Amenorrhoea Flashcards
(38 cards)
How do you know if a woman is ovulating?
-Regular menstrual cycle
-Progesterone from corpus luteum (7 days before period so Day 21)
-Serial progesterone testing if irregular (urine): progesterone increases as oestrogen increases
Hormones in control of menstruation
-FSH
-LH
-Prolactin
-Testosterone
-Thyroid
-Oestrogen
Classes of amenorrhoea
-Primary: defined as the failure to establish menstruation by 15 years of age in girls with normal secondary sexual characteristics (such as breast development), or by 13 years of age in girls with no secondary sexual characteristics
=Girls who have not established menstruation within 3 years of the start of breast development (thelarche), or within 5 years if breast budding occurred before the age of 10.
-Secondary: cessation of menstruation for 3-6 months in women with previously normal and regular menses, or 6-12 months in women with previous oligomenorrhoea/ infrequent irregular
Causes of primary amenorrhoea
-Gonadal dysgenesis (e.g. Turner’s syndrome)= the most common causes
-Testicular feminisation
-Congenital malformations of the genital tract
-Functional hypothalamic amenorrhoea (e.g. secondary to anorexia)
-Congenital adrenal hyperplasia
-Imperforate hymen
-Hypogonadotropic hypogonadism
-Hypergonadotropic hypogonadism
Causes of secondary amenorrhoea
-Pregnancy
-Hypothalamic amenorrhoea (e.g. secondary stress, excessive exercise)
-Polycystic ovarian syndrome (PCOS)
-Hyperprolactinaemia
-Premature ovarian failure/ Menopause
-Thyrotoxicosis*
-Sheehan’s syndrome
-Asherman’s syndrome (intrauterine adhesions)
Hypothalamic and pituitary causes of secondary amenorrhoea
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 amenorrhoea include:
Pituitary tumours, such as a prolactin-secreting prolactinoma
Pituitary failure due to trauma, radiotherapy, surgery or Sheehan syndrome
History in primary amenorrhoea
-History of pubertal development, particularly breast development and appearance of pubic hair.
-Sexual history and contraception (to exclude pregnancy or a contraceptive cause of amenorrhoea. Consider the possibility of sexual abuse).
-Cyclical lower abdominal pain (suggesting haematocolpos, caused by a genital tract malformation).
-Stress, depression, weight loss, disturbance of perception of weight or shape, level of exercise, and chronic systemic illness (suggesting hypothalamic dysfunction).
-Headache, visual disturbance, or galactorrhoea (suggesting prolactinoma).
-Anosmia (suggesting Kallman syndrome).
-Past medical history: head injury or infection, medication, surgery, chemotherapy, radiotherapy, or chronic illness.
-Age at menarche of mother and sisters (family history of late menarche suggests constitutional delay of puberty).
-Family history of genetic anomalies (for example, androgen insensitivity [46XY female]).
History in secondary amenorrhoea
-Exclude pregnancy, lactation, menopause
-Contraceptive use (extended-cycle combined oral contraceptives, injectable progesterone, implantable etonogestrel, and levonorgestrel intrauterine systems may cause amenorrhoea).
-Hot flushes and vaginal dryness (suggesting premature ovarian insufficiency [POI] or natural menopause).
-Headaches, visual disturbances, or galactorrhoea (suggesting a pituitary tumour).
-Acne, hirsutism, and weight gain (suggesting polycystic ovary syndrome [PCOS]).
-Stress, depression, weight loss, disturbance of perception of weight or shape, level of exercise, and chronic systemic illness (suggesting hypothalamic dysfunction).
-Symptoms of thyroid and other endocrine disease.
-A history of obstetric or surgical procedures (such as endometrial curettage) that may have resulted in intrauterine adhesions.
-A history of chemotherapy and pelvic radiotherapy (which can cause POI); and cranial radiotherapy, head injury, or major obstetric haemorrhage (which can cause hypopituitarism).
-Drugs (such as antipsychotics, which can cause increased prolactin levels) and illicit drug use (in particular cocaine and opiates, which can cause hypogonadism).
-A family history of cessation of menses before 40 years of age (suggesting POI).
Initial investigations of amenorrhoea
-Exclude pregnancy with urinary or serum bHCG
-Full blood count, urea & electrolytes, coeliac screen, thyroid function tests (TSH)
-Gonadotrophins
=Low levels indicate a hypothalamic cause where as raised levels suggest an ovarian problem (e.g. Premature ovarian failure)
=Raised if gonadal dysgenesis (e.g. Turner’s syndrome)
-Prolactin: >1000 warrant pituitary MRI, drug review
-Androgen levels
=Raised levels may be seen in PCOS, total testosterone if features of androgen excess: androgen insensitivity, CAH, Cushing’s, androgen secreting tumour
-Oestradiol
-Pelvic ultrasound (if the presence of a vagina and uterus cannot be confirmed by physical examination, or in place of a pelvic examination in young girls who are not sexually active).
