Quick revise Flashcards
Glycolysis
Occurs int he cytosol of cells
Glucose (C6) – > Pyruvate (2 x C3)
–> Acetyl-coA which can enter the citric acid cycle.
Net ATP gain = 2 ATP (4 produced, 2 used).
NADH plus H+ produced = 2 molecules per glucose.
pelvic floor muscles
coccygeus (back)
levator ani (lat to med)
iliococcygeus
pubococcygeus
puborectalis
Obesity and EC
LNG-EC – double dose if BMI>26 or >70kg
Bosentan
used to treat pulmonary arterial hypertension
ERA – endothelial receptor antagonist
decreases prog and eostro levels in contra
VTE risk and progesterones
Doubles the risk (9-10 in 10,000)
Baseline VTE risk = 2 in 10,000
Pregnancy & puerperium = 20 in 10,000
Lower risk progestogens (6 in 10,000)
Levonogestrel
Norethisterone
Norgestimate
Moderate risk progestogens (8 in 10,000)
Etonogestrel
Norelgestromin
Higher risk progestogens (10 in 10,000)
Desogestrel
Gestodene
Drospirenone
What oestrogen does zoely and qlaria use
oestradiol valerate
Zeoly: Nomegestrol acetate progestin
Qlaria: Dienogest progestin
First line COCP
A monophasic COC containing
20 - 35 micrograms of ethinylestradiol
norethisterone or levonorgestrel
Dianette components
Ethinylestradiol 35
Cyproterone acetate 2000
UKMEC Known BRCA1/2 mutation
CHC: UKMEC 3
All other hormonal forms UKMEC 2
Filshie clip
Titanium clip lined with silicone
UKMEC Hx of bariatric surgery
All 1 other than CHC
BMI <30 = 1
BMI 30-34 =2
BMI >34 = 3
UKMEC Organ transplant
a) Complicated: graft failure (acute or
chronic), rejection, cardiac allograft vasculopathy
Coils UKMEC 3 initiation/ 2 continuation
CHC UKMEC 3
b) Uncomplicated
UKMEC 2 for all
UKMEC CVD
RFs
Known dislipidaemia
Cardiomyopathy
AF
QT
RF multiple:
DMPA and CHC: UKMEC 3
All other methods (other than copper):UKMEC 2
Known dislipidaemia
UKMEC 2 (other than copper)
Cardiomyopathy
Normal cardiac fx: CHC UKMEC 2, all UKMEC 1
Impaired cardiac fx: CHC UKMEC 4, all UKMEC 2
AF
CHC UKMEC 4, Copper UKMEC 1, rest UKMEC 2
Known long QT
Coils UKMEC 3 initiation/ 1 continuation
DMPA and CHC UKMEC 2
IIH UKMEC
CHC 2, rest 1
GC VS CT infectivity
Single episode of UPSI
M->F spread
GC: 60-80% (40% with condom) 40/60/80
CT: 10% transmission rate (75% concordance within partners, condoms reduce by 40%)
F->M spread
GC: 20% (5% with condom)
CT: 10% same as above
Men symptoms and complications GC
Only 5-10% asymptomatic
Typical incubation of 2-5 days (up to 14)
Urethral discharge in 80%, typically profuse and purulent; dysuria in 50%
Complications are rare
(1) Infection of the median raphe (line down middle of scrotum -> perineum)
(2) Tysonitis – swollen parafrenal gland/s
(3) Meatal gland abscess / peri-urethral cellulitis/ abscess -> strictures and fistulae if left
(4) Epididymitis in <1%
Note: MSM: FVU, pharyngeal and rectal swabs all recommended even if no history of RAI
Women symptoms and complications GC
Women ~50% symptomatic vs asymptomatic
When present, symptoms usually appear within 10 days
Increased vaginal discharge, which again may be purulent, most common symptom
Dysuria without frequency, lower abdominal discomfort and less often IMB/ menorrhagia
Complications are rare
(1) Inflamed paraurethral (Skene) glands
(2) Bartholin’s abscess
(3) PID may develop in 10-20% of cases if left untreated
GC rectal
usually asymptomatic but can cause discharge (12%), pain or itching
In women: + rectal GC, + correlation with length of infection suggests transmucosal spread to rectal infection, with anal intercourse thought to be attributable in only ~10%
GC pharyngeal
asymptomatic in >90% of cases with almost 100% spontaneous clearance in 3 /12
Strongest association with disseminated infection
GC Conjunctival infection
Conjunctival infection in adults is rare and can present with purulent discharge and -> keratitis and blindness
GC disseminated infection
Occurs in <1%
4 x more likely in women, especially if recent menstruation, in pregnancy, and pharyngeal infection (which is likely to have been asymptomatic)
