OGCO- Management in reproductive endocrinology clinic Flashcards
What is secondary amenorrhea/oligomenorrhea and how to approach?
Define as absence of periods of a length of time equivalent to a total of at least 3 of the previous cycle intervals or 6 months. Oligomenorrhea refers to cycle lengths of more than 35 days.
A careful history and PE should seek the following: evidence for pyschological dysfunction or emotional stress, signs of a physical problem with a focus on nutritional status and evidence for CNS disease
Investigations for secondary amenorrhea/oligomenorrhea?
- Exclude pregnancy. Check FSH, LH, estradiol, testosterone, prolactin and TSH levels and a progestogen challenge with MPA 10mg/day for 7 days. Patients with significant hyperandrogenism, abnormal hyperprolactinemia or TSH level should be treated accordingly
- USS for PCO
- Patients with hirsutism should have blood taken for testosterone and 17-hydroxyprogesterone. If total testosterone is above 5nmol/L, ovarian and adrenal imaging should also be carried out to exclude androgen secreting tumors. If there are features suggestive of Cushings syndorme, a 1mg overnight dexamethasone suppression test can be arranged.
What is the Tx for secondary amenorrhea?
- In the presence of withdrawawal bleeding (after progestogen withdrawal test), a dx of WHO2 anovulation is made. These women require administration of MPA 10mg/day for 10 days at least every 3 months to protect the endometrium from developing hyperplasia or carcinoma. When reliable contraception is essential, a low dose contraceptive pill is appropriate. Patients who wish to get pregnant can be offered ovulation induction with oral fertility drugs first.
- If there is no withdrawal bleeding, combined estrogen and progestogen can be given. If withdrawal bleeding still does not occur, there is uterine cause and further Ix should be done to identify the uterine cause.
- If serum FSH elevated to >25IU/L on 2 occasions with >4 weeks apart, a dx of ovarian insufficiency is made. All patients under the age of 40 should have karyotyping and fragile X screening in TYH. Anti adrenal antibody and anti-TPO antibody checked, and those with raised anti-TPO antibody should have thyroid function monitored annually. HRT may be done if DXA scan in osteopenic/osteoporotic range till age 51.
- If no progestogen withdrawal bleeding but bleeding after E+P –> most likely dx is hypogonadotrophic hypogonadism. MRI of the pituitary is indicated in the absence of obvious functional cause. Functional cause: stress, excessive excercise or weight loss, anorexia, or bulimia. In the absence of these associated conditions, HRT or OCP can be prescribed
- Symptoms of androgen excess without an obvious cause (androgen secreting tumor, CAH or cushings syndrome), a low dose oral contraceptive pill can be given.
Initial assessment for PCOS?
History
Menstrual history: cycle length and regularity, LMP, note any history of abnormal intermenstrual bleeding since women with chronic anovulation at higher risk of endometrial pathology
Hyperandrogenic symptoms: hirsutism, acne, greasy skin, male pattern alopecia
Family history of PCOS and metabolic syndrome
Weight changes, diet and excercise pattern
In patient presenting with oligo-amenorrhea, symptoms associated with hyperprolactinemia (galactorrhea, headache, visual disturbance), thyroid dysfunction and climacteric symptoms should be enquired as well
PE
* Height, weight and BMI
* Waist circumference
* BP
* Hirsutism assessed by Ferriman-Gallwey scoring, acne and male pattern baldness
* Acanthosis nigricans (marker of insulin resistance)
* Galactorrhea and goitre
* Pelvic examination
* Signs of virilization e.g. clitoromegaly
Initial Ix for PCOS
Ix:
* Pelvic USG (TVS preferred) to look for PCO features in all patients presenting with oligomenorrhea or amenorrhea. USG of PCO is ovary with >20 follicles measuring 2-9mm in diameter. Transrectal USG will be used in women without previous sexual exposure for counting antral follicles. Only 1 ovary fitting this definition is sufficient for defining PCO.
* Blood for total testosterone
* OGTT for confirmed PCOS
* FSH, LH, TSH and prolactin if there is oligomenorrhea
* Endometrial biopsy if there is Hx of abnormal uterine bleeding
* In women with hirsutism, women should be assessed clinically as well as by appropriate Ix to exclude late onset CAH and overnight dexamethasone suppression test to exclude cushing syndrome, as well as imaging (USG of pelvis and CT adrenals) to exclude androgen secreting tumor
What is the diagnostic criteria for PCOS?
2 of the 3 following criteria
* Oligo and/or anovulation (irregular cycles is defined in adults as cycles <21 or >35 days or <8 cycles per year)
* Clinical or biochemical hyperandrogenism
* Polycystic ovaries (20 or more follicles measuring 2-9mm in diameter, and/or ovarian volume >10cm3)
What is the counselling on physical/health implications of PCOS?
- Endocrine disturbance: menstrual disturbance and acne/hirsutism
- Risk of endometrial hyperplasia and cancer with long term amenorhea-hence regular withdrawal bleeding at least 3 monthly is desired
- Reproduction: anovulatory infertility
- Metabolic disturbance: hypertension, DM, hyperlipidemia
Stop smoking
Advise weight reduction if BMI >25kg. Excercise: moderate excercise >30 mins per day
Tx of PCOS with menstrual disturbance?
- Periodic induction of withdrawal bleeding to protect the endometrium against endometrial hyperplasia and cancer secondary to chronic unopposed estrogen stimulation
- COC pills are one of the 1st line treatments if fertility is unwated.
