Adolescent Sexual and Reproductive Health Flashcards
If female phenotype is the default, what happens to create male external genitalia in utero?
- Male genitalia requires testosterone to develop
- Sex-determining region SRY gene on Y chromosome is responsible for development of testes
- This, in turn, secretes AMH causing regression of the paramesonephric (Mullerian) ducts
- If any part of this fails, offspring will be genetically male but phenotypically female
Describe congenital adrenal hyperplasia
- Autosomal recessive condition
- Enzyme defects in adrenal steroidgenesis pathways
- Cortisol deficiency
- Increased ACTH secretion with build-up of cortisol precursors
- Increased androgen production
- 90% due to 21-hydroxylase deficiency
- If severe, aldosterone production = salt wasting
- Incidence 1:14 000 births
What are the clinical features of CAH?
- Commonest cause of ambiguous genitalia at birth
- Neonatal salt wasting crisis and hypoglycaemia
- Childhood virilisation = accelerated growth = early epiphyseal closure = restricted final height
- Hirsutism and oligomenorrhoea
Diagnosis:
- Elevated plasma 17-hydroxyprogesterone levels
- 24-hour urinary steroid analysis
If a woman has CAH, what can be expected of her fertility?
- Menstrual irregularities in 50%
- Natural fertility only 10% in salt losers
- PCO
- Fertility treatment same for women without CAH
- High levels of progesterone may be a contraceptive??
What is mainstay of treatment for CAH?
- Replacement of glucocorticoid to suppress ACTH and reduce excess androgen production
- Salt-losing CAH requires fludrocortisone and to replace aldosterone
- In pregnancy, requirement for both of these are increased further
What is XXY?
Klinefelter syndrome
- Male born with extra X chromosome
- Do not produce usual level of testosterone
- Infertile
What is XO?
Turner Syndrome
- Girl is born missing X chromosome
- Often infertile
- Shorter than average, lower IQ
Describe tanner I staging of puberty
- Prepubertal, no breast or pubic hair
Describe tanner II stage of puberty
- Accelerated growth, breast budding, spare straight pubic hair
Describe tanner III stage of puberty
- Peak growth velocity, elevation of breast contour, coarse curly pubic hair spreading to mons pubis, axillary hair
Describe tanner IV stage of puberty
- Growth slowing, araeloe form secondary mount, adult pubic hair, no spread to thigh
Describe tanner V stage of puberty
- No further increase in height, adult breast contour, adult pubic hair and distribution
Which tanner stage does menarche occur in?
III or IV
Define precocious puberty
Appearance of secondary sexual characteristics <8 in girls and <9 in boys
What causes gonadotrophin-dependent and gonadotrophin-independent precocious puberty?
Gonadotrophin-dependent
- HPO axis activated
- Idiopathic or CNS tumours and malformations
Gonadotrophin-independent
- Pubertal sex steroids but gonadotrophin levels suppressed
- Disorders of gonads/adrenals
- Secretion of sex steroids by tumours
- Ingestion of estrogen
Describe pre pubertal vulvovaginitis
- Peaks 3-7 years
- Offensive yellow/green discharge, soreness, itching
- Poor perineal hygiene, lack of estrogen, chemical irritation
- Conservative tx, resolves as approaches puberty
What would make you suspect a foreign body in pre pubertal girl?
FB is uncommon
May suspect if vaginal bleeding or persistent offensive discharge
EUA if suspected
Describe labial adhesions in pre pubertal girls
- 3.3% of pre-pubertal girls
- Peaks in 1st year of life
- Thin membrane in midline extending from posterior fourchette towards urethral opening
- Most asymptomatic, may have urinary symptoms
- Other investigation not indicated
- Estrogen cream if symptomatic
- Resolves by early puberty
- Do not need surgery
Describe androgen insensitivity syndrome
- X-linked recessive defect in androgen receptor gene
- XY karyotype
- Testes and normal testosterone production + metabolism, no mullerian structures
- Complete type = female external genitalia
- Partial type = ambiguous genitalia
- Complete may present with primary amenorrhoea or inguinal hernia
- Recommend gonadectomy (can delay until after puberty) as 5% risk of malignant change
- HRT until age 50 and BMD monitoring
- Psychological management
- Vaginal development variable - can use dilation
Primary amenorrhoea
- What are the causes of hypogonadotrophic hypogonadism?
