Gynaecology Flashcards

Question

Where is p53 located

Answer 1

short arm chromosome 17

Answer 2

Serous, clear cell and carcinosarcomas are considered high-grade by definition. For Endometriod ECs, grade is based on the proportion of solid areas: low grade = grade 1 (≤5%) and grade 2 (6%–50%); high grade = grade 3 (>50%)

Answer 3

Endometriod Serous Clear cell

Answer 4

All discussed at MDT FIGO STAGE 1A and LOW GRADE 1 or 2 can be managed by gynaecologist at gynaecology centre who is a member of MDT team. For HIGH GRADE or ABOVE stage 1A should have surgery at cancer centred by a sub spec surgeon Pelvic lymphadenectomy determines which patients are eligible for adjuvant radiotherapy, and it may also be therapeutic.

Answer 5

CA-125 can detect unexpected metastatic disease CT chest / CXR in all women CT pelvis in some women High risk histo or deep myometrial invasion of locally advanced disease - CTAP (helps plan adjuvent therapy)

Answer 6

Standard: TAH and BSO without vaginal cuff or parametrectomy. Overt Stage II. Radical hyst should only be considered to obtain tumour free margins. Hysterectomy/ salpingectomy with ovarian conservation can be considered in pre-menopausal patients with GRADE 1 ENDOMETRIOD EC, <50% invasion and no extrauterine disease on imaging Sentinel LN biopsy for staging at time of op. Surgical staging - SLNB and omental biopsy - disease greater than low risk

Answer 7

https://www.youtube.com/watch?v=D5dypTKqfa0 12 mins in

Answer 8

Oxytocin and vasopressin (antidiuretic hormone)

Answer 9

Adrenocorticotrophic hormone (ACTH) Thyroid-stimulating hormone (TSH) Luteinising hormone (LH) Follicle-stimulating hormone (FSH) Prolactin (PRL) Growth hormone (GH) Melanocyte-stimulating hormone (MSH)

Answer 10

The pelvic inlet (also known as the pelvic brim) represents the boundary between the greater pelvis superiorly and lesser pelvis inferiorly. The anatomical borders are defined as follows: Anterior: Pubic symphysis (upper border) Lateral: Iliopectineal line (arcuate and pectineal line combined) Posterior: Sacral promontory, sacral alae and sacroiliac joints

Answer 11

"central tendon of the perineum," is a fibromuscular structure located in the midline of the perineum Fibromuscular structure located at the border of the urogenital and anal triangles Central attachment site for the pelvic floor and perineal muscles (levator ani, bulbospongiousus, superficial/deep transverse perineal, external anal sphincter and external urethral sphincter muscles) Vaginal delivery may cause tears to the perineal body; this can be prevented by episiotomy

Answer 12

The most inferior structure of the pelvis with the pelvic floor sitting superiorly Formed of the perineal body, ischiocavernosus, bulbocavernosus and transverse perineal muscles Functions: urination, defecation, intercourse, vaginal delivery Anatomically appears as a diamond structure divided into two triangles: the anterior urogenital and posterior anal triangles The neurovascular supply to the perineum travels via the pudendal (Alcock’s) canal The deep perineal nerve supplies the perineal muscles

Answer 13

The pudendal nerve (S2-4) descends towards the perineum and enters the pudendal canal where it divides. The perineal branch divides into the superficial and deep branches The superficial perineal nerve supplies the skin of the posterior labia The deep perineal nerve supplies the perineal muscles Vascular supply is from the internal pudendal artery and vein, both of which travel with the pudendal nerve via the pudendal canal

Answer 14

LH FSH HCG TSH AFP EPO It is the beta subunit which varies between LH, FSH, TSH and HCG and this is responsible for their differing functions. The alpha subunit is identical.

Answer 15

Receives blood from the uterine artery (superior aspect of the vagina) and vaginal artery (middle and inferior aspect of the vagina), both of which are branches of the internal iliac artery Venous drainage is via the vaginal venous plexus which drains into the uterine vein

Answer 16

pelvic and para-aortic lymph node groups.

Answer 17

The anteroposterior (AP) or ‘conjugate’ diameter of the pelvic inlet is the distance from the sacral promontory to the pubic symphysis. The obstetric conjugate is a term used to describe the diameter from the sacral promontory to the closest border of the posterior aspect of the pubic symphysis. This represents the shortest anteroposterior diameter of the birth canal. The oblique (or diagonal) diameter of the pelvic inlet is the largest.

Answer 18

Increased number of lifetime ovulations: nulliparity, early menarche, late menopause BRCA1/BRCA2 mutations Lynch syndrome First childbirth after 35 years

Answer 19

Follicular (the most common) Corpus luteal Theca luteal Note: simple ovarian cysts <3 cm are categorised as ovarian follicles and are considered a normal finding in women during the reproductive years

Answer 20

Also known as ‘inclusion cysts’ Benign, mucus containing cysts trapped within the cervical transformation zone Occur following squamous metaplasia of columnar epithelium Endocervical crypts become trapped underneath the new layer of squamous cells Columnar cells within the trapped endocervical crypts continue to secrete mucus leading to cyst formation Follicles are usually small, measuring <5mm Larger follicles >10mm may be visible on transvaginal ultrasound

Answer 21

The deep perineal branch of the pudendal nerve

Answer 22

1: 90% 2: 70% 3: 40% 4: 17%

Answer 23

The average age at diagnosis is around 60 in the UK and the most cases of uterine cancer is seen in the 60-64 age group (see the graph). It should be noted the incidence rate (cases per 100,000) is highest in the 70-74 age group.

Answer 24

Tubal 95% Interstitial 1-6% Ovarian 3% Abdominal 1% Cervical <1% Heterotopic <0.1% Tubal pregnancies can be further subdivided into: Ampullary section 70-75% Isthmus 12% Fimbrial 11% Cornual and interstitial part of the tube 2-3%

Answer 25

Maternal age at conception Miscarriage rate 20-24 9% 25-29 11% 30-34 15% 35-39 25% 40-44 51% >45 93% (20s =10%, 30s=20%, 40s=50%, >45=90%)

Answer 26

(decrease ovulatory cycles) Oral contraceptive use Higher Parity Breast feeding Hysterectomy Tubal Ligation Statins SLE

Answer 27

Increasing age — peaks in 80s Genetic factors, including: 1. Gene mutations — BRCA1(28–44%) and BRCA2 (27%). 2. Family history of ovarian cancer — about 3% of ovarian cancer cases occur in women with a family history of ovarian cancer. 3. Family history of cancer gallbladder, and urinary tract cancers. Increased number of ovulatory cycles, nulliparity, early menarche, late menopause. Use of HRT Medical conditions, including: Cancer Endometriosis Diabetes Lifestyle factors: Tobacco smoking. Being overweight or obese. Occupational exposure to asbestos.

Answer 28

Lynch syndrome (also known as hereditary non-polyposis colorectal cancer) is associated with mutations in DNA mismatch repair (MMR) genes and deletions in the epithelial cellular adhesion molecule (EPCAM) gene. Family history of colorectal, endometrial, and/or ovarian cancer is often observed. Cowden syndrome, related to mutation in the PTEN tumour suppressor gene. Carriers have an increased risk for endometrial, breast, thyroid, colorectal, and renal cancer.

Answer 29

mutations in, or near, the DNA sequence of mismatch repair (MMR) genes and deletions in the epithelial cellular adhesion molecule (EPCAM) gene.

Answer 30

IHC testing then MLH1 promoter testing. If both these tests show that a person may have Lynch syndrome, genetic testing of a person's non-tumour DNA should be done to confirm this.

Answer 31

1.colorectal cancer 2. endometrial if identified RF (age at diagnosis, family history of Lynch syndrome-related cancers)

Answer 32

If sperm count abnormal repeat in 3 months (or asap if azoospermia or severe oligozoospermia i.e. <5 million sperm/mL detected)

Answer 33

When assessing a women who has failed to conceive NICE advise 2 tests be performed in ALL women: 1. Chlamydia screen 2. Mid luteal phase Progesterone (7 days before start of next period) Others FSH and LH patients with irregular periods, anovulation or oligo-ovulation Prolactin those with an ovulatory disorder, galactorrhoea or a pituitary tumour. Thyroid function testing is only advised if the patient has signs or symptoms of thyroid disease

Answer 34

47 XXY Klinefelters The extra X chromosome leads to testicular hypofunction and testosterone deficiency, which can result in small testes, infertility, and other symptoms/signs of hypogonadism (e.g., reduced facial/pubic hair, gynaecomastia). Developmental delay in childhood is common, particularly affecting speech. 47 XYY XYY Syndrome Normal size testes. Normal phenotype 47 XXX Triple X syndrome Normal phenotype

Answer 35

Gen pop 12% BRCA 1 70% BRCA 2 is 45%.

Answer 36

Gen pop 1.3% BRCA 1 is 40% BRCA 2 is 15%

Answer 37

Congenital Adrenal Hyperplasia (CAH) refers to a group of autosomal recessive disorders that result in deficiencies of enzymes involved in mediating the production of cortisol, aldosterone or both. These result in excessive or deficient steroid hormone production 90% of cases are due to 21-hydroxylase deficiency as a result of abnormal CYP21A genes. This results in androgen excess and mineralocorticoid deficiency. 5% of cases are due to 11-hydroxylase deficiency.

Answer 38

Progesterone 21 Test 19 Oest 18 C24 - Spironolactone based progestins (so testosterone based progestins which is most of the new ones have C19)

Answer 39

Norelgestromin

Answer 40

etonogestrel

Answer 41

Drosperinone Dienogest

Answer 42

1st generation Norethisterone Cyproterone acetate Medroxyprogesterone 2nd generation Levonorgestrel (Microgynon/ other first like COCP options) Norgestrel 3rd generation Desogestrel (Mercilon, Marvelon) Gestodene (Femodette, Femodene) Norgestimate (Cilest) 4th generation Drosperinone (Yasmin) Dienogest (Qlaira) Newer progestogens = less androgenic (skin) and glucocorticoid (bloating/weight side effects of 1st/2nd generation) BUT maybe higher VTE

Answer 43

Combined hormonal contraception often reduces androgenic effects of progestogens Via oestrogen -> reduces ovarian androgen release AND increases sex hormone binding globulin (SHBG) SHBG binds to testosterone and renders it less active à less of its androgenic effects are felt

Answer 44

Congenital malformation Failure of the Mullerian duct to develop results in absent uterus and variable degrees of upper vaginal hypoplasia Implicated in 15% cases primary amenorrhoea Karyotype 46XX Normal FSH/LH/E2 profile Prevalence 1 in 5000 WNT 4

Answer 45

Secreted by ovaries in response to LH/FSH Inhibition of activin (and therefore GnRH) (Activin --> GnRH production)

Answer 46

Serum oestrogen level >300nmol/L for 2-3 days, negative gonadotropin feedback switches to positive feedback --> rapid LH surge stimulates the primary oocyte frozen at PROPHASE 1 of meiosis I, to complete first meiotic division -> 1 x secondary oocyte and 1 x polar body Meiosis II is then also commenced following this, but freezes at METAPHASE II until fertilisation

Answer 47

Pregnenolone

Answer 48

LH --> theca cells --> progesterone and testosterone production Both theca and granulosa cells can convert cholesterol to progesterone, but ONLY THECA cells express CYP-17 (encodes for 17-alpha hydroxylase and 17,20-lyase needed for androgen production), and ONLY GRANULOSA cells contain aromatase (needed for oestrogen production)

Answer 49

FSH -> granulosa cells -> oestrogen production (via aromatisation)

Answer 50

-ve feedback HPO Cervical mucus changes -- reduced vol -- less alkaline -- increased viscosity and cellularity (all make unfav for sperm penetration) Stimulates secretory phase of menstrual cycle - inhibits endometrial proliferation and increases endometrial secretions and maturation by promoting cell differentiation Decrease tubal motility Increase body temp 0.5 degrees Downregs ER expression and SHBG production Prevents further ovulation in pregnancy Placental prog inhibits uterine contractions by limiting pg production Maintains and promotes development of preg Breast development

Answer 51

Polyp Adenomyosis Leiomyoma Malig/hyperplasia Coagulopathy Ovulatory dysf Endometrial Iatrogenic Not otherwise classified

Answer 52

Multiparity/miscarriage, previous D&C, previous LSCS MRI = thickening of junctional zone between myo and endometrium to >=12mm

Answer 53

Obesity (conversion of androstenedione -> estrone by adipocytes) PCOS Oestrogen producing tumours (usually granulosa cell)

Answer 54

5% risk of malignant change over 20 years Manage with progestogens – LNG IUD 1st line (continuous medroxyprogesterone 10–20 mg/day or norethisterone 10–15 mg/day) Repeat endometrial biopsies every 6 months until persistently normalised 2 samples negative for hyperplasia changes Consider hysterectomy if: Progression to atypia Persistent hyperplasia after 12 months LNG IUD use Relapse after treatment

Answer 55

30% risk of malignant change If fertility not desired/family complete recommended tx is TAH If fertility desired careful counselling re risk Initial trial of management with LNG IUD as above 3 (rather than 6!) monthly endometrial biopsies until persistently normalised (2) Then monitor w biopsies every 6 months One normal biopsy advised before trying to conceive Once fertility no longer desired -> TAH

Answer 56

Majority adenocarcinoma (87%) Aged 70s (Only 15% of cases seen in pre-menopausal women, and rare at <40 years) Risk factors – sustained/unopposed oestrogen exposure; anovulatory disorders/ prolonged amenorrhea, obesity Multiple subtypes; best prognosis = Endometroid endometrial carcinoma (type 1) Type 2 endometrial carcinomas are not oestrogen driven; worse prognosis Serous, mucinous, clear cell, squamous – many different types Associated with endometrial atrophy and p53 tumour suppressor mutations Psomomma bodies on histology (calcified deposits)

Answer 57

1 Confined to uterus 85-90% 1A < ½ myometrial invasion 1B > ½ myometrial invasion 2 Cervical stromal invasion but not beyond uterus 65% 3 Extension beyond uterus 45-60% 3A Tumour invades serosa or adnexa 3B Vaginal and/or parametrial invasion 3C1 Pelvic nodal involvement 3C2 Para aortic nodal involvement 4Distant Metastasis 15% 4A Tumor invasion bladder and/or bowel mucosa 4B Distant metastases including abdominal metastases and/or inguinal lymph nodes

Answer 58

Effects ~1% of the population Estimated to account for ~10% of abnormal uterine bleeding cases Should be tested for early in those who present with menorrhagia from menarche

Answer 59

Majority of women have amenorrhoea/ oligomenorrhoea but when bleeding does occur it may be very heavy

Answer 60

52mg levonorgestrel releasing device 80% reduction of menstrual blood loss by end of month 3. Initial release rate 20mcg/24 hours --> 7mcg/24 hours by end of 8 year contraceptive licence

Answer 61

Competitive inhibitor of plasminogen activation Binding of plasminogen to fibrin -> fibrinolysis (clot breakdown) Competitive inhibition of this process -> TXA ANTIFIBRINOLYTIC action Prevents fibrinolysis (fibrin breakdown), stabilises clots and reduces menstrual loss Contraindications: Severe renal impairment Previous or current history of DVT/PE History of convulsions; rarely TXA can induce seizures (Binds to glycine receptors) Fibrinolytic coagulopathies i.e. DIC Cautious use (dose reductions) for those with mild-moderate renal impairment Cautious use in women taking concurrent anti-coagulants (futile) or CHC (VTE risk) Cautious use in children <15 years (lack of evidence) Most common adverse effect is GI upset More rarely, impaired colour vision has been reported (discontinue if so!)

Answer 62

Cyclooxygenase (COX) inhibitors -> reduce prostaglandin synthesis Prostaglandins = important in inflammatory response (uterine pain and bleeding) Menorrhagia can be associated with increased prostaglandin levels Less prostaglandins -> less inflammatory response -> less pain AND bleeding Mefenamic acid 500mg TDS (also ibuprofen, naproxen) Started on first day or pain OR bleeding -> continue for no more than 7 days NSAIDs used in this way may reduce mean blood loss by ~30%

Answer 63

5mg TDS 10days to STOP/ARREST bleeding Duration of use variable as per individual practice and indication --> Can be used for up to 6 months (licensed dosing for endometriosis) If cycles regular may be recommended from days 19 – 26 of cycle (luteal phase) to PREVENT bleeding. Evidence = taking on D5-26 of cycle is more effective than luteal phase only. “Long-cycle” use here. Contraindications: Current breast cancer Current/ previous VTE Active/ recent IHD – angina or MI Severe/ active liver disease Acute porphyria or history of pemphigoid gestationis Cautious use in: Hypertension Diabetes Multiple cardiovascular disease or VTE risk factors Previous breast cancer – consult with oncology prior to use Liver tumours Antiphospholipid antibodies/ diagnosed systemic lupus Rheumatoid arthritis Conditions that can be exacerbated by fluid retention (common side effect) Renal impairment Cardiac dysfunction Epilepsy Migraine Asthma Discontinue use if: New onset migraine Jaundice/ deterioration of LFTs Increase in BP Side effects include: Menstrual irregularity (amenorrhoea, spotting/ breakthrough bleeding) Breast tenderness Less commonly – HTN, VTE

Answer 64

Typically/traditionally 10mg PO OD for 5-10 days, starting between days 16-21 of cycle. Repeated for 3 cycles. Increasing evidence to advocate for use on longer term/continuous basis “Long-cycle” use as per norethisterone, for 3-4 weeks at a time. 10mg PO OD for 3 months (licensed dose regime for endometriosis)

Answer 65

Rare – smooth muscle cancer Rapid growth after menopause Reliable diagnosis is by histology only Limited evidence on whether these uterine malignancies are the result of new growth vs malignant transformation of pre-existing benign uterine fibroids

Answer 66

GOSRELIN (Zolodex branded – 1 monthly) or LEUPRORELIN (Prostap branded – 1 monthly or 3 monthly as per dose) Downregulation of/desensitisation to endogenous hypothalamic GnRH release AFTER initial gonadotropin (FSH/LH) inducing effects (Symptoms may worsen initially before improving with desensitisation effects in time) - Over time leads to GnRH desensitisation - Downregulation of pituitary FSH/LH release - Suppression of ovarian function; less ovarian/follicular oestrogen synthesis - Fibroid shrinkage (growth is oestrogen sensitive) and amenorrhoea 6 months OR 1 year with HRT cover Temp menopause HRT: CHC (if <50 years and no CIs) or tibolone

Answer 67

(branded Livial) Synthetic steroid hormone; sex hormone metabolites Metabolised into 3 metabolites -> 2 oestrogenic and 1 progestogenic/ androgenic

Answer 68

combination of HRT and relugolix as one oral medication 40 mg relugolix 1 mg estradiol (hemihydrate) 0.5 mg norethisterone

Answer 69

Pituitary adenomas (57% of all pituitary tumours; presents most commonly in women of reproductive age) Anti-psychotic medication (Majority have raised prolactin, ~50% have AUB) traditional antipsychotic drugs: haloperidol, chlorpromazine, and flupenthixol atypical antipsychotics like risperidone and amisulpride Stress can cause mild elevation of prolactin

