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Year2 Endo > Infertility II ( treatments) > Flashcards

Infertility II ( treatments) Flashcards

1
Q

What would you do to replace testosterone if fertility is not desired

A

Treat Symptoms- loss of early morning erections, libido, decreased energy, shaving

Testosterone Replacement: 
Daily Gel (eg Tostran). Care not to contaminate partner.
3 weekly intramuscular injection (eg Sustanon)
3 monthly intramuscular injection (eg Nebido)
Less Common (Implants, oral preparations)
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2
Q

What investigation must you make before you start testosterone replacement

A

At least 2 low measurements of serum testosterone before 11am.
Investigate the cause of low testosterone.

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3
Q

What must you monitor while on testosterone replacement

A

Safety Monitoring:
Increased Haematocrit (risk of hyperviscosity and stroke)
Prostate (Prostate Specific Antigen (PSA) levels)

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4
Q

How do you secondary hypogonadism for males

/ testosterone deficiency with fertility required

A

Secondary Hypogonadism-
(deficiency of gonadotrophins ie hypogonadotrophic hypogonadism):
Treat with Gonadotrophins (ie LH and FSH) to induce Spermatogenesis.
DON’T GIVE TESTOSTERONE

give hCG injection with act on Lh receptors
LH stimulates Leydig cells to increases intratesticular testosterone to much higher levels than in circulation (x100).

FSH stimulates seminiferous tubule development and spermatogenesis

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5
Q

How do you treat primary hypogonadism in men

A

you don’t –> difficult to treat

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6
Q

what is PCOS

A

Cysts on ovaries making to much hormone will cause hyperandrogenism

anterior pituitary makes too much LH, at least double the amount as FSH
excessive LH causes the theca cells to produce excess amounts of androstenedione, way too much for those granulosa cells to convert.
excess androstenedione flows into the blood and some of it gets converted into estrone by aromatase in fat or adipose tissue
estrone, like estradiol, is a member of the estrogen family, and it acts as a negative feedback signal, stopping the anterior pituitary from releasing FSH.
Because LH levels are really high, there’s no LH surge to trigger the dominant follicle to break away from the ovary, so it may remain there, appearing as a cyst, or it might degenerate with the other follicles. Essentially, ovulation does not occur.

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7
Q

What are the symptoms of PCOS

A

Symptoms can be weight gain, oligomenorrhea , hiruisism , acne

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8
Q

What is a condition linked with PCOS

A

majority of patients have insulin resistance, it is thought that this contributes to excess LH

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9
Q

How to diagnose PCOS

A

Rotterdam PCOS diagnostic criteria (2 out of 3)
Oligomenorrhoea or amenorrhoea
Assessed by menstrual frequency <21d or >35d <8-9 cycles per year >90d for any cycle
Clinical evidence of androgen excess
(Hirsutism (Ferriman-Galleway score), acne, alopecia (Ludwig score) or biochemical evidence: raised androgens
Polycystic ovaries ( PCO morphology found on ultrasound)
>12 antral follicles in one ovary . Do not use US until 8y post-menarche (due to high incidence of multi-follicular ovaries at this stage).

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10
Q

What is hypothalamic amenorrhoea

A

Insufficient energy causes hypothalamus to decrease in function → insufficient energy for ovulation

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11
Q

what are methods to treat PCOS

A

1) ovulation induction ( fertility related)
2) Non fertility related: progesterone (prevents endometrial cancer), creams, waxing, diet, lifestyle, oral contraceptive (irregular menses), metformin (irregular menses and insulin resistance)
3) OCP to reduced Lh and hyperandrogenism

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12
Q

What is ovulation induction

and why must you only develop 1 follicle

A

Ovulation Induction
Aim to develop one ovarian follicle

If >1 follicle develops, this risks multiple pregnancy (ie Twin / Triplet)

Multiple pregnancy has risks for mother and baby during pregnancy

Ovulation induction methods aim to
cause small increase in FSH

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13
Q

How can you restore ovulation to anovulatory PCOS

A

weightloss/metformin
Letrozole
Clomiphene
fsh stimulation (superovulation

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14
Q

what is the function and mechanism of action of letrozole?

