REPRODUCTIVE TREATMENTS Flashcards
To which type of patients is testosterone replacement given to?
Men not desiring fertility
Wish to treat loss of early morning erections, libido, decreased energy and shaving
Must have had at least 2 low measurements of serum testosterone before 11am
How can testosterone replacement carried out?
Daily gel
3 weekly intramuscular injection
3 monthly intramuscular injection
Less common implants, orals
What do you monitor for the safety of a patient who is taking testosterone replacement?
Haematocrit
Prostate (prostate specific antigen (PSA) levels)
If a patient with hypogonadism wishes to be fertile and produce sperm, how do you treat?
Primary hypogonadism - difficult
Secondary hypogonadism - give gonadotrophins to induce spermatogenesis
- LH stimulates Leydig cells to increase intratesticular testosterone
- FSH stimulate seminiferous tubules development and spermatogenesis
What is the role of LH and FSH in spermatogenesis?
LH - stimulates Leydig cells to increase intratesticular testosterone
FSH - stimulates seminiferous tubule development and spermatogenesis
What is the aim for ovulation induction and why?
Aim to develop 1 ovarian follicle
If > 1 follicle develop risks multiple pregnancy (twin…) which has risks for mother and baby during pregnancy
How is ovulation induction carried out in e.g. PCOS?
- Lifestyle/weight loss/metformin
- Letrozole (aromatase inhibitor)
- Clomiphene (oestradiol receptor antagonist)
- FSH stimulation (low dose FSH)
Why is an aromatase inhibitor used in ovulation induction?
Prevents testosterone becoming oestradiol which decreases the negative feedback on hypothalamus and pituitary gland so increased LH and FSH
Why is an oestradiol receptor antagonist used in ovulation induction?
Decreases the negative feedback on hypothalamus and pituitary gland so increased LH and FSH
List the 4 main steps of IVF treatment
- Oocyte retrieval
- Fertilisation in vitro by IVF or intra-cytoplasmic sperm
injection (ICSI) - Embryo incubation
- Embryo transfer
List the steps of oocyte retrieval in IVF
- FSH stimulation to induce growth of follicles
(superovulation) - Prevent premature LH surge
- LH exposure for egg maturation from diploid (metaphase
1) to haploid (metaphase 2)
Why must a premature LH surge be prevented in IVF?
Stops premature ovulation so that there will be eggs in the ovary to collect
What are the 2 ways we use to prevent premature LH surge?
GnRH antagonist protocol (short protocol: day 6-9)
GnRH agonist protocol (long protocol: day -7-9)
Should you use pulsatile or non-pulsatile GnRH when trying to suppress LH?
Non-pulsatile as it causes desensitisation and after an initial flare LH is inhibited
List some methods of contraception?
Barrier (condoms, diaphragm/cap with spermicide)
Combined oral contraceptive pill (OCP)
Progestogen-only pill (POP)
Long acting reversible contraception (LARC)
Emergency contraception
Permanent methods:
- Vasectomy
- Female sterilisation
What are the positives of condoms?
- Protect against STI
- Easy to obtain
- No contra-indications
What are the negatives of condoms?
- Can interrupt sex
- Can reduce sensation
- Can interfere with erections
- Some skill to use
- Two are not better than one
How does the oral contraceptive pill (OCP) work?
Contains oestrogen and progesterone which:
- More -ve feedback so less LH/FSH (anovulation)
- Thickens cervical mucus (reduce sperm entering)
- Thins endometrial lining (reduces implantation)
What are the positives of the OCP?
- Easy to take (one a day)
- Effective
- Doesn’t interrupt sex
- Can take several packets back to back and avoid
withdrawal bleeds - Reduces endometrial and ovarian cancer
- Weight neutral
What are the negatives of the OCP?
- Difficult to remember to take
- No protection against STI
- Not best choice during breast feeding
- P450 enzyme inducers may reduce efficacy
- Adverse effects
What are the possible side effects of the OCP?
- Spotting (bleeding in between periods)
- Nausea
- Sore breasts
- Changes in mood/libido
- More hungry
- Blood clots in legs/lungs (extremely rare)
What are the non-contraceptive uses of the OCP?
- Makes periods lighter and less painful
- Withdrawal bleeds usually very regular
- Reduces LH and hyperandrogenism for PCOS
What are the positives of the progesterone only pill (POP)/”Mini-pill”
- Works like OCP but less reliable to inhibit ovulation
- Suitable if you can’t take oestrogen
- Easy to take
- Doesn’t interrupt sex
- Helps heavy/painful periods
- Periods may stop temporarily
- Can be used when breastfeeding
What are the negatives of the progesterone only pill (POP)/”Mini-pill”
- Difficult to remember
- No protection against STIs
- Shorter acting - needs to be taken at same time each
day - Side effects
What are the possible side effects of the progesterone only pill (POP)/”Mini-pill”
Irregular bleeding Headaches Sore breasts Changes in mood Changes in sex drive
List examples of long-acting reversible contraceptives (LARCs)
Intra-uterine device (IUD)
Intra-uterine systems (IUS)
Progesterone-only injectable contraceptives/sub-dermal implants
Explain what an IUD is
ie copper coil which mechanically prevents implantation, decreases sperm egg survival. Lasts 5-10 years
Can cause heavy periods
Explain what an IUS is
Secretes progesterone to thin lining of the womb and thicken cervical mucus (helps with heavy bleeding)
Lasts 3-5 years
What is the most effective emergency contraception?
IUD can be fitted up to 5 days after unprotected sex
< 1% chance of pregnancy
List some emergency contraceptive pills
Ulipristal acetate (ellaOne) Levonorgestrel (Levonelle) - least effective
How does ulipristal acetate work?
Progesterone antagonist preventing ovulation
Must be taken within 5 days of unprotected sex
Emergency contraceptive pill
How does levonorgestrel work?
Synthetic progesterone which prevents ovulation
Must be taken within 3 days of unprotected sex
What are the possible side effects of emergency contraceptive pills?
Headache
Abdominal pain
Nausea
Liver P450 enzyme inducer medications make it less effective
If vomit within 2-3hrs of taking it, need to take another
Patients with what medical history should avoid the OCP and why?
Migraine with aura Smoking + age > 35 years Stroke/CVD history Current breast cancer Liver cirrhosis Diabetes with complications e.g. retinopathy/nephropathy/neuropathy
Risk of venous thromboembolism (VTE)/ CVD/Stroke
What should you consider when choosing a contraception for a patient?
Risk of venous thromboembolism (VTE)/ CVD/Stroke
Other conditions that may benefit
Need to prevent STI?
Other current medication
What concurrent medications should cause you to reconsider to a more effective method of cotnraception?
P450 liver enzyme-inducing drugs e.g. anti-epileptics
Teratogenic drugs e.g. lithium, warfarin
What are the risks of HRT?
Venous thrombo-embolism (DVT/PE)
Hormone sensitive cancers
Increased risk of CVD (if age > 60)
Small increased risk of stroke
Why should patients with a BMI > 30 avoid oral oestrogens?
Oral oestrogens undergo first pass metabolism in liver causing increase in SHBG, triglycerides and CRP
Increases risk of venous thrombo-embolism
Use transdermal oestrogens instead
How is breast cancer risk affected by HRT?
Slight increase only in women with combined HRT
Duration of treatment and continuity increases risk
How is ovarian cancer risk affected by HRT?
Small increase in risk after long-term use
How is endometrial cancer risk affected by HRT?
Must prescribe progestogens in all women with an endometrium
Assess HRT safety/efficacy at 3 months and then annually
Unscheduled bleeding common in first 3 months
What type of bleeding could indicate endometrial cancer?
Post-menopausal bleeding
What are the hormone sensitive cancers?
Breast cancer
Ovarian cancer
Endometrial cancer
Which type of HRT (oral or transdermal) (combined/oestrogen only) has a greater risk of stroke?
Oral combined HRT
What increases the risk of CVD when taking HRT?
If started 10 years after menopause
What are the benefits of HRT?
Relief of symptoms of low oestrogen
Less osteoporosis related fractures
How is gender reassignment carried out in prepubertal young people?
GnRH agonist for pubertal suppression 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 bleeding if needed
What are the feminising hormones for transgender women?
Oestrogen (transdermal, oral, intramuscular)
Hormones which reduce testosterone:
- GnRH agonists (induce desensitisation of HPG axis)
- Anti-androgen medications e.g. spironolactone
What is the time frame of male to female gender reassignment?
1-3 months: decrease in libido/function, baldness slows/reverses
3-6 months: softer skin, change in body fat distribution, decrease in testicular size, breast development
6-12 months: hair becomes softer and finer
What is the time frame of female to male gender reassignment?
1-6 months: balding, deeper voice, acne, change in distribution of body fat, enlargement of clitoris, menstrual cycle stops, increased muscle mass and strength
