🧪Endocrinology🧪 - Reproductive treatments Flashcards
How can a man with low testosterone (hypogonadism) be diagnosed?
Confirm minimum 2 low fasting serum testosterones - measured in the morning
What are the symptoms for male hypogonadism?
Loss of early morning erections
Changes in libido
Decreased energy
Decreased shaving frequency
What are the treatment drug options for male hypogonadism?
Daily - gel, care not to contaminate partner
3 weekly - IM testosterone injection
3 monthly - IM injection
Less common - Implants, oral preparations
What are some of the risks of testosterone replacement?
Increased haematocrit (risk of hyperviscosity and stroke)
Prostate damage/enlargment (Prostate specific antigen levels - PSA, acts as a biomarker)
A 35-year old man presents with infertility, accompanied by his partner. He has low sperm, morning testosterone, LH/FSH, as well as fatigue and reduced shaving frequency. Him and his partner have been attempting to conceive for 2 years, with no success. Should he be given testosterone to improve his fertility?
No - testosterone alleviates symptoms but will not improve fertility
LH and FSH required for spermatogenesis
LH stimulates Leydig cells to increase intratesticular testosterone levels to up to 100x that of in circulation
FSH stimulated seminiferous tubule development and spermatogenesis
Why could giving testosterone to a male presenting with infertility who wants to have children be potentially counterproductive?
Giving testosterone could further decrease LH/FSH levels, further worsening spermatogenesis
What treatments can induce spermatogenesis?
hCG injections (act on LH-receptors)
If no response after 6 months, add FSH injections
What is the goal of ovulation induction?
To develop one ovarian follicle
Aim is to cause a small increase in FSH
Why do we only want to develop one ovarian follicle when inducing ovulation?
If >1 follicle develops, risks multiple pregnancies (i.e. twins, triplets)
Multiple pregnancies are inherently much riskier than normal pregnancies for both mother and child(ren)
What is the mechanism of action of letrozole?
It inhibits aromatase in the ovaries, therefore stopping testosterone from being converted to oestradiol, and so decreasing the negative feedback on the hypothalamus
What is the mechanism of action of clomiphene?
It acts as a competitive inhibitor of oestradiol on the oestrogen receptors in the hypothalamus, decreasing the negative feedback
What is the mechanism of action of gonadotrophin injections?
Injection can be given either subcutaneously or intramuscularly
Injected gonadotropins act directly to increase FSH and LH levels
What is hypothalamic amenhorroea?
Hypothalamic amenorrhea (HA) is a condition in which menstruation stops due to a disruption in the normal function of the hypothalamus
What similarities does hypothalamic amenorrhoea have with PCOS?
Patients will present with similar menstrual symptoms - oligo/amenorrhoea and infertility
What are the differences in symptoms between PCOS and hypothalamic amenorrhoea?
How is ovulation restored in PCOS?
- Lifestyle/weight loss by 5%
- Metformin
- Letrozole (aromatase inhibitor)
- Clomiphene (oestradiol receptor modulator)
- FSH stimulation
Steps are sequential, when one doesn’t work, add the next step and so on until ovulation is achieved
How is ovulation restored in hypothalamic amenorrhoea?
- Lifestyle/weight gain/reduce exercise
- Pulsatile GnRH pump
- FSH stimulation
- Letrozole (Aromatase inhibitor)
- Clomiphene (Oestradiol receptor modulator)
Steps are sequential, when one doesn’t work, add the next step and so on until ovulation is achieved
What is the difference in steps between stimulation ovulation in PCOS and hypothalamic amenorrhoea?
FSH is given before letrozole and clomiphene in HA, and afterwards in PCOS
Outline the steps for in vitro fertilisation (IVF) treatment
What percentage of pregnancies are unplanned?
19-30%
What are the contraception methods available?
Barrier: male/female condom, diaphragm, cap with spermicide
Combined oral contraceptive pill (OCP)
Progestogen-only pill (POP)
Long-acting reversible contraception (LARC)
Emergency contraception
What are the permanent methods of contraception?