A

Letrozole : aromatase inhibitor
inhibits the aromatase-mediated conversion of testosterone to oestradiol
levels of oestradiol drop, hence there is less negative feedback exerted on GnRH secretion ( aka GnRH will increase)
Greater GnRH pulsatile release increases FSH and LH levels. FSH is required to stimulate ovaries to grow a follicle.

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15
Q

What is the function and the mechanism of action of clomiphene

A

Clomiphene: oestradiol receptor modulator ( aka can act as agonist and antagonist)
prevents negative feedback of oestrogen being exerted on hypothalamic-pituitary axis leading to a marked response with increased GnRH and FSH/LH.

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16
Q

describe the process of IVF treatment

A

1) FSH stimulation (superovulation)

2) Prevent premature LH surge (this reduces premature ovulation) . 2 methods:
GnRH antagonist protocol (short protocol) aka pulistile GnRH – this blocks LH release from gonadotrophs.
Note this can be given in short term to restore ovulation
GnRH agonist protocol (Long protocol) aka continuous GnRH – disrupts the pulsatility of gonadotrophin release and causes desensitization of LH due continuous stimulation (Initial flare is proceeded by LH inhibition).

3) Egg maturation with hcG
4) 2 ways to fertilize in vitro : IVF or ICSI ( sperm injection into egg → used when male factor sperm is not working properly)

5) Embryo incubation
6) Embryo transfer into uterus

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17
Q

what is short protocol GnRH used for in IVF

A

Prevent premature LH surge (this reduces premature ovulation)

GnRH antagonist protocol (short protocol) aka pulistile GnRH – this blocks LH release from gonadotrophs.
Note this can be given in short term to restore ovulation

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18
Q

what is long protocol GnRH used for in IVF

A

(Long protocol) aka continuous GnRH – disrupts the pulsatility of gonadotrophin release and causes desensitization of LH due continuous stimulation (Initial flare is proceeded by LH inhibition).

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19
Q

What are the 2 ways to fertilise and egg in vitro

A

IVF and ICSI ( sperm injection into egg → used when male factor sperm is not working properly)

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20
Q

what is ovarian hyperstimulation

A

gonadotropin therapy used for ovulation induction may cause ovarian hyperstimulation syndrome, especially in individuals with PCOS
Symptoms range from mild, like abdominal discomfort and distention, enlarged ovaries with multiple cysts, to severe forms with nausea, vomiting, ascites, pleural effusion, hypovolemia and oliguria or anuria.
Critical presentation: signs of end-organ damage - like respiratory distress, acute kidney injury, cardiac arrhythmias and disseminated intravascular coagulation

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21
Q

suggest some methods of contraception

A

Methods:
Barrier: male / female condom / diaphragm or cap with spermicide
Combined Oral Contraceptive Pill (OCP)
Progestogen-only Pill (POP)
Long Acting Reversible Contraception (LARC)
Emergency Contraception

Permanent methods:
Vasectomy
Female sterilisation

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22
Q

what are the pros of using barrier contraception

A

Protect against STI’s
Easy to obtain – free from clinics
/ No need to see a healthcare professional
No contra-indications as with some hormonal methods

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23
Q

what are the consof using barrier contraception

A 
Can interrupt sex
 Can reduce sensation    
 Can interfere with erections 
 Some skill to use eg correct fit.
 Two are not better than one
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24
Q

what is the OCP and what does it do

A

OCP can be oestrogen / progesterone. THis will reduced -ve feedback on the hypo-pit system causes reduced LH/FSH . This will :
Prevent anovulation ( o + prog)
Thicken cervical mucus ( prog only)
Thin endometrial lining to reduce implantation ( prog only)

