3.13 - Reproductive treatments Flashcards
What are the symptoms for low testosterone? (4)
- loss of early morning erections
- lower libido
- decreased energy
- lower frequency of shaving
How do we diagnose low testosterone?
- at least 2 low fasting measurements of serum T before 11am (meant to be high)
- investigate cause of low T
What different types of testosterone replacement treatments are there? (4)
- daily gel - care not to contaminate partner
- 3 weekly intramuscular injection
- 3 monthly intramuscular injection
- less common (implants, oral preparations)
What do we need to monitor for safety when replacing testosterone?
- increased haematocrit (risk of hyperviscosity and stroke)
- prostate (prostate specific antigen - PSA levels)
- gynaecomastia, acne, aggression, prolonged painful erection
- disturbed liver function
What is secondary hypogonadism in males?
Deficiency of gonadotrophins (LH/FSH) i.e. hypogonadotrophic hypogonadism
How do we treat primary and secondary hypogonadism in males?
- primary - hard to treat
- secondary - treat with gonadotrophins (LH/FSH) to induce spermatogenesis
What would LH and FSH do to the testes?
- LH stimulates Leydig cells to increase intratesticular testosterone levels to much higher than in circulation (x100)
- FSH stimulates seminiferous tubule development and spermatogenesis
Why do we avoid giving testosterone to men desiring fertility and what do we give instead?
- for secondary hypogonadism (low sperm and T) , giving T would lower LH and FSH further = worsen spermatogenesis
- instead give treatment inducing spermatogenesis:
- hCG injections (act on LH receptors)
- if no response after 6 months, add FSH injections
What are the main signs of polycystic ovary syndrome (PCOS)? (3)
- hyperandrogenism (clinical or biochemical) - hirsutism / acne
- PCO morphology on ultrasound
- irregular periods
(Rotterdam PCOS Diagnostic Criteria) - need 2/3
What is hypothalamic amenorrhoea?
When you have insufficient energy for fertility due to decrease in hypothalamus function
What are the causes of hypothalamic amenorrhoea?
- low body weight
- excessive exercise
- stress
- genetic susceptibility
- (anorexia nervosa)
Essentially causes of hypothalamic hypogonadism
What is the aim of ovulation induction?
- to develop one ovarian follicle
- if >1 follicle develops, this risks multiple pregnancy (twins/triplets) - has risks for mother and baby during pregnancy
- ovulation induction methods aim to cause small increase in FSH
What are the different methods to restore ovulation in PCOS? (In order)
- lifestyle / weight loss by 5%
- metformin
- letrozole (aromatase inhibitor - stops T—>E2 = lower E2 = higher FSH&LH)
- clomiphene (oestradiol receptor modulator/antagonist = lower E2 = higher FSH&LH)
- FSH stimulation (injection)
What are the different methods to restore ovulation in hypothalamic amenorrhoea? (5)
- lifestyle / weight gain / reduce exercise
- pulsatile GnRH pump
- FSH stimulation (injection)
- letrozole (aromatase inhibitor)
- clomiphene (oestradiol receptor modulator)
What are the steps to in vitro fertilisation (IVF)?
- give high dose FSH to stimulate production of multiple follicles (superovulation)
- prevent LH surge to delay ovulation (e.g. GnRH antagonist)
- when follicles good size, give hCG injection = LH-like exposure to mature eggs
- oocyte retrieval
- fertilisation in vitro - either put in dish with sperm and let sperm fertilise egg, or intra-cytoplasmic sperm injection (male factor infertility)
- embryo incubation
- embryo transfer –> endometrium
What % of pregnancies are unplanned?
19-30%
What are non-permanent methods of contraception? (5)
- barrier: male/female condom / diaphragm / cap with spermicide
- combined oral contraceptive pill (OCP)
- progesterone-only pill (POP)
- long acting reversible contraception (LARC)
- emergency contraception
What are permanent methods of contraception? (2)
- vasectomy
- female sterilisation
What are the positives of condoms? (3)
- protect against STIs
- easy to obtain - free from clinics/no need to see healthcare professional
- no contra-indications as with some hormonal methods
What are the negatives of condoms? (5)
- can interrupt sex
- can reduce sensation
- can interfere with erections
- require some skill to use e.g. correct fit
- two are not better than one
How does the combined oral contraceptive pill (OCP) work - three methods?
- anovulation
- thickening of cervical mucus
- thinning of endometrial lining to reduce implantation
How does the OCP affect the HPG axis to cause anovulation?
- pill has oestrogen and progesterone
- this has negative feedback on hypothalamus and pituitary
- this decreases LH and FSH leading to anovulation
What are the positives of the combined OCP? (6)
- easy to take - one pill a day at any time
- effective
- does not interrupt sex
- can take several packets back to back and avoid withdrawal bleeds
- reduces endometrial and ovarian cancer
- weight neutral in 80% (10% increase, 10% decrease)
What are the negatives of the combined OCP? (4)
- can be difficult to remember to take
- no protection against STIs
- P450 enzyme inducers may reduce efficacy
- not the best during breast feeding
What are the possible side effects of combined OCP? (5)
- spotting (bleeding in between periods)
- nausea
- sore breasts
- changes in mood or libido
- feeling more hungry
- (try different OCPs to see which suits best)
What is an extremely rare side effect of combined OCP?
Blood clots in legs or lungs (2 in 10,000)
What are some non-contraceptive uses of the combined OCP?
- helps make periods lighter and less painful (e.g. endometriosis/fibroids, dysmenorrhoea - painful periods, menorrhagia - heavy periods)
- regular withdrawal bleeds / no bleeds
- PCOS - OCP reduce LH and hyperandrogenism (acne and hirsutism)
What are the advantages of the progesterone only pill (POP) aka mini-pill? (7)
- works as OCP but less reliably inhibits ovulation
- often suitable if you cannot take oestrogen
- easy to take - one pill a day
- does not interrupt sex
- can help heavy/painful periods
- periods may stop (temporarily)
- can be used when breastfeeding
What are the negatives of the progesterone only pill (POP)? (3)
- can be difficult to remember to take
- no protection against STIs
- shorter-acting - needs to be taken at the same time everyday
What are the possible side effects of the POP? (5)
- irregular bleeding
- headaches
- sore breasts
- changes in mood
- changes in sex drive
What are the two main methods of long-acting reversible contraceptives (LARC)?
- coils
- intra-uterine device (IUD) i.e. copper coil
- intra-uterine systems (IUS) i.e. Mirena coil - progesterone-only injectable contraceptives or subdermal implants
What are coils suitable for and what do they do overall?
- suitable for most women
- prevent implantation of conceptus - important in some religions
- rarely can cause ectopic pregnancy (so exclude STIs and do cervical screening)
- can be used as emergency contraception
What are intra-uterine devices (IUDs)?
- mechanically prevent implantation
- decrease sperm/egg survival
- last 5-10 years
What are side effects of IUDs? (2)
- can cause heavy periods
- 5% can come out especially during first 3 months with periods
What are intra-uterine systems (IUS)?
e.g. Mirena coil
- secrete progesterone to thin the lining of the womb and thicken cervical mucus
- can be used to help with heavy bleeding
- lasts 5 years
What is the problem with progesterone-only injectable contraceptives/subdermal implants?
Long-lasting so may not be best option if desiring fertility soon
When can a copper IUD be used as emergency contraception?
- most effective
- can be fitted up to 5 days after unprotected sex (<1% chance of pregnancy)
What are the two types of emergency contraceptive pills?
- ulipristal acetate 30mg (ellaOne)
- levonorgestrel 1.5mg (Levonelle)
How does ulipristal acetate 30mg (ellaOne) work?
- stops progesterone working normally and prevents ovulation
- must be taken within 5 days of unprotected sex (earlier better)
- 1-2% can get pregnant if ovulation has already occurred
How does levonorgestrel 1.5mg (Levonelle) work?
- less effective especially if BMI > 27kg/m2
- synthetic progesterone prevents ovulation (does not cause abortion)
- must be taken within 3 days of unprotected sex
- 1-3% failure rate
What are the side effects of the morning after (emergency contraceptive) pills? (3)
- headache
- abdominal pain
- nausea
What do you do if you vomit 2/3 hours after taking the emergency contraceptive pill?
Need to take another
What can make the emergency contraceptive pill less effective?
Liver P450 enzyme inducer medications
What is the efficacy for different types of contraception?
- most effective <1% chance: implant, IUD, IUS
- user dependent: condoms, OCP, POP etc
- least effective: fertility awareness, withdrawal, no contraception
When should you avoid OCPs due to contraindications (e.g. risk of venous thromboembolism/CVD/stroke)? (4)
- migraine with aura (risk of stroke)
- smoking (>15/day) at age of >35
- stroke or CVD history
- current breast cancer
What other conditions may benefit from OCP? (6)
- menorrhagia
- endometriosis
- fibroids
- PMS
- acne
- hirsutism
What type of contraception is best when there is need for prevention of STIs?
Barrier methods better than hormonal
What concurrent drugs affect the efficacy of OCP? (2)
- P450 liver enzyme-inducing drugs (e.g. anti-epileptics, antibiotics)
- teratogenic drugs (e.g. lithium, warfarin) = more effective methods of contraception needed e.g. progesterone-only implant, IU contraception
What are the benefits of hormone replacement therapy (HRT)? (2)
- relief of symptoms due to low oestrogen e.g. flushing, sweats, disturbed sleep, decreased libido, low mood
- reduction in osteoporosis related fractures
(Transdermal E2 reduces risk of VTE and stroke, lower risk of CVD in younger/recently PM women)
What are the risks of HRT? (4)
- venous thrombo-embolism (DVT or PE)
- hormone sensitive cancers (breast, ovarian, endometrial)
- cardiovascular disease
- risk of stroke
(And need for progesterone as well as oestrogen increases risk of VTE and breast cancer)
How does HRT cause venous thrombo-embolism (DVT/PE)?
- oral oestrogens undergo first pass metabolism in the liver –> increased clotting factors
- transdermal oestrogens are safer for VTE risk than oral
- avoid oral oestrogens in BMI > 30kg/m2
How can HRT cause breast cancer?
- slight increase in women on combined HRT (oestrogen and progesterone)
- risk related to duration of treatment and reduces after stopping
- continuous worse than sequential (oes then prog)
- assess risk in each individual before prescribing
How can HRT cause ovarian cancer?
Small increase in risk after long-term use
How can we reduce the chance of endometrial cancer caused by HRT?
And what clinical sign could indicate endometrial cancer?
- must describe progestogens in all women with an endometrium
- oestrogen only - only if no uterus e.g. had hysterectomy
- everyone else - oestrogen AND progesterone as progesterone protects endometrium
- progestogens - synthetic progestins and the natural hormone progesterone
- post-menopausal bleeding could indicate endometrial cancer
Who is at increased risk of CVD after HRT?
- improved risk in younger women and sooner after menopause
- increased risk if started later i.e. 10y after menopause
- likely benefit in younger women e.g. POI
How can HRT increase risk of stroke?
- small increased risk
- oral have more risk than transdermal oestrogens
- combined (E2+P) more risk than oestrogen only
What is the definition of gender?
A social construct - how you see yourself as male, female or non-binary
What is the definition of sex?
Biologically defined e.g. male, female or intersex
What is the definition of cisgender?
Same sex and gender
What is the definition of gender non-conforming and gender dysphoria?
- gender non-conforming: gender does not match assigned sex
- gender dysphoria: when that causes distress
What is the definition of non-binary?
Gender does not match to traditional binary gender understanding e.g. agender, bigender, pangender, gender fluid
What is the definition of transgender?
- transitioning or planning to transition physical appearance from one gender to another
- transgender man - female sex at birth, but male gender
- transgender women are 3x more common than transgender men
How do prepubertal young people transition?
- GnRH agonist to delay puberty then sex steroids
- waiting list for specialist clinic around 4y
- post treatment regret is 1-2%
- gender reassignment surgery after 1-2 years of hormonal treatment
What do you treat transgender men with?
- masculinising hormones
- testosterone (injections, gels)
- progesterone (to suppress menstrual bleeding if needed - endometrial hyperplasia 15%)
What do you treat transgender women with?
- feminising hormones
- reduce testosterone - GnRH agonists (induce desensitisation of HPG axis), anti-androgen medications
- oestrogen (transdermal, oral, intramuscular) - high dose oestrogen e.g. 4-5mg per day (side-effects: higher risk of VTE 2.6%)
