Investigation of Erectile Dysfunction and Amenorrhoea Flashcards
(49 cards)
1
Q
What is Menarche?
A
Age at first period
2
Q
What is Oligomenorrhoea and Amenorrhoea?
A
- Amenorrhoea: Complete absence of menstruation or cycle length >6 months
- Oligomenorrhoea: Menstrual cycle length >6 weeks but <6 months
3
Q
What is Primary and Secondary Amenorrhoea?
A
- Primary Amenorrhoea: Failure to begin spontaneous menstruation by age 16
- Secondary Amenorrhoea: Absence of menstruation for 3 months in a woman who has previously had cycles
4
Q
What is Erectile Dysfunction?
A
Erectile dysfunction: Inability of the male to achieve or sustain an erection adequate for satisfactory intercourse
5
Q
How is Gonadal function regulated?
A
Hypothalamic GnRH secreted
Pituitary LH & FSH secreted in response
Males
- LH stimulates testosterone synthesis in Leydig cells
- FSH stimulates spermatogenesis and synthesis of inhibin in Sertolli cells
- Negative feedback of inhibin on FSH and of testosterone on GnRH
Females
- LH & FSH (& follicular AMH) regulate E2 synthesis and oocyte maturation
6
Q
What is the role of Kisspeptin Neurons?
A
- Kisspeptin neurons may act as central processors for relaying signals from the periphery to GnRH neurons
- Kisspeptins (Kiss1 gene) are secreted by neurons in discrete hypothalamic nuclei, directly innervating and stimulating GnRH neurons through GPR54 receptors (Kiss1r gene)
- They are required for puberty and normal reproductive function. Kiss1 and Kiss1r mutations cause profound hypogonadotropic hypogonadism
7
Q
How do Kisspeptin neurons regulate GnRH?
A
- Kisspeptin neurons express E2 and androgen receptors and are direct targets for the action of gonadal steroids in males and females.
- Kiss1 mRNA is both negatively and positively regulated by sex steroids
8
Q
What are the roles of Kisspeptin signalling?
A
- Negative feedback of sex steroids on gonadotropin secretion
- Generation of preovulatory GnRH/LH surge
- Triggering and guiding the tempo of sexual maturation at puberty
- Controlling seasonal reproduction
- Restraining reproductive activity during lactation
9
Q
How is Kisspeptin signalling regulated?
A
- Hypothalamic-pituitary-adrenal axis
Metabolic cues
- Kiss1 may be induced by leptin
Environmental cues:
- Time of day via suprachiasmatic nucleus (SCN) of the hypothalamus
- Day length via melatonin from the pineal gland
10
Q
How does Kisspeptin signalling take place in reproductive life?
A
Pulsatile GnRH stimulates pubertal LH & FSH release to causes gamete formation, gonadal steroid hormone production and feedback loops regulate GnRH, LH & FSH release
Kisspeptin neurons relay steroid feedback on GnRH
In Females: high oestrogen & progesterone levels
- Stimulate kisspeptin neurons of the AVPV to induce the preovulatory surge of GnRH & LH
- Inhibit Kiss1 expression in the arcuate nucleus (ARC)
In Males: High testosterone levels
- Suppress GnRH, LH & FSH release, partly via kisspeptinneurons of the ARC
11
Q
What are factors of the examination considered in the clinical assessment of amenorrhoea?
A
- General health
- Body shape and skeletal abnormalities
- Weight and height
- Hirsutism and acne
- Evidence of virilization
- Maturity of secondary sexual characteristics
- Galactorrhoea
- Normality of vagina, cervix and uterus
12
Q
What is involved in the biochemical assessment of amenorrhoea?
A
- LH, FSH & E2 (follicular ideally day 2-3)
- Prolactin
- Progesterone (day 21 or 7 days before expected bleed)
- >30 nmol/L = ovulation
- Testosterone, androstenedione, DHEAS & SHBG
- 17-hydroxyprogesterone (basal + ACTH-stimulated)
- Thyroid function tests
- HCG
- Steroid profiling
13
Q
What are factors of the history considered in the clinical assessment of amenorrhoea?
A
- Date of onset
- Age of menarche, if any
- Sudden or gradual onset
- ? Pregnant
- General health
- Weight, absolute and changes in recent past
- Stress (job, lifestyle, exams, relationships)
- Excessive exercise
- Drugs
- Hirsutism, acne, virilization
- Headaches/visual symptoms
- Sense of smell
- PMH of pregnancies
- PMH of gynaecological surgery
14
Q
What are some pituitary function tests?
A
- GnRH test – investigation of gonadotrophin deficiency
- Clomifene test
15
Q
What is the GnRH test?
A
- 100 µg intravenous GnRH
- Samples at 0, 20, 60 min
- Expect LH & FSH increase; post-pubertal LH rise > FSH rise (reverse if pre-pubertal LH rise < FSH rise)
16
Q
What is the Clomifene test?