(Reduced FSH, reduced LH, reduced estradiol)
Constitutional delay
- Reassure, follow-up, consider inducing puberty
Chronic systemic disease
- T1DM, hypothyroidism, coeliac, chronic renal disease, prader-willi
Underweight
- BMI>19 required for normal puberty
Kallmann’s syndrome
- Congenital absence of GnRH neurones
- Anosmia, colour blindness
- X-linked recessive or autosomal dominant
Primary amenorrhoea
- What are the causes of hypergonadotrophic hypogonadism?
Increased FSH and LH, reduced estradiol
- Perform karyotype
46XX - POI
45XO - Turners Syndrome
46XY - Swyer Syndrome
- Chromosomal male
- Dysgenic testes - do not inhibit mullerian system and don’t produce androgens
- Therefore fallopian tubes, uterus and vagina can remain
- Remove testes
- USS differentiates between AIS due to presence of internal female genitals
Klinefelter syndrome in men
XXX females
Testicular/ovarian failure
AIS
Can induce puberty
- Start age 10, very low dose of EE
- Add progestogen after 6 months
- COC vs HRT
In a female teenager with primary amenorrhoea, what could cause normal FSH and LH, reduced estradiol, and increased testosterone?
Androgen insensitivity syndrome
46XY
Normal breasts, sparse hair
USS - absent uterus + upper vagina, no ovaries
Testes still present
Primary amenorrhoea
- What would cause normal FSH/LH/estradiol, with normal secondary characteristics, and 46XX chromosomes?
Rokitansky syndrome
- USS absent uterus and upper vagina, ovaries present
- Failure of development of mullerian duct
- May have renal abnormalities
- Vaginal reconstruction
Imperforate hymen / absent vagina
- USS normal uterus and ovaries
- Cyclical pain
- Surgical management
What investigations would you do for a prepubertal ovarian cyst?
<10% of malignant, but malignant ovarian tumours = 1% of all childhood cancers
- Check FSH, LH, estradiol, TFTs
- If complex, hCG, AFP, LDH, Ca125 +/- MRI
What malignant ovarian masses occur in children?
- Dysgerminoma
- Endodermal sinus tumour (increased AFP)
- Embryonal carcinoma
- Choriocarcinoma (increased hCG)
A 13 year old girl attends clinic with HMB, what investigations can you do?
Similar management to adults, anovulatory cycles are leading cause
- FBC
- Ferritin
- Coag screen (20% have a bleeding disorder)
- TFTs
- Pelvic USS
- Consider STI screen and PT
What is catamenial epilepsy?
Increased seizure frequency during sections of menstrual cycle
Define primary and secondary amenorrhoea
Primary
- Failure of menstruation by age 16 in the presence of normal secondary sexual characteristics
- By age 14 in the absence of other evidence of puberty
Secondary
- Absent periods for 6+ months when has had previously regular periods (or 12+ months if previous oligomenorrhoea)
You measure a patient’s prolactin level, and it is <500 - what do you advise?
Nothing, normal range and reassure
A patient’s prolactin level is between 500 and 1000, what do you advise?
This could be consistent with stress or recent breast examination
Action: repeat
A patient’s prolactin level is 700-2500, what do you advise?
Could be consistent with hypothyroidism or PCOS
- Check TSH, T4, FSH/LH, testosterone and SHBG
A patient’s prolactin level is 1500-4000, what do you advise?
