Menstruation and Menopause Flashcards
How is the menstrual cycle controlled
Release of pituitary gonadotrophins, triggered by the hypothalmus - hypothalamic-pituitary-ovarian (HPO) axis
Also changes in ovarian hormones which are controlled by the HPO
Describe the follicular phase of the menstrual cycle
FSH released from the pituitary and stimulates the ovarian follicle development and the theca cells to secrete oestrogen
The granulosa cells secrete inhibin
The rise in oestrogen levels and inhibin produced by the developing follicles inhibit production of FSH
Fall in FSH cause atresia off all except the main follicle - dominant follicle
This will most likely be the one with the efficient aromatase activity and highest concentration of FSH-induced LH receptors
Describe ovulation
Production of oestrogen increases until it reaches the threshold to exert a positive feedback effort on the hypothalamus and pituitary to cause the LH surge.
The surge of LH from the pituitary triggers ovulation
The dominant follicle ruptures and releases the oocyte - around 12 hours after surge
Describe the luteal phase
The corpus luteum forms from the ruptured follicle - theca and granulosa cells
It starts producing progesterone - starts secretory phase of endometrium
If there is no conception and therefore no BHCG release then 14 days later luteolysis occurs and the corpus luteum breaks down
Describe what happens in the proliferative phase of the endometrium
The endometrial glands and stroma grow under the influence of oestrogen
It changes from a single layer of columnar cells to a pseudostratified epithelium with frequent mitoses.
Describe what happens in the luteal/secretory phase of the endometrium
Glands dilate, grow blood supply and start secreting under influence of progesterone
Decidualisation occurs in the late secretory phase - formation of a specialised glandular epithelium (irreversible)
Apoptosis of this layer occurs if no embryo implantation
Menstruation occurs
What happens to the endometrium during menstruation
The arterioles supplying it constrict and the apoptosed functional layer is shed
This is caused by falling hormone levels
Fibrinolysis inhibits clot and scar formation
What is normally lost during menstruation
Less than 80ml of blood and should be no clots
usually lasts 4-6 days with peak on day 1 or 2
How long is a normal menstrual cycle
The average is 28 days
between 21 and 35 is considered normal
What is meant by flooding
Blood leaking out onto clothes/surroundings when wearing sanitary products
What is menorrhagia
Prolonged and increased menstrual flow - heavy bleeding (>80ml per period)
What is metrorrhagia
Regular intermenstrual bleeding
What is polymenorrhea
Menstruation occurring at <21 day intervals
What is polymenorrhagia
Increased bleeding and a frequent cycle (<21 days)
What is menometrorrhagia
Prolonged menses and intermenstrual bleeding
What is secondary amenorrhea
Absence of menstruation for over 6 months in a woman who previously menstruated
Pregnancy is the most common cause
What is oligomenorrhea
Menses at intervals of over 35 days OR presence of five or fever menstrual cycles over a year.
If there is no organic cause of menorrhagia what is it called
Dysfunctional uterine bleeding
No organic pathology
List some local causes of menorrhagia
Fibroids Endocervical or Endometrial polyp Cervical eversion Endometrial hyperplasia IUD - copper Pelvic inflammatory disease Endometriosis Malignancy of the cervix or uterus Hormone producing tumours Trauma Adenomyosis Arteriovenous malformation
Which age group is endometrial cancer most commonly seen in
Usually only seen in the over 60s
Which age group is more likely to get cervical cancer
Younger women
What causes endometriosis
Ectopic endometrium out with the uterus
Will be under hormonal influence and bleeds each month
Bleeding leads to inflammation and pain
Which endocrine disorders can cause menorrhagia
Hyper/hypothyroidism
Diabetes mellitus
Adrenal disease
Prolactin disorders - more likely to cause amenorrhea
Which drugs can cause menorrhagia
Anticoagulants
