1
Q
What does WHO say about infertility as a disease?
A
“A disease of the reproductive system defined by failure to achieve a clinical pregnancy after 12 months or more of regular unprotected sexual intercourse”
2
Q
What are the main things the Wilkinson & Williams 2016 paper says about infertility as a disease?
A
If perceived as a disease, public funding for its treatment is construed as justified & what remains to be determined is its prioritization in relation to other required treatments competing for limited resources…if not, funding it may not be justified from the outset
3
Q
Who is the legal father and mother in surrogacy?
A
- Legal mother= person who gave birth (legal change through parental orders/adoption)
- Legal father= genetic father
4
Q
What does the Warnock & Brazier reports say about surrogacy?
A
- Brazier (1997) stated that agreements should continue to remain unenforceable
- Warnock (1984): “inconsistent with human dignity that a woman should use her uterus for financial profit”
5
Q
What according to NHS Scotland (2013) are prenatal screening tests?
A
- Offered to all pregnant women to assess chance of baby having a particular health problem/disability
- Do NOT provide definitive diagnosis
6
Q
What according to NHS Scotland (2013) are prenatal diagnostic tests?
A
- Follow-on tests carried out to find whether baby does have a particular condition
- Offered to “Higher-chance” result from screening
7
Q
What are 5 reasons why you would carry out screening & testing?
A
- Reassure parents
- Inform & prepare parents for birth of an affected infant
- Allow in utero treatment, or delivery at a specialist centre for immediate postnatal treatment
- Allow termination of affected foetus
- Provide information so that parents may choose between 2,3,4. issue= choice
8
Q
What are the 3 different types of screening & diagnostic testing for natural conception?
A
- Non-invasive ie. ultrasound, serum test, questionnaire
- Invasive prenatal dianostic (PND) testing ie. chorionic villus sampling, amniocentesis (increased chance of miscarriage)
- NIPT/ NIPD
9
Q
What is the screening & diagnostic test for in vitro fertilisation (IVF)?
A
- Preimplantation genetic diagnosis (PGD)
- (CRISPR if it was used)
10
Q
What, when, why is ultrasound screening?
A
- WHAT: sound waves, painless, no risk
- WHEN: dating scan 12 weeks, anomaly scan 20 weeks
- WHY: anomaly, physical abnormalities ie. spina bifida
11
Q
What is the ethical issues arising from ultrasound screening?
A
Everyone is offered anomaly scan, not everyone chooses to take it
12
Q
What, when, why is a Down’s Syndrome screen?
A
- WHAT: combination of ultrasound & serum test
- WHEN: 10-13 weeks
- WHY: measures chance of DS, not a diagnostic test (can also detect Edward’s Syndrome T18)
13
Q
What is the ethical issues arising from Down’s Syndrome screen?
A
- Risk (low v high)
- If greater than 1:150 then option to take diagnostic test (amniocentesis or CVS)
14
Q
What does a serum test analyse?
A
- Markers in blood including:
- Pregnancy associated plasma protein-A (PAPP-A)
- Free beta-human chorionic gonadotrophin (free beta-hCG)
15
Q
How good is the “combined” screening test for Down’s Syndrome?
A
- False positives (2.2%): test abnormal, foetus not affected
- False negatives (16%): test normal, foetus affected
16
Q
What is the Quadruple test for Down’s Syndrome?
A
- Used if women presents later (14 weeks 2days +)
- Blood test: alpha-fetoprotein (AFP), total human chorionic gonadotrophin (hCG), unconjugated oestriol, inhibin-A
- FN: 20%, FP 3.5%
17
Q
What, when, why is the amniocentesis diagnostic test?
A
- WHAT: needle inserted through abdomen & into amniotic fluid
- WHEN: 15+ weeks
- WHY: previous pregnancy with fetal problems, family history, >35yrs, antenatal screening result suggests a problem
18
Q
What 4 things is Amniocentesis used to test for?
A
- Down’s syndrome
- Other Chromosomal disorders
- Blood disorders (sickle cell)
- Genetic disorders (sex)
19
Q
What are the ethical issues arising from amniocentesis?
A
- 0.5-1% risk of miscarriage (also, delay in getting results)
- Infection
- Injury
- FP 0.1-0.6%
- FN 0.6%
20
Q
What, when, why is Chorionic villus sampling?
A
- WHAT: fine needle inserted through abdomen & into uterus, through cervix & small piece of developing placenta removed
- WHEN: 11 weeks
- WHY: tests inherited disorders (cystic fibrosis, sickle cell, thalassemias, muscular dystrophy) & chromosomal disorders (sex).
21
Q
What are the ethical issues arising from chorionic villus sampling?
A
- 1-2% risk of miscarriage (delay in getting results)
- Infection
- Heavy bleeding
- FP 1-2%
- FN 2%
22
Q
Give 6 examples of diseases for which DNA tests are available?
A
- Cystic fibrosis
- Phenylketonuria
- Tay-Sachs
- Duchenne muscular dystrophy
- Huntington’s disease
- Inherited breast & ovarian cancers
23
Q
What is the recent development of non-invasive prenatal genetic testing (NIPT)?
A
- Cell-free foetal DNA (DNA from placenta, v similar to DNA from foetus)
- Early use 9-10weeks
24
Q
What are the positives of cell-free foetal DNA (NIPT)?
A
- Risk of chromosomal abnormalities with more accuracy than other non-invasive methods (invasive still required for definitive results)
- Definitive diagnosis of some conditions (cystic fibrosis, achrondroplasia)
- Determine gender
25
What report discusses the use of NIPT?
Nuffield Report, March 2017
26
Describe preimplantation genetic diagnosis?
- Offered to couples at risk of passing on genetic disorder
- Removing 1 cell from early embryo (4-8 cell embryo)
- PGD not common & expensive
27
What are the types of disorders acceptable for preimplantation genetic diagnosis (HFE Act 2008)?
- Disorder that may affect capacity for live birth
- Risk of child being born with/developing serious disability (genetic, chromosomal, mitochondrial)
- Gender-related disorder, can use to select gender
- 100+ conditions on HFEA site
28
According to Code of Practice, how serious is a "serious" disability?
- Take into consider the views of those seeking treatment
- Likely degree of suffering
- Availability of effective treatment
- Speed of degeneration
- Extent of intellectual impairment
- Social support available
- Family circumstances
29
Describe Huntington's Disease?
- Inherited, late onset, degenrative condition
- Manifests ~30-50yrs
- 50/50 chance of inheriting it from affected parent
- Non sex linked dominant inheritance pattern
30
What case talks about the preference for disabled embryos?
- Tomato Lichy & Paula Garfield
| - They did NOT want to positively select but it opened the debate
31
What is Saviour siblings?
- Create embryo (PGD) that will be tissue match (Human leukocyte antigen (HLA)) for existing child who has a condition that requires ie. bone marrow transplant
- 2001 this was approved for removal of cord blood cells & embryo had to be at risk of inheriting same disorder
- 2004 both of these conditions were removed, hence bone marrow transplant now possible
32
What are 3 examples of saviour siblings?
1. Hashmi family (2002)- beta-thalassaemia inherited, UK (HFEA) granted permission
2. Whittaker family (2002)- diamond Blackfan anaemia, no inherited, UK (HFEA) refused, US granted
3. Fletcher family (2004)- diamond Blackfan anaemia, not inherited, UK (HFEA) granted approval
33
Is saviour siblings ethical?
- Savious sibling being "used" as a means to help other child than an end in themselves?... but people have children for all kinds of reasons
- What is psychological effect on saviour sibling (& existing child) & resultant relationship?... what impact of bereavement on a family
34
What is CRISPR?
Gene editing technology at embryo stage (IVF) & post-birth
35
Where do the female reproductive organs lie within the pelvic cavity?
- Above pelvic floor
| - Vagina & urethra pass through pelvic floor & urogenital triangle
36
Where does the obturator nerve lie?
Lateral wall of pelvis (ovary lies just medial to it)
37
Describe the ovary?
- Almond-shaped
- Lateral pelvic wall in ovarian fossa
- Between internal & external iliac vessels
- Medial to obturator nerve & thin wall of acetabulum
- Produces ovum monthly in response to FSH & LH
- Also produces oestrogen & progesterone
- Truly intraperitoneal
38
What is a possible clinical problem with the ovary being near the acetabulum?
Central dislocation of the hip may injure the ovary
39
What ligaments support the ovary?
Hangs off posterior aspect of broad ligament on mesovarium & supported by ovarian ligament & suspensory ligament
40
Describe the round ligament of the ovary?
- Continuation of ligament of ovary (both remnants of gubernaculum)
- Passes from uterus through inguinal canal to labia
41
What is at risk during surgery to the ovary?
Ureter as it lies posteriorly to ovary
42
Where does referred pain go to in ovarian disease?
Medial thigh due to obturator nerve lying laterally
43
What is the arterial supply of the ovary?
Ovarian artery from aorta at L1/2
44
What is the nerve supply of the ovary?
| Where is the referred pain?
- Pre-aortic sympathetic nerves from T10/11
| - Referred pain peri-umbilical region
45
What is the venous supply of the ovary?
- Ovarian vein forms plexus
- Left drains to left renal vein
- Right ovarian vein drains to IVC
46
What is the lymph drainage of the ovary?
Para-aortic nodes (lateral)
47
What forms the suspensory ligament?
Ovarian vessels about to enter the broad ligament
48
Describe the uterine tube?
- Ostium surrounded by fimbriae within peritoneal cavity
- Infundibulum, Ampulla (fertilisation occurs), Isthmus, Intramural part through uterine wall
- Lies upper, free edge of broad ligament
- Blood supply from anastomosis between ovarian & uterine arteries
49
Where does pain from uterine tube go?
Lower abdominal
50
Describe the uterus?
- Pear-shaped
- Thick, muscular walled
- Narrow cavity
- Implantation of fertilised ovum & growth of foetus & placenta
51
What supports the uterus?
- Levator ani
- Perineal body
- Perineal membrane
- Fascial thickenings on pelvic floor passing from uterus & cervic to sacrum, pubis & lateral pelvic walls
52
What forms the Tendinous Arch of Pelvic Fascia?
Visceral & parietal fasciae meeting & fusing as the organs pierce the pelvic floor
53
What are the different supportive uterine ligaments?
- Transerve cervical/cardinal ligament with uterine artery
- Pubocervical
- Lateral ligament of bladder
- Uterosacral
- Paracolpium
- Tendinous Arch of Pelvic fascia
54
Describe the peritoneum of the pelvis in relation to the female reproductive system?
Sheet over uterus, uterine tubes & ovarian ligaments to form broad ligament from uterus to lateral pelvic wall
55
What hold the uterus in an anteverted (entry to vagina) & anteflexed (between cervix & body) position over the bladder?
Broad & Round ligaments
56
What does the cervix of the uterus form?
Posterior & anterior fornices at the vagina
57
What is the clinical problem with vaginal fornices?
- They are distensible & foreign bodies may get "lost"
| - Peritoneal cavity may be accessed via the posterior fornix
58
Describe the female cervix?
- Isthmus of uterus leads to internal ostium
| - Vaginal part opens into vagina as external ostium & has vaginal fornices around it
59
The ureter lies ______ to the uterine vessels?
BELOW
60
What can retroversion &/or retroflexion of the uterus cause?
Back-ache & difficulty in conception
61
What is related to posterior vaginal fornix?
Recto-uterine pouch of Douglas
62
What is the blood supply of the uterus & vagina?
Anastomosing uterine & vaginal arteries (+ superior vesical artery)
63
Describe the vagina?
- Angled upwards & backwards
- Passing from cervix to vestibule
- Between labia minora
- Anterior & posterior walls in contact
- Passes through levator ani into perineum where its surrounded by urethral/urethrovaginal sphincter
64
What arteries supply the urethra?
Vaginal & Internal pudendal
65
Describe the female urethra?
- Many small mucous glands & lacunae
- Para-urethral glands & ducts near orifice
- Passes through deep perineal pouch with external sphincter & perineal membrane
- External sphincter signet ring
- Other longitudinal muscle to make urethra shorter, wider during micturition
66
What is the epithelial of the female urethra?
Urinary but quickly becomes stratified squamous
67
What is the lymph drainage of the bladder & urethra?
External & internal iliac nodes
68
What is the lymph drainage of the uterus & proximal vagina?
Internal iliac nodes
69
What is the lymph drainage of the uterine tube?
Para-aortic but may also pass superficial inguinal nodes
70
What is the lymph supply of the distal vagina & urethra?
Deep & superficial inguinal nodes
71
What is the nerve supply of the female pelvis?
- Sympathetic pre-aortic plexus (T10-L2), continues as superior hypogastric plexus --> left & right pelvic plexuses (T12-L2)
- Parasympathetic to pelvic plexuses (S2,3,4)
- Somatic pudendal (S2,3,4)
72
Where does pain from the uterine body & proximal uterine tube go?
Via branches of pelvic plexus with sympathies mainly from T12 & L1 = suprapubic
73
Where does pain from the uterine cervix & proximal vagina go?
"Pain line" via the parasympathetic pelvic splanchnics & pelvic plexuses therefore felt deeply in the pelvis
74
What is the nerve supply of the distal vagina?
Somatic pudendal
75
Where does the diamond-shaped perineum lie?
Inferior to pelvic outlet & pelvic floor
76
Describe the location of the urogenital triangle of perineum?
Between pubic symphysis & ischiopubic rami, anterior to ischial tuberosities
77
What passes through the lesser sciatic foramen?
Pudendal nerve with internal pudendal vessels recurving into perineum, inferior to pelvic floor
78
What does the perineal membrane (between the ischiopubic rami) divide the urogenital triangle into?
Superficial, deep pouch & inferior, superficial pouch
79
What does the anterior aperture of the perineal membrane allow the passage of?
Nerves & vessels to penis/clitoris
80
Describe the inferior & superior boundary of the deep pouch in a male?
- INFERIOR: thick perineal membrane
| - SUPERIOR: thinner fascia covering superior surface
81
What does the deep pouch contain in the male?
- External urethral sphincter
- Deep transverse perineal muscles
- Urethra
- Bulbo-urethral glands
82
What does the superficial pouch contain?
- Penis/Clitoris
- Labia minora & majora
- Vulva & vaginal vestibule
83
What are the comparable features of the penis & clitoris?
- 2 crura, attached to ischiopubic rami become corpora cavernosa that fill with blood in erection
- 1 central bulb split in female as bulb of vestibule, in male becomes corpus spongiosum housing urethra to prevent its compression during erection
84
What 2 things form the root?
Crura & bulb
85
What are the 3 corpora on the body of the penis?
- 2 dorsal cavernosa
| - 1 ventral spongiosum
86
Describe the skin of the penis?
- Dark, loose, no fat
- Superficial, dartos fascia surrounds whole penis
- "Doubles back on itself" to form prepuce/foreskin continuous with glans at corona
87
Describe the corpora cavernosa of the penis?
- Divided by septum that is complete proximally, but pectiniform distally (to even out pressure & stay straight)
- Each surrounded by thick tunica albuginea & deep fascia (Buck's) surrounds them all
88
Describe the corpus spongiosum of the penis?
- Transmits urethra
| - Forms glands as a cap over corpora cavernosa
89
Describe the 2 muscles which support the penis & contribute to erection?
1. Ischiocavernosus surrounds each crus
| 2. Bulbospongiosis surrounds bulb & also compresses urethra during ejaculation/ to expel urine
90
What are the 2 supportive ligaments of the penis?
1. Fundiform
| 2. Triangular (suspensory) from lines alba & pubic symphysis
91
Describe the foreskin of a penis?
- Fold of skin, continuous with glans & also mucous membrane of urethra
- Small frenulum, ventrally between foreskin & glans with increased sensation
- Sebaceous glands form smegma
92
Describe the membranous part of the urethra in the male?
- Narrowest part except for external orifice
- Fibro-elastic tube & smooth muscle, within striated external sphincter & pubo-urethral/puboprostatic part of levator ani to resist surges of raised intra-abdominal pressure
93
Describe the external sphincter in the membranous urethra in the male?
- Inverted pear shape
- Base on perineal membrane
- Apex pushing into prostatic urethra
94
Describe the spongy/anterior/bulbar/penile urethra in the male?
- Narrowest part at external orifice
- Bulbo-urethral glands
- Many scattered glands esp. in navicular fossa (lacuna magna)
95
What must be straightened when passing a urethral catheter?
- Right angle bend between membranous & bulbar urethra
| - Right angle bend between spongy urethra as it becomes pendulous
96
Describe the different types of epithelium in the urethra in male?
- Urothelium until ejaculatory ducts
- Pseudostratified columnar
- Stratified squamous in distal urethra
- Keratinised at external orifice
97
What may glandular fossae (urethral lacunae) contain in elderly?
Concretions
98
What does navicular fossa, like vagina, produce?
Defensive lactobacilli
99
Describe the female external genitalia (vulva)?
- Labium majus laterally, then labium minus, vagina & urethra opening in vestibule
- Labia minora divide into medial & lateral folds to form prepuce of clitorus
- Labia majora meet anteriorly = mons pubis, meet posteriorly = commissure/fourchette
100
How must episiotomy be performed & why?
Backwards & angled laterally, usually to right, to avoid cutting the anal sphincter
101
Describe the female clitoris?
- Body is 2 crura
- Bulb contributes minimally as a little cap over highly sensitive glans
(urethra opens inferiorly to it, NOT in the clitoris)
102
What can occur at the greater vestibular or Bartholin's glands in the female genitalia?
Site of painful cyst or abscess formation
103
What arteries does the internal pudendal artery give off?
- Supplies perineum
- Urethra
- Posterior 2/3 of scrotum & labia
- Cavernous tissue of penis/clitoris
- Skin of shaft & glans of penis/clitoris
104
What supplies the anterior 1/3 of the scrotum & labia?
External pudendal artery from femoral artery
105
What is the venous drainage of the penile skin & foreskin?
Superficial dorsal veins to external pudendals
106
What is the venous drainage of the glans & shaft of penis?
Deep dorsal vein to prostatic plexus & then internal iliac
107
What is the venous drainage of the corpora cavernosa of the penis?
Deep arteries accompanied by veins draining to internal pudendal
108
What is the lymph drainage of the corpora cavernosa, corpus spongiosum, bulb of penis & vesibule, proximal vagina & urethra (deep structures)?
Internal iliac nodes
109
What is the lymph drainage of the superficial penis, scrotum & labia?
Superficial inguinal nodes
110
What is the lymph drainage of the glans penis & clitoris?
Deep inguinal (Cloquet) & external iliac nodes
111
Describe the branches that the pudendal nerve (S2,3,4 somatic motor & sensory) gives off?
- Muscular brnahces to bulbospongiosum, Ischiocavernosus, external urethral sphincter
- Dorsal nerve of penis/clitoris, sensory as far as glans
- Perineal nerve giving posterior scrotal/labial nerves
112
Describe the passage of cavernous nerves?
Directly to prostate & urethra, corpus spongiosum & erectile tissue of corpora cavernosa, penis & clitoris
113
What is the different autonomic nerve supply of erection & ejaculation?
- Erection: parasympathetic
| - Ejaculation: sympathetic
114
Describe the shape of the rectum?
- Follows sacral curve
| - Lateral curvatures/concavities that form left, right, left rectal folds or valves internally
115
Describe the peritoneum on the rectum?
- Upper 1/3: front & sides
- Middle 1/3: front only
- Lower 1/3: none
116
What does the mesorectum, posterior to rectum, contain?
- Superior rectal artery & vein
| - Lymph nodes & nerves
117
What nerves are at risk during rectal surgery?
- Urogenital nerves & vessels
| - Pelvic plexus
118
Where is the recto-anal junction?
Pelvic floor, puborectalis & behind the perineal body
119
What is special about the pectinate line in anal canal?
Embryological & afferent nerve supply changes: sensitive to pain below line
120
Describe the changes in epithelium of the anal canal?
Columnar --> stratified squamous --> skin
121
Describe the internal sphincter of the anal canal?
- Smooth muscle
- Autonomic
- Derived from circular muscle layer
- Ends at intersphincteric groove
122
Describe the external sphincter of the anal canal?
- Striated muscle
- Deep, superficial & subcutaneous parts
- One functional unit
- Fuses with puborectalis, transverse perineal muscles, anococcygeal ligament & perineal body in female but not male
123
Describe the puborectalis muscle?
- Part of levator ani
- Sling around anorectal junction, drawing it anteriorly to make more acute angle
- Recto-anal continence
124
Describe the anococcygeal ligament?
- Formed by fused levator ani
| - Attached the anal canal to coccyx
125
Describe the internal features of the anal canal?
- Anal columns
- Valves
- Pectinate line
- Anal cushions
- Anal sinuses
- Glands§
126
Describe the mucous membrane & submucosa of the anal canal?
- Loose, mobile & distensible to allow expansion for defecation
- Rich underlying vasculature (haemorrhoids/piles)
127
What is the function of anal cushions & internal sphincter?
Maintain anal closure when there is no pressure or content from the rectum
128
Describe the 4 recto-anal arteries?
- Superior rectal: from inferior mesenteric
- Middle rectal: from internal iliac (highly variable/absent)
- Inferior rectal: from internal pudendal
- Median sacral (may cause bleeding during surgery)
129
Describe the recto-anal veins?
- Superior rectal veins to inferior mesenteric to portal vein
- Middle & inferior rectal veins to internal iliac veins, systemic
130
What do the recto-anal veins form?
External & internal (submucosal) venous plexuses: porto-systemic anastomosis
131
Describe the recto-anal lymph drainage (initially to nodes adjacent to rectum and then...)?
- Inferior mesenteric nodes for superior rectum, possibly via sacral nodes
- Internal iliac nodes for lower rectum & proximal anal canal
- Superficial inguinal nodes for distal anal canal
132
Describe the recto-anal nerve supply?
- Parasympathetic, pelvic splanchnics (S2,3,4) to pelvic plexus
- Pelvic plexuses carry sensation & control internal sphincter
- Internal pudendal nerve (somatic) from S2,3,4 giving inferior rectal branches to supply external anal sphincter, adjacent pelvic floor muscles (puborectalis) & sensation to distal anal canal
133
Describe the process of defecation?
- Abdominal pressure flattens anterior wall of lower rectum over upper anal canal
- Anal cushions close canal
- Rectum can partially fill without increase in pressure
- Sensation can allow cortex to distinguish between gas, fluid, solid
- Stretch receptors in levator ani & anal canal tissue
134
What prevents defecation?
- Prevented by learned, cortical inhibition
- Only gas may be allowed to escape
- External sphincter forces faeces up into the rectum
135
When is defecation allowed?
- Puborectalis relaxes, allowing recto-anal angle to straighten
- External sphincter relaxes (S2,3,4)
- Lower colon & rectum contract, internal sphincter relaxes (parasympathetic pelvic splanchnics S2,3,4) via pelvic plexus
136
When can recto-anal incontinence occur?
- Following cortical/cord lesions above S2,3,4
- Damage to external sphincter during obstetric or perineal procedures
- Entrapment of pudendal nerve
137
What are the arteries, veins, nerves and lymph above the pectinate line?
- Autonomic (visceral) innervation
- Inferior mesenteric artery
- Veins to portal circulation
- Lymph to internal iliac nodes
138
What are the arteries, veins, nerves & lymph below the pectinate line?
- Somatic innervation (sensitive to pain)
- Inferior rectal artery & vein: systemic
- Lymph to superficial inguinal nodes
139
Where does the anal triangle lie between?
Ischial tuberosities, sacrotuberous ligaments & coccyx
140
Describe the ischio-anal fossa?
- Fat-filled pyramid region
- Below levator ani
- Either side of anal canal
- Allows distension of anus during defecation
141
Can the 2 ischio-anal fossae communicate with eachother?
YES- behind the anal canal
142
The ischio-anal fossa has a small anterior extension above what?
Deep perineal pouch (urogenital diaphragm)
143
Where does the pudendal neuromuscular bundle lie?
Laterally in Alcock's canal (obturator fascia)
144
Where is a site of infection and absecesses that may require surgical intervention?
Inferior rectal neuromuscular bundle passing across the apex to supply external sphincter & anal canal sensation
145
What are the 2 common clinical conditions occurring in the anal-canal & ischia-anal fossa?
- Dilatation of venous plexuses giving haemorrhoids/piles
| - Ischio-anal abscess caused by sinus from anal canal
146
Describe the 5 stages of pubertal maturation of male genitalia?
- STAGE 1: no pubic hair or enlargement of penis/testes
- STAGE 2: testicular enlargement to >2.5cm, start of pubic hair
- STAGE 3: penal enlargement, enlarging testicles, more pubic hair
- STAGE 4: further enlargement of scrotum & testes, darkening of pubic hair
- STAGE 5: adult genital appearance
147
What is the average age for puberty in boys and girls?
- BOYS: 14yrs
| - GIRLS: 13yrs
148
What are the 3 possible causes for hypogonadism in phenotypic males?
1. Temporary delay of puberty
2. Hypogonadotrophic hypogonadism
3. Hypergonadotrophic hypogonadism
149
Give examples of things which would cause Temporary delay of puberty in male?
- Constitutional delay of puberty (familial, sporadic)
- Chronic illness (malabsorption, malnutrition, malignancy)
- Hormonal disturbance (GH deficiency, hypothyroidism)
150
Give examples of things which would cause Hypogonadotrophic hypogonadism?
- Kallman's syndrome (with anosmia)
| - Hypopituitarism (tumour, trauma)
151
Give examples of things which would cause hypergonadotrophic hypogonadism?
- Klinefelter's syndrome (XXY)
- Anorchia
- Orchitis (mumps)
- Radiation treatment &/or cytotoxic chemotherapy (leukaemia)
- Surgical/traumatic castration
152
What can cause arrest in puberty in females?
Anorexia nervosa
153
What are the symptoms/consequences of male hypogonadism?
- Sexual dysfunction
- Fatigue
- Depressed mood
- Osteoporosis
- Decrease in muscle mass & strength
- Loss of facial & body hair
154
What is the treatment for Constitutional delay in puberty resulting in hypogonadism?
Short-term low does sex steroid treatment (testosterone 100mg monthly for 3 months)
155
What is the treatment for Hypergonadotrophic hypogonadism?
- Sex steroid replacement (testosterone)
- Bisphosphonates & calcium
- Reduction mammoplasty (for reducing possible gynaecomastia)
156
What is the treatment for hypogonadotrophic hypogonadism?
- Sex steroid replacement (testosterone)
| - Exogenous GnRH administration to promote spermatogenesis
157
Describe the current therapies for testosterone replacement?
- Intramuscular injection: every 2-3weeks
- Oral : 3-4 times daily
- Subcutaneous pellets: every 4-6 months
- Transdermal
- Buccal
158
What tests would be done to investigate a patients hypogonadism?
1. FSH, LH & testosterone
| 2. Chromosome analysis
159
What is Craniopharyngioma?
Brain tumor derived from pituitary gland embryonic tissue, can suppress puberty from occurring resulting in hypogonadotrophic hypogonadism
160
What sexual health problems can blood test screen for?
- HIV 1+2 antibodies & p24 antigen
- Hepatitis B antigen
- Syphilis
161
What is Chlamydia (common STD)?
- Bacterium Chlamydia trachomatis
- Can damage woman's reproductive organs
- Symptoms mild/absent
- Potential for irreversible damage including infertility
162
What is the incidence of Chlamydia in Europe?
10 million new cases per year
163
How do people catch Chlamydia?
- During vaginal, anal or oral sex
| - Passed from infected mother to baby during vaginal childbirth
164
Why are teenage & young girls at a higher risk of catching Chlamydia?
Cervix is not fully matured
165
What are the possible symptoms of the "silent" Chlamydia STD in women?
- Abnormal vaginal discharge/ burning when urinating
- Spread to fallopain tubes some women have no signs/symptoms
- Lower abdominal pain, low back pain, nausea, fever, pain during intercourse, bleeding between menstrual periods
166
What are the possible symptoms of the "silent" Chlamydia STD in men?
- Discharge from penis/ burning when urinating
- Burning & itching around opening of penis
- Pain & swelling in testicles
167
What is Pelvic Inflammatory disease (PID) and how can this occur in females?
- Due to untreated chlamydial infection spread into uterus/fallopian tubes
- 40% of women
- Causing permanent damage leading to chronic pelvic pain, infertility & fatal ectopic pregnancy outside uterus
168
What is the risk of women infected with chlamydia catching HIV?
5x more likely if exposed
169
What serious complication (rare) can occur in untreated chlamydia in males?
Spread to epididymis causing pain, fever & rarely sterility
170
What are the tests used to detect Chlamydia?
- Traditional method: physical examination for collection of samples from urethra
- Urine testing using immunoassays (home testing kits)
171
Describe the Outreach Study regarding Chlamydia screening?
- Aarchus county
- All 21-23yr olds were offered home sampling test
- RESULTS: 0.8% females, 0.4% males took up offer
172
What was the conclusion for the BMJ Randomised controlled trial for Chlamydia trachomatis screening to prevent PID?
- Effectiveness of single chlamydia tests in preventing PID might have been overestimated
- Focus on more frequent testing of women at higher risk
173
What are 3 approaches to behaviour change?
1. Motivational interviewing
2. Problem-focused conselling
3. Modelling & rehearsal of change
174
What is the correlation of patient change talk?
Change Talk --> Clinician listen + Clinician reframe
175
What is the correlation of patient resistance?
Clinician confront --> Patient argue. Patient interrupt. Patient negative. Patient off-task
176
Describe the Randomised controlled trial to test women at risk for HIV (carey et al 1997)?
- US
- 102 women from community
- MI is4 group MET sessions
- Comparison was waiting list group
- Followed up after 3months
177
What did the Carey et al 1997 show regarding MI vs waiting list control group?
- MI group showed greater: HIV knowledge, preception of risk, intention to protect, communication with partner
- MI group had significantly lower rates of: unprotected sex, substance abuse before sex
178
What are the social aspects of screening?
- Screening healthy individuals is ethically different from everyday practice
- Individual attributes of health imply a message of dependency on experts & technology
- Health aspects as belonging, competence, mastering & well-being disregarded & social emphasis on health determinants disappear
179
What should health promotion & life style advice become so to be ethically defensible?
- Alter natural history of diseases
| - Be approved by patients
180
What is the backlash from the public regarding screening?
Organisers of screening programmes seen to be paternalistic
181
What can be done to reduce backlash from patients of screening programs?
- Give people information to make an informed choice
- Provide pros & cons
- Effects of decisional aids are unknown & controversial
182
Where is estrogen synthesised?
- Ovary
- Placenta
- Small amounts in adrenal cortex & testis
183
What is the most potent estrogen (3 main estrogens)?
Estradiol
184
What is the effect of pharmacological estrogen at different sexual maturities?
- Before puberty: stimulate secondary sexual characteristics
- Cyclically in female adult to induce menstrual cycle/ contraception
- At/after menopause to prevent symptoms & protect against osteoporosis
185
What are the different therapeutic uses of estrogens?
- Replacement therapy in primary ovarian failure (Turners syndrome)
- Replacement therapy for menopausal symptoms
- Contraception, used in combo with progestins
- Prostate & breast cancer
- Given to males cause feminisation
186
What are the 2 natural estrogens?
- Estradiol
| - Estriol
187
What are the 3 synthetic estrogens?
- Mestranol
- Ethinylestradiol
- Diethylstilbestrol
188
What are estrogens bound to in blood?
Albumin & sex hormone-binding globulin
189
What can changes in the levels of binding proteins do to estrogen?
Active estrogens are in unbound state
190
What does SERMs stand for?
Selective Estrogen Receptor Modulators
191
What are SERMs?
Competitive antagonists or partial agonists of estrogens depending on the tissue
192
Describe the use of Clomiphene (SERM)?
Estrogen antagonist in hypothalamus & anterior pituitary to inhibit negative feedback effect to induce ovulation
193
Describe the use of Tamoxifen (SERM)?
Estrogen-dependent breast cancer as its has an anti-estrogenic on mammary tissue
194
Describe the use of Raloxifene (SERM)?
Treat & prevent osteoporosis due to its estrogenic action on bone
195
Where is the natural progestational hormone (progesterone) secreted?
Corpus luteum late in the menstrual phase & by placenta during pregnancy
196
Estrogen ______ synthesis of Progesterone receptor (PR) & progesterone ______ synthesis of estrogen receptors?
- Stimulates
| - Inhibits
197
Why is progesterone NOT given therapeutically?
Rapid clