1) Speculum
2) Bimanual
3) Vaginal swabs for STIs
4) Assessment for anaemia e.g. conjunctival pallor, iron studies
5) Height, weight and BMI (helpful for identifying PCOS and other causes of anovulation)
Relevant investigations in menorrhagia?
1) Pregnancy test if risk of pregnancy (bleeding does not completely exclude pregnancy)
2) Bloods: FBC, TFTs, coagulation
3) Transvaginal US
4) Interventional:
- hysteroscopy (to assess the endometrial cavity for structural abnormalities and macroscopic appearance)
- endometrial biopsy (to exclude atypical hyperplasia or endometrial malignancy)
Role of transvaginal US in menorrhagia?
Can identify structural causes such as polyps, fibroids and adenomyosis.
Can also assess endometrial thickness – a thickened and heterogeneous appearance may suggest hyperplasia or malignancy.
What is often used as 1st line for heavy menstrual bleeding?
IUS (Mirena coil)
Also manage any iron deficiency anaemia.
2nd line treatment for heavy menstrual bleeding?
- tranexamic acid (antifibrinolytic)
- NSAIDs e.g. mefenamic acid
- COCP
What endometrial thickness is normal in post-menopausal women?
<4mm is normal
> 4mm may indicate hyperplasia/cancer
Why do decreased levels of cortisol & aldosterone cause increased levels of androgens (e.g. in congenital adrenal hyperplasia)?
To compensate for low cortisol levels, the body stimulates the adrenal glands, leading to increased production of androgens.
What is the function of 21-hyroxylase?
This enzyme is found in the adrenal glands, where it plays a role in producing cortisol and aldosterone.
Role of insulin like growth factor for GH?
Insulin-like GF-1 is a hormone that manages the effects of GH in the body.
What does a decreased level of IGF-1 indicate about GH?
If the IGF-1 level is decreased, then it is likely that there is a GH deficiency or an insensitivity to GH.