When might menorrhagia occur as a result of pregnancy
Miscarriage
Ectopic pregnancy
Gestational trophoblastic disease
Postpartum haemorrhage
What are the two subtypes of dysfunctional uterine bleeding
Anovulatory
Ovulatory
Describe anovulatory dysfunctional uterine bleeding
Makes up 85% of DUB cases
Common in the 2 extremes of age – girls just starting periods and women just before the menopause
More common if obese
Will have an irregular cycle
Describe ovulatory dysfunctional uterine bleeding
Common in women aged 35-45
Will have regular but heavy periods
Caused by inadequate progesterone production by the corpus luteum
How do you investigate dysfunctional uterine bleeding
Full blood count - looking for anaemia Cervical smear - if due TSH Coagulation screen Renal/Liver function tests Transvaginal ultrasound scan - look for thickness of endo and for fibroids etc Endometiral sampling
List some examples of non-surgical management of dysfunctional uterine bleeding
Progestogens- synthetic analogue of progesterone
Combined oral contraceptive pill
GnRH analogues
Anti-fibrinolytics - tranexamic acid; taken during menstruation only
NSAIDs - e.g. mefenamic acid – taken during menstruation only
Mirena IUS
Capillary wall stabilisers
Which type of DUB is well treated with hormonal treatments
Irregular cycles
List some of the surgical managements of DUB
Endometrial ablation - burn the endometrium to reduce blood flow
Endometrial resection
Hysterectomy - sub-total or total
What is a sub-total hysterectomy
You leave the cervix behind and only take top 2/3 of uterus
What is the main contra-indication to surgical treatment of DUB
If someone still wants to have kids
Fertility is lost with both ablation and hysterectomy
Do you still need to have smear tests if you’ve had a sub-total hysterectomy
YES
The cervix is left behind so could still get cancer
What is the average age of menopause
51 years old
Normal from 46-53
What is considered early and premature menopause
Early menopause <45yrs
Premature menopause <40yrs
How do you diagnose menopause
Only diagnoses after a whole year of amenorrhea
Diagnosed based on symptoms and blood tests for FSH
What is considered late menopause
Late menopause >54yrs
What are the physical symptoms of menopause
Hot flushes - 3-5 mins Night sweats Palpitations Insomnia Joint aches Headaches Dry and itchy skin Hair changes Osteoporosis Recurrent UTI or urgency Most women say this is the worst part
Is a single high FSH diagnostic of the menopause
Nope
It is released in a pulsatile fashion so could get false positive
Need multiple measurements at least 2 weeks apart
What are the psychological symptoms of the menopause
Mood swings Irritability Anxiety Tearfullness Difficulty concentrating Forgetfulness
What are the sexual symptoms of the menopause
Vaginal dryness - due to decrease in collagen in the vaginal tissue
Decreased libido
What symptoms can appear late in the menopause
Frequency Recurrent UTIs Dysuria Incontinence Dry hair and skin Atrophy of breast and genitals
Due to a loss of collagen
What conservative management is available for menopausal symptoms
Diet Weight loss Exercise - good for joints, CV risk, bone density CBT - for mood symptoms Fans and avoid spicy food to help sweats
What treatments are available for menorrhagia in the menopause
Mefenamic acid Tranexamic acid Progesterones Intra-uterine system - Mirena is best as works as HRT and contraception Endometrial ablation Hysterectomy
What causes the symptoms of the menopause
The decrease in oestrogen
What are the risks of HRT
HRT increases risk of stroke, heart disease, venous thromboembolism
Also increases risk of breast and endometrial cancer
Why cant you give oestrogen alone as HRT
Could cause endometrial cancer
Can be given to women without a uterus though
What is given in HRT
Give oestrogen alongside progesterone
Can be continuous or sequential (still have a bleed)
Continuous is typically for post-menopausal and cyclical for peri-menopausal who still get periods
A 3rd hormone, testosterone, can be added in cases of reduced libido.