=If present and normal secondary characteristics: outflow obstruction (imperforate/transverse vaginal septum) or PCOS
=Present with no secondary: Turner’s 46XO, gonadal agenesis 46XX/XY
=Absent/abnormal: androgen insensitivity syndrome
Management of secondary amenorrhoea
-Exclude pregnancy, lactation, and menopause (in women 40 years of age or older)
-Treat the underlying cause
What is hypogonadism?
Hypogonadism refers to a lack of the sex hormones, oestrogen and testosterone, that normally rise before and during puberty. A lack of these hormones causes a delay in puberty. The lack of sex hormones is fundamentally due to one of two reasons:
-Hypogonadotropic hypogonadism: a deficiency of LH and FSH
-Hypergonadotropic hypogonadism: a lack of response to LH and FSH by the gonads (the testes and ovaries)
What is hypogonadotropic hypogonadism?
Hypogonadotropic hypogonadism involves deficiency of LH and FSH, leading to deficiency of the sex hormones (oestrogen). LH and FSH are gonadotrophins produced by the anterior pituitary gland in response to gonadotropin releasing hormone (GnRH) from the hypothalamus. 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.
Causes of hypogonadotropic hypogonadism
-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 hypergonadotropic hypogonadism?
Hypergonadotropic hypogonadism is where the gonads fail to respond to stimulation from the gonadotrophins (LH and FSH). 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
Causes of hypergonadotropic hypogonadism
-Previous damage to the gonads (e.g. torsion, cancer or infections such as mumps)
-Congenital absence of the ovaries
-Turner’s syndrome (XO)
Overview of Kallman syndrome
Kallman syndrome is a genetic condition causing hypogonadotrophic hypogonadism, with failure to start puberty. It is associated with a reduced or absent sense of smell (anosmia).
It is usually inherited as an X-linked recessive trait. Kallmann’s syndrome is thought to be caused by failure of GnRH-secreting neurons to migrate to the hypothalamus.
The clue given in many questions is lack of smell (anosmia) in a boy with delayed puberty.
-Features
‘delayed puberty’
hypogonadism, cryptorchidism
anosmia
sex hormone levels are low
LH, FSH levels are inappropriately low/normal
patients are typically of normal or above-average height
Cleft lip/palate and visual/hearing defects are also seen in some patients
Management
testosterone supplementation
gonadotrophin supplementation may result in sperm production if fertility is desired later in life
Overview of congenital adrenal hyperplasia
-Congenital adrenal hyperplasia is caused by a congenital deficiency of the 21-hydroxylase enzyme. This causes underproduction of cortisol and aldosterone, and overproduction of androgens from birth. The deficiency in cortisol production leads to compensatory overproduction of adrenocorticotropic hormone (ACTH) by the anterior pituitary. Elevated ACTH levels increase the production of adrenal androgens, which can result in the virilization of female infants and affect genital development.
-It is a genetic condition inherited in an autosomal recessive pattern. In a small number of cases, it involves a deficiency of 11-beta-hydroxylase (5%) rather than 21-hydroxylase (90%).
In severe cases, the neonate is unwell shortly after birth, with electrolyte disturbances and hypoglycaemia. In mild cases, female patients can present later in childhood or at puberty with typical features:
=Tall for their age, shorter adult as early epiphyseal closure
=Facial hair
=Absent periods (primary amenorrhoea)
=Deep voice
=Early puberty (precocious)
=Virilisation (female infants present with ambiguous genitalia due to excessive androgen exposure in utero, male appear normal at birth)
=Salt-wasting crisis: dehydration, hypotension, electrolyte imbalance
=Infertility
-Diagnosis: ACTH stimulation testing
-M: glucocorticoid replacement to reduce ACTH, in cases of mineralocorticoid deficiency fludrocortisone is also prescribed
Overview of Androgen Insensitivity syndrome
Androgen insensitivity syndrome is a condition where the tissues are unable to respond to androgen hormones due to lack of androgen receptors (e.g. testosterone), so typical male sexual characteristics do not develop (testicular feminisation syndrome)
-It results in a female phenotype, other than the internal pelvic organs as extra androgens converted into oestrogen. X-linked recessive, mutation to androgen receptor gene on X chromosome. Genetically XY 46XY
-P: 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. The female internal organs do not develop because the testes produce anti-Müllerian hormone, which prevents males from developing an upper vagina, uterus, cervix and fallopian tubes.
