1B reproductive treatments Flashcards
What are the symptoms for low T?
- Loss of early morning erections
- Lower libido
- Decreased energy
- Lower frequency of shaving
How do we diagnose low T?
- at least 2 low measurements of serum T before 11am (when it’s meant to be high)
- Investigate the cause of low T
What different types of T replacement treatments are there?
- Daily- gel (e.g. Tostran)- care not to contaminate partner
- 3 weekly intramuscular injections (e.g. Sustanon)
- 3 monthly intramuscular injections (e.g. Nebido)
- Less common (implants, oral preparations)
What do we need to monitor for safety in testosterone replacement?
- increased haematocrit (risk of hyperviscosity and stroke)
- Prostate (Prostate specific antigen (PSA) levels)
How do we treat primary and secondary hypogonadism?
- Primary- hard to treat
- Secondary (deficiency of gonadotrophins i.e. hypogonadotrophic hypogoandism)- treat with gonadotrophins (i.e. LH and FSH) to induce spermatogenesis
What would LH and FSH do to testes?
- LH stimulates Leydig cells to increase intratesticular T to much higher levels than in circulation (x100)
- FSH stimulates seminiferous tubule development and spermatogenesis
Why do we avoid giving T to men desiring fertility?
For secondary hypogonadism (low sperm and T levels) in men desiring fertility, giving T would lower LH and FSH further and further reduce spermatogenesis
What do we give instead of T to men desiring fertility?
- hCG injections (which act on LH receptors)
- If no response after 6 months, add FSH injections
What is hypothalamic amenorrhoea?
When you have insufficient energy for fertility from decrease in hypothalamus function
What are the causes of hypothalamic amenorrhoea?
- Low body weight
- Excessive exercise
- Stress
- Genetic susceptibility
What is the aim of ovulation induction?
- To develop 1 ovarian follicle
- If >1 follicle develops, there’s risk of multiple pregnancy (twins/triplets) which has risks for mother and baby during pregnancy
- Ovulation induction aims to cause small increase in FSH
What are different methods to restore ovulation?
- Lifestyle/weight loss/metformin
- FSH stimulation by injection
- Letrozole (aromatase inhibitor)
- Clomiphene
How does letrozole work?
- Inhibits aromatase which converts T to E2
- E2 usually causes negative feedback on hypothalamus and pituitary gland to reduce LH and FSH production
- There’s decreased negative feedback now however due to low E2 so there’s increased FSH which stimulates follicle growth
How does clomiphene work?
- It’s called a modulator since it acts like an agonist/antagonist depending on tissue its in
- We’re interested in it being an E2 receptor antagonist- works in same way as letrozole
- Decreased negative feedback since E2 receptors are blocked → less negative feedback → more FSH → stimulation of follicle growth
What are the steps to IVF?
1) Induce growth of multiple follicles through giving large FSH dose
2) Collect eggs directly from ovary
3) Fertilise eggs in vitro by either:
- putting it in dish with sperm and naturally letting sperm fertilise egg
- ICSI (intracytoplasmic sperm injection)- take a single sperm and inject it directly into egg- usually done when there’s problem in sperm (male factor infertility)
4) Eggs grown in incubator for few days
5) After 3-5 days, we choose strongest embryo and transfer it back into endometrium of woman
What is premature ovulation?
Release of egg from follicle before we collect eggs for IVF
How do we prevent premature ovulation?
We give a hormone that suppresses LH surge. There are 2 ways of doing it:
- GnRH antagonist protocol (short protocol)
- GnRH agonist protocol (long protocol)
How does GnRH antagonist protocol work?
- Start FSH from day 2 of menstrual cycle
- At day 6 we start GnRH antagonist- will prevent LH surge
How does GnRH agonist protocol work?
- Start GnRH agonist from day 21 of previous cycle (day -7 of current cycle)
- Start FSH like usual on day 2
How can both a GnRH agonist and antagonist be used to block an LH surge?
- GnRH needs to be given in pulsatile manner to stimulate LH
- Agonist: If we give non-pulsatile continuous GnRH, we get desensitisation of GnRH receptor- causing initial flare of LH, but then LH inhibition
- So giving GnRH agonist can act like an antagonist and be used to induce LH inhibition
Antagonist is more self-explanatory- it’s preferred in cases where an immediate effect is needed
How do we mature the egg after preventing premature ovulation?
- We give LH exposure to induce oocyte maturation
- When eggs are immature, they’re at metaphase 1 and are diploid
- After being exposed to LH, they go into metaphase 2 and become haploid (can now be fertilised by sperm)
Which hormones do we give commonly to induce oocyte maturation?
- hCG- acts on LH receptors but is much longer acting than LH
- GnRH agonist is second most common
How many pregnancies are unplanned?
19-30%
What are the advantages of condoms?
- Protect against STIs
- Easy to obtain- free from clinics/no need to see a healthcare professional
- No contra-indications as with some hormonal methods
What are the disadvantages of condoms?
- Can interrupt sex
- Can reduce sensation
- Can interfere with erections
- Some skill to use e.g. correct fit
- 2 aren’t better than 1
How does the oral contraceptive pill work?
- HPG axis negative feedback:1) Pill has oestrogen and progesterone2) This has negative feedback on hypothalamus and pituitary3) This decreases LH and FSH leading to anovulation
- Thickening of cervical mucus
- Thinning of endometrial lining to reduce implantation
What are the advantages to the oral contraceptive pill?
- Easy to take- 1 pill a day at any time
- Effective
- Doesn’t interrupt sex
- Can take several packets back to back and can avoid withdrawal bleeds through this
- Reduces endometrial and ovarian cancer
- Weight neutral in 80% of people (10% gain weight and 10% lose- usually progesterone leads to this)
What are the disadvantages of the oral contraceptive pill?
- Can be difficult to remember to take
- No protection against STIs
- P450 enzyme inducers may reduce efficacy (if you’re on other medication that affects liver enzymes since that’s also where OCP is metabolised)
- Not the best choice during breastfeeding
What are possible side effects to the oral contraceptive pill?
Try different OCPs to see which suits best
- Spotting (bleeding in between periods)
- Nausea
- Sore breasts
- Changed in mood or libido
- Feeling more hungry
What is an extremely rare side effect of the oral contraceptive pill?
Blood clots in the legs or lungs (2 in 10,000)
What are non-contraceptive uses of the pill?
- 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 are the advantages of the progesterone only pill (POP) aka minipill?
- Works same as OCP but less reliably inhibits ovulation
- Often suitable if you can’t take oestrogen
- Easy to take- 1 pill a day every day
- Doesn’t interrupt sex
- Can help heavy or painful periods
- Periods may stop (temporarily)
- Can be used when breastfeeding
What are the disadvantages of the progesterone only pill (POP) aka minipill?
- Can be difficult to remember
- No protection against STIs
- Shorter acting- needs to be taken at the same time each day
What are the side effects of the progesterone only pill (POP) aka minipill?
- Irregular bleeding
- Headaches
- Sore breasts
- Changes in mood
- Changes in sex drive
What are coils suitable for and what do they do overall?
- Suitable for most women including nulliparous women (no previous children)
- Prevent implantation of conceptus- important consideration for some religions
- Can be used as emergency contraception
What do we need to check before insertion and what is a rare thing that can happen with coils?
- Exclude STIs and cervical screening up to the day before insertion
- Rarely can cause an ectopic pregnancy where embryo may implant in fallopian tube
What are the 2 types of coil?
- Intra-uterine device (IUD) i.e. copper coil
- Intra-uterine systems (IUS) e.g. Mirena coil
What does the IUD do?
- mechanically prevent implantation
- decrease sperm egg survival
How long does an IUD last?
5-10 years
What are the side effects to an IUD?
- Can cause heavy periods
- 5% can come out especially during first 3 months with periods
What does the IUS do?
- Secretes progesterone to thin the lining of womb and thicken cervical mucus
- Can be used to help with heavy bleeding
How long does an IUS last for?
3-5 years
What is the 3rd type of LARC?
Progesterone-only injectable contraceptives or subdermal implants
When can an IUD be used?
- It’s the most effective
- Can be fitted up to 5 days after unprotected sex (<1% chance of pregnancy)
What are the 2 morning after pills?
- Ulipristal acetate 30mg (ellaOne)
- Levonorgestrel 1.5mg (Levonelle)
How does ulipristal acetate work?
- Stops progesterone working normally and prevents ovulation
- Must be taken within 5 days of unprotected sex (earlier the better)
How does levonorgestrel work?
- Least effective esp if BMI is more than 27 kg/m^2
- Synthetic progesterone prevents ovulation (doesn’t cause abortion)
- Must be taken within 3 days of unprotected sex
What are the side effects of the morning after pills?
- Headache
- Abdominal pain
- Nausea
If you vomit within 2/3 hours of taking it, you have to take another.
What can make the morning after pill less effective?
Liver P450 enzyme inducer medications
What factors matter for choice of contraception?
- Risk of venous thromboembolism (VTE)/CVD/stroke
- When they have other conditions that may benefit from OCP
- Are they taking concurrent drugs that will affect contraceptives?
- If there’s a need for STIs (barrier contraception would help)
When should women avoid OCP?
If they have:
- Smoking (>15 a day) and age >35 years
- Diabetes with complications e.g. retinopathy/nephropathy/neuropathy
- Migraine with aura (risk of stroke)
- Stroke or CVD history
- Current breast cancer
- Liver cirrhosis
What conditions can benefit from OCP?
- Menorrhagia
- Endometriosis
- Fibroids
What concurrent drugs can affect contraceptives?
- P450 liver enzyme inducing drugs (e.g. anti epileptics, some antibiotics)
- Teratogenic drugs (e.g. lithium or warfarin)- more effective methods of contraception needed (e.g. progesterone only implant, or intrauterine contraception)
Describe the efficacy of different types of contraception
User dependent: dependent on users remembering to take it, etc
What are the risks of HRT?
- Venous thrombo-embolism: DVT or pulmonary embolism
- Risk of stroke
- Hormone sensitive cancers
- Risk of cardiovascular disease
How is HRT a risk of venous thrombo-embolism?
Oral oestrogens undergo first pass metabolism in liver where they can increase SHBG, triglycerides, CRP and increase chance of clots
How can we reduce the chance of VTE?
- Transdermal oestrogens are safer for VTE risk than oral because the drug goes straight into bloodstream
- Avoid oral oestrogens in BMI >30 kg/m^2
How is stroke a risk of HRT?
- Small increased risk
- Oral is better than transdermal oestrogen in terms of risk
- Combined is better than oestrogen only in terms of risk
What hormone sensitive cancers are a risk of HRT?
- Breast cancer
- Ovarian cancer
- Endometrial cancer
How is breast cancer a risk of HRT?
- slight increase in only women on combined HRT (both oestrogen and progesterone)
- Risk related to duration of treatment and reduces after stopping
- Continuous combined HRT worse than sequential (e.g. oestrogen first then progesterone)
- Assess risk in each individual before prescribing
How is ovarian cancer a risk of HRT?
Small increase in risk after long term use
How can we reduce the chance of endometrial cancer?
- Must prescribe progestogens in all women with an endometrium to decrease risk of endometrial cancer
- Assess HRT safety/efficacy at 3 months and then annually
- Unscheduled bleeding is common within first 3 months
What are progestogens?
Synthetic progestins and the natural hormone progesterone
What can indicate endometrial cancer?
Post-menopausal bleeding
At what age does cardiovascular disease become a risk of HRT?
- No increased risk if started before age 60 years
- Increased risk if started 10 years after menopause
To which group can oestrogen supplements be beneficial?
Possible benefits in young women e.g. premature ovarian insufficiency (POI)
What are the benefits of HRT?
- Relief of symptoms of low oestrogen e.g. flushing, disturbed sleep, decreased libido, low mood
- Less osteoporosis related fractures- decreased by one third
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?
Gender doesn’t match assigned sex
What does gender dysphoria mean?
When sex and gender don’t align and it causes distress
What does non-binary mean?
Gender doesn’t match to traditional binary gender understanding.
Includes agender, bigender, pangender, gender fluid
What does transgender mean?
Transitioning or planning to transition physical appearance from one gender to another
What is the definition of a transgender man?
Female sex at birth, but male gender (FtM no longer used)
How do prepubertal young people transition?
- GnRH agonist for pubertal suppression and then sex steroids
- Post treatment regret is 1-2%
- 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 bleeding if needed (endometrial hyperplasia is 15%)
What are the side effects of T?
- Polycythaemia
- Lower HDL
- Obstructive sleep apnoea (OSA)
- No increase in CVD
What happens in 1-6 months of taking masculinising hormones for transgender men?
- Balding (depending on age and family pattern)
- deeper voice/acne/increased and coarser facial and body hair
- Change in distribution of body fat
- Enlargement of clitoris
- Menstrual cycle stops
- Increased muscle mass and strength
What are the feminising hormones for transgender women?
- Oestrogen (transdermal, oral, intramuscular)
- Reduce testosterone
How much oestrogen is taken for transgender women?
High dose oestrogen e.g. 4-5mg per day to aim for oestradiol levels of 734 pmol/L
What are the side effects of taking oestrogen for transgender women?
- VTE dose related at 2.6%
- cardiovascular disease
- hormone sensitive cancers e.g. breast cancer, abnormal liver function tests 3%
- High bp
- high triglycerides
How is testosterone reduced?
- GnRH agonists (induce desensitisation of HPG axis)
- Anti-androgen medications (e.g. cyproterone acetate, spironolactone)
- Height, voice and Adam’s apple won’t change
- Consider sperm banking before starting hormone therapy
What happens in 1-3 months of taking feminising hormones?
Decrease in sexual desire/function (including erections)/ baldness slows or may reverse
What happens in 3-6 months of taking feminising hormones?
Softer skin/ change in body fat distribution/ decrease in testicular size/ breast development/ tenderness
What happens in 3-6 months of taking feminising hormones?
Hair may become softer and finer