What are the contraindications for HRT
Absolute: Breast cancer Endometrial cancer Pregnancy Active thrombo-embolic disorder Recent Myocardial infarction Active liver disease with abnormal LFT Porphyria cutanea tarda Uncontrolled hypertension Otosclerosis
Relative Undiagnosed abnormal vaginal bleeding Large uterine fibroids Past history of benign breast disease Unconfirmed personal history or a strong family history of VTE Chronic stable liver disease Migraine with aura
How long after the menopause can a women be on HRT
Safe up to 10 years after
What is primary amenorrhea
Failure to menstruate by age 15 years in presence of secondary sexual characteristics
OR
13 years in absence of secondary sexual characteristics
List physiological causes for amenorrhea
The person hasn’t reached puberty
Pregnancy - this is the cause until proven otherwise
Lactation
Menopause
List hypothalamic causes of amenorrhea
Anorexia/bulimia - most common
Excessive exercise
Psychological stress
Idiopathic - hypogonadotropic hypogonadism)
Tumours - craniopharyngiomas, germinomas, gliomas and dermoid cysts)
Cranial irradiation
Head injury
Sarcoidosis
TB
Kallman’s syndrome - genetic syndrome which causes GnRH deficiency
List pituitary causes of amenorrhea
Hyperprolactinaemia - prolactinoma Tumours Sheehan syndrome - damage to the pituitary following serious blood loss at childbirth (O2 deprivation) Cranial irradiation Head injury Sarcoidosis TB
List ovarian causes of amenorrhea
PCOS
Premature ovarian failure - genetic i.e., Turner’s syndrome, XXX, autoimmune, infective, radio/chemotherapy
Congenital adrenal hyperplasia
List outflow obstruction causes of amenorrhea
Cervical stenosis Asherman’s syndrome - adhesions Imperforate hymen Vaginal agenesis Mullerian aplasia (Kokitansky syndrome)- Mullerian ducts fail to develop resulting in absent uterus and variable malformations of the vagina -
Which endocrine disorders can result in amenorrhea
Thyroid disease - hyper or hypo Cushing syndrome Acromegaly (will usually also present with other symptoms) PCOS
Testosterone secreting tumours
Congenital adrenal hyperplasia
Which systematic disorders can result in amenorrhea
Many chronic debilitating disorders
Chronic renal failure
The body basically shuts down so menstruation stops
Which drugs can result in amenorrhea
Oestrogen - COC etc.
Depo-Provera
Dopamine depleting drugs like metoclopramide, phenothiazides
This is because it usually negatively controls prolactin so depletion can cause hyperprolactinaemia
All patients presenting with amenorrhea should be offered which test first
PREGNANCY TEST
When taking a history for amenorrhea what should you focus on
primary and secondary sexual characteristics
Medical conditions
Family history
Drugs - especially contraception,
Diet, exercise and weight change
Stress
Hot/cold flushes (suggest premature menopause)
Galactorrhea (suggests hyperprolactinemia)
Acne/hirsutism (suggest PCOS)
When would you do a visual field examination on a patient presenting with amenorrhea
If you suspect a brain tumour may be the cause
Would so optic disc and visual field exam
When would you do a bimanual examination on a patient presenting with amenorrhea
Only when appropriate
e.g. when you think it may be an outflow obstruction
Which examinations would you do on a patient presenting with amenorrhea
BMI
Examine sexual characteristics and external genitalia
Assessment of hirsutism, acne, galactorrhea
Which hormone levels should be checked in a patient presenting with amenorrhea
HCG - urine and blood
LH, FSH, oestradiol, PRL, testosterone, TSH – these tests help differentiate between hypothalamic, pituitary and ovarian causes
When would you perform a pelvic US in a patient with amenorrhea
If primary amenorrhea or PCOS
When would you perform a CT or MRI pf the head in a patient with amenorrhea
If you suspect hyperprolactinaemia or a brain tumour is the cause
When would you perform a genetic study in a patient with amenorrhea
If they have premature ovarian failure (<40 years old) as this could be a genetic thing
Turner’s or fragile X
When would you perform a hysteroscopy in a patient with amenorrhea
If you suspect Ascherman’s syndrome - pelvic adhesions
When would you perform a DEXA scan in a patient with amenorrhea
If they are found to have premature ovarian failure
This is because they lose the protective effect of oestrogen which can lead to osteoporosis
How do you treat amenorrhea
• Correct underlying cause e.g. surgery to imperforate hymen, dopamine agonist if hyperprolactinaemia
Treat any side effects of cause such as endometrial hyperplasia in PCOS or osteoporosis in POF
Offer fertility treatment if required
A raised PRL and testosterone is suggestive of which cause of amenorrhea
PCOS
A raised FSH and LH is suggestive of which cause of amenorrhea
POF
Requires repeat blood tests to confirm the diagnosis - 4 months apart
What hormonal changes would be seen in a woman going through the menopause
The cessation of oestradiol and progesterone production in the ovaries.
Due to this decrease, FSH and LH levels will often increase.
List symptoms of Turner’s syndrome
Short stature.
Poor pubertal development.