Skin signs in 67% - ‘gonococcal dermatitis’ – petechiae, necrotic pustules usually at extremities
Tenosynovitis in ~ 1/3 of cases -> migratory arthralgia
Rarely: endocarditis, hepatitis, meningitis
GC microscopy endocervical vs urethral vs proctoscopic
Endocervical microscopy sensitivity of only 45% - not routinely recommended for asymptomatic but should be performed if symptoms
Microscopy of urethral smears has good sensitivity for those with symptoms (95%) so is recommended -> POC diagnosis and treatment facilitation
Sensitivity less good for asymptomatic (65%) therefore not recommended here
Proctoscopy and microscopy 75% sensitivity»_space;> blind swab microscopy only 40% sensitivity
Listeria
non-spore forming Facultative anaerobe
GRAM POSITIVE bacilli
obligate anaerobes
If you are asked about obligate anaerobes you are likely dealing with either:
Clostridium gram positive
Bacteroides (also called Prevotella) gram negative
Actinomyces not appropriately classified : Actinomyces mostly facultative, one strain is an obligate anaerobe
primordial germ cells
Early in development at the time of gastrulation a small group of cells are “put aside” – primordial germ cells.
The cells migrate initially through the primitive streak (at gastrulation) into the posterior endoderm that forms the hindgut
from there later into the genital ridge VIA VITILLINE DUCT that will be the site of the developing gonad.
whats formed from the urogenital ridge
from int mesoderm
Gonads
ductal system
primordial germ cells (primitive streak, ORIGIN YOLK SAC)
quadruple screening
Hcg
Quad
UE3
Inhibin A
aFP
14+3 - 20
Amniocentesis
comb screening
Comb
Hcg
Imaging
Papp A
10-14
CVS
<1:150 low risk
Likelihood Ratios
LR+ = Sensitivity / (1 - Specificity)
LR- = (1- Sensitivity) / Specificity
Actinomyces
Gram positive anaerobe
“Sulphur granules with filamentous organisms” seen on histopathology review
Treatment of partners of PID
doxycycline 100mg BD 7/7
first line for treatment of confirmed mycoplasma associated PID
moxifloxacin
current partners should also be tested +/- treated for M gen as per result
Theca Lutein cysts
Form of functional ovarian cyst associated with pregnancy
Seen as large, (almost always) bilateral, multiple ovarian cysts
Differential diagnosis:
OHSS
Mucinous ovarian malignancy
Highly associated with GTD
Present in >20% of molar pregnancies
Following evacuation of a molar pregnancy typically self-resolve within 2-4 months
More likely to occur if:
GTD
Ovulation induction/ clomiphene > natural conception
Multi-fetal pregnancies
Patient with pre-existing PCOS or type 2 diabetes
Rarely found in typical/ uncomplicated pregnancies
In these rare reports the cyst(s) have been seen to spontaneously resolve following delivery
Not commonly associated with torsion (<2%)
Ovarian malignancy
epithelial tumours (~80%), germ cell tumours (~15%)
sex cord stromal tumours (<=5%)
Most common type of ovarian malignancy is high grade serous ovarian carcinoma (HGSOC)
Almost all cases have a mutation in the p53 tumour suppressor gene
Risk factors = more ovulations (early menarche, late menopause, nulliparity)
Protective factors = fewer ovulations (CHC use, pregnancy)
Krukenberg tumours
GI tumours to the ovary (typically from stomach cancer)
Epithelial ovarian tumours including 5 types
Most common form of ovarian neoplasm
CA125 glycoprotein/ tumour marker is released by 85% of epithelial ovarian tumours
Benign (adenomas) or malignant( (adenocarcinoma)
Often bilateral, especially serous forms
5 types of epithelial tumours
(1) High grade serous ovarian cancer (HGSOC - most common)
(2) Low grade serous ovarian cancer (LGSOC – younger demographic, better prognosis)
(3) Endometroid (associated with endometriosis)
(4) Clear cell (rare but very aggressive)
(5) Mucinous (often benign, usually unilateral)
Germ cell tumours: ovarian
More common in younger women, contain extraembryonic elements of germ cell layers