Answer 70

Irregular if >10 days variation in cycle length

Answer 71

Rotterdam 2/3 (1) Hyperandrogenism (clinical / biochemical) (2) Ovulatory dysfunction --> menstrual irregularity (<9 cycles / year or >35 days between cycles) (3) Polycystic ovarian morphology often observed on ultrasound follicle number per ovary of 20 or more in at least one ovary. ((If using transabdominal ultrasound ovarian volume >=10ml should be used for diagnosis Not possible to reliably assess follicle number with TA route of scanning )) 8 years post-menarche

Answer 72

Consider PCOS (if LT hx of oligoammen) androgen-secreting tumours ovarian hyperthecosis (presence of nests of luteinized theca cells in the ovarian stroma)

Answer 73

(1) LH, FSH, prolactin and TSH Excludes other causes of irregular periods/ amenorrhea POI; High FSH/LH Hypogonadotropic hypogonadism; Low FSH/LH HYPOthyroidism; High TSH (with low T4) HYPERprolactinaemia (normal = <500); may be normal- mildly elevated in PCOS alone, significant elevation suggestive of other pathology i.e prolactinoma, especially if concurrent symptoms of prolactin excess (galactorrhoea) (2) LH:FSH ratio >2.5 (3) Total testosterone – may be normal or moderately elevated in PCOS (4) Sex hormone binding globulin (required to calculate free androgen index)

Answer 74

Free androgen index= total testosterone x100 / SHBG as per NICE Assesses amount of physiologically active testosterone present Normal value = <5 May be normal or elevated in PCOS FAI >=5 is suggestive of PCOS Note: cannot perform on people on hormonal contraception: Inhibition of adrenal and ovarian androgen synthesis Increased levels of SHBG If biochemical androgen testing is required test after a period of 3 months on alternative non-hormonal contraception

Answer 75

If no contraindications, COC use (à supresses androgen production and improves symptoms) Preventing prolonged amenorrhea (preventing endometrial hyperplasia) Cyclical progesterone MPA 10mg for 14 days --> withdrawal bleed EVERY 3 MONTHS. Mirena. Metformin (off-label) alone or in combination with COC Especially if BMI >25 or other metabolic risk factors (IGT) Evidence demonstrates it acts as an effective ovulation induction agent in many PCOS patients Some evidence has shown it also reduces the risk of miscarriage and gestational diabetes

Answer 76

PCOS Simple obesity Primary hypothyroidism (May have goitre. Other clinical features – weight gain, cold intolerance, fatigue, constipation etc) Elevated prolactin (Galactorrhoea) Congenital adrenal hyperplasia (most commonly due to 21-hydroxylase deficiency Cushing’s syndrome (cortisol excess) Androgen secreting tumour (adrenal or ovarian origins) Acromegaly

Answer 77

Most commonly due to 21-hydroxylase deficiency Classical = ambiguous genitalia +/- adrenal crisis at birth Non-classical = milder and may present later in life due to early pubertal changes (secondary to androgen excess) or absent/ irregular menses If there are signs of virilisation (e.g. deep voice, reduced breast size, increased muscle bulk, clitoral hypertrophy), rapidly progressing hirsutism (less than 1 year between hirsutism being noticed and seeking medical advice) or high total testosterone levels (greater than 5 nmol/l or more than twice the upper limit of normal reference range), androgen-secreting tumours and late-onset/nonclassical congenital adrenal hyperplasia (CAH) should be excluded. 17-hydroxyprogesterone should be measured in the follicular phase and will be raised in CAH. It is possible to have CAH without the testosterone being > 5 nmol/l, particularly if the woman is heterozygous for this condition. Hence measurement of 17-hydroxyprogesterone should be considered if there is a high index of suspicion, for example, specific groups such as Ashkenazi Jews or those with a family history of CAH. If 17- hydroxyprogesterone is borderline, it will have to be confirmed by an ACTH stimulation test to diagnose CAH. If there is a clinical suspicion of Cushing’s syndrome or acromegaly, this should be investigated as per local practice.2

Answer 78

from onset of ovulatory cycles, typically within 6 months - 1 year of menses If severe symptoms and/ or no response to first line treatment (NSAID/anovulatory hormonal contraception) within 3-6 months --> referral

Answer 79

due to pelvic pathology and typically presents at a later stage Most common cause of secondary dysmenorrhoea = endometriosis Other Adenomyosis Fibroids PUD Ectopic CU-IUD

Answer 80

Early menarche and late menopause, nulliparity and delayed childbearing (more cycles) Family history Vaginal outlet obstruction White ethnic group Late first sexual encounter Smoking

Answer 81

Endometriosis has prevalence of 25-40% in infertile women, compared to <5% in fertile

Answer 82

During early puberty LH levels insufficient to trigger ovulation and majority of cycles anovulatory Positive feedback from increasing oestrogen release à increased LH à ovulation By 4-5 years post-menarche the majority of cycles are ovulatory (80%+) During anovulatory cycles the ovaries may appear multi-cystic in nature Do NOT USS ovaries as part of PCOS work up if <8 years post-menarche or <20 y/o (if age of menarche not known)

Answer 83

Signs of secondary sexual characteristic development at <8 years in girls (<9 years in boys) (1)GnRH dependent (complete or ‘true’) > idiopathic (80%) > Kisspeptin (GnRH stimulating peptide) mutation in some >Hypothalamic hamartoma – rare cause (Triad of precocious puberty, developmental delay and gelastic (laughter) seizures) (2)GnRH independent, for which a definitive diagnosis/ underlying cause is usually found --- ovarian or adrenal disorders > Granulosa cell tumour (and other gynae tumours) >Adrenocortical tumours >Congenital adrenal hyperplasia >McCune-Albright syndrome

Answer 84

most common type of solid tumour --> precocious puberty (if occurring prior to onset of puberty, which only ~5% do) Produce excess oestrogens

Answer 85

Rare with incidence from 1: 10,000 – 1: million Triad of endocrine disturbances: (1) Precocious puberty, (2) abnormal bone lesions (fibrous dysplasia) (3) café-au-lait spots Spontaneous mutation of GNAS1 gene in chromosome 20

Answer 86

boys usually GnRH independent/pathology girls usually GnRH dependent/ ‘true’ and idiopathic or ‘constitutional’ in nature

Answer 87

No secondary sexual characteristic (typically breast bud development) and not begun menstruation by age 13 OR no increase in testicular volume to >4mls (marks onset of puberty in boys) by age 14 years Girls with normal secondary sexual characteristic development and not begun menstruation by age 15 13, 14, 15

Answer 88

Imperforate hymen Transverse vaginal septum ****Uterovaginal agenesis**** The second most common cause of primary amenorrhoea (after primary gonadal failure) and accounts for ~15% of presentations >> Absent vagina and functioning uterus >>Absent vagina and non-functioning uterus = MRKH XY female: androgen insensitivity syndrome Feminine secondary sexual characteristics due to aromatisation of testosterone to oestrogen, but without axillary hair development (androgenic process) Presentation often due to primary amenorrhoea

Answer 89

Hypogonadotrophic hypogonadism (Low GnRH/LH/FSH – poor stimulation of gonadal sex hormone production) Low GnRH/LH/FSH – poor stimulation of gonadal sex hormone production (1) Congenital hypogonadotropic hypogonadism (CHH) Rare and more common in males with 3.6:1 M:F ratio Failure of GnRH release from hypothalamus (2) Kallman’s syndrome Defect in migrating neurons from olfactory placode (olfactory and GnRH releasing neurons) CHH with reduced or absent sense of smell Multiple associated gene mutations and patterns of inheritance (3) Pituitary prolactinoma Although rare in children/adolescents, prolactinoma (raised prolactin) inhibits GnRH release and may delay/ prevent puberty (4) Acquired – weight loss/anorexia, excessive exercise Low leptin levels Leptin = hormone produce by adipocytes, stimulator of hypothalamic GnRH release --> hypogonadotropic hypogonadism picture: anovulatory cycles/ delayed puberty Minimum body weight of ~47kg required to initiate /activate puberty Hypergonadotrophic hypogonadism (Failure of the gonads to produce adequate sex hormones despite stimulation ++ via GnRH/LH/FSH release) (1) Gonadal agenesis (2) Gonadal dysgenesis >> Turner mosaic (as full Turner’s syndrome typically presents with short stature) >> Other (more niche) X deletions of mosaicism >> XY Swyer syndrome or lack of Mullerian inhibition **** (3) Primary ovarian failure/ insufficiency ****Most common cause of primary amenorrhoea -50% of presentations FSH >30

Answer 90

Complete gonadal dysgenesis (only gonadal streak develops) Varied genetic mutations can cause, can be new or inherited ~20% cases caused by mutations on Y chromosome sex determining regions but other chromosomes implicated, and the Y chromosome can be normal XY genotype AFAB with unambiguous female genitalia present --> no AMH during embryological development --> Mullerian/paramesonephric duct develops and female reproductive organs/ external genitalia develop in absence of AMH but absence of gonads (dysgenetic gonadal streaks only) Diagnosed around puberty due to lack of endogenous oestrogen or testosterone to be converted to oestrogen via aromatisation--> lack of development of secondary sexual characteristics (as opposed to those with androgen insensitivity syndrome who may have some phenotypically female secondary sexual characteristics) Often noted to have a TALL stature Swyers = only syndrome in which XY individuals have a female reproductive organs Treated with HRT and removal of streak gonads to prevent gonadoblastoma (with ~20% rate of testicular malignancy if left in situ beyond 20 years)

Answer 91

as a rare cause of POI Autosomal recessive defect on chromosome 9 with incidence 1:60,000 births Metabolic disorder; lack of GALT enzyme to breakdown sugar galactose Despite appropriate dietary management >90% of those with galactosaemia develop very early POI à amenorrhoea (can either be primary or secondary)

Answer 92

Hypogonadotrophic hypogonadism (1)Congenital hypogonadotropic hypogonadism (CHH) Rare and more common in males with 3.6:1 M:F ratio Failure of GnRH release from hypothalamus (2) Acquired (rare) Trauma Empty sella turcica Tumours Hypergonadotrophic hypogonadism (1) Turner syndrome (2) Other (more niche) X deletions or mosaicism

Answer 93

Measure serum FSH Elevated FSH (hypergonadotropic) suggestive of gonadal failure Should have karyotyping to confirm if Y chromosome present If present or hyperandrogenic features --> removal of gonads to prevent gonadoblastoma If FSH low (hypogonadotropic) then karyotyping not required, but should have cranial imaging to rule out CNS tumour

Answer 94

5XO karyotype (aneuploidy) In 10-15% of Turner’s cases = isochromosome X (incorrect chromosomal division -> 2 short arms on one X chromosome and 2 long arms on one X chromosome) 1:2500 live female births  >99% of XO foetuses’ self-abort  Only viable monosomy in humans   >> In typical XX females one copy of the X chromosome in each cell is functionally inactivated in a process called Lyonisation  --> Formation of the Barr body  >> Absent Barr body = diagnostic feature in Turner's  Often present with short stature/ growth concerns around puberty, failed/delayed puberty (lack of secondary sexual characteristics) and/ or primary amenorrhea  Gonadal hypoplasia with other associated abnormalities  >> Webbed neck  >>Broad chest with wide spaced nipples  >>Cubitus valgus (valgus deformity of the elbow -> increased carrying angle (lower arms ‘stick out’ from midline)  >> Short 4th metacarpal  >>Lymphoedema of the extremities in the neonate; especially feet  >>Low set ears (80%)  >>Low hairline   >>Hypoplastic nails  >>Congenital heart defects in 10-20%  >>Coarctation of the aorta  >>Early aortic stenosis due to bicuspid aortic valves   >>ASD  >>VSD  >>Hypertension; idiopathic or secondary to coarctation of the aorta  Characteristic ‘streak’ gonads are seen posterior to the broad ligaments of the uterus  Fibrous tissue only  Devoid of germ cells  High incidence of concurrent horseshoe kidneys (shared embryological origin of genital and urinary tracts!)  Short stature (125-1.5m average height) with failure of pubertal growth spurt  May have specific learning difficulties but usually good overall mental development  (vs Noonan’s which is strongly associated with low IQ/ intellectual disability) Infertility (lack of gonadal tissue) but normal genitalia otherwise   Association with autoimmune conditions ; particularly thyroiditis and IBD  Normal life span  Diagnosis:  1. Raised FSH/LH and low oestrogen on hormonal profile  2. XO karyotype confirmation/ absence of Barr body = confirmatory  3. If diagnosis is made early hormone replacement can be initiated:  Human growth hormone -> improved stature  Oestrogen -> attainment of secondary sexual characteristics  Regardless of time of diagnosis hormone replacement with oestrogen/progesterone cover is recommended to protect bone density and should be continued until age of the natural menopause (51)  Rarely patients can be Turner’s mosaics  XO/XX – “pure” gonadal dysgenesis without other associations of Turner’s ie short stature   XO/XY – 50% rates of gonadal neoplasia (gonadoblastoma) -> Gonadal removal is recommended prophylactically  

Answer 95

Turner’s syndrome bodily phenotype with normal (XX) genotype  Autosomal dominant condition with sporadic occurrence  Chromosome 12 Mutations in PTPN11 gene >=50% of cases, most common cause  SOS1 = 10-15%  Some phenotypic distinctions:  >>Characteristic facies  Broad forehead  Ptosis and hypertelorism (broadly spaced eyes)  Epicanthic folds and down-slanting eyes  Flat nasal bridge  >>Kyphoscoliosis   >>Right sided congenital heart disease associations (compared to left sided associations in Tuner’s)  Pulmonary artery stenosis  Tetralogy of Fallot  >>More strongly associated with learning difficulties/ low IQ  Management focuses on addressing congenital heart defects and supporting mental development/ additional needs  Variable prognosis as per severity of heart defects 

Answer 96

Occurs due to failure of X chromosome separation during mitosis or meiosis processes At least one extra X chromosome in the male --> reduced testosterone production (elevated LH + FSH) Each additional X chromosome increases oestrogen: testosterone ratio --> more feminisation Symptomatic with hypogonadism around puberty Often having some gynaecomastia and broader hips Usually associated with male infertility Testosterone replacement therapy +/- assisted conception

Answer 97

Extra Y chromosome in the male Increased incidence of learning difficulties / developmental delays Usually normal sexual development however is some association with male infertility

Answer 98

Extra X chromosome in the female Increased incidence of learning difficulties / developmental delays Often no reproductive symptoms and fertility usually unaffected

Answer 99

cessation of menses for 3 months or more in those with previously regular cycles, or 6 months or more in those with previous irregular cycles

Answer 100

GP PCOS Hypothyroidism Pregnancy Menopause (in those aged >=40 years) Gynae 1. Suspected premature ovarian insufficiency 2. Recent history of uterine/cervical surgery or severe pelvic infection suggestive of Asherman’s syndrome (intrauterine adhesions) or cervical stenosis 3. associated infertility Endo 1. Hyperprolactinaemia (level >1000 or >500 on 2 occaisions, includes drugs known to cause high prolactin 2. Low FSH and LH levels – to exclude hypopituitarism or a pituitary tumour, though stress/ exercise /weight loss are more likely causes of FSH/LH suppression here 3. Raised testosterone level not felt to be explained by diagnosis of PCOS (?androgen secreting tumour, late onset/ non-classical congenital adrenal hyperplasia or Cushing’s syndrome) 4. Any other features of Cushing’s syndrome or late onset congenital adrenal hyperplasia

Answer 101

Scar tissue/ adhesions forming web like structures in uterus. Trauma to basal layer of uterus and failure to regenerate. Causes 1. Surgery 2. Infection less common tuberculosis schistosomiasis

Answer 102

generally defined as periods occurring at <21 days OR >35 days Depends on timing from menarche: (1) Irregular cycles are normal in the 1st year post-menarche (2) At any time post-menarche a cycle of >90 days is considered irregular/ abnormal (3) From 1-3 years post menarche = <21 or >45 days (greater accepted variation) (4) 3 years post-menarche --> menopause = <21 or >35 days or <8 cycles per year

Answer 103

(1) Idiopathic Mild and not associated with other hyperandrogenic symptoms ie irregular periods May have a family history of hirsutism Cosmetic treatment +/- spironolactone (anti-androgenic action) (2) Ovarian PCOS = common Ovarian secretory tumours = uncommon (3) Adrenal – uncommon Congenital adrenal hyperplasia (non-classical = milder and may be diagnosed later in life) ---> Early morning (fasting) 17-hydroxyprogesterone testing Should be done 08:00 - 09:00 in absence of hormonal contraceptive use and ideally in the early follicular phase (days 1-5) of the cycle Adrenal tumours, most commonly adenomas (benign), less commonly carcinomas

Answer 104

(1) CAH 21-hydroxylase is the most common enzyme deficiency -> raised androgens , others 17 and 11. (2) Females 46 XX DSD – virilised external genitalia; often a result of congenital adrenal hyperplasia >> Androgen exposure <12 weeks gestation = ‘labioscrotal fusion’ -> retention of urogenital sinus (single tract which urethra and vagina empty in to before reaching the perineum) >> Androgen exposure >12 weeks gestation = clitoromegaly >> No palpable gonads at external genitalia = suggestive of virilised female (3) Males 46 XY DSD – under-virilised external genitalia >>5a-reductase deficiency >>Autosomal recessive mutation on chromosome 2 >> Failed conversion of testosterone -> more potent dihydrotestosterone -> impaired virilisation >>Does not present clinically in females as no clinical/ developmental need for DHT >> Palpable gonads at external genitalia = suggestive of under-virilised male

Answer 105

(1) Labial fusion Usually with clitoromegally as part of excess androgen pic >CAH most common cause, but can be exogenous androgen intake/exposure or endogenous. (2) Labial adhesion Very common in pre-school children 2-6 years; low oestrogen naturally Occurs as non-oestrogenised labia undergo ‘denudation’ (loss of epithelium) à fuse as adhesions Usually self resolve at puberty with higher oestrogen levels If not self resolving, use of oestrogen cream to better oestrogenise the skin à reduces recurrence following surgical division

Answer 106

Imperforate hymen 1:1000 Endoderm (from the urogenital sinus epithelium) ddx :Transverse vaginal septum

Answer 107

Vaginal agenesis AKA Mullerian agenesis AKA MRKH Androgen insensitivity syndrome (previously testicular feminisation syndrome) Vaginal atresia Transverse vaginal septum Vertical or complete vaginal septum (septum down the length of the vagina - assoc with didelphys) Vaginal adenosis

Answer 108

Primary ammenorrhoea (make up 15% of primary) Absent vagina non-functioning uterus Vaginal agenesis in association with cervical and uterine agenesis/hypoplasia 75% have complete vaginal agenesis / 25% have a short vaginal pouch Rare ~1:5000 female births 46 XX genotype with normal hormone profile Confirmed on MRI Fertility - could egg harvest, need surogate No cervix - no smears vaginal dilation for sex / neovagina if no vag present OVARIES are NORMAL 2 TYPES: Type I – reproductive anatomy differences alone Agenesis upper 2/3 vagina along with absent cervix and absent or under-developed uterus Type II – other associated anatomical differences (40%-50%) Renal tract (most commonly!) Hearing difficulties (middle ear) Bone effects (fused or absent vertebrae)

Answer 109

46XY genotype Defective androgen receptors Developing fetus cannot sense any androgens --> feminisation of external genitalia A short vaginal pouch can form from the urogenital sinus Mullerian (paramesonephric) ducts reabsorb as normal due to testicular production of AMH Wolffian (mesonephric) ducts persist Undescended, androgen producing testes present Testosterone -> aromatised to oestrogen -> phenotypic females, often tall and without pubic hair due to lack of androgenic stimulation Present with primary amenorrhoea Testes should be removed to prevent gonadoblastoma

Answer 110

Persistence of Mullerian (paramesonephric) duct tissue (cervical/endometrial in appearance) within the lower 2/3 vagina (usually originating solely from the urogenital ridge) Associated with in utero diethylstilboestrol (DES) exposure; discontinued 1971

Answer 111

Congenital anomalies of the uterus Mullerian anomalies have an incidence of between 1-3% 1. Uterine agenesis / hypoplasia - primary amenorrhoea, MRKH, renal 2. Unicornuate uterus (unicornis unicollis) - accounts for ~15% of uterine anomalies REPRO IMPACT 3. Uterine didelphys (duplication) 7.5% uterine anomalies REPRO IMPACT 4. Bicornuate uterus 2nd most common uterine anomaly type at ~25%. 5. Septate uterus – the most common form of uterine anomaly accounting for ~45% of cases 6. Arcuate uterus (“heart shaped”) - technically the mildest form of septate uterus as same pathogenesis 7. T shaped uterus - from in utero exposure to diethylstilboestrol (DES)

Answer 112

Primary ammenohea Concurrent renal anomalies in around 1/3 Associated with Mayer-Rokitansky-Kuster Hauser (MRKH) syndrome = absent upper 2/3 vagina also

Answer 113

15% of uterine anomalies Poor pregnancy outcomes (most significant reproductive impact along with uterine didelphys) Failure of one Mullerian/ paramesonephric duct to elongate, whilst the other develops normally Predominantly tends to occur on the right – unexplained as to why this preference exists (A) Communicating contralateral rudimentary horn; contains endometrium (10%) (B) Non communicating contralateral rudimentary horn; contains endometrium (22%) - Adolescent presentation with persistent ++ dysmenorrhoea - Likely to have heamatometra - Likely to have degree of retrograde menstruation -> endometrioma (C) Contralateral horn present but with no endometrial cavity (33%) (D) No contralateral horn present (35%)

Answer 114

Complete duplication of uterine horns AND cervix with no communication between them; 2 uterine bodies (each with one fallopian tube and one cervix) FAILURE OF FUSION MULL DUCT Result of failed Mullerian/ paramesonephric ductal fusion between 12th-16th weeks of development -> Two distinct and widely spaced uterine bodies with significant fundal cleft (compared to bicornuate – smaller fundal cleft for separation of horns only – or septate uteri – fibrous septum only no fundal cleft/division) Poor pregnancy outcomes

Answer 115

2 distinct uterine horns which open into a single vagina INCOMPLETE FUSION MULL DUCT 2 types: Complete division of uterus down to external os -> 2 cervical canals within one cervical body structure (bicornuate bicollis) Partial division of the uterus does not extend to the internal os, therefore only one cervical canal (bicornuate unicollis) Does not usually require surgical intervention, though cervical sutures may be required for pregnancy If recurrent pregnancy loss -> Strassman metroplasty (reconstruction of one cavity/ horn) can be done

Answer 116

The most common form of uterine anomaly accounting for ~45% of cases Tends to be associated with poor pregnancy outcomes; subfertility, recurrent early loss and preterm labour Effects ~15% of all women presenting with recurrent pregnancy AFTER FUSION Result of complete or partial failure of resorption of the uterovaginal septum after fusion of the paramesonephric ducts In septate uterus the septum tends to be fibrous (vs bicornuate where it tends to be muscular) and as such can be divided relatively safely and easily through hysteroscopy May be associated with a vaginal septum (though less commonly here than in uterine didelphys)

Answer 117

tool for adolescent safeguarding consultations Home and environment Education and employment Activities Drugs Sexuality Suicide/ depression

Answer 118

progesterone induced pre-menstrual disorder = cyclical symptoms in context of exogenous progesterone use (usually CHC or HRT) progesterone only contraception adverse effects are non-cyclical in nature

Answer 119

PROSTPECTIVE symptom monitoring via symptom diary over at least 2 cycles (cannot be retrospective) Daily Record of Severity of Problems (DRSP) If completed symptom diary is inconclusive, GnRH analogues may be used for up to 3 months to confirm the diagnosis 5-8% of women who experience pre-menstrual symptoms meet criteria for PMSyndrome diagnosis

Answer 120

Exercise, balanced diet, sleep hygiene, stress management Supplements: Vit D, Ca and Mg, Vit B6 (pyridoxine), evening primrose (breast tenderness) Simple analgesia for pain, including topical NSAIDs, and well-fitting bras Other herbal remedies: chasteberry/ vitex agnus-castus or gingko bilboa

Answer 121

Primary hormonal treatment of PMS focuses on oestrogen therapy There is no evidence of a beneficial role for progesterone only hormonal therapy in PMS management FIRST LINE continuous use of drosperinone-containing COC (not liscenced) - YASMIN SSRI ALTERNATIVES >> HRT – transdermal oestradiol + cyclical progestogen for 10-12days/cycle for endometrial protection >>Danazol/ danocrine – androgen medication 200mg BD >> GnRH analogues – only in severe cases where other treatment options have not been of benefit >>Spironolactone

Answer 122

transdermal oestradiol + cyclical progestogen for 10-12days/cycle for endometrial protection Insufficient evidence on long term effects on pre-menopausal endometrial and breast tissue Micronized progesterone recommended as less likely to reintroduce/mimic PMS symptoms Should be used alongside further contraceptive cover Intrauterine or barrier methods of contraception best supported by RCOG green top guide in these cases, to minimise systemic progestogen exposure In women with PMS, LNG-IUD can initially produce PMS-type adverse effects po

Answer 123

Never actually used?? significant luteal phase breast symptoms only androgen medication 200mg BD Effective for significant luteal phase breast symptoms only; not commonly used Also used in benign mastalgia patients; good evidence that it helps with breast tenderness Potential for irreversible virilising effects Teratogenic (potential virilisation of female fetus); recommend IUC / SDI contraceptive cover

Answer 124

only in severe cases where other treatment options have not been of benefit Highly effective for treatment of severe PMS Optimise bone health: vitamin D/calcium, diet, weight bearing exercise, smoking cessation If using for >6 months add-back HRT cover is recommended ***Continuous-combined HRT OR tibolone as per green top guidance *** If using for >2 years need annual DEXA scans to monitor BMD, and treatment should be stopped if significant decline in bone density is observed Very rarely following a successful trial of GnRH analogue use (which mimics the effects of surgical menopause) TAHBSO may be considered as permanent/ surgical treatment for severe and refractory cases of PMS Surgical treatment should NOT be used without a pre-surgery trial of GnRH analogues to ensure benefit, and test tolerability of HRT Oophorectomy alone would necessitate use of progesterone component to HRT and risks reintroduction of PMS symptoms, therefore TAHBSO is recommended if surgical tx indicated

Answer 125

a first line treatment option for PMS as per patient preference Daily OR for 2 weeks throughout secretory/luteal phase approaching menses Evidence of increased efficacy and lower adverse effects if used only in luteal phase Common adverse effects: insomnia, low libido, fatigue and nausea If being used continuously and wishing to stop, need gradual reduction to avoid withdrawal SSRIs can be withdrawn prior to conception as PMS symptoms are expected to resolve during pregnancy

Answer 126

There is some evidence to suggest a link with SSRI use and congenital malformation More evidence needed - not proven

Answer 127

symptoms must follow luteal phase worsening, with at least 1 week symptom free following menses Symptoms must include at least one mood/ anxiety symptom, and have a severe impact on social and/or occupational wellbeing Must have 5 or more of the following (vs PMS where no symptom limit/ restriction for diagnosis): 1 or more of the following >> Mood changes >> Irritability/ anger/ conflict >> Depressed >> Anxiety 1 or more of the following (to reach total of 5) >> Decreased interest >> Difficulty conc >> Lethargy >>Change in eating >> Change in sleep >>Overwhelmed >>Out of control >> Physical symptoms

Answer 128

Estradiol (from granulosa cells within developing follicles surrounding oocytes) Progesterone (some production from both T>>G cells) Testosterone (from theca cells outlining developing follicles surrounding oocyes) INHIBIN B (from granulosa cells; plays a role in negative feedback control)

Answer 129

Glycoprotein synthesised/ secreted by granulosa cells within ovary heterodimeric protein: inhibin A and inhibin B Inhibin A = produced by granulosa cells of the dominant follicle and corpus luteum >> Rises at end of follicular phase (when follicle largest) >> Declines from mid-luteal phase onwards (as corpus luteum regresses) Inhibin B = produced by granulosa cells of non-dominant follicles >> Rises during early follicular and reduces later follicular. >> Does not contribute significantly during the luteal phase (minimal follicular activity here) Provides negative feedback at anterior pituitary -> less FSH/LH release During menopause follicular activity decreases - Less inhibin produced - Less suppression of FSH - FSH levels rise NOTE: Sertoli cells of the testis in males produce inhibin

Answer 130

gold standard for characterising the reproductive aging -> menopause SEE SCREEN GRABS Stage +1b is the 12 months following completion of the menopause FSH levels are continuing to rise here and systemic symptoms are most likely to occur during this time Menopausal symptoms of any kind can occur before periods stop however are most likely to occur in the first year following completion of the menopause Vasomotor symptoms = most common

Answer 131

Average age of meno = 51 Early menopause = menopause occurring between 40 – 45 years, in the absence of other causes of secondary amenorrhea POI <40years

Answer 132

Growth restriction in late gestation Low weight gain in infancy Starvation/ poor nutrition in early childhood Down’s syndrome Early menarche (<11 years) and nulliparity/low parity (more cycles) Smoking Living at higher altitude Social deprivation

Answer 133

Being breastfed Higher childhood cognitive ability Increased parity

Answer 134

(1) Primary/ genetic (2) Autoimmune (3) Secondary/ Iatrogenic

Answer 135

Often occurring <30 years and with associated strong maternal family history Karyotyping in <30 / suspect turners. Chromosomal abnormalities: Turner’s syndrome / Down’s syndrome/ Fragile X syndrome (FMR1) Enzyme deficiencies Galactosaemia (auto-recessive def. of galactose-1 phosphate uridyltransferase) More rarely: >>Cholesterol desmolase deficiency (produce minimal steroid hormones and rarely survive to adulthood) >> 17-aplha hydroxylase deficiency (form of congenital adrenal hyperplasia - hypertension, hypokalaemia and ovarian failure) >> Isolated 17-20 desmolase deficiency (-> isolated ovarian failure) Check BRCA1

Answer 136

More commonly found in those with 'AI predisposition' Test thyroid and adrenal antibodies routinely due to frequency of association with POI

Answer 137

Post-chemotherapy/ radiotherapy >> Likelihood depends on type of chemo, dosage of chemo and age when chemo received >> Pre-pubertal uterus --> uterine dysfunction: Higher rates of adverse pregnancy outcomes even if ovaries do not fail Post treatment with gonadotrophin releasing hormone analogues Post bilateral oophorectomy >>Results in immediate menopause >>Often intensely symptomatic >> HRT should be commenced immediately following More rarely can occur following an infection ie mumps or tuberculosis Most causes of POI following mumps infection àeventual return of normal ovarian function

Answer 138

Cessation of menses for more than 1 year before 40 years UPT 2 x FSH > 30 4-6 weeks apart (An FSH of <10 is well within normal, an FSH of >15 is generally considered to be elevated) LH (HIGH) FSH better than LH (If LH is significantly elevated versus FSH, autoimmune oophoritis may be suspected) Oestradiol Usually low but variations often present espec in early disease Testosterone Karyotyping (if <30 years) Rule out reversible causes Prolactinoma (prolactin) Thyroid disease (TSH elevated if AI hypothyroidism) NICE do not recommend routine testing of AMH for diagnostic purposes in women with ?POI

Answer 139

HRT up to the average age of the naturally occurring menopause (51) at which point the need for ongoing HRT should be assessed as per symptoms The combined contraceptive pill can be used as a HRT alternative if <50 years old >>> However HRT gives better bone protection and may provide better symptom control (greater ability to titrate oestrogen dosing)

Answer 140

Consider in: < 40 (for dx POI) 40 - 45 years with typical symptoms >=45 years with atypical symptoms FSH should NOT be used in otherwise healthy women who are not using any hormonal contraceptive agents and who are aged >=45 years with typical menopausal symptoms

Answer 141

Hot flushes and night sweats 70% western women (Japanese less) More noticable in smoking/high bmi Less oestrogen -> DECREASED density of 5HT(serotonin) receptors + lower serotonin activity Less oestrogen -> INCREASED noradrenaline ---> Narrowed thermoneutral zone: Smaller changes in core temperature trigger heat dissipation mechanisms Increase in body temperature -> vasodilation and increase HR (‘hot flush’) Palpitations and anxiety often associated with vasomotor symptoms

Answer 142

Common, effecting ~ 50% of menopausal women Effects the vagina, female urethra, bladder and pelvic floor; all have ER + PR present Loss of oestrogen -> thinning of vaginal epithelium >> loss of vascularity of tissues >> loss of rugae, collagen and elasticity of tissues --> increase laxity of pelvic floor muscles predisposes to prolapse Skin becomes pale with erythematous areas and petechial heamorrhage Reduced vaginal and cervical secretions -> dryness Vaginal pH also increases (less production of lactic acid) -> encourages growth of pathogens Can cause subjective symptoms of – vaginal dryness, dyspareunia, urinary frequency and dysuria >> sex dysfunction >> exacerbate / cause recurrent UTIs >> corrected with vaginal oestrogens Offer low dose topical/ local (vaginal) oestrogen only as first line HRT for isolated urogenital symptoms If not effective/contraindicated then consider ospemifene (selective oestrogen receptor modulator: as per NICE menopause guideline) - CI: breast ca treatment.

Answer 143

Gene: FMR1 intellectual disability FXS affects both males and females. However, females often have milder symptoms than males.

Answer 144

Oestrogen stimulated exfoliation of the vagina epithelial cells --> increased glycogen ---> converted to lactic acid by lactobacilli --> acidic environment (3.5 - 4.5)

Answer 145

1. HRT 2. Switch HRT Oral oestrogens can reduce naturally circulating testosterone (via increase in SHBG) Switching from oral to transdermal oestrogen can be helpful for sexual desire as may increase circulating testosterone levels without requiring exogenous use 3. Testosterone (off lable) Specialist use Only if symptoms + low levels STOP if no perceived benefit in 3-6 months Adverse androgenic effects: Acne Hair growth Weight gain Rare: alopecia, deepening of voice clitoral enlargement Check levels PRIOR to rx Monitor 6-12 months to ensure levels remain within the female physiological range (to reduce chances of side effects)

Answer 146

Presence of fragility fracture DEXA showing BMD -2.5 standard deviations below healthy mean (T score of less than - 2.5)

Answer 147

T score = comparison of BMD to average of young person (aged 20-29) of the same sex Normal T score = +1 to -1 Osteopenia T score = -1 to -2.5 Osteoporosis T score = <-2.5  Z score = compared BMD to people of the same age and gender

Answer 148

Mostly dependant on calc levels PTH, calcitonin and vit D PTH produced by PT in response to LOW serum calc (stimulates osteoblasts to make RANK-L - breaks down bone) Calcitonin produced by thyroid in response to HIGH serum calc (inhibits bone resorption) Vit D - calcium absorption from the gut - increased calcitonin.

Answer 149

Low calcium -> PTH produced -> osteoblasts produce RANK-L -> stimulates production/ differentiation of osteoclasts Changes to the bone in osteoporosis: Less trabeculae and thinning of cortical bone

Answer 150

PPI SSRIs Medroxyprogesterone acetate (long term/significant history of use in particular) Aromatase inhibitors Thiazolidinediones Most anticonvulsants

Answer 151

FRAX should be calculated in all women aged >=65 or those aged 50-65 years with any risk factors --> DEXA as per FRAX result Oestrogen = first line therapy for the prevention of osteoporosis in women under 60 years i.e. reasonable to use HRT solely for this purpose >>> Women with osteopenia; don’t meet criteria for bisphosphonate treatment >>> Women with premature ovarian insufficiency --> bisphosphonates not first line here!) HRT alongside bisphosphonates if osteoporosis confirmed in perimenopausal women; dual action

Answer 152

HRT acts as an anti-resorptive agent by reducing osteoclast number and activity HRT may also increase new bone formation by stimulation of osteoblast activity significant reduction in fracture risk is seen following 2 years of HRT treatment -> persists for several years upon withdrawing HRT Starting HRT at >=60 years for the sole purpose of preventing osteoporotic # is not recommended (BMS)

Answer 153

Responsible for bone resorption Derived from mesenchymal cells (haematopoietic progenitors within bone marrow) Formed by monocyte/ macrophage fusion Multinucleate (2 -12 nuclei / osteoclast) Form resorption bays/ "Howships lacunae" where lysosymes then act to release H + ions and dissolve inorganic matter (bone) NB Interleukin 6 is a potent activator of osteoclast activity, and acts to promote bone reabsorption Part of bisphosphonates mechanism -> inhibits IL-6 production -> osteoclast apoptosis

Answer 154

Bisphosphonate Plus calcium and vitamin D Consider HRT additionally (first line if <60 years old or <10 years since menopause)

Answer 155

Oestrogen as a first-line treatment to prevent all types of fracture for women under 60 years of age (<10 years past menopause). Some might change to bisphosphonate following menopause due to small breast ca risk.

Answer 156

Under 60 years of age (<10 years past menopause)

Answer 157

Contra-indicated in women with fertility aspirations - effects on the fetal skeleton as 1/2 life >12 years. Use with caution in younger PM women (<65) as very long skeletal retention time.

Answer 158

All work by inhibiting bone resorption HRT Bisphos Denosumab SERMs PT hormone peptides (only one that DOESNT work by inhibiting bone resorption) Romozosumab

Answer 159

Oestradiol 2mg Conjugated equine oestrogens 0.625mg Transdermal 50mcg patch LOWER DOSES also conserve bone mass - tailor dose to age of the woman. Continuous use is required.

Answer 160

EG Alendronate 70mg once weekly ( reduces vertebral and non-vertebral fractures by 50%), Risedronate 35mg once weekly. chemical analogues of naturally occurring pyrophosphates (calcium crystal) inhibit osteoclastic bone resorption: (1) attach to hydroxyapatite binding sites on bony surfaces (2) As osteoclasts resorb bone, the bisphosphonate embedded in the bone is released and impairs the osteoclast’s ability to continue bone resorption. >> Nitrogen containing bisphos: - inhibiting farnesyl pyrophosphate synthase - lose ruffled border - detach from bone. >> Non nitrogen bisphos - metabolised inside osteoclast cause apoptosis. Secondary mechanisms: (a) inhibition of IL-6 production: Reduce activity of osteoclasts and induce increased osteoclast apoptosis SE: also interferes with normal bone healing and remodelling >> fatigue damage due to oversuppression of bone remodelling with long-term use in some individuals leading to femoral fragility fractures and also development of osteonecrosis in the jaw. RARE (1 in 5000) but still do 5 years treatment then 2 year holiday to reduce risk.

Answer 161

monoclonal antibody to receptor activator of RANK-L, a major signal promoting osteoclast activity Same as bisphos in terms of spine/ hip fracture reduction BUT risk of osteonecrosis of the jaw and femoral fragility fractures. PRO: not retained in the skeleton and may be a safer option for younger women. CON: associated with an increased risk of infections and should be avoided in patients with increased susceptibility When stopping... accelerated loss --> concern about an increased risk of fractures

Answer 162

EG Raloxifene 60mg/day, reduces fracs by 35%. for women, after the menopause Oestrogenic actions in certain tissues and anti-oestrogenic actions in others. Also reduces risk of breast ca SE: hot flushes calf cramps VTE

Answer 163

(only OP rx that DOESNT work by inhibiting bone resorption) Recombinant 1-34 parathyroid hormone (teriparatide), given as a subcutaneous daily injection of 20 µg, reduces vertebral and non-vertebral fractures in postmenopausal women with osteoporosis (not hip). Costly.

Answer 164

monoclonal antibody - binds sclerostin, a natural inhibitor of the Wnt/LRP pathway which is a major signal to osteoblasts to promote bone formation ---> increase in bone formation. Romozosumab is given by subcutaneous injection every 2 weeks for a 12 month course.

Answer 165

ergocalciferol: 1000 units orally once daily and calcium: adults 51-70 years of age: 1000 mg/day orally

Answer 166

Benefits are mainly related to increased wellbeing, muscle strength, postural stability and a reduction of chronic pain rather than an increase of skeletal mass.

Answer 167

FRAX Consider bisphosphonate treatment in those with other risk factors/ scoring highly on FRAX DEXA if intermediate FRAX score -> recalculate FRAX as per DEXA result -> consider bisphosphonate

Answer 168

PCOS Need to rule out (1) Androgen secreting tumours (imaging of the adrenal glands and ovaries) and/or (2) Ovarian hyperthecosis

Answer 169

Hyperthecosis (HT) = ‘nests’ of luteinised theca cells in ovarian stroma --> testosterone release Non-neoplastic Usually bilateral ovaries effected Gold standard for diagnosis is confirmation via histology of an ovarian sample Ultrasound appearances of the ovaries may be normal, even in pre-menopausal women with HT Becomes unmasked post-menopausally due to loss of follicular granulosa cells --> testosterone no longer being aromatised into oestradiol here --> more marked hyperandrogenis

Answer 170

Vaginal tablets (Vagifem) Creams (Ovestin or Gynest) Gels (Blissel) Vaginal ring (Estring – in situ for 3 months, maximum continuous use of 2 years) Pessaries (Imvaggis)

Answer 171

History of previous VTE/ other VTE risk factors Cardiovascular risk factors ie BMI >=30, uncontrolled hypertension or cholesterol Concomitant enzyme inducing medications (wanting to avoid hepatic first pass metabolism) Malabsorptive conditions of the GI tract History of gallstones History of migraine headache Lactose sensitivity (most oral HRT contains lactose) Side effects or persistent/ suboptimal symptom control with previously trialled oral regime

Answer 172

Estradiol (E2) Made: Granulosa cells (ovaries) When: Reproductive years Potency: most potent Used in HRT: YES - PO/TD Estrone (E1) Made: Adrenal glands/ adipose tissue When: Post menopause Potency: 10 x less Used in HRT: YES - conj equine oestrogen Estriol (E3) Made: Placenta When: Pregnancy Potency: 100x less Used in HRT: YES - cream Estetrol (E4) Made: Fetal liver during pregnancy When: Pregnancy Potency: Used in HRT: Not yet! (new COCP)

Answer 173

Oral Conjugated equine - E1 Estradiol 17 beta - E2 Estradiol valerate - E2 (prodrug) All go through first pass metabolism and become estrone (E1) - much less potent so higher doses. Patch/ gel/ spray Estradiol 17 beta Avoid first pass metabolism through liver, absorbed as estradiol - can check levels Less effect on clotting factors - no increased VTE More suitable for: VTE/CVD risk, enzyme inducers, malabsorption, migraine

Answer 174

Combined patches contain either norethisterone or levonorgestrel

Answer 175

Medroxyprogesterone, Dydrogesterone and drosperinone are less androgenic (better SE profile) Micronized progesterone or dydrogesterone for women with high cholesterol – triglyceride neutral Drosperinone particularly good for women who suffer with fluid retention in progestogenic phase of cyclical HRT due to it’s aldosterone antagonistic effect LNG-IUD results in very low systemic levels of progesterone but provides endometrial protection >> Good if having heavy withdrawal bleeds on cyclical combined HRT regime >> Good if ongoing progestogenic side effects with multiple systemic routes trialled >> Good for those who need contraception alongside HRT (dual effect)

Answer 176

progesterone only taken for part of the month (10-14 days) Allows withdrawal bleeds to occur following progesterone withdrawal Bleeds occur towards end of progesterone containing phase Recommended for women if it has not been >=12 months since their last menstrual bleed A 3 monthly cyclical regime can be considered for women who have infrequent menses or who are poorly tolerant of the progestogen component of their HRT Unscheduled vaginal bleeding is a common side effect of HRT within the first 3 months of use >> Quoted rates of 80% of women experience this in first 3 months (any type of HRT) >>If persistent/ problematic and pathology has been excluded -> change progestogen Sequential HRT is beneficial if you are still having periods as adding in progesterone all the time at this point can lead to erratic, prolonged and, sometimes, heavy, bleeding

Answer 177

Same doses of oestrogen and progesterone taken each day Suitable for women who are >12 months from last menses (post-menopausal) No withdrawal bleeding should occur May result in irregular spotting/ light bleeding for first 4-6 months of use If bleeding becomes heavy, persists beyond 6 months or recurs following a period of amenorrhea then endometrial pathology should be excluded If persistent and pathology excluded -> changing progestogen component often helpful

Answer 178

If <50 years with no UKMEC contraindications, a combined contraceptive can be used in place of HRT e.g. if still need contraception and dont want mirena

Answer 179

Cardioprotective when commenced at <60 years of age / within 10 years of reaching menopause ‘Cardiovascular window of opportunity’ Oestrogen -> increased HDL and reduced LDL

Answer 180

Reduced risk of colorectal cancer with oral combined HRT regime use (no transdermal data)

Answer 181

VTE Coronary heart disease/ stroke Ovarian ca Endometrial ca Breast ca

Answer 182

Oral HRT increases the risk of VTE by 2-4 x compared to baseline, greatest in 1st year of use No increase in risk seen with use of transdermal HRT delivery Transdermal HRT should be offered first line to women with any VTE risk factors, including women with a BMI of >=30

Answer 183

Oral but not transdermal oestrogen is associated with a small increase risk of stroke >> Use transdermal if additional stroke risk factors, or if age >=60 years HRT does not increase CVD risk when started in women aged <60 years HRT with oestrogen alone is associated with no or reduced risk of CHD >> Oestrogen increases HDL and reduces LDL in normal physiology – cardioprotective Combined HRT is associated with little or no increase in risk of CHD Presence of existing CVD is not a contraindication to HRT use; consider transdermal >oral

Answer 184

Slight increase risk in developing serous and endometroid ovarian cancers in HRT users

Answer 185

increases risk; minimised by progestogenic endometrial protection

Answer 186

Oestrogen only = little/ no increase risk (Low dose vaginal oestrogen = no evidence to suggest any increase in risk) Combined HRT = increased risk during treatment if used for >1 year, which reduces upon stopping treatment (time taken to return to baseline depends on length of HRT treatment) Risk increase from post-menopausal obesity or drinking >=2 units/ day of alcohol = greater Use of HRT does not effect likely breast cancer outcomes (death rates) Do not routinely offer HRT to women with a past history of breast cancer Systemic HRT should be stopped immediately in women who are newly diagnosed with breast cancer (including removal of a Mirena coil if in-situ)

Answer 187

Do not routinely offer HRT to women with a past history of breast cancer In exceptions, case by case risk-benefit decisions may be made between menopause specialist and oncology team about the appropriateness of HRT use Low dose vaginal oestrogens is generally acceptable (minimal systemic absorption) UNLESS using aromatase inhibitors: >> Prevent aromatase enzyme from fat tissue from producing oestrogen (Anastrozole, letrozole, exemestane). Women who are carriers of the BRCA1 and BRCA2 gene mutation who have undergone risk-reducing surgery including BSO (therefore in surgical menopause), can receive add-back HRT and this has not been shown to diminish the risk-reducing benefit of BSO on subsequent risk of breast cancer diagnosis Women on tamoxifen should also not use paroxetine or fluoxetine (for their vasomotor symptoms) as it can inhibit the efficacy of the tamoxifen >>Tamoxifen (raloxifene and clomiphene) = selective oestrogen receptor modulators/ SERMs

Answer 188

TSH levels should be checked 6 – 12 weeks after commencing /changing dosage of HRT (as HRT can CAUSE Hypothyroidism) Levothyroxine dose increase may be required, particularly if using oral HRT Mechanism: HRT (ostrogen) metabolism -> increased thyroxine binding globulin (hepatic synthesis) -> Increasing binding of thyroxine to TBG (and less free thyroxine) -> elevated TSH -> women with hypothyroidism on treatment unable to naturally compensate -> higher dose of levothyroxine needed to control TSH levels back to normal range This effect is not reported with transdermal HRT (as avoids first pass metabolism -> TBG) Transdermal HRT may be preferable route of administration if patient has existing hypothyroidism

Answer 189

For (1) Antidepressants (SSRIs or SNRIs; makes sense when consider mechanism of vasomotor syx) (2) Clonidine (alpha-2 adrenergic receptor agonist -> less sympathetic tone -> lowers BP + HR) (3) Gabapentin (off-label) +/- cognitive behavioural therapy

Answer 190

synthetic steroid hormone Oral daily tablet, HRT alternative Only suitable post-menopause (unless also using gonadotrophin releasing hormone analogue) Metabolised into 3 metabolites -> 2 oestrogenic and 1 progestogenic/ androgenic

Answer 191

+3 months when starting/ changing then yearly

Answer 192

All methods of progesterone only contraception are safe when used alongside cyclical HRT (unless other CI)