Could be a non-functioning macroadenoma or a functioning microadenoma
- Needs MRI/CT head
- Compression of pituitary is possible
- Threshold for imaging is >1500 on two occasions
How can you aid a patient with hyperprolactinaemia to conceive?
80% will achieve a pregnancy on dopamine agonist treatment
Breastfeeding can occur as normal (will not stimulate pituitary tumour growth)
Bromocriptine can be started/restarted in pregnancy without adverse fetal outcomes
What medications can cause hyperprolactinaemia?
- Phenothiazines
- Domperidone
- Metaclopramide
How might a disorder of sex development present?
- Ambiguous genitalia
- Primary amenorrhoea
- Virilisation at puberty
- Inguinal hernia containing gonads
- FH screening
How do you treat Turner’s Syndrome?
Physically they may have short stature, high arched palate, wide spaced nipples, cardiac and renal anomalies (these will need management)
Treat with HRT
Can conceive with donor eggs and IVF
Describe androgen insensitivity syndrome
Defect in androgen receptor gene (5a-reductase deficiency, 17b-hydroxysteroid dehydrogenase deficiency)
X-linked recessive disorder
Normal male karyotype with complete and partial clinical manifestations
Will have testes and normal testosterone production and metabolism (but failure of spermatogenesis) but female or ambiguous phenotype
No mullerian structures
May have breasts due to peripheral aromatisation of testosterone to estrogen
How do you manage a patient with rokitansky syndrome?
- Function of HPO axis is normal
- Vagina will be blind-ending, likely shortened
- USS: ovaries but no uterus
- Psychotherapy
- Vaginal dilators
- Ova retrieval and assisted conception with surrogate mother
Describe central precocious puberty (CPP)
- Premature activation of HPO axis
- 74% idiopathic
- May present with tall stature but may not reach true adult height if not treated
- Treated with monthly GnRH analogues (stop at age of normal puberty)
- Psychological issues, increased risk of sexual abuse and early pregnancy
How do you investigate precocious puberty?
- GnRH luteneising hormone-releasing hormone stimulation test
- Measure FSH and LH levels after administering a GnRH analogue
- In CPP, LH>FSH with a ratio of >1
- Bone age is often advanced
- US: uterine volume >2ml or length >34ml, pear-shaped and endometrial thickening
- MRI if progressive to rule out CNS tumour
Describe some causes of peripheral precocious puberty
Ovarian
- Functioning follicular cysts
- Granulosa cell tumours
- Sertoli leydig cell tumours
Adrenal
- CAH
- Adrenal tumours
McCune-Albright syndrome
- GNAS1 gene mutations
What medical therapy can you give for an adolescent with Turner’s syndrome?
- 2 years of estrogen to achieve normal growth and development
- Monthly progestogen to induce withdrawal bleed to protect endometrium
What sex hormones are released in males, and where from?
- LH stimulates the leydig cells in the testes – causes release of testosterone
- FSH stimulates the sertoli cells in the testes – causes release of inhibin B
What causes androgen insensitivity syndrome?
- Mutation on the androgen receptor gene, found on the X chromosome
(Is an x-linked recessive disorder)
What helps the fetal gonads turn into testes, in someone with XY chromosomes?
SRY gene
What does 5-a reductase do?
Converts testosterone to its more potent form, dihydrotestosterone (responsible for male external genitalia)
What does testosterone do to the internal ducts?
Prompts the wollfian ducts to stimulate the male reproductive system
What does AMH do to the internal ducts (in XY chromosomes)
Inhibits the mullerian ducts (which would normally stimulate the female reproductive system)
Do people with XX chromosomes have SRY gene?
No - found only on the Y chromosome - so as a result, ovaries develop from internal gonads in first trimester
What does testosterone do in the 3rd trimester for someone with XY chromosomes?
Causes the testes to descend into the male external genitalia / scrotum
What is cryptorchidism?