A
- Selective oestrogen receptor modulator (SERM). Helps distinguish gonadotrophin deficiency from weight-related hypogonadism
- 50 mg clomifene given for 5 days and LH & FSH measured on day 0 and 7
- LH & FSH should increase to above reference range or 2x basal values
- Lack of response suggests LH & FSH deficiency due to pituitary/hypothalamic disease
17
Q
What are side effects of Clomifene test?
A
- Depression
- Visual disturbances
18
Q
What are non-biochemical assessments of amenorrhoea?
A
Imaging:
- MRI/CT scan
- Ovarian/trans-vaginal ultrasound
Surgical:
- Hysteroscopy
- Laparoscopy
- Biopsy
19
Q
What are possible diagnoses of Primary Amenorrhoea?
A
- Ovarian dysgenesis
- Premature ovarian failure
- Steroid biosynthetic defect
- Oophorectomy
- Chemotherapy
20
Q
What are tests for Primary Amenorrhoea?
A
- Karyotype
- Ultrasound of ovary/uterus
- Autoantibodies
- Laparoscopy/biopsy of ovary
- HCG stimulation
- Urine steroid profiling
21
Q
What are biochemical tests for Primary Amenorrhoea?
A
- LH↑
- FSH↑
- E2↓
- PRL-
- T-
22
Q
What are possible diagnoses for secondary/tertiary amenorrhoea?
A
- Kallmann’s syndrome*
- Hypothalamic amenorrhoea*
- Weight-related amenorrhoea*
- Exercise-induced amenorrhoea and anorexia*
- Post-pill amenorrhoea
- General illness*
- Hyperprolactinaemia
23
Q
What are tests for causes of secondary/tertiary amenorrhoea?
A
- TSH, free T4 & free T3
- Prolactin
- GnRH test
- Clomifene test
- Consider full pituitary screen
- Pituitary MRI
24
Q
What are biochemical markers of secondary/tertiary amenorrhoea?
A
- LH↓
- FSH↓
- E2↓
- PRL-
- T-
25
What are possible diagnoses for hyperprolactinaemia related amenorrhoea?
* Prolactinoma
* Idiopathic hyperprolactinaemia
* Hypothyroidism
* Polycystic ovarian disease
* Physiological in lactation
* Dopamine antagonist drugs
26
What are tests for hyperprolactinaemia related amenorrhoea?
* Serum free T4/TSH
* Other tests for PCOS
* Pituitary MRI
* (Macroprolactin)
27
What are biochemical markers of Hyperprolactinaemia related Amenorrhoea?
* LH ↓
* FSH ↓
* E2 ↓
* PRL ↑ or ↑↑
* T -
28
What are biochemical markers for PCOS and Cushing's syndrome?
* **LH:** ↑/N
* **FSH:** N
* **E2:** N
* **PRL:** N/↑
* **T:** N/↑
29
What are tests for PCOS and Cushing's syndrome?
**Polycystic Ovarian Syndrome**
* Androstenedione, DHEAS, cortisol
**Cushing's Syndrome (rarely)**
* SHBG
* Ovarian ultrasound
30
What are biochemical markers of androgen excess, gonadal or adrenal tumour, and congenital adrenal hyperplasia?
* **LH:** N/↓
* **FSH:** N/↓
* E2: N/↓
* PRL: N
* T: ↑↑
31
What are tests for adrogen excess, gonanal or adrenal tumur, and congential adrenal hyperplasia?
* **Androgen excess** - Imaging ovary/adrenal
* **Gonadal or adrenal tumour** - 17α-OH-progesterone
* **Congenital adrenal hyperplasia** - Steroid profiling
32
What are biochemical markers of Uterine/Vaginal abnormality, Imperforate hymen, absent uterus and lack of endometrium?
* **LH:** N
* **FSH:** N
* **E2:** N
* **PRL:** N
* **T:** N
33
What are tests Uterine/vaginal abnormality, Imperforate hymen, Absent uterus, Lack of endometrium?
* Uterine/vaginal abnormality - Examination findings
* Imperforate hymen\* - Ultrasound of pelvis
* Absent uterus\* - Progesterone challenge
* Lack of endometrium - Hysteroscopy
34
How is Amenorrhoea treated?
* Treat underlying pathology if possible
* Lifestyle management
* Oestrogen replacement
35
What is Menopause?
* Cessation of menstruation at the end of a woman's reproductive life
* Mean age of the menopause in the UK is about 53 years and average female life expectancy is 81 years
* A woman may thus spend nearly 40% of her life in an oestrogen-deficient state
* Premature menopause/ovarian failure defined as \<40 years
* Hypergonadotrophic hypogonadism (↑↑↑ FSH & LH, ↓ E2)
36
What are symptoms of Menopause?
* Headaches and Hot flashes
* Teeth loose and Gums recede
* Breast droop and flatten
* Weight Gain and Abdomen loses muscle tone
* Backaches
* Vaginal dryness/itching
* Bones lose mass and more fragile
37
How is menopause diagnosised and managed?