Primary amenorrhoea
Raised FSH and LH
List symptoms of an imperforate hymen
Cyclical abdominal pain
Sometimes urinary retention, constipation, and lower back pain.
A few cases have led to peritonitis due to retrograde menstruation
What is Turner’s syndrome
aAcongenital disease caused by the partial or full absence of the second X chromosome in phenotypically female patients
How would a prolactinoma cause amenorrhea in females
By inhibiting the secretion of GnRH which in turn results in low levels of oestrogen
When is the menstrual cycle at its most irregular
Around the extremes of reproductive life- menarche and menopause
Due to anovulation and inadequate follicular development.
Which part of the menstrual cycle is responsible for the variation in length
The follicular phase - can range from 10-16 days
The luteal phase has a constant duration of 14 days
Which hormone is released by the hypothalamus to influence the menstrual cycle
Gonadotrophin-releasing hormone (GnRH)
Released in a pulsitile fashion
It triggers the pituitary to release FSH and LH
What are ovulation predictor tests looking for
The LH surge
When in the menstrual cycle do progesterone levels peak
7 days before the start of the next menses
This level is used for assessing infertility and checking for ovulation
What triggers the menstrual cycle to restart if there is no pregnancy
A reduction in progesterone, oestrogen and inhibin feeding back to the pituitary cause an increase in gonadotrophin hormones and it starts again
How does haemostasis in the endometrium differ from elsewhere in the body
it does not involve the process of clot formation and fibrosis.
Why do NSAIDs work in the treatment of heavy peroids
They are prostagladin inhibitors so act by increasing the ratio of vasoconstrictor to the vasodilator.
Prostagladins are one of the vasodilators involved
List some systemic disorders which can cause menorrhagia
Endocrine disorders - hyper/hypothyroism, diabetes mellitus, adrenal disease, prolactin disorders
Haematological diseases - Von willebrand’s disease, immune thrombocytopenic purpura (ITP), factor II, V, VII and XI deficiency
Liver disorders – cirrhosis
Renal disease
Drugs – anticoagulants
Which examinations might you perform on a woman with menorrhagia
Look for signs of anemia
Abdominal and pelvic exam - look for masses
Speculum - visualize cervix, take swabs if necessary
Which treatments for DUB are useful if the patient wants to conceive
Antifibrinolytics - tranexamic acid
NSAIDs
Many of the others are contraceptives
List potential causes of intermenstrual bleeding
Cervical ectropion
Pelvic inflammatory disease (PID) and sexually transmitted disease
Endometrial or cervical polyps
Cervical cancer
Endometrial cancer
Undiagnosed pregnancy/ pregnancy complications
Hyatidiform molar disease.
List causes of post-coital bleeding
Cervical ectropion Cervical carcinoma Trauma Atrophic vaginitis Cervicitis secondary to sexual transmitted diseases. Polyps Idiopathic
What is pre-menstrual syndrome
PMS
The occurrence of cyclical somatic, psychological and emotional symptoms that occur in the luteal (premenstrual) phase of the menstrual cycle and resolve by the time menstruation ceases
What are the main features of PMS
Bloating Cyclical weight gain Mastalgia Abdominal cramps Fatigue Headache Depression Changes in appetite and increased craving Irritability
Will occur in a cyclical pattern
How can you treat PMS
Mild symptoms - lifestyle (stress reduction, more exercise etc.)
Severe symptoms - SSRIs
Psychological symptoms - CBT
Medical - COOP, short-term GnRH analogues, transdermal oestrogen
Last resort - hysterectomy with bilateral salpingo-oophorectomy
What causes cervical ectropion
Most often hormonal changes due to high oestrogenic states in pregnancy or use of hormonal contraceptives, especially the combined pill.
List potential causes of post-menstrual bleeding
Atrophic vaginitis Endometrial polyps Endometrial hyperplasia Endometrial carcinoma Cervical carcinoma Ovarian cancer – especially the oestrogen-secreting (theca cell) tumours Vaginal cancer – rare
When is post-menopausal bleeding ‘normal’
If they are on combined cyclical HRT which causes cyclical bleeding during the progesterone free period
How should you investigate PMB
A thorough history and abdominal and pelvic examination
1st line is a TVUS
NICE guidelines state that women over the age of 55 with PMB should be investigated within 2 weeks by ultrasound for endometrial cancer
What is atrophic vaginitis
A benign condition where the epithelium thins and breaks down in response to low oestrogen levels.