The insensitivity to androgens also results in a lack of pubic hair, facial hair and male type muscle development. Patients tend to be slightly taller than the female average. Patients are infertile, and there is an increased risk of testicular cancer unless the testes are removed (undescended testes cause groin swellings). Androgen insensitivity syndrome often presents in infancy with inguinal hernias containing testes. Alternatively, it presents at puberty with primary amenorrhoea.
-I: raised LH, normal/raised FSH, normal/raised testosterone after puberty, raised oestrogen levels. Buccal smear or chromosomal analysis 46XY
-M: Management is coordinated by a specialist MDT, involving paediatrics, gynaecology, urology, endocrinology and clinical psychology. Medical input involves:
Bilateral orchidectomy (removal of the testes) to avoid testicular tumours
Oestrogen therapy
Vaginal dilators or vaginal surgery can be used to create an adequate vaginal length
Generally, patients are raised as female, but this is sensitive and tailored to the individual. They are offered support and counselling to help them understand the condition and promote their psychological, social and sexual wellbeing.
Examples of structural pathology
Structural pathology in the pelvic organs can prevent menstruation. If the ovaries are unaffected, there will be typical secondary sexual characteristics, but no menstrual periods. There may be cyclical abdominal pain as menses build up but are unable to escape through the vagina. Structural pathology that can cause primary amenorrhoea include:
=Imperforate hymen: cyclical pelvic pain and cramping with no vaginal bleeding, retrograde menstruation can lead to endometriosis
=Transverse vaginal septae: imperforate/perforate, surgery complications vaginal stenosis and recurrence
=Vaginal agenesis: failure of Mullerian ducts to develop, dilator
Absent uterus
Female genital mutilation
Primary amenorrhoea assessment
Assessment aims to look for evidence of puberty and to assess for possible underlying causes. The first step is to take a detailed history of their general health, development, family history, diet and lifestyle. Examination is required to assess height, weight, stage of pubertal development and features of any underlying conditions.
The threshold for initiating investigations is 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 assess for underlying medical conditions:
=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:
=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:
=Turner’s syndrome (XO)
-Imaging can be useful:
=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 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, treatment involves a reduction in stress, cognitive behavioural therapy and healthy weight gain.
Where the cause is due to an underlying chronic or endocrine condition, management involves optimising treatment for that condition.
In patients with hypogonadotrophic hypogonadism, such as 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.
In patients with an ovarian cause of amenorrhoea, such as polycystic ovarian syndrome, damage to the ovaries or absence of the ovaries, the combined contraceptive pill may be used to induce regular menstruation and prevent the symptoms of oestrogen deficiency.
-Investigate and treat any underlying cause
-With primary ovarian insufficiency due to gonadal dysgenesis (e.g. Turner’s syndrome) are likely to benefit from hormone replacement therapy (e.g. to prevent osteoporosis etC)
Overview of Hyperprolactinaemia
High prolactin levels act on the hypothalamus to prevent the release of GnRH. Without GnRH, there is no release of LH and FSH. This causes hypogonadotropic hypogonadism. Only 30% of women with a high prolactin level will have galactorrhea (breast milk production and secretion).
The most common cause of hyperprolactinaemia is a pituitary adenoma secreting prolactin. Where there are high prolactin levels, a CT or MRI scan of the brain is used to assess for a 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.
Often no treatment is required for hyperprolactinaemia. Dopamine agonists such as bromocriptine or cabergoline can be used to reduce prolactin production. These medications treat hyperprolactinaemia, Parkinson’s disease and acromegaly.
Hormone tests in secondary amenorrhoea
Beta human chorionic gonadotropin (HCG) urine or blood tests are required to diagnose or rule out pregnancy.
Luteinising hormone and follicle-stimulating hormone:
=High FSH suggests primary ovarian failure
=High LH, or LH:FSH ratio, suggests polycystic ovarian syndrome
-Prolactin can be measured to assess for hyperprolactinaemia, followed by an MRI to identify a pituitary tumour.
-Thyroid stimulating hormone (TSH) can screen for thyroid pathology. This is followed by T3 and T4 when the TSH is abnormal.
=Raise TSH and low T3 and T4 indicate hypothyroidism
=Low TSH and raised T3 and T4 indicate hyperthyroidism
-Raise testosterone indicates polycystic ovarian syndrome, androgen insensitivity syndrome or congenital adrenal hyperplasia.
Presentation of PCOS
-5-20% women
-Oligomenorrhoea or amenorrhoea
-Infertility/sub
-Obesity (in about 70% of patients with PCOS)
-Hirsutism
-Acne
-Hair loss in a male pattern
-Insulin resistance and diabetes
-Acanthosis nigricans
-Cardiovascular disease
-Hypercholesterolaemia
-Endometrial hyperplasia and cancer
-Obstructive sleep apnoea
-Depression and anxiety
-Sexual problems