Clinical diagnosis in women aged \> 45 years:
* Perimenopause if vasomotor symptoms and irregular periods
* Menopause if 12 months no period and no hormonal contraception
Do NOT use FSH testing:
* In women aged \> 45 years
* If combined contraception/high-dose progestogen
Do consider FSH if \<40 years (? premature)
Do consider FSH if aged 40-45 with symptoms
38
What is Erectile dysfunction?
* Inability of the male to achieve or sustain an erection adequate for satisfactory intercourse
39
What are congenital casues of Erectile Dysfunction?
* Anorchia/Leydig cell agenesis
* Cryptorchidism (testicular maldescent)
* Chromosome abnormality (e.g. Klinefelter's syndrome)
* Enzyme defects: 5α-reductase deficiency
* Androgen receptor deficiency/abnormality
* Sickle cell disease
40
What are acquired causes of Erectile Dysfunction?
* Testicular torsion
* Orchidectomy
* Local testicular disease
* Chemotherapy/radiation toxicity
* Orchitis (e.g. mumps)
* Chronic kidney disease
* Cirrhosis/alcohol
* Infections – STI
* Autoimmune
41
What are causes of secondary (pituitary) / tertiary (hypothalamic) erectile dysfunction?
* Reduced gonadotrophins (Hypopituitarism)
* Selective gonadotrophic deficiency (Kallmann's syndrome)
* Normosmic idiopathic hypogonadotropic hypogonadism
* Severe systemic illness
* Severely underweight
* Hyperprolactinaemia
42
* **Diuretics:** Thiazides (e.g. bendroflumethiazide), spironolactone
* **Anti-hypertensives:** Methyldopa, clonidine, beta-blockers (e.g. propranolol), verapamil
* **Fibrates:** Clofibrate, gemfibrozil
* **Antipsychotics:** Phenothiazines (e.g. chlorpromazine), butyrophenones (e.g. haloperidol)
* **Antidepressants:** Tricyclics (e.g. amitriptyline), monoamine oxidase inhibitors (e.g. phenelzine), selective serotonin reuptake inhibitors (e.g. fluoxetine), lithium
* **H2-antagonists:** Cimetidine, ranitidine
* **Hormones and hormone-modifying drugs:** Oestrogens (e.g. estradiol), progesterone, corticosteroids (e.g. prednisolone), cyproteroneacetate, 5-alpha reductase inhibitors (e.g. finasteride)
* **Cytotoxics:** Cyclophosphamide, methotrexate
* **Anti-arrhythmics and anticonvulsants:** Disopyramide
43
How is Erectile dysfunction investigated?
* Fasting glucose / HbA1c (diabetic neuropathy)
* Semen analysis
* WHO/Kruger classification
* Karyotyping
* MRI/CT scan of pituitary
* USS of testes
* Testicular biopsy
* Laboratory
44
What are biochemical investigations of ED?
* Testosterone/SHBG (9 am)
* LH/FSH/E2
* Prolactin
* 17-OHP
* TFTs
* GGT/MCV/U&E
* (Seminal fluid fructose and zinc)
* Pituitary function tests
* GnRH test
* Clomifene citrate test (oestrogen antagonist)
* HCG stimulation test
45
What is the HCG stimulation test?
* 2000 IU HCG given on days 0 and 2
* Measure serum testosterone on days 0, 2 and 4.
* Normal response testosterone increases above normal RR
* No rise in testosterone indicates absence of functional testicular tissue
Useful if you think there is disrupted orchidogenesis
46
How is testosterone transported?
Testosterone and dihydrotestosterone circulate in plasma
* Unbound (‘free’) ~2–3% = biologically active
* Bound to non-specific proteins e.g. albumin = biologically available
* Bound to SHBG = biologically inactive
47
How can testosterone be measured?
**Can be measured - technically difficult!**
* Free testosterone assay measures unbound fraction
* Bioavailable testosterone includes free plus weakly bound to albumin
**Can also be calculated**
48
How is Erectile dysfucntion managed?
Counselling/Lifestyle
Medical
* DM/Cardiovascular disease - control
* PDE 5 inhibitor e.g. viagra (1st line treatment)
* Intracavernous injection (2nd line treatment)
* Penile implant (3rd line treatment)
* **Testosterone:** Supraphysiological replacement has a negative effect on spermatogenesis
* **HCG:** Hypogonadotrophic hypogonadism, intramuscularly twice weekly
* **Dopamine agonists:** Hyperprolactinaemia, with dopamine agonists
High-dose corticosteroids – used in patients with sperm autoantibodies (side effects!)
Surgery
49
What is Andropause?
* Age related testicular failure
* Poorly defined
* Decreased bioavailable testosterone due to increasing SHBG
* FSH tends to increase more with age than LH
* Gynaecomastia increases with age
