Amenorrhoae and Erectile dysfunction Flashcards
Match the following A.Oligomenorrhoea B. Amenorrhoea C. Primary amenorrhoea D. Secondary amenorrhoea E. Erectile dysfunction
- Failure to begin spontaneous menstruation by 16
- Absene of menstrucation for 3 months in a woman who has previosuly had cycles
- Menstrual cycle length >6 weeks but <6 months
- Inability of the male to achieve or sustain an erection adequate for satisfactory intercourse.
- Complete absence of menstruation or cycle length >6months
A3 B5 C1 D2 E4
What hormones are involved in the female axis?
GnRH, LH, FSH, progesterone, oestrogen
- Ovary end organ
What hormones are involved in the male axis?
GnRH, LH, FSH, testosterone
- Testes end organ
How does the hypothalamus regulate steroid synthesis?
Steroid synthesis is reguated by the kisspeptin neurons
What is the function of kisspeptin neurons?
Act as central processors to relay peripheral signals to GnRH neurons
What secretes kisspeptin?
Kisspeptin is secreted by neurons in discrete hypothalamic nuceli, directly innervating and stimulating GnRH neurons through GPR54 receptors (Kiss1r gene)
What conditions occur in mutations to Kiss1 and Kiss1r?
Profound hypogonadotropic hypogonadism
How does kisspeptin induce GnRH release?
Kisspeptin signals directly to the GnRH neurons through the action on the kisspeptin receptor to release GnRH into the portal circulation.
What is kisspeptins function in development?
Required for normal puberty and reproductive function
How is kisspeptin signalling regulated?
Regulation occurs via metabolic cues where leptin can induce kisspeptin signallin.
There is some regulation via negative feedback.
- Females:high levels of oestrogen and progesterone stimulate the pre-ovulatory stage (increase GnRH and LH). It will also inhibit Kiss1 expression in the arcurate nucleus
- Males: males high testosterone levels suppress GnRH, LH and FSH release, partly via kisspeptin neurons of the ARC.
Describe the hormone levels in the menstrual cycle?
In the follicular phase LH and FSH is low, which gradually rise in the cycle peaking in the middle. E2 pattern is similar to LH. Progesterone rises after ovulation (day 14)
What is amenorrhoea?
Complete absence of menstruation or cycle length >6months
What does the investigation of amenorrhae combine?
Clinical history, clinical examination, laboratory and imaging
What are primary and secondary causes of amenorrhoae associated with?
Primary= ovarian
Secondary=pituitary
What does the clinical evaluation include?
General health, body shape and skeletal abnormalities, weight and height, evidence of virilisation, galactorrhoea, normality of vagina, cervix and uterus
What does the history examination entail?
analysing date of onset, age of menarche, sudden or gradual onset, general health, weight, stress, excessive exercise, drugs, sense of smell, PMH in pregnancies or gynaecological surgery
What are the test for amenorrhoae and when should it be carried out?
- LH, FSH, E2 (follicular ideally day 2-3)
- prolactin
- progesterone on day 21/7days before expected bleed (>30nm/L=ovulation)
- testosterone, adristenedione, DHEAS & SHBG
- 17-OH progesterone (basal + ACTH stimulated)
- TFT
- HCG
- steroid profile
Describe pituitary function tests
GnRH test is used to investigate gonadotrophin deficiency (low LH and FSH)
- 100ug GnRH is administered IV and samples collected at 0, 20, 60min. Expect to see significant rise in LH and FSH
- If LH rise>FSH rise then post-pubertal (vice versa for pre)
Clomifene test a selective oestrogen receptor modulator (SERM) used to distinguish between distinguish gonadotrophin deficiency from weight related hypogonadism.
- 50g of clomifene administered for 5 days
- LH and FSH measured on day 0 and 7
- Expect to see rise above reference range or 2x basal
- Lack of response= LH and FSH deficiency due to a pituitary/hypothalamic disease
What are some non-biochemical assessments of amenorrhoea?
By imaging or surgically.
- MRI/CT scans or ovarian/trans-vaginal ultrasounds
- Surgical approach involves hysteroscopy, laparascopy or biopsy
What are some primary causes of amenorrhea?
Associated with high LH, FSH and low E2.
- Ovarian failure and the pituitary tries to stimulate secretion of damaged ovaries
- Overstimulated pituitary gland
The causes include; ovarian dysgenesis, premature ovarian failure, steroid biosynthetic defect, oophorectomy or chemotherapy
Mathc the primary causes to correct investigation.
A. Ovarian dysgenesis B. Premature ovarian failure C. Steroid biosynthetic defect D. Oophorectomy E. Chemotherapy
- hCG stimulation
- Urine steroid profiling
- Laparoscopy/biopsy
- Ultrasound of ovary/uterus autoantibodies
- Karyotyping
1D 2E 3C 4B 5A
What are secondary causes of amenorrhoae?
These are defects in the pituitary or hypothalamus resulting in decreased LH, FSH and E2.