What is the most common cause of menstrual irregularity
PCOS
Which features are required for a diagnosis of PCOS
Clinical or biochemical evidence of hyperandrogenism (hirsutism, acne; high free testosterone, low sex hormone binding globulin, high free androgen index respectively)
Polycystic ovaries on ultrasound scan – defined as an increase in ovarian volume to >10cm3, at least 12 follicles in one ovary measuring 2-9mm in diameter.
Oligo/amenorrhea.
List some of the features of PCOS
Obesity/overweight
Hypertension
Acanthosis nigricans (thickening and pigmentation of the skin of the neck, axillae and intertriginous areas)
Acne and hirsutism – due to increased testosterone
Alopecia
There is a link to insulin resistance, diabetes, lipid abnormalities therefore an increased cardiovascular risk.
irregular periods
PCOS increased your risk of which cancer
Increased risk of endometrial hyperplasia and carcinoma
Due to oligo/amenorrhea in the presence of pre-menopausal levels of oestrogen.
How do you manage the acne seen in PCOS
Co-cyrprindol (Dianette) - reduces acne and hirsutism
The COCP
What is dysmenorrhea
Excessive pain during the menstrual period.
What is primary dysmenorrhea
When there is no underlying pelvic pathology
It affects up to 50% of menstruating women and usually appears within 1-2 years of the menarche.
Excessive endometrial prostaglandin production is thought to be partially responsible.
What is secondary dysmenorrhea
Dysmenorrhea which develops many years after the menarche
It is the result of an underlying pathology.
In contrast to primary dysmenorrhoea the pain usually starts 3-4 days before the onset of the period.
What can cause secondary dysmenorrhea
endometriosis adenomyosis Pelvic inflammatory disease Intrauterine devices - copper coil Fibroids – differs in terms of location within the uterus.
What is adenomyosis
Presence of endometrium between the muscle layers of the uterus
Uterus will often appear large and globular.
How do you manage dysmenorrhea
NSAIDs such as mefenamic acid
Combined oral contraceptive pills are used second line
Levonogestrel Intrauterine system (LNG-IUS) – when dysmenorrhea occurs with menorrhagia
GnRH analogues – they are the best to manage symptoms, especially due to fibroids, when awaiting for hysterectomy
List causes of primary amenorrhea
Genital tract abnormalities Mullerian agenesis Premature ovarian failure or insufficiency Genetic disorders Hypothalamic disorders Iatrogenic - chemo or radiation Autoimmune desturction Endocrine causes Pituitary disorders
Which genetic disorders can cause primary amenorrhea
Turner’s syndrome Pure gonadal agenesis Androgen insensitivity syndrome 5-alpha reductase deficiency Kallman’s syndrome - absence or failure of respond to GnRH
Which endocrine disorders can cause primary amenorrhea
Hypothyroidism Constitutional delay Congenital adrenal hyperplasia PCOS Androgen secreting tumour
List causes of secondary amenorrhea
Hypothalamic disorders - stress, weight loss
Autoimmune conditions
Pituitary disorders
Iatrogenic - oophorectomy, radiation, chemotherapy, use of antidopaminergic drugs
Endocrine abnormalities – hypothyroidism/hyperthyroidism, PCOS
Ashermann’s syndrome
Other uterine problems – endometrial atrophy, cervical stenosis from aggressive treatment for cervical cancer.
Physiological causes – lactation, pregnancy.
What is the main medical management for the menopause
Hormone replacement therapy
Oestrogen being the main hormone
Can be given as patches, gel, tablets or implants
How long after starting HRT do women usually see improvement
Usually 4-6 weeks after starting HRT
Get a review at 3 months to assess effectiveness
List oestrogen related side effects of HRT
Breast enlargement, leg cramps, dyspepsia, fluid retention, nausea, headaches
Usually dose-related and settle with time
List progestrogen related side effects of HRT
luid retention, breast tenderness, headaches, acne, mood swings, depression, irritability, constipation, increased appetite
Does HRT act as contraception
No
Women with premature menopause can occasionally ovulate so contraception will be needed for those who are sexually active and don’t wish to conceive
How long after menopause should women continue on contraception
2 years after the last menstrual period in women under 50 and for a year in women over 50