can be used for non contraceptive uses

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25
what is the Combined oral contraceptive pill
pill with O and prog
26
what are the pros of taking the OCP
``` Positives 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) ```
27
what are the cons of taking OCPS
Negatives It can be difficult to remember No protection against STIs P450 Enzyme Inducers may reduce efficacy Not the best choice during breast feeding ``` Possible side effects : Spotting (bleeding in between periods) Nausea Sore breasts Changes in mood or libido Feeling more hungry (try different OCPs to see which suits best) ``` Extremely rare side effects: Blood clots in the legs or lungs (2 in 10,000
28
what are the side effects associated with taking OCPS
``` Possible side effects : Spotting (bleeding in between periods) Nausea Sore breasts Changes in mood or libido Feeling more hungry (try different OCPs to see which suits best) ``` Extremely rare side effects: Blood clots in the legs or lungs (2 in 10,000
29
what are the non contractive uses of the OCP
Non-contraceptive uses: Helps make periods lighter and less painful (eg endometriosis or period pain or menorrhagia) Withdrawal bleeds will usually be very regular PCOS: help reduce LH and hyperandrogenism
30
what is the POP
Progesterone Only Pill (POP) or ‘Mini-Pill
31
What the pros in taking the POP
Positives Works as OCP but less reliably inhibits ovulation Often suitable if can't 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 ```
32
what are teh cons of taking the POP
Negatives Can be difficult to remember No protection against STIs Shorter acting – needs to be taken at the same time each day ``` Possible side effects Irregular bleeding Headaches Sore breasts Changes in mood Changes in sex drive ```
33
What are the side effects of taking POP
``` Possible side effects Irregular bleeding Headaches Sore breasts Changes in mood Changes in sex drive ```
34
what are Long acting reversible contraceptives ( LARCs) | and what can they be used for
Coils are suitable for most women incl Nulliparous (no previous children). Exclude STI’s and cervical screening up to date before insertion Prevent implantation of conceptus – important for some religions Rarely can cause ectopic pregnancy Can be used as emergency contraception
35
What must be done before a LARC is implanted
Exclude STI’s and cervical screening up to date before insertion
36
What are the 3 types of LARc
1) Intrauterine device ( IUD) ie copper coil 2) IUS ( systems) which secretes progesterone ie mirena coil 3) progesterone only injectable contraceptives/ subdermal implants
37
what is the function of IUDs ( ie copper coils) and what are the pros / cons of using them
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
38
what is the function of IUS ( intrauterine systems ie mirena coil)
Secretes progesterone to thin lining of the womb and thicken cervical mucus (can be used to help with heavy bleeding). Last 3-5yrs.
39
What are the 3 types of emergency contraception
Moring after pill and IUD 1)Copper intrauterine device (IUD) most effective can be fitted up to 5 days after unprotected sex (<1% chance of pregnancy) Emergency contraceptive pill: 2. Ulipristal acetate 30 mg (ellaOne) Ulipristal acetate stops progesterone working normally and prevents ovulation. Must be taken within 5 days of unprotected intercourse (earlier better). 3. Levonorgestrel 1.5 mg (Levonelle) least effective (esp if BMI >27 kg/m2) Synthetic Progesterone prevents ovulation (don’t cause abortion). Must be taken within 3 days of unprotected intercourse.
40
what are the side effects of the morning after pills
Side effects- 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.
41
what considers must be made when choosing the form of contraception
``` 1. Risk of Venous Thromboembolism (VTE) / CVD / Stroke Comorbidities- Avoid OCP if: Migraine with aura (risk of stroke) Smoking (>15/day) + age >35yrs Stroke or CVD history Current Breast cancer Liver Cirrhosis Diabetes with complications eg retinopathy/nephropathy/neuropathy ``` 2. Other conditions that may benefit from OCP eg Menorrhagia / Endometriosis / Fibroids 3. Need for prevention of Sexually Transmitted Infections (STI’s) ``` 4. Concurrent medication — 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).  ```
42
what are the 2 forms of hormone replacement therapy?
COMBINED HRT: oestrogen + progestogens (synthetic progestins and the natural hormone progesterone) – to prevent endometrial hyperplasia – this reduces risk of cancer HRT – oestrogen-only – only for women that have had hysterectomies (as no endometrium!)
43
why do you give combines HRT
Relief of symptoms of low oestrogen (eg Flushing, disturbed sleep, decreased libido, low mood) and less osteoporosis related fractures (decreased by one third) Does increase risk of breast cancer, VTE, stroke and gallstones but absolute risk for postmenopausal >50s women is very low. NOTE that absolute risk is very low but it may DOUBLE the relative risk! HRT to OLDER women has a much more increased risk (better in younger postmenopausal)
