Female reproductive physiology, amenorrhoea and premature ovarian failure Flashcards
What are the 2 phases of the menstrual cycle
Follicular (onset of mess and ends on the day of LH surge
Luteal (begins on the day of the LH surge and ends at the onset of the next menses
How long is the average adult menstrual cycle
28 days - 15 days in each phase
What is the first day of the cycle
the first day of menses
What are longer menstrual cycles normally associated with
anovulation
In terms of oocytes, what happens during each normal menstrual cycle
a single mature oocyte is released from a pool of hundred of thousands of primordial oocytes
What hormone levels are low during the follicular stage
serum oestradiol and progesterone
What does a low serum estradiol and progesterone result in
Negative feedback which results in increased GnRH pulse frequency
What is the effect of an increased GnRH pulse frequency
Increases serum FSH levels and LH pulse frequency
What does the increase in FSH stimulate
the recruitment and growth of a cohort of ovarian follicles
What do ovarian follicles consist of
oocytes surrounded by granulosa cells and theca cells
What enzyme does FSH stimulate
Aromatase (in the granulosa cells of the dominant follicle)
What is the function of aromatase
It converts androgens (synthesised in the theca cells) to oestrogen
What does the increase in estradiol production initially do
suppresses serum FSH and LH levels
What else plays a role in suppressing FSH
Serum inhibin B
What happens to the rest of the growing follicles
They undergo atresia after a single dominant follicle is selected
How does the LH surge arise
The negative feedback effect of ovarian steroids (particularly oestradiol) switches to a positive feedback effect
What is the LH surge associated with
an increased frequency of FnRH secretion and enhanced pituitary sensitivity to GnRH
What happens to estradiol secretion just before ovulation
It reaches a peak and then falls
How long does it take for the oocyte to be released following the LH surge
36 hours
What do the granulosa cells begin to produce and what do they develop into post oocyte release
Progesterone
Corpus luteum
What starts to rise towards the end of the luteal phase and why
FSH starts to rise to stimulate the development of the next follicle usually in the contralateral ovary.
This occurs due to the progesterone and oestrogen levels falling
Describe the levels of Inhibin A during the menstrual cycle
Low in the follicular phase and increased in the luteal phase
What happens to the corpus luteum and progesterone production if the oocyte becomes fertilised
The corpus luteum is maintained and progesterone production is also maintained
What is the effect of the serum estradiol concentrations during the follicular phase on the endometrium
Proliferation of the uterine endometrium and glandular growth occurs
What happens to the arterioles supplying the endometrium as the function of the corpus luteum declines
The arterioles undergo vasospasm (caused by locally synthesised protaglandins) causing ischaemic necrosis, endometrial desquamation (shedding) and bleeding
What is the principal and most potent oestrogen secreted by the ovary
Oestradiol
What do oestrogens promote
Development of secondary sexual characteristics (breast development etc.)
cause uterine growth
play an important role in regulation of menstrual cycle
How do oestrogens act
They bind to a nuclear receptor which binds to specific DNA sequences and regulates the transcription of various genes
What is the principle hormone secreted by the corpus luteum
Progesterone
What is progesterone responsible for
Pro gestational effects - including induction of secretory activity in the endometrium in preparation for the implantaion of a fertilised egg
Inhibition of uterine contractions
increased viscosity of cervical mucus
glandular development of the breasts
Describe the change in temperature during the menstrual cycle
It increased by 0.3-0.5 degrees after ovulation and persists during the luteal phase and returns to normal after the onset of menses
What is inhibit
a glycoprotein consisting of two disulphide-linked subunits, alpha and beta
Why are there two forms of inhibit
The beta subunit can exist in 2 forms
Where is inhibin B secreted and what is its function
secreted by the follicle and inhibits the release of FSH from he pituitary
Where is inhibin A secreted and what is its function
Secreted by the Corpus luteum of the last cycle
levels are low in follicular phase and increased i the luteal phase
What is amenorrhoea
the absence of menstrual periods in a woman during her reproductive year
It can be primary or secondary
What is primary amenorrhoea
The absence of menstrual periods by age 14 in a girls without breast development or by age 16 in a girl with breast development
What is secondary amenorrhoea
The absence of menstrual periods for more than 3 months in a woman who has previously had an established menstrual cycle
What has a higher incidence, primary or secondary amenorrhoea
Secondary
What are some of the causes of amenorrhoea
Functional - street, weight loss, excessive exercise, eating disorders
Pituitary and hypothalamic tumours - adenomas, craniopharyngiomas, haemochromatosis
Hyperprolactinomas - cause pituitary stalk compression
Kallmann’s syndrome
