W10L3 Thurs Ovarian disorder and disease Flashcards
Folliculogenesis
primordial follicles → 20-30 recruited = primary follicles → antrum formation → atresia → 1 follicle ovulates
§ Atresia always occurring within primordial, primary + secondary follicle pools
§ Preantral follicle growth (primordial → primary) takes 4 months
§ Antral follicle growth (primary/secondary follicle onwards) takes 2 cycles due to GnRH/FSH/LH stimulation
Premature Ovarian Insufficiency (POI), what is it? cause and and symptom
§ POI: early menopause <40yo affecting ~2% of population
§ Cause: genetic (Turner + Fragile X syndromes, inhibin alpha gene), mostly unknown (autoimmune), side effects of cancer/fertility issues + treatment
§ Symptoms: no periods for 4 months before age 40, FSH levels >40mIU/ml on 2 occasions at least 1 month apart (day 2-6 if cycling) – high FSH = body trying to recruit follicles, abnormally low AMH (fewer small-medium size follicles in ovary) + oestrogen level, exclusion of all other causes of absent periods
POI treatment
no known treatment; sometimes responsive to ovarian stimulation but mainly need donor eggs to conceive, at risk pre-puberal girls may opt for ovarian cryopreservation, still need contraception (5-10%)
Ø HRT/contraception until ~50yo = body systems require sex steroids (oestrogen, progesterone)
Ø ↓oestrogen can cause osteoporosis, heart disease, hypothyroidism, auto-immune diseases
Anovulation, cause and symptom
no ovulation = no egg = no pregnancy (40% infertile women)
§ Causes: hormone deficiency, very low body weight (<20%), obesity (10-15% above normal BMI) + weight fluctuations, diet + stress, overexercise, hormone resistance (insulin), damaged/diseased ovaries, pituitary tumour (high prolactin levels suppress reproduction)
§ Symptoms: oligomenorrhoea (infrequent period), amenorrhoea (absent period >6 months)
Anovulation diagnosis
-ultrasound (abnormalities – ovarian cysts, uterine growths, endometriosis),
-blood tests (steroids, gonadotrophins, prolactin, thyroid, AMH)
Anovulation treatment
-lifestyle changes (diet, stress),
- hormonal ovulation induction (clomid – oestrogen antagonist = more FSH/LH produced to stimulate folliculogenesis or gonadotrophins FSH/LH/hCG to trigger follicle growth + ovulation) but this have a high risk or multiple ovulation> twining or more
-IVF treatment
Polycystic Ovary Syndrome prevelance
Affects 5-18% of women- most common endocrine disorder
* Australians 12-18%- Indigenous Australian women up to 21%
* Issues with diagnosis, could be more?
* Syndrome- multifaceted symptoms, several diseases
Polycystic Ovary Syndrome symptom list
– centralised weight gain (apple shape)
– ↑ acne & bad skin
– Hirsutism- face (male patterns hair grown)
– Anovulation, irregular menstrual cycles
– Subfertility- lack of pregnancy + higher miscarriage
– Mood swings, ↓ libido, ovulation kit useless
* Variation in symptoms and how many are evident
* Effects on embryo/fetus- programming
Polycystic ovary syndrome (PCOS) diagnosis
Strict but changing criteria (Rotterdam criteria 2003)
1. ↑ androgens - Hirsutism (70%), ↑ acne
2. Anovulation, irregular menstrual cycles
3. Presence of cystic follicles – enlarged ovaries, ↑ small surface cysts
* Must have 2 of 3- can have PCOS and NOT have cystic ovaries (40%)!