Adv: good cycle control, protects endometrium, provides contraception, lowers androgen and hence ameliorates hyperandrogenic symptoms - Periodic progestogen treatment is an alterantive: provera 10mg daily x 10 days at least every 3 months.
Adv: protects endometrium, avoids metabolic AE of estrogen, particularly in women already manifesting metabolic disturbances - Levonorgestrel intrauterine system (Mirena) can be another alternative providing both long acting reversible contraception as well as endometrial protection
Tx of PCOS with hyperandrogenic symptoms?
Hirsutism
* Cosmeitc measures: plucking, shaving, waxing, electrolysis, laser treatment
* COC pills: increase SHBG and suppresses androgen. Diane-35 and Yasmin contains anti-androgenic progestogens and may be preferred
* Anti androgens: spironolacftone (50-100mg bd orally), cyprotereone (need proper contraception owing to potential teratogenicity), flutamaide (rarely used)
Treatment may take 6 months or more to produce appreciable effects
Acne
* Personal hygiene
* COC pills
Tx of PCOS women with anovulatory infertility?
- Weight reduction
- Letrozole/clomiphene citrate: letrozole is 1st line therapy for patietns with PCOS
- Metformin: lowers fasting insulin level –> decreases BMI compared with placebo.
- Laparoscopic ovarian drilling: indication as an alternative to gonadotrophin treatment in anovulatory PCOS subjects with letrozole or CC resistance
- Gonadotrophins: 2nd linef for letrozole or CC resistant patients
- IVF: 3rd line treatment for thoese resistant to letrozole or CC, 2nd line for those failing anovulation induction by letrozole or CC, or those with other concurrent indications for IVF
Ix for hyperprolactinemia?
Drug history, in particular psychiatric drugs, must be sought in history. Galactorrhea and visual field defects should be looked for
Ix
* TFT to rule out hypothyroidism
* RFT to exclude renal insufficiency
* MRI study of the pituitary is indicated
* Screen for macroprolactin in Ix of hyperprolactinemic subjects (reflex screening by PEG precipitation is performed by QMH)
* Venipuncture stress can cause high prolactin level. Blood test can be repeated for confirmation.
Tx for hyperprolactinemia?
- Annual prolactin level estimation is adequate for patients with regular menses even if they have a mildly elevated prolactin or a pituitary microadenoma
- Medical treatment only indicated when there is amenorrhea/oligomenorhea, or galactorrhea
- Treatment starts with 1.25mg bromocriptine taken with meals at night to avoid side effects
- Other dopamine agonists e.g. cabergoline 0.5mg twice per week can be considered if bromocriptine cannot be tolerated.
- Refer to medical endocrine team in the presence of macroadenoma (>10mm)
- In case of antipyshotic induced hyperprolactinemia, liase with the psychiatrist regarding the feasibility to stop the drug or to substitute by another drug which has less effect on prolactin.
What is the FU for hyperprolactinemia?
- Most patients, normal menses resume within 4 weeks after the start of therapy
- If amenorrhea persists despite nromal prolactin level, a pregnancy test should be performed
- Contraception should be advised for those patients who do not wish to get pregnant. Bromocriptine should be discontinued as soon as pregnancy is confirmed.
- Pregnant patients with microadenomas should be referred to the endocrine clinic, department of medicine for serial visual field examination
- Dopamine agonist may be tapered and discontinued in patients who have been treated for at least 2 years, who no longer have elevated serum prolactin and have no visible tumor remnant on MRI. After drug discontinuation, serum prolactin monitored every 3 months for first year, than annually thereafter. if prolacitn level increases above normal levels –> repeat MRI
- In women with microprolactinomas or no visible prolactinoma, dopamine agonist therapy can be stopped after menopause
What are the medical problems associated with Turner syndrome?
- CVS: increased risk of congenital heart disease, lymphatic vasculature abnormalities and cystic hygroma, CHD, HT, HL
- Bone metabolism: lower BMD
- Autoimmune thyroiditis: hyper/hypo
- Hearing problems: otitis media due to abnormal cranial anatomy which may lead to conductive hearing loss
- Developmental delay and learning difficulties
- Liver dysfunction (raised liver enzymes): HRT is not contraindicated unless deranged liver function >2xULN
- Renal problem: congenital structural anomalies of the kidney are normal. UTIs are more common (related to obstructive uropathy)
- Gonadectomy recommended if presence of Y chromosomes material on standard karyotyping. To perform FISH for SRY probe only if presence of virilization and test at least 2-3 tissues including buccal cells
Points to discuss in Turner syndrome for medical adult care?
What Ix to be done?
- Continuation of HRT
- Optimize bone accrual: maintain adequate calcium intake and weight bearing excercise, maintain optimal BW
- Increased risk of osteoporosis, hypertension, diabetes and dyslipidemia
- Fertility issue: options of oocyte cryopreservation if still menstruating and oocyte donation
- Associated medical conditions (e.g. congenital heart disease, thyroid dysfunction, renal problem, hearing problem)
- Psychological support
- Arrange baseline DXA
- Body weight, height, BMI, waist/hip ratio
- BP
- OGTT, lipid profile, TSH and fT4, antimicrosomal/antithyroglobulin antibodies, liver/renal function test
- Cardiac MRI
- Refer to adult congenital heart disease
- Baseline audiological assessment if not done before
- Baseline USG of urinary tract if not done before