Match the secondary cause with lab test.
A. kallmanns syndrome
B. hypothalamic amenorrhoea
C. weight-related amenorrhoea
D. exercise-induced amenorrhoea and anorexia
E. post- pill amenorrhoea
F. general illness or hyperprolactinaemia
- prolactin
- GnRH
- prolactin interferes with normal production of other hormones
- consider full pituitary screen
- Test for TSH, free T4 and T3
- clomifene test
1B 2C 3F 4E 5A 6D
How does prolactinoma produce amenorrhoea picture?
Decrease LH, FSH, E2, but prolactin increase (well above 1000)
What types of prolactinoma can cause amenorrhoae and how do we investigate?
Causes
- prolactinoma, idopathic hyperlacticaemia, hypothyroidism, polycystic ovarian disease, physiological in lactation, or dopamine agonist drugs
Tests
- serum free T4/TSH
- pit MRI
- Macroprolactin
How is amenorrhoae treated?
- Treat underlying cause - e.g. remove tumour
- lifestyle changes and/or consider the use of oestrogen replacement to regain a healthy hormonal picture
What is menopause?
Cessation of menstruation at the end of a woman’s reproductive life.
When is the onset of menopause
53
Define premature menopause
Premature menopause/ovarian failure is defined as <40 years
What does the onset of menopause cause?
Hypergonadotrophic hypogonadism
- Increase in FSH and LH and decreased E2 (pituitary continuously secrete but ovaries dont respond)
What is the endocrinological cause of menopause?
Its the failure of the pulse generator
What are symptoms of menopause?
Headaches & hot flashes, teeth loosen and gums recede, breasts drops/flatten, weight gain & abdomen losses muscle tone, backaches, vaginal dryness/itching, bone lose mass and more fragile.
What are the NG23 guidelines for diagnosing and managing menopause?
- Diagnostically the women should be older than 45 years old
- Perimenopause: vasomotor symptoms (hot flashes) and irregular periods, whereas menopause if 12months no period and no hormonal contraception
- Inappropriate to test FSH in women aged>45 and if combined contraception/high-dose progesterone
- FSH testing can be considered for premature menopause or if 40-45 years are presenting symptoms
Define erectile dysfunction?
Inability to achieve and sustain an erection adequate for satisfactory intercourse
What is the clinical evaluation in erectile dysfunction?
Self-reporting followed by medical and psychosexual history
What should be investigated in erectile dysfunction?
Measure total testosterone or glucose-lipid profile
What are primary causes?
Indicate problem with the testes. Can be split into congenital and acquired causes.
- Congenital: anorchia/leudig cell agenesis, cryptorchidism, chromosome abnormaility, enzyme defects, androgen receptor deficiency/abnormality, sickle cell disease.
- Acquired: testicular torsion, orchidectomy, local testicular disease, chemotherapy, CKD, cirrhosis/alcohol, autoimmune
What are secondary causes?
These causes are associated with hypothalamic causes.
Include: reduced gonadotrophins, selective gonadotrophic deficiency, normosmic idiopathic hypogonadotrophic hypogonadism, severe systemic illness, severely underweight, hyperprolactinaemia
What are drugs that cause ED?
- Diuretics
- anti-hypertensive
- antipsychotics
- antidepressants
What investigations can be done for ED?
- Fasting glucose/HbA1c test (test for diabetic neuropathy cause)
- Semen analysis
- WHO/Kruger classificaiton
- Karyotyping
- MRI/CT scan of pituitary
- Ultrasound of testes
- Testicular biopsy and lab
Biochemical investigations of ED?
- Testosterone
- LH/FSH/E2
- Prolactin
- 17-OHP
- TFTs
- GGT/MCV/U&E
- Pituitary function test
- GnRH test
- Clomifene citrate test (oestrogen antagonsit)
- HCG stimulation test
What is the HCG stimulation test?
Test to measure the amount of sex hormones produced in the body.
- Patient administered 2000IU HCG on day 0 and 2, to then measure testosterone levels on day 0,2 and 4.
- Normal response is to increase testosterone above normal reference range
- If there is no rise then there is an absence of functional testicular tissue
Why is it hard to measure free and bioavailable testosterone?
Testosterone circulate in the plasma as testosterone or as dihydrotestosterone. Bound binds to non-specific proteins.
Measurement of bioavailable and free testosterone is possible, but it is technically difficult.
Treatment of erectile dysfunction is…
Medical
- 1st line is viagra a PDE5 inhibitor
- 2nd line IV
- 3rd line penile implant
Testosterone
- can be given if deficient - has negative effect on spermatogenesis
HCG
- Given to treat hypogonadotropic hypogonadism
Dopamine agonist
- hyperprolactinaemia treatment
What is andropause?
Male counterpart for menopause. Age related testicular failure. It is associated with decreased bioavailable testosterone due to increasing SHBG, and increased FSH.
- Gynaecomastia can also occur with age