* Blood tests
– ↑LH, ↓ FSH, ↓ SHBG, ↑Androgens, ↑ Oestrogens (Oestrone)
* Ultrasound
– >12 follicles 2-9mm (small), ↑ ovary size
Polycystic ovary syndrome (PCOS) Causes and risk factors
- genetic factors unknown,
-weight (change, over/under, hard to lose as it is a metabollic disorder, and ½ not overweight)
Ø Insulin resistant = ↑circulating insulin = ↑fatty acid synthesis + inhibition of SHBG (sex hormone binding globin) from liver = ↑androgen
Associated problem with PCOS
- Obesity and metabolic sequelae
- Type II diabetes
- Cardiovascular disease
- Uterine/Ovarian carcinomas (↑ Oestrone)
Polycystic ovary syndrome (PCOS) treatment
-oral contraceptive pill (w/ androgen inhibitors)
- clomid (boosts FSH)
- block androgen receptors (flutamide),
-metformin (insulin sensitiser)
- weight loss, exercise, diet
Ø Patient specific due to syndrome nature = symptoms differ
PCOS characteristic
high LH = high [androstenedione] + [testosterone] formed that enter blood → androgens in peripheral circulation to adipocytes which convert androgens to oestrone which modulates FSH/LH release in ant. pituitary (decrease via feedback loop)
Ø High LH (unknown reason) but low FSH (turned off by oestrogens)
Ø Decreases FSH-stimulated converesion of androgens into oestrone + oestradiol
Ø Lack of FSH lead to death of granulosa cells (8mm), theca cell remain due to insuline = cyst
Ovarian Tumours
Ovarian tumours may arise at any age but are most common between 30 and 60 yrs old
1. Ovarian tumours are particularly liable to be or to become malignant
2. In their early stages they are asymptomatic and painless
3. They may grow to a large size and tend to undergo mechanical complications such as torsion and perforation
Diagnosis and incidence of ovarian tumor
- Difficult to diagnose- lack of specific symptoms
- Approximately 25% of all tumours are malignant
- 80% primary and 20% secondary growths
- In developed countries, the lifetime risk of developing ovarian cancer is ~2%. Slightly greater than the risk of cervical or endometrial cancers (well below the 7% risk of breast cancer)
- In 2010 USA, ~22,000 new cases and ~14,000 women died of ovarian cancer (>50% deaths in women 55-74 years old)
- Poor prognosis as when identified 60% of women have stage III or IV
Suggestive feature of tumor
- Age- over 50 yrs old chance > 50%, under 50 <15%
- Rapid growth
- Ascites (excess ovarian fluid)
- Solid tumour or multilocular cysts
- Referred pain suggests nerve involvement
- Identification of blood markers (CA125)
Tumor origin
- Primary- epithelial carcinomas (90%), stromal, germ cell
- Secondary
– Krukenberg tumour- from a stomach carcinoma
– Breast
– Other parts of genital tract
4 Risk factor of ovarian cancer
- Age is the strongest risk factor. Especially postmenopausal and after HRT
- Genetic factors can account for 10% of ovarian tumours, as in the Lynch Syndrome of familial breast, colorectal and ovarian cancer (BRAC1/BRAC2gene). Epigenetics??
- Obesity increases the risk and the heaviest women have the greatest risk
- Ovulation induction with Clomiphene over more than a year carries a 10-fold increased risk of ovarian cancer
Risk reducer of ovarian cancer
-long-term oral contraceptives,
-childbearing (high progesterone low oestrogen),
- tubal ligation + hysterectomy,
- removing ovaries if at risk,
-healthy diet
Screening for ovarian cancer
- Screening methods
a) Blood test for CA-125 protein (germ cell- hCG, AFP, LDH)
b) Ultrasound/CT scans
Treatment and survival rate for ovarian cancer
- Surgery – Remove ovary (S1) and other tissues (S2-4)
- Chemotherapy – Post-surgery (all stages)- oral, i.v., i.p. administration of drugs
- Targetted therapies
– Inhibitors of angiogenesis e.g. Avastin
– New area of research, side effects?? - Subsequent treatment – Trigger for ↑ risk of other medical conditions, fatigue (exercise)
* Survival Dependent on stage at diagnosis
– Epithelial 18-89% after 5 yrs, LMP 77-99% after 5 yrs
Ovarian Fertility
Treatments
§ Ovarian freezing + grafting: application for POI, cancer or beyond natural reproduction, inefficient
§ In vitro follicle culture: culture entire follicle + grow egg sufficiently before freezing/IVF
§ In vitro activation: POI/PCOS patients, multiple techniques
Ø Remove ovaries + cryopreserve → thawed in vitro + stimulate follicle growth → tissue returned to body → natural hormones to stimulate eggs → retrieve + IVF