Premature ovarian failure - chromosomal abnormalities, autoimmune, iatrogenic,
Uterine and vaginal outflow - congenital anatomical abnormalities
Thyroid dysfunction - Hypothyroidism or thyrotoxicosis
Hyperandrogenism- congenital adrenal hyperplasia, PCOS
Imperforate hymen
transverse vaginal septum between the cervix and the hymenal ring (prevents the egress o menses)
Amenorrhoea may be due to a defect at what levels
Hypothalamus Pituitary Ovaries Uterus Vaginal outflow tract
What is functional hypothalamic amenorrhoea characterised by
abnormal hypothalamic GnRH secretion, resulting in decreased gonadotrophin pulsations
What might pituitary/ hypothalamic tumours cause
hypogonadotrophic hypogonadism and amenorrhoea
What does hypoerprolactinaemia do
It can interrupt the transport of dopamine to the anterior pituitary which normally exerts an inhibitory effect on prolactin secretion
What is Kallmann’s syndrome
Patients have congenital GnRH deficiency associated with anosmia
How can congenital GnRH be inherited
Autosomal dominant
autosomal recessive or
X linked
What is premature ovarian failure
Primary hypogonadism (lack of folliculogenesis and ovarian oestrogen production) before the age of 40
What do the largest number of patients with primary amenorrhoea and ovarian failure have
turner’s syndrome
What might acquired ovarian faker be cdue to
chemotherapy
radiotherapy
Autoimmune
What is Mullein agenesis characterised by
congenital absence of the vagina with variable uterine development
What is the most common cause of primary amenorrhoea with excess androgen production
congenital adrenal hypoerplasia (CAH)
What does PCOS have a strong association with
insulin resistnace
What are the features of Turner’s syndrome
lack of secondary sexual characteristics
short stature
widely spaced nipples
low posterior hairline
High arched palate, wide carrying angle, short 4th and 5th metacarpals
Cardio - congenital lymphoedema, aortic dissection, cortication of the aorta, hypertension
GI: angiodysplasia, coeliac disease
Renal: horseshoe kidneys, abnormal vascular supply
Endocrine: increased risk of hypothyroidism and Diabetes mellitus
What are some areas to ask the patient about when presenting with amenorrhoea
Change in weight, stress, excessive dieting, exercise or illness
Drugs - contraceptive pill
Hypothalamic-pituitary disease e.g. headaches, visual field defects, fatigue, polyuria or polydipsia
Galactorrhoea (suggestive of hyperprolactinaemia
Symptoms of oestrogen deficiency e.g. hot flush, dry vagina, poor sleep or reduced libido
Hirsutism, acne or deepening of the voice
Hx of lower abdominal pain at the time of expected menses
History of dilatation and curettage or endometritis that might have caused scarring
What should the physical exam for amenorrhoea include
Tanner staging for pubertal development
Measurements of height, weight and BMI
signs of associated underlying causes e.g. visual field defect, imperforate hymen, thyroid problems
What is a sign of insulin resistance that patients with PCOS may have
Acanthosis nigricans (darkened areas of the skin) often in the armpits
What are some of the initial tests for amenorrhoea
Pregnancy test (serum or urine human chorionic gonadotrophin) Pelvic imaging (US or MRI) Serum FSH serum prolactin serum TSH and T4 Serum androgens
Why are serum FSH levels tested in amenorrhoea
elevated in premature ovarian failure due to reduced inhibition due to ovarian oestradiol and inhibin
What should patients have done if they have high FSH or are suggestive of primary ovarian failure
Karyotype to look for chromosomal abnormalities e.g. Turner’s
When is a hypothalamic -pituitary MRI indicated
In women with hypogonadotrophic hypogonadism and no clear explanation
Those with visual field defects, headaches or any other signs of hypothalamic - pituitary dysfunction
What should be included in the differential diagnosis for patients with hyperandrogenism
PCOS
CAH
androgen-secreting tumours
What should also be tested for if a patient is suspected to have Turner’s syndrome
Echocardiogram (congenital heart disease / aortic aneurysm) Renal US (renal anomalies) Thyroid function tests (a lot develop thyroid disease)
Why should women with unexplained premature ovarian failure be screened for permutation in the FMR1 gene.
There is a risk that a patient with an FMR1 mutation would have a child with mental retardation and also has a link to fragile X syndrome
How are the majority of women with prolactinomas successfully treated
Dopamine agonist
What should patients with irreversible gonadotrophin deficiency receive
Oestrogen replacement therapy and progesterone if they have a uterus
What should be started in girls with primary amenorrhoea and delayed puberty
Oral ethinylestradiol at a low dose to promote breast development and adult body habitus
Dose is gradually increased
Cyclical oral progesterone is added with the onset of breakthrough bleeding
What can premature initiation of progesterone therapy cause
compromise ultimate breast growth
What is required for the prevention of osteoporosis and coronary heart disease
Oestrogen-progestin replacement therapy
What might adult women with premature ovarian failure be treated with
100ug of transdermal estradiol daily
What must be performed in patients with Y chromosome material
gonadectomy - to prevent the development of gonadal tumours