Answer 193

1 year if aged >=50 2 years if aged <50 OR until age 55 if on hormonal contraception that could be masking presence of natural menses

Answer 194

TAMOXIFEN Breast ca/ reduce incidence of HR patients Anovulatory infertility ER Antagonist: breast ER Agonist: endometrium, bone, lipids Can cause hot flushes CVD: Reduce tot chol and LDL, no change in HDL SE: increase thickness of endo, polyps. Increase VTE. RALOXIFENE to prevent and treat osteoporosis PMW (not first ling) ER agonist in bone Inhibits bone resorption CVD: Reduce tot chol and LDL, no change in HDL Increase VTE. CLOMIPHENE Induction of ovulation Increases GNRH release SE: Hot flushes, 12 cycles increase ovarian ca risk, multiple gestations, ovarian cysts NO increase VTE

Answer 195

Oral progesterone not absorbed well; if micronized (oil and gelatin) -> better bioavailability Vaginal absorption (i.e. in recurrent miscarriage) is quicker and less variable than oral (HRT) >> Oral - metabolised by liver/P450 cytochrome -> similar metabolites to ‘natural’ pathway >> Vaginal – metabolites present at lower levels due to lack of first-pass metabolism Drug interactions – P450 enzyme inducing agents will reduce progesterone levels achieved Generally considered to be the ‘safest’ oral progestogen Has anti-mineralocorticoid activity -> reduces sodium reabsorption and produces diuresis Dose dependent BP reducing effect Mild sedative effect with oral use; recommended to take at night time Made with soy – should not be used in soy or peanut allergy

Answer 196

Qlaira and Zoely (COCPs), Vagifem pessaries (vaginal atrophy), HRT (oral and transdermal) Oestradiol valerate is a pro-drug of oestradiol Acute ingredient is 17β-estradiol, synthetic compound which is chemically and biologically identical to endogenous oestradiol (E2) 1 mg oestradiol valerate -> 0.76 mg 17ß-estradiol Binds to and acts on oestrogen receptors (ER) >> ER(a) = endometrium, bone, breast cancer cells, ovarian stromal cells, hypothalamus (repro) >>ER(b) = kidney, brain, bone, heart, lungs, intestine, prostate, endothelium (non-repro) Oral administration -> high levels of first pass metabolism to less potent Estrone (E1) >>Bioavailability as low as 2% >>Much higher doses needed >>Topical or transdermal application routes bypass first pass metabolism; lower doses effective Following vaginal administration -> potent local activity but minimal systemic absorption Transdermal application ~20X higher bioavailability rates First pass metabolism via liver from P450 enzymes >>Dose reduction with concurrent use of P450 enzyme inducing agents >>Dose effective increased (less metabolism) with concurrent use of P450 enzyme inhibitors --> Increased rates of adverse effects

Answer 197

Embryological origin via integration of the two mesonephric ducts at the base of the bladder for the rest of the bladder... origins from the anterior division of the cloaca – urogenital sinus –

Answer 198

Superior vesical branch of the internal iliac artery

Answer 199

internal iliac veins

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Superior -> external iliac nodes Neck and fundus (posterior-inferior aspect) of the bladder -> internal iliac, sacral and common iliac nodes

Answer 201

SNS Hypogastric nerve (T12-L2) -> relaxation of detrusor & bladder neck (retention of urine). PNS pelvic nerve (S2 – S4) -> contraction of detrusor & relaxation internal urethral sphincter (micturition). Somatic pudendal nerve (S2-4) – external urethral (and external anal) sphincter, vol Visceral afferent via pelvic splanchnic nerves to reach the sc

Answer 202

Adrenergic (NE/NA) Α1, β3 in bladder wall Hypogastric nerve (T12 – L2)

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Muscarinic (Ach) M3 Pelvic nerve (S2 – S4)

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Progressive change from stratified transitional epithelium ----> stratified squamous keratinising

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internal pudendal arteries and vaginal arteries internal pudendal vein and branches of vaginal vein

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Distal urethra = superficial inguinal nodes Proximal urethra = internal iliac nodes

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S2-4 = the micturition centre/ Onuf’s nucleus Receives afferent from stretch receptors in bladder wall Sends efferent signals – both somatic (pudendal nerve) and autonomic (e.g. parasympathic pelvic nerve)

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Causes Urethral hypermobility Intrinsic sphincter deficiency RFs Increasing age Parity Deficiency in supporting tissues (Prolapse, Hysterectomy, Menopause, CT disorders) Smoking Obesity Constipation

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#1 Supervised PMFT 3/12 #2 Mmx Duloxetine #2 Surgical mx *Colposuspension (POP =SE) *Autologous rectus fascial sling *Retropubic mid-urethral mesh sling (mesh-related comps: pain/ vaginal problems, can be done w/o GA) #3 Intramural bulking agents

Answer 210

Pelvic floor contractions assessment 0 = no contraction. 1 = flicker. 2 = weak (no lift) 3 = mod. Lift of musc + elevation of post vaginal wall. 4 = good. Increased tension and a good contraction elevate the posterior vaginal wall against resistance. 5 = strong. Strong resistance is applied to the elevation of the posterior vaginal wall. The examiner's finger is squeezed and drawn into the vagina.

Answer 211

SNRI Increases availability of serotonin and noradrenaline within Onuf’s nucleus – increases motor neuron activation of external urethral sphincter – increasing tone and improving continence Metabolised in liver Side Effects: Dry mouth Anxiety Decreased appetite Fatigue Sexual Dysfunction Cautions: Hepatic impairment Hx seizures uncontrolled hypertension Bleeding disorders – may increase risk PPH if taken month before delivery

Answer 212

Causes: overactivity of detrusor muscle. Risk factors: Increasing age Neurological condition: Parkinsons, MS, DM, spinal cord injury Dementia, Stroke Idiopathic: often no specific cause found

Answer 213

#1 Lifestyle intervention Caffeine reduction Modify fluid intake Lose weight (BMI >30) #1Bladder training 6/52 Urge or mixed #2 Med Mx 2.1 Anticholinergics 2.2 Mirabegron +/- Desmopressin *urodynamic investigation if don’t respond to #1 and #2* #3 Invasive treatments 3.1 Botulinum toxin type A 3.2 Percutaneous sacral nerve stimulation (PSNS)

Answer 214

Give 4 weeks to see effect

Answer 215

Tolterodine Non Selective muscarinic receptor antagonist M2/M3 – longer filling time and less urgency Oxybutynin Non Selective muscarinic receptor antagonist M1-3 Solifenacin Competitive muscarinic, selective for M3 Side effects: Dry mouth Constipation Flushing Visual disturbance Tachycardia Contraindicated: Angle closure glaucoma Myasthenia Gravis Urinary Retention Pyloric Stenosis Ulcerative Colitis   Anti cholinergic Burden – score to assess risk of multiple drugs in elderly, >3

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M1 cognitive M2 CVS M3 bladder

Answer 217

Selective Beta 3 adrenergic agonist Clinical effectiveness of mirabegron similar to that of antimuscarinic drugs but has different side effect profile. Side Effects: UTI, Headache, Dizziness, Tachycardia, GI upset Cautions/ contraindications: Hepatic/renal impairment, Uncontrolled hypertension **Blood pressure should be measured before starting treatment and monitored regularly during treatment, especially in patients with hypertension.**

Answer 218

The use of desmopressin may be considered specifically to reduce nocturia in women with urinary incontinence or overactive bladder who find it a troublesome symptom. Use particular caution in women with cystic fibrosis and avoid in those over 65 years with cardiovascular disease or hypertension.

Answer 219

urge-predominant mixed UI unclear type UI symptoms suggestive of voiding dysfunction anterior or apical prolapse a history of previous surgery for stress urinary incontinence

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Urge/ detrusor overactivity Pabdo no rise, SUI Pdet no rise

Answer 221

100 units as the initial dose – can be increased to 200 units (if lasted for less than 6 months)

Answer 222

Lifestyle modification Weight loss (BMI > 30 kg/m2) Minimise heavy lifting Prevent or treat constipation Vaginal oestrogens PFMT 16/52 Symptomatic POP-Q stage 1 or stage 2 Pessaries May cause new stress urinary incontinence

Answer 223

Vaginal hysterectomy, with or without sacrospinous fixation with sutures. 65% resolution of symptoms at 1 year Vaginal sacrospinous hysteropexy with sutures. Manchester repair (also called the Fothergill operation). Sacro-hysteropexy with mesh Colpocleisis - do not intend to have penetrative vaginal sex and who have a physical condition that may put them at increased risk of operative and postoperative complications

Answer 224

Decidua = endometrial mucosa during the SECRETORY phase of the menstrual cycle in preparation for implantation and pregnancy. Decidualisation = differentiation of endometrial stromal cells (ESCs) (fibroblast-like cells) into decidual stroma. Decidual Cell Characteristics: >> Enlarged and rounded nuclei, increased numbers of nucleoli, and accumulate glycogen and lipid droplets (polygonal). >> Exhibit increased secretory activity -> cytokines, growth factors and proteins to support an implanting trophoblast;as well as fibronectin and laminin to form a dense extracellular matrix Uterine natural killer cells become abundant and produce cytokines to facilitate trophoblast invasion while providing immunoprotection from the maternal immune response.

Answer 225

Sex cord-stromal tumour, arising from theca cells Almost always benign Ultrasound features are variable, may be hypoechoic, solid or mixed Most common in postmenopausal women Oestrogen secreting so cause endometrial hyperplasia resulting in post-menopausal bleeding High risk for endometrial cancer

Answer 226

(in order of strength) Dihydrotestosterone Testosterone Androstenediol Oestradiol Oestrone

Answer 227

True (lesser) pelvis: Inferior to the pelvic brim, contains the bladder, colon and reproductive organs False (greater) pelvis: Superior to the pelvic brim, supports organs of the lower abdomen and the gravid uterus