Endo - Reproductive Treatments Flashcards
What is testosterone replacement given for?
not looking for fertility
but wants to improve symptoms
What symptoms does T replacement treat?
→ loss of early morning erections
→ low libido
→ decreased energy
→ reduced shaving frequency
Why is testosterone not given to people wanting fertility, even if they have low T?
→ testosterone leads to negative feedback on LH + FSH
→ reduces FSH and LH
→ reduces spermatogenesis
What levels of testosterone are required for T replacement to be given?
→ at least 2 low measurements of serum T before 11 am
→ low measurements < 9 mol/L
What forms of T replacement are available?
→ daily gel (e.g. Tostran)
→ 3 weekly intramuscular injections (e.g. Sustanon)
→ 3 monthly intramuscular injections (e.g. Nebido)
→ implants + oral prep (less common)
Why do you have to be careful with daily gel T replacement?
have to be careful and not contaminate partner
What factors need to be monitored when taking T replacement? Why?
→ increased haematocrit (ratio of RBC to blood vol) : could lead to hyperviscosity and stroke
→ PSA levels (prostate specific antigen) : overstimulation of prostate could cause cancer
What is primary hypogonadism?
→ high LH + FSH
→ but problems with gonads themselves
→ so low T produced from gonads
How hard is it to treat?
difficult to treat
What is secondary hypogonadism?
→ low LH and FSH produced
→ so low T
How is secondary hypogonadism treated induce spermatogenesis?
treat with LH + FSH
How do LH and FSH induce + promote spermatogenesis?
→ LH stimulates Leydig cells to increase intratesticular testosterone (to x100 the levels than in circulation)
→ FSH stimulates seminiferous tubule development + spermatogenesis
How is low T in secondary hypogonadism treated in those who want fertility?
→ hCG injections (acts on LH-receptors
→ if no response after 6 months, add FSH injections
What are the symptoms of PCOS?
2/3 of these qualify for PCOS:
→ hyperandrogenism (clinical or biochemical
→ PCOS morphology on ultrasound
→ irregular periods
What are the features of hyperandrogenism?
→ hirutism
→ acne
What are the signs or features of hypothalamic amenorrhoea?
→ low body weight → excessive exercise → stress → genetic susceptibility → irregular periods
What is hypothalamic amenorrhoea?
stress on the body causes hypothalamus to stop releasing GnRH, stopping release of LH and FSH
What is ovulation induction?
→ aim to develop one ovarian follicle
→ methods aim for small increase in FSH
Why is only one ovarian follicle the aim for ovulation induction?
→ if more than 1 develops, has risks of multiple pregnancies (twins or triplets)
→ multiple pregnancies = many risks for mother + baby during preganancy
What are the 4 methods in which ovulation can be induced?
→ lifestyle / weight loss / metformin
→ letrozole
→ clomiphene
→ FSH stimulation
How does letrozole induce ovulation?
→ aromatase inhibitor
→ aromatase = converts T to Oestradiol
→ inhibiting aromatase = low oestradiol
→ low oestradiol = reduced negative feedback on pituitary and hypothalamus
→ this increases GnRH + LH + FSH
→ stimulates follicle growth + egg release
How does clomiphene induce ovulation?
→ oestradiol receptor antagonist
→ reduces the amount of oestradiol produced
→ reduces negative feedback on hypothalamus and pituitary
→ increases GnRH + LH + FSH
→ stimulates follicle growth + egg release
What are the different steps of IVF?
→ oocyte retrieval
→ fertilisation in vitro
→ embryo incubation
→ embryo transfer
What is oocyte retrieval?
→ high doses of FSH to stimulate follicle growth
→ eggs collected outside of utero
What is fertilisation in vitro?
either:
→ IVF (in vitro fertilisation) : sperm + egg mixed in a dish)
→ ICSI (intra-cytoplasmic sperm injections) : single sperm injected directly into the egg
What in embryo incubation?
waiting 3-5 days
What is embryo transfer?
the strongest embryo in implanted into the endometrium
When in ICSI preferred over IVF?
when there’s problems with male fertility or sperm
What are the key steps in IVF in terms of hormones?
→ FSH stimulation (super ovulation so that multiple follicles develop )
→ prevent premature LH surge (to prevent premature ovulation before eggs can be collected)
→ expose eggs to LH when mature
Why does premature ovulation need to be prevented in IVF patients?
→ prevents egg form being collected before it’s ready to be collected
What medications or hormones prevent premature LH surge in IVF patients?
→ GnRH antagonist protocol (short protocol)
→ GnRH agonist protocol (long protocol)
When is FSH given in accordance with GnRH antagonist?
→ FSH = day 2 to day 10
→ GnRH antagonist = day 6 to approx. day 10
When is FSH given in accordance with GnRH agonist?
→ FSH = day 2 to day 10
→ GnRH agonist = day -7 to day 10
Why can’t LH be used to induce oocyte maturation?
→ very short-acting so would have to be given in very large doses
→ still not as effective as hCG injections
How are GnRH antagonists or GnRH agonists used to prevent an LH surge?
→ GnRH needs to be given in a pulsatile manner to stimulate LH
→ continuous high dose of GnRH causes desensitisation of GnRH receptors, leading to LH inhibition
→ GnRH agonists given over a long period cause this desensitisation
→ GnRH antagonists inhibit receptors and inhibit LH
How are eggs exposed to LH?
→ hCG (acts on LH receptors)
→ GnRH agonists (causes an LH surge at first)
Why are eggs exposed to LH?
→ to induce maturation
→ allows them to go from diploid to haploid
Why is LH not given when trying to induce oocyte maturation?
→ short-acting so large doses needed
→ less effective than hCG
What are the common methods of contraception?
→ Barrier: male / female condom/ diaphragm or cap with spermicide
→ Combined Oral Contraceptive Pill (OCP)
→ Progestogen-only Pill (POP)
→ Long Acting Reversible Contraception (LARC)
→ Emergency Contraceptio
What are some permanent methods of contraception?
→ vasectomy
→ female sterilisation
What are the positives of barrier contraception?
→ protects against STIs
→ easy to obtain (free form clinics and there’s no need to see a healthcare professional)
→ no contra-indications
What are some negatives of barrier contraception?
→ Can interrupt sex → Can reduce sensation → Can interfere with erections → Some skill to use eg correct fit → Two are not better than one
What is the OCP?
→ oral contraceptive pil
→ contains progesterone and oestrogen
→ results in an ovulation
How does the oral contraceptive pill stop conception?
→ Oestrogen + progesterone - anovulation due to negative feedback on GnRH and gonadotrophins (LH and FSH)
→ Progesterone - thickening of the cervical mucus and thinning of endometrial lining
What are the positives of the OCP?
→ Easy to take – one pill a day (any time of day)
→ Effective- doesn’t interrupt sex
→ Can take several packets back to back and avoid withdrawal bleeds
→ Reduce endometrial and ovarian cancer
→ Weight neutral in 80% (10% gain, 10% lose)
What are the negatives of the OCP?
→ It can be difficult to remember
→ No protection against STIs
→ P450 Enzyme Inducers may reduce efficacy
→ Not the best choice during breast feeding
What are the possible side effects of the OCP?
→ Spotting (bleeding in between periods) → Nausea → Sore breasts → Changes in mood or libido → Feeling more hungry
What non-contraceptive uses does the OCP have?
→ Helps make periods lighter and less painful (e.g. endometriosis or period pain or menorrhagia)
→ Withdrawal bleeds will usually be very regular
→ PCOS: help reduce LH and hyperandrogenism
What is the POP?
→ progesterone only pill
→ works like OCP
→ less reliable than OCP in inhibiting ovulation
What are the positives of POP?
→ often suitable if you cannot take oestrogen
→ Easy to take – one pill a day, every day with no break It doesn’t interrupt sex
→ Can help heavy or painful periods
→ Periods may stop (temporarily)
→ Can be used when breastfeeding
What are the negatives of POP?
→ Can be difficult to remember
→ No protection against STIs
→ Shorter acting – needs to be taken at the same time each day
What are the possible side effects of POP?
→ Irregular bleeding → Headaches → Sore breasts → Changes in mood → Changes in sex drive
What are LARCs?
long acting reversible contraceptives
What are some examples of LARCs?
→ IUD (intr-uterine device)
→ IUS (intra-uterine systems) -
→ Progestogen-only injectable contraceptives or subdermal implants
What is an IUD?
→ intra-uterine device
→ copper coil, mechanically prevents implantation,
→ decreases sperm egg survival, lasts 5-10 years
→ can cause heavy periods, and 5% can come out especially during the first 3 months with periods
What is an IUS?
→ intra-uterine systems
→ acts as the coil but also secretes progesterone
→ thickens cervical mucus (Can be helpful for women with heavy bleeding)
→ Lasts 3-5 years
What are the advantages of LARCs?