When testes do not descend into the male external genitalia (maybe because of androgen insensitivity)
- Higher risk of testicular cancer
In AIS, what do the external genitalia look like?
Will look female, with a rudimentary vaginal opening
Will also have a clitoris
Why don’t individuals with AIS have a uterus or fallopian tubes?
The internal testes still produce AMH which inhibits female reproductive organs from developing
Why do/can individuals with AIS develop secondary female sex characteristics?
- Excess androgens circulating
- Aromatase can then convert these to estrogen
How is 5-a reductase deficiency inherited?
- Autosomal recessive
- Sex-linked (only on Y chromosome)
What does the external genitalia look like in 5-a reductase deficiency?
- Testosterone is not converted into DHT (therefore male external genitalia do not develop)
- External genitalia appear either ambiguous or female
- Scrotum may be split in two (bifid scrotum)
- Penis doesn’t fully elongate
When is 5-a reductase deficiency diagnosed?
- Usually in newborns with ambiguous genitalia
- When these patients go through puberty, the testosterone surge can cause the penis to elongate and for secondary male sexual characteristics to develop
What is aromatase deficiency?
- Mutation in gene which does for aromatase
- Aromatase is responsible for converting androgens to estrogens in genotypical females
What can happen to the mother in pregnancy if a fetus has aromatase deficiency?
- Excess fetal androgens can cross the placenta and cause virilisation of the mother
- These effects will usually disappear after birth
Sperm is produced by what cells in the testes?
Sertoli cells (seminiferous tubules)
What cells make up an ovarian follicle?
- Oocyte at course
- Surrounded by granulosa cells and theca cells
What do theca cells produce and why?
Androstenedione (an androgen) stimulated by LH
What do granulosa cells produce?
They respond to FSH and convert androstenedione to estrogen and progesterone
Primary hypogonadism: what are some acquired and some congenital causes?
Acquired: chemo/radio, trauma
Congenital: Klinefelter or Turner syndrome
Describe what’s happening with hypergonadotrophic hypogonadism?
- Primary hypogonadism (i.e. testes/ovaries aren’t working)
- No testosterone/estrogen/progesterone is being produced
- Increased LH and FSH (due to HPG axis)
Describe what’s happening in hypogonadotrophic hypogonadism
- Reduced LH and FSH being produced and so not stimulating production of sex hormones
- Hypothalamus or pituitary dysfunction, or suppression from other hormones such as prolactin or thyroid
Name some acquired, congenital, and general causes of secondary hypogonadism (hypogonadotrophic hypogonadism)
- Acquired: radio/chemo, trauma
- Congenital: Kallmans, panhypopituitarism
- General: chronic illness, excessive exercise, malnutrition, obesity, stress
What is constitutional delay?
- ‘Natural’ delay in puberty
- Delay in the production of GnRH
- Not pathological, usually runs in families
- Puberty onset can then be normal and fertility is usually not impaired
What is the treatment for constitutional delay?
- Doesn’t usually need treatment
- Usually resolves on its own
In Klinefelter syndrome, what does the extra X chromosome mean happens to the testes?
- Reduction in testosterone and inhibin
- Therefore increase in LH and FSH
- The reduction in testosterone = impaired/reduced sperm, reduced testes maturation, and reduced male secondary characteristics
- The additional X also means more estrogen
What bloods can you do to diagnose Klinefelter syndrome?
- Low testo, high FSH/LH
- Karyotype
What are the 3 possible Turner syndrome karyotypes?
- 45XO (one X chromosome missing - non disjunction of sex chromosomes during meiosis)
- Mosaicism (some cells 45X some cells 46XX - happens due to an error following conception - non disjunction during mitosis)
- Microdeletion of part of X chromosome
Why are women with Turner’s infertile?
- One X chromosome means accelerated loss of oocytes
- ‘menopause’ happens before menarche
- Ovaries become fibrous ‘ streak ovaries’ and don’t produce estrogen/progesterone
- Therefore increased LH and FSH