2nd most common form of ovarian neoplasm (making up ~15% of cases)
Arise from cells of the germ cell layers, younger demographic
Can be benign or malignant
Usually unilateral (can be bilateral in minority)
Most common benign germ cell tumour = mature teratoma (“dermoid cyst”)
Most common malignant germ cell tumour = dysgerminoma
»Dysgerminoma is more common in those with abnormal karyotypes (e.g. 45 XO Turner’s)
»Contains syncytiotrophoblast cells -> raised hCG
Other malignant forms = immature teratoma (younger patients), yolk sac tumours
»Both of these may secrete aFP (majority of yolk sac secrete AFP»_space; ~1/3 immature teratomas)
NB: Gonadoblastoma is very rare form of ovarian neoplasm with mixed germ cell and sex cord origins
Typically begin as a benign growth, but strongly associated with dysgerminoma (malignant)
dysgerminoma
Most common malignant germ cell tumour
Dysgerminoma is more common in those with abnormal karyotypes (e.g. 45 XO Turner’s)
Contains syncytiotrophoblast cells à raised hCG
Sex cord stromal ovarian tumours:
Significantly less common, secrete hormones <5%
Derived from sex cords of the developing gonads (granulosa cells/ stroma, theca cells/ fibroblasts)
3 types:
(1) Fibromas and thecomas – typically benign
(2) Granulosa cell tumours – most common type of SCST and are malignant
(3) Sertoli-Leydig tumours – either
Granulosa cell tumours
<5% of ovarian tumours but >95% of sex cord stromal ovarian tumours
Generally produce oestrogen
Can occur in adulthood (most commonly) or pre-puberty (rare); can cause oestrogenic symptoms
Juvenile granulosa cell tumours may be associated with precocious puberty
Post-menopausal granulosa cell tumours may be associated with post-menopausal bleeding
90% present early, at stage 1, and are generally managed surgically
Majority of cases have a mutation in FOXL2 (required for ovarian differentiation)
Meig’s syndrome/ triad
Fibroma – benign and always non-secretory
Ascites
Pleural effusion
Ovarian fibroma
Mmx SUI
Duloxetine 40mg BD
Selective serotonin and noradrenaline reuptake inhibitor/ SSNRI
Theory: increases serotonin and noradrenaline level within Onuf’s nucleus (S2-S4)
à Increased activity of pudendal nerve à improved tone of external urethral sphincter and therefore improvement in function
Mirabegron
Beta-3 adrenoreceptor agonist à detrusor relaxation/ reduced voiding
Wilson and Jungner Criteria for Screening Tests (1968)
We must have knowledge of the disease (3)
» condition important
» recognisable asypm latent / early symptomatic stage
» natural course of the condition understood
We must have knowledge of the proposed test (3)
» Suitable
» Acceptable to pop
» Continuous (not just a ‘once and for all’ project)
We must have an effective treatment for the disease (3)
» Accepted treatment
» Facilities for diagnosis and treatment available
» Agreed policy on whom to treat
The screening must be cost appropriate (1)
» Costs of case finding economically balanced
% that hpv is responsible for cancers
> 90% of cases of anal cancer,
> 40% of cases of penile/ vulval cancers
> 99% of cervical cancer
(16 and 18 responsible for >70% of cervical cancers)
Chemicals applied to cervix at colp
Acetic acid; neoplastic cells w higher nuclear:cytoplasmic ratio –> white (“acetowhite”)
Iodine solution; normal tissue à brown, neoplastic cells are glycogen deficient and do not stain brown
CINs
CIN = Cervical Intra-epithelial Neoplasia of the squamous cells of the external cervix
CIN 1 (low-grade or mild dysplasia) – 1/3 thickness of surface layer affected; starts at base
»> CIN 1 = “HPV infection correlate” and NOT pre-cancerous condition by definition
»> Usually resolves if HPV clears
»> CIN 1 = repeat colposcopy should be arranged for further testing in 12 months
CIN 2 and 3 are high grade changes - 20% of high grade changes (CIN 2+3) progress to cervical cancer. pre-cancerous condition.
CIN 2
moderate – 2/3 thickness of surface layer is affected; starts at base
Up to 5% progress to cervical cancer if not treated appropriately
For CIN 2 some cases (~40%) will self resolve but this can take up to 2 years
Excisional treatment is usually offered for CIN 2 (LLETZ)
Conservative management > excision may be appropriate if <2 quadrants of the cervix are effected, as long as the patient is agreeable to follow up
If patients want conservative management they should be followed up with 6 monthly colposcopy until resolution (maximum of 2 years)
If persistent CIN 2 at 2 years then excision should be recommended
CIN 3
high-grade or severe dysplasia – full thickness of surface layer is affected
Highest rates of progression to cervical cancer (up to 30% progression)
For CIN 3 excision is always recommended (LLETZ)
If CIN completely excised à follow up smear with ‘test of cure’ for high risk HPV strains in 6 months
If this TOC is negative for high risk HPV strains à discharge to 3 yearly recall
CGIN
Cervical Glandular Intra-epithelial Neoplasia; glandular cells within the endocervical canal
Most strongly associated with HPV type 18
May be more difficult to achieve clear margins/ have higher recurrence risk – skip lesions
Cone biopsy»_space; LLETZ usually given as treatment (need to get deeper into endocervical canal)
If CGIN is completely excised -> follow up smear with ‘test of cure’ for high risk HPV strains is recommended at 6 and 18 months following treatment
If both of these TOCs are negative for high risk HPV strains -> discharge to 3 yearly recall
BV on gram stain
Absence of polymorphs (pus cells)
Use of Hay-Ison Gram-stain method for scoring:
Grade 0 – epithelial cells with no bacteria
Grade 1/ normal – epithelial cells with lactobacilli dominant
Grade 2/ intermediate – epithelial cells w some lactobacilli and mixed bacteria
Grade 3/BV consistent – epithelial cells w mixed bacteria and few/ absent lacto
Grade 4 – epithelial cells with gram + cocci only (typically streptococci)
Spironolactone MOA
mineralocorticoid receptor antagonists (non selective - can bind to androgen and progesterone receptors)
Reduces NA absorption (water follows NA by osmosis)
Reduces K secretion
Both in DT (principal cells)
(Reduces H+ secretion in CT - alpha intercal –> decrease in PH)
K sparing
Drosperinone is derived from 17alpha spironolacton
HYPERkalemia, HYPOnatremia, HYPOtension
Ectopic measurements
FP NO MSD
>=25mm on TV - 2nd opinion
<25MM on TV - rescan 7/7
TA always 2nd scan 14/7
FP YES CRL
>=7 -2nd opinion
<7 - rescan 7/7
TA always 2nd scan 14/7
How does oestrogen interact with RAAS
Stimulates synthesis of angoitensinogen (the precursor to Ang I)
But downregs ACE (so Ang 1 not converted to Ang 2) - reduces inflammatory response.
Congenital adrenal hyperplasia
21 hydroxylase
17 less common
Needed for corticosteroid and mineralocorticoid production.
But not needed for progesterone and androgen.
–> so steroid synthesis is directed towards making androgens
REDUCED cortisol: high ACTH, prog, androgens.
(due to neg feedback on pituitary)
–> androgens dominate over oestogen –> male like genitalia, precesious puberty and virualization.
REDUCED aldosterone: salt and water wasting.
(hypotension, hyponatremia, hypERkalemia)
INCREASED 17OH progesterone.
<200 no CAH
200-800 ACTH stimulation test
> 800 CAH dx
XX: Uterus, vagina, fallopian tube and ovaries.
XY: go through puberty earlier
Rx: steroids
Levator ani arterial and nerve supply
A: inferior gluteal
N pudendal, perineal and inferior rectal (S3/4)
Posterior vs anterior pituitary originates:
Posterior pituitary - neural tube ectoderm
Anterior pituitary- surface ectoderm epithelial tissue of nasal cavity –> Rathke’s pouch –> anterior pituitary
Layers of adrenal gland cortex
glomerulosa GC
fasciculata MC
reticularis Androgens
Plasma ACTH and cortisol in adrenal insufficiency
Plasma ACTH: A low serum cortisol with an elevated plasma ACTH hormone level indicates Addison’s disease as it suggests a primary insufficiency of the adrenal gland.
On the other hand, if there is a low serum cortisol accompanied by a normal or low ACTH level, this would suggest a secondary cause of adrenal insufficiency.
(Addison disease)
adrenocortical insufficiency
primary adrenal insufficiency
Acute (crisis) or chronic
Adrenal cortex gets progressively damaged
ZG: low aldosterone - low NA, high K, low BP, acidosis.
ZF: low cortisol - high ACH and MSH - hyperpigmentation in joints
Rarely ZR affected: decreased sex drive and hair in women.
Causes
AI (unsure why)
TB
Met carcinoma
Cushing’s syndrome,
increased cortisol levels
ACTH dep: cortisol excess is driven by ACTH, either from the pituitary or ectopic sources.
** pituitary adenoma **
(( ACTH-dependent types (and some adrenal cancers) –> elevated androgens. ))
ACTH indep: cortisol excess is independent of ACTH. Includes exogenous causes (consumption of cortisol) and adrenal lesions (adenomas, carcinomas).
Ix
(1) 24-hour urinary cortisol –>
high = cushings
(2)plasma acth
LOW ACTH indep
HIGH ACTH dep
(3A) ACTH indep (low plasma ACTH) –> CT adrenal gland
(3B) ACTH dep (high plasma ACTH) –> Dex suppresion test
ACTH suppressed by hd dexamethazone - Pit source (MRI PITUITARY)
ACTH unsuppressed - Ectopic source.
hyper- aldosteronism
Primary = conns
Adrenal adenoma
Secondary
high aldosterone, high renin
RA stenosis / HF etc
phaeochromocytoma
a rare neuroendocrine tumour of the adrenal glands - chromaffin cells
It can present with palpitations, diaphoresis, pallor, and paroxysmal hypertension
Diagnosed by increased levels of metanephrines and normetanephrines.
paraganglioma (PPGL).
PPGLs are rare neuroendocrine tumours arising from
neural crest-derived cells of the sympathetic and
parasympathetic nervous systems.
results from excessive production
of catecholamines by the chromaffin cells located in the
extra-adrenal sympathetic paraganglia, typically in the
abdomen and pelvis.
PPGL can be
sporadic, it can also form part of hereditary syndromes,
such as Von Hippel–Lindau syndrome, multiple endocrine
neoplasia-type 2 (MEN-2) and neurofibromatosis type 1
(NF1) – all of which have autosomal dominant patterns
of inheritance.
High blood pressure, headache
Hypoaldosteronism causes
(1) hyporenin hypoaldosteronism
both low
- diabetic nephropathy, nsaids
(2) non-hyporenin hypoaldost
renin n/high
aldosterone low
ACEi
Chronic heparin
Primary adrenal insufficiency
Genetic
(3) Aldosterone resistance
Renin n/h
aldosterone n/h
Aldosterone receptor antagonists
Trimethoprim/ sulfamethoxazole
Genetic disorders
which mutations have been linked to increasing quinolone resistance in GC
mutations in gyrA and gyrB)
epithelial ovarian tumour - types/ semicirc
80%
Serous (high G and low G)
Endometroid (assoc with endometriosis)
MUcinous = Unilat
i
Circle = clear cell (rare but v aggresssive)
Three germ cell ovairian tumours
15%
(1) Mature teratoma - benign, dermoid cyst
(2) dysgerminoma- malig
Most common malignant germ cell tumour. raised hCG
more common in those with abnormal karyotypes (e.g. 45 XO Turner’s)
(3) immature teratoma - malig secrete aFP
Sex cell ovarian tumours; three types
(1) Fibromas and thecomas – typically benign
Fibroma = meigs syndrome
(2) Granulosa cell tumours – most common type of SCST and are malignant
Produce oestrogen - PMB, precious puberty. FOXL2
(3) Sertoli-Leydig tumours – either
LS % to vulval SCC
5% risk
Wickham’s striae
shiny flat topped papules with “white lacy lines”
mucosal
LP
LP vs LS
LS
Does not affect vaginal walls
White and flat lesions
5% risk vulval scc
LP
Affects vaginal walls
Red and raised
Wickham’s striae - mucousal lesions
Lesions else where
Lower risk of vulval squamous cell carcinoma of <3%
LP and the Ps
Skin lesions 6Ps
Puritic
Polygonal
Purple
Planar
Papule
Plaque
FGM types
Type I – Clitoridectomy
Partial/ total removal of clitoris/ prepuce
Type II – Excision
Partial/ total removal of clitoris and the inner labia +/- outer labia
Type III – Infibulation
Narrowing of the vaginal opening by creating a covering seal. The seal is formed by cutting and repositioning the inner or outer labia, with or without removal of the clitoris..
Type IV – Other
Solifenacin
Selective and competitive M3 antimuscarinic agent
What do they look for on cytology
(1) DYSKARYOSIS: high nuclear: cytoplasmic ratio (hyperchromatic nucleu)
(2)POILKILOCYTOSIS: Abnormal shape
(3) KOILIOCYTOSIS: Abnormal density (bigger nucleus)
HPV associated with CGIN
HPV type 18
TOC at 6 and 18 months following treatment (rather than others just 6 months)
Breast screening
50 - 70, 3 yearly
(First invitation should be received before 53rd birthday)
It is recommended that breast screening for trans women should continue beyond the age of 70 if oestradiol continues to be used
Mammograms require at least 2 x-rays to be taken of each breast
Mammograms interpreted using standardised BI-RADS system
Breast cancer
Most common ca in women in uk
Types:
1. Invasive ductal carcinoma (IDC) makes up 80%
Significant family hx of breast ca: definition and tests
1st degree male relative diagnosed with breast cancer at any age
1st degree female relative diagnosed with breast cancer at <40 years
1st degree relative with bilateral breast cancer first diagnosed <50 years
2 x 1st degree relatives diagnosed with breast cancer at any age
1 x 1st degree and 1 x 2nd degree relative diagnosed with breast OR ovarian cancer at any age
3 x 2nd degree relatives diagnosed with breast cancer at any age
—-> specialist referral for genetic testing (BRCA 1, BRCA 2 and TP53 genes)
Prognosis of breast cancer based on receptor status
Oestrogen receptors (present in 70-80%)
Progesterone receptors
> > > > Hormone sensitive (ER + PR +) cancers have more favourable prognoses
Suitable for treatment with SERM agents (e.g. Tamoxifen) during follow up if ER +
HER2 (human epidermal growth factor receptor 2) receptors
Triple negative (no receptors)
MEN with BRCA (1 or 2)
mutations the risk of breast cancer is between 1.2-8%
Also have double the risk of prostate cancer compared to male baseline risk (10% -> 20%)
BRCA 1 and 2
BRCA mutations are responsible for >90% of inherited breast (and ovarian) cancers
BRCA1 – highest risk
Long arm of chromosome 17, ***triple neg breast cancers
(Aggressive, difficult to treat and poorer prognosis)
Lifetime risk breast ca 70%
Ovarian ca 45%
BRCA 2 – lower risk
Long arm of chromosome 13,
Lifetime risk of breast ca is 40%
Ovarian cancer is 15%
Patients with identified BRCA mutation who do NOT wish to undertake risk reducing surgery
offered annual screening with MRI and/ or mammography as per their age
25-39 MRI
40-50 MRI plus mam
51-71 mamm +/- MRI
Li Fraumeni syndrome
= Transcription factor p53 (TP53) mutation
The most frequently identified genetic mutation across all cancer types
Identified in ~30% of all breast cancer cases
Most TP53 mutations are acquired -> spontaneous cancer cases (NOT inherited/familial - but is AD)
Tested if breast ca <30, adrenocortical carcinoma, early onset GI ca
People with known TP53 gene mutation should have breast cancer screening annually via MRI: From age 20+. Mammography not recommended for people with TP53 mutations (NICE)
Bowel screening
Offered to people of all genders between ages of 50 – 74 years
Home FIT kit –> looks for traces of blood in the stool à if + invited for further tests (colonoscopy)
Invited to take part routinely every 2 years
After age 75 you can request a kit every 2 years if you wish to continue with the screening
Lynch syndrome (Hereditary Non-Polyposis Colorectal Cancer HNPCC):
AD
~3% of colorectal cancer due to Lynch syndrome
Implicated genes – MLH1, MSH2, MSH6 and PMS2
Screening colonoscopy every 2 years, from 25
Lynch syndrome increases risk of
Endometrial ca
Ovarian ca
No screening is recommended for gynaecological cancers with Lynch syndrome
> > If confirmed Lynch syndrome, risk reducing surgery (TAHBSO) can be considered
Usually recommended after the age of 35 (with add-back HRT cover)
Limited evidence linking Lynch syndrome and breast cancer; no additional screening recommended
AAA screening
From 65 for men
Trans women will have similar AAA risk levels to cis men and should consider requesting screening if not registered as male with their GPs (not routinely invited)
No AAA
Small AAA (3 – 4.4 cm) – annual monitoring USS
Medium AAA (5.4 – 5.4cm) – USS every 3 months
Large AAA (5.5cm +) - prophylactic repair
CAH
21-hydroxylase deficiency
Autosomal recessive genetic inheritance via chromosome 6
Classical: ambiguous genitalia +/- adrenal crisis at birth
Non: milder - early pubertal changes (secondary to androgen excess) or absent/ irregular menses
17-hydroxyprogesterone HIGH
–> should be measured in the follicular phase and will be raised in CAH. 8AM d 1-5
–> Testosterone can be normal or high
–> If 17- hydroxyprogesterone is borderline, it will have to be confirmed by an ACTH stimulation test to diagnose CAH.
Hymenal origin
Endoderm (from the urogenital sinus epithelium)
Embryological development of vagina
Müllerian ducts –> inferior/ fused structure –> uterus, cervix and upper 1/3 vagina
Urogenital sinus –> lower 2/3 of the vagina develop from the (sinovaginal bulbs - fuse to form vaginal plate)
— both of these are from intermediate mesoderm—
—Happens at about 10 weeks Entire process is complete by 20 weeks of gestation (think: in time for anatomy scan!) —
MRKH
Primary ammenorrhoea (make up 15% of primary)
Absent vagina (upper 2/3 and cervix)
Non-functioning uterus
Normal ovaries!
T1: above
T2: other assoc (40%-50%)
Renal tract (most commonly!)
Hearing difficulties (middle ear)
Bone effects (fused or absent vertebrae)
Androgen insensitivity syndrome (previously testicular feminisation syndrome)
46XY genotype
Defective androgen receptors
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
diethylstilboestrol (DES)
Drug has been discontinued since 1971
Previous oestrogenic compound used for management of recurrent miscarriage
Exposure associated with
Vaginal adenosis
T shaped uterus
Congenital anomalies of the cervix;
(1) Cervical agenesis
Can occur in isolation or alongside uterine/ vaginal agenesis (MRKH syndrome)
Incomplete or failed development of the Mullerian/paramesonephric ducts
Primary amenorrhoea
If isolated cervical agenesis -> development of heamatometra
(2) Cervical duplication/ didelphys
Most commonly in association with uterine didelphys
Does not typically interrupt menses
Failed fusion of Mullerian/paramesonephric ducts
Congenital anomalies of the uterus
Mullerian anomalies have an incidence of between 1-3%
What % of 1st and 2nd trimester miscarriage is linked to mullerian anomalies
~15% of recurrent first trimester miscarriage patient cohort have one, and
~25% of those who have had a second trimester miscarriage)
Strassman metroplasty
Operation done on bicornuate uterus if recurrent preg loss
uterine anomalies associated with vaginal septum
uterine didelphys - vaginal septum in 75% of cases
Septate uterus - less assoc
When do females have max number of oocytes
20 weeks gestation
Causes of high inhibin levels
Inhibin levels
Tend to be inhibin B levels measured.
Granulosa cell tumours (inhibin B 60 fold increase, 90-100%)
Mucinous epithelial ovarian tumours. (55%)
Assessing infertility issues: Inhibin B levels can be used to assess ovarian reserve and it is suggested that levels can also predict the success of ovulation-inducing drugs
Day 3 of the cycle!
ospemifene
SERM for vaginal atropy in people not suitable for oestrogen
Testosterone levels in women in 20s compared to women in 40s
A women in her mid 40s has approx. half as much circulating testosterone as a woman in her 20s
Prevalence of OP in older men/ women
1 in 3 older women
1 in 5 older men
(Peak in 20s, BMD begins to reduce from age 30)
When is rate of BMD loss greatest in women
1 year prior to menopause –> 2 years following menopause
DXA T score and Z score
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
Drug therapy known to impact BMD
PPI
SSRIs
Medroxyprogesterone acetate (long term/significant history of use in particular)
Aromatase inhibitors
Thiazolidinediones
Most anticonvulsants
Vitamin D sources
But between October and early March we do not make enough vitamin D from sunlight.
Vitamin D is also found in a small number of foods:
oily fish – such as salmon, sardines, herring and mackerel
red meat
liver (avoid liver if you are pregnant)
egg yolks
fortified foods – such as some fat spreads and breakfast cereals
Special populations that should take vit D
OP (BMS rec 1000units)
Pregnant/ people in gen - 400 IU (10mcg)
Trans and non binary - OTC 400 IU (10mcg)