44
what is an example of a HRT drug
e.g. Tibolone – a synthetic prohormone. Has oestrogenic, progestogenic and weak androgenic actions. Does increase risk of stroke, and possible increase in risk of breast cancer. Can be given oral, transdermal, transvaginal. Can be given cyclical (oestrogen every day and progesterone on 12-14 days in) OR continuously.
45
what are the risk of HRT
1) venous thrombo embolism 2) Hormone sensitive cancers 3) concerns about the risk of cardiovascular disease 4) risk of stroke ( cerebrovascular disease) see table on google docs
46
what is a venous thrombo - embolism and what can cause it ?
. Venous Thrombo-embolism: Deep Vein Thrombosis (DVT) or Pulmonary Embolism (PE) Oral oestrogens undergo first pass metabolism in liver Oral >> Increase SHBG, Triglycerides, CRP Transdermal estrogens are safer for VTE risk than oral Avoid oral oestrogens in BMI > 30 kg/m2
47
what are the 3 types of hormone sensitive cancers can how do they react to HRT
Breast Cancer Slight increase only in women on Combined HRT (ie oestrogen AND progesterone) Risk related to duration of treatment and reduces after stopping Continuous worse than Sequential Assess risk in each individual before prescribing Ovarian cancer- Small increase in risk after long-term use. Endometrial Cancer- Must prescribe Progestogens in all women with an endometrium ! Progestogens: synthetic progestins and the natural hormone progesterone.
48
Why must you give progesterone to women with an endometrium
prevents endometrial cancer
49
How do you monitor HRT treatment in relation to cancer
Assess HRT Safety / Efficacy at 3 months and then annually Unscheduled bleeding is common within first 3 months. Post-menopausal bleeding could indicate endometrial cancer
50
what is the relationship between HRt and risk of cardiovascular disease
3. Concern about increased risk of Cardiovascular disease No increased risk if started before age 60 yrs Increased risk if started 10 years after menopause Possible benefits of oestrogen supplementation in young women e.g. Premature Ovarian Insufficiency (POI)
51
what is the relationship between HRT and risk of stroke
. Risk of Stroke (cerebrovascular disease) Small increased risk Oral > transdermal oestrogens Combined > oestrogen only
52
what are the benefits of HRT
Benefits of HRT Relief of symptoms of low oestrogen eg Flushing, disturbed sleep, decreased libido, low mood Less osteoporosis related fractures decreased by one third
53
definition of a) gender b) sex c) cisgender d) gender non conforming e) gender dysphoria f) non binary g) transgender
Gender is social construct, how you see yourself as male, female, or non-binary. Sex is biologically defined eg male, female, or Intersex. Cisgender – Same Sex and Gender. Gender non-conforming – Gender does not match assigned sex. Gender Dysphoria- when that causes distress. Non-binary- Gender does not match to traditional binary gender understanding, includes agender, bigender, pangender, gender fluid. Transgender- Transitioning or planning to transition physical appearance from one gender to another. Transgender men - Female Sex at birth, but male gender (FtM is no longer used). Prevalence- Transgender women 3x more common than transgender men
54
what would you give to transgender young ppl
Prepubertal Young people – GnRH agonist for pubertal suppression and then sex steroids. Post-treatment regret 1-2% Gender Reassignment surgery after 1-2 yrs of hormonal treatment
55
what is the procedure for giving masculinising hormones for trans men
Testosterone (injections, gels) (S/E: Polycythaemia, lower HDL, Obstructive Sleep Apnoea (OSA). No increase in CVD). Progesterone to suppress menstrual bleeding if needed (endometrial hyperplasia 15%) 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
56
what are teh side effects of giving testosterone for trans men
(S/E: Polycythaemia, lower HDL, Obstructive Sleep Apnoea (OSA). No increase in CVD).
57
why do you give transmen progesterone
Progesterone to suppress menstrual bleeding if needed (endometrial hyperplasia 15%)
58
what is the procedure for giving feminising hormones for transwomen
1. Estrogen (transdermal, oral, intramuscular) High dose oestrogen eg 4-5mg per day to aim for estradiol levels of 734 pmol/L. (Side Effects: VTE dose-related at 2.6%, high BP, Cardio-Vascular Disease, high Triglycerides, hormone sensitive cancers eg breast cancer, abnormal Liver Function tests 3%) 2. Reduce Testosterone GnRH agonists (induce desensitisation of HPG axis) Ant-Androgen medications (eg Cyproterone acetate, Spironolactone) - Height, voice and Adam’s apple will not change. - Consider Sperm Banking before starting hormone therapy. 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
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Year2 Endo (13 decks)

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