→ Suitable for most women including those with no previous children
→ Can be used as emergency contraception
→ Rarely can cause ectopic pregnancy
→ Prevent implantation of conceptus – important for some religions
What are some examples of emergency contraceptions?
→ IUD - most effective (less than 1% chance of pregnancy) - fitted up to 5 days after unprotected sex
→ Emergency contraceptive pill, ULIPRISTAL ACETATE - 30mg, taken within 5 days of unprotected sex (earlier the better)
→ Emergency contraceptive pill, LEVONORGESTREL - synthetic progesterone, 1.5mg, taken within 3 days of unprotected sex (least effective)
What are the possible side effects of emergency contraceptives?
→ Headache
→ Abdominal pain
→ Nausea
→ Liver P450 enzyme inducer medications make it less effective
→ If vomit within 2-3 hours of taking it, need to take another
What factors need to be taken into consideration when choosing contraception?
→ Risk of Venous Thromboembolism (VTE) / CVD / Stroke
→ Comorbidities
→ Other conditions that may benefit from a contraception e.g. menorrhagia/endometriosis/fibroids
→ Need for prevention of STIs
→ Concurrent medication
What comorbities mean that OCP should be avoided?
→ Migraine with aura (risk of stroke) → Smoking (>15/day) + age >35yrs → Stroke or CVD history → Current Breast cancer → Liver Cirrhosis → Diabetes with retinopathy / nephropathy / neuropathy
What concurrent medication should be considered when taking contraception?
→ P450 liver enzyme-inducing drugs (eg anti epileptics, some antibiotics)
→ Teratogenic drugs (eg lithium or warfarin), more effective methods of contraception needed (eg progestogen-only implant, or intrauterine contraception
What is the general disadvantage of user dependent contraceptions?
more chance or failure due to incorrect use
What are the symptoms of menopause?
→ Hot flushes → sweating → disturbed sleep → Low libido → vaginal dryness → low mood → Joint and muscle aches → Absent periods
What is HRT?
hormone replacement therapy
What are the risks of HRTs?
→ VTEs (venous thrombo-embolisms): Deep
Vein Thrombosis (DVT) or Pulmonary Embolism (PE)
→ Oral oestrogens - go through liver to undergo first pass metabolism (more risky) VS transdermal = straight into the bloodstream
→ Breast cancers = slight increased risk with combined HRT (oest and prog)
→ Ovarian cancer - increased risk after long term use
→ Endometrial cancers = must prescribe progestogens to minimise risk (post-menopausal bleed may indicate endometrial cancer)
→ No increased risk of CVD (cardiovascular disorder) if started before aged 60
→ Increased risk if started 10 years after menopause
→ Possible benefits of oestrogen supplementation in young women e.g. Premature Ovarian Insufficiency (POI)
→ Risk of stroke - small increase, most increase with oral combined pill (least = transdermal oestrogen only)
What are the benefits of HRT?
→ Relieves symptoms caused by low oestrogen- e.g. flushing, disturbed sleep, decreased libido, low mood
→ Less osteoporosis related fractures
What are some HRTs that can be used for transgender + gender non-binary individual?
→ GnRH agonist
→ high dose continuously pre- puberty
→ delays prepubertal effects to make the decision and then sex steroids
→ Gender reassignment surgery after 1-2 years of hormonal treatment
What are the masculinising hormones for transgender men?
→ Testosterone (injections, gels)
→ Progesterone to suppress menstrual bleed (if needed)
What are the changes experienced after HRT for transgender men?
In 1 to 6 months:
→ Balding (depending on your age and family pattern)
→ Deeper voice / Acne /
→ Increased and coarser facial and body hair
→ Change in the distribution of your body fat
→ Enlargement of the clitoris
→ Menstrual cycle stops
→ Increased muscle mass and strength
What are the feminising hormones for transgender women?
→ Oestrogen (transdermal, oral, intramuscular)
→ GnRH angonists/ant-androgen medications = reduce testosterone levels
→ consider sperm bank before start of HRT
What can HRT not change for transgender women?
Height, voice and Adam’s apple will not change
What are the effects of feminising hormones for transgender women?
→ 1 TO 3 MONTHS: Decrease in sexual desire / function (including erections) / Baldness slows or may reverse
→ 3 TO 6 MONTHS: Softer skin / Change in body fat distribution / Decrease in testicular size / Breast development / tenderness
→ 6 TO 12 MONTHS: Hair may become softer and finer