Vasectomy
Female sterilisation (many methods)
What are the advantages of barrier contraception (condoms)?
Protects against STIs
Easy to obtain - free from clinics/no need to see healthcare professional
No contra-indications (unlike some hormonal methods)
What are the disadvantages of barrier contraception (condoms)?
Can interrupt sex
Can reduce sensation
Can interfere with erections
Relies on proper use/personal skill
Two are not better than one
What is the mechanism of function of the oral contraceptive pill?
Contains oestrogen and progesterone
Activates the negative feedback system, stopping the release of GnRH and LH/FSH, resulting in anovulation
What is the result of using the OCP?
Anovulation
Thickening of cervical mucus
Thinning of endometrial lining to reduce implantation
What are the advantages of the OCP?
Easy to take - one pill a day at any time
Effective
No interruption of sex
Can take several packets back to back and avoid withdrawal bleeds
Reduces endometrial and ovarian cancer
Weight neutral in 80% (10% gain and 10% lose)
What are the disadvantages of the OCP?
Easy to forget
No protection against STIs
Additional medications with induce P450 enzymes can reduce the efficacy of the OCP (e.g. rifampicin, some anti-epileptics, anti-retrovirals)
What are some side-effects of the OCP?
Spotting (bleeding between periods)
Nausea
Sore breasts
Changes in mood or libido
Hunger
Extremely rare
Blood clots in legs or lungs (2 in 10,000)
What are some of the non-contraceptive uses of the OCP?
Help makes periods lighter and less painful
Helpful with endometriosis/fibroids
Dysmenorrhoea (painful periods)
Menorrhagia (heavy periods)
Regular withdrawal bleeds/ no bleeds
PCOS: helps reduce LH and hyperandrogenism (treats acne/hirsutism)
What are the advantages of the progesterone only pill (POP)?
Also known as the “Mini-Pill”
Works similarly to the OCP (slightly less reliably inhibits ovulation however)
Often suitable if person can’t take oestrogen
Easy to take - one pill per day with no break
Doesn’t interrupt sex
Can help heavy or painful periods
Periods may stop (temporarily)
Can be used while breastfeeding
What are the disadvantages of the progesterone only pill (POP)?
Easy to forget
Shorter acting - needs to be taken at the same time each day
No protection against STIs
What are the possible side effects of the POP?
Irregular bleeding
Headaches
Sore breasts
Changes in mood
Changes in sex drive
What are the main long-acting reversible contraceptives (LARC)?
Coils
Intra-Uterine Devices - IUD (i.e. copper coil)
INtra-Uterine Systems - IUS which secrete progesterone (e.g. Mirena coil)
Progesterone-only injectable contraceptives/subdermal implants
Outline coils as a form of contraception
Suitable for most women
Prevent implantation of conceptus – important for some religions
Rarely can cause Ectopic Pregnancy
Can be used as emergency contraception
Outline IUDs
Mechanically prevent implantation, decrease sperm / egg survival Lasts 5-10yrs.
Can cause heavy periods, and 5% can come out especially during first 3months with periods
Outline IUS
Thins lining of the womb and thicken cervical mucus (can be used to help with heavy bleeding)
Lasts 5yrs
What is the main drawback of progestogen-only injectable/subdermal implants?
Long lasting effects, so not best option if desiring fertility soon/changes mind
What is emergency contraception?
Contraceptions which can be taken after unprotected sex to prevent pregnancy
What are the main options of emergency contraception?
Copper IUD (most effective)
Pills:
Ulipristal acetate 30mg (ellaOne)
Levonorgestrel 1.5mg (Levonelle)
Why are copper IUDs so effective?
Can be fitted up to 5 days after unprotected sex (<1% chance of pregnancy)
Outline the 2 types of pill that can be taken as emergency contraceptives
Ulipristal acetate 30mg (ellaOne)
Ulipristal acetate stops progesterone working normally and prevents ovulation
Must be taken within 5 days of unprotected intercourse (earlier has better efficacy)
1-2% can get pregnant if ovulation has already occurred.
Levonorgestrel 1.5mg (Levonelle)
Less effective (especially if BMI >27 kg/m2)
Synthetic Progesterone prevents ovulation (doesn’t cause abortion, so ineffective if ovulation has occurred)
Must be taken within 3 days of unprotected intercourse. 1-3% failure rate
What are the side effects of the 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
What considerations should be taken for choice of contraception?
Contraindications for OCP (e.g. risk of venous thromboembolism (VTE)/CVD/Stroke)
Other conditions that may benefit from OCP
Need for protection against STIs
Concurrent medication
Ease of use
What are some contraindications for the OCP?
Risk of VTEs, CVD or stroke
Migraines with aura (sensory disturbances), indicates risk of stroke
Smoking (15>/day) at age 35 or older
Stroke or CVD history
Current breast cancer
Liver cirrhosis
Diabetes with nephropathy/neuropathy/retinopathy
What other conditions may benefit from the OCP?
Menorrhagia / Endometriosis / Fibroids
PMS (Pre-Menstrual Syndrome)
Acne or hirsutism
What concurrent medications would make the OCP a poor choice?
P450 liver enzyme-inducing drugs (e.g. anti-epileptics, antibiotics)
Teratogenic drugs (eg lithium or warfarin), more effective methods of contraception needed (e.g progestogen implants/IUD/IUS)
Why is it so important to have a more effective contraception when someone is using teratogenic drugs?
Can cause great harm/deformities to the foetus
What are the benefits of HRT (aka Menopause Hormone Treatment (MHT))
Symptom relief from symptoms due to low oestrogen
(e.g. flushing, sweats, disturbed sleep, joint pains, brain fog, decreased libido, low mood)
Reduction in osteoporosis severity (and so reduced osteoporosis related fractures)
What are the risks of HRT?
Venous thromboembolisms
Hormone sensitive cancers (including endometrial cancers)
CVD
Stroke
Expand on VTEs as a risk of HRT
Venous thromboembolism: Deep vein thrombosis (DVT) or Pulmonary Embolism (PE)
Oral oestrogens undergo first pass metabolism in the liver
Oral increases clotting factors
Transdermal oestrogens safer in terms of VTEs (avoid oral oestrogens if BMI>30)
Expand on hormone sensitive cancers as a risk of HRT
Breast cancer - slight increase in risk in women with on combined HRT
Risk related to duration of treatment - reduces after stopping HRT
Continuous poses more risk than sequential
Ovarian cancer - small increase in risk after long term use
Expand on endometrial cancers as a risk of HRT
All women undergoing HRT who have not had their uterus removed (i.e. still have an endometrium) need progestogens to simulate endometrial shedding
Post-menopausal bleeding could indicate endometrial cancer
Expand on CVD as a risk of HRT
Improved risk in younger Women & sooner after Menopause
Increased risk if started later i.e. 10 years after menopause
Likely benefit to CVD risk in younger women e.g. Premature Ovarian Insufficiency (POI)
Expand on stroke as a risk of HRT
Small increased risk
Oral have more risk than transdermal oestrogens
Combined (E2+P) more risk than oestrogen only
Summarise HRT risks
Summarise the benefits vs risks of HRT
What is “sex”?
Biologically defined (i.e. male, female, or Intersex)
What is gender?
A social construct
How an individual sees themself/identifies
Define non-binary
Gender does not match to traditional binary gender understanding,
includes agender, bigender, pangender, gender fluid
Define cis-gender
Cis meaning same
Birth sex and gender are aligned
Define gender non-conforming
Gender does not match assigned sex
Define gender dysphoria
Gender does not match assigned sex, causing distress
Define transgender
Transitioning from one gender to another
Define a transgender man
A person who is assigned female sex at birth, but transitions to male gender
Define a transgender woman
A person who is assigned male sex at birth, but transitions to female gender
What is the prevalence of transgender men vs women?
3x more transgender women than men
How should transgender men be treated?
Masculinising hormones
Testosterone (injections, gels)
Progesterone to suppress menstrual bleeding if needed (endometrial hyperplasia 15%)
How should transgender women be treated?
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%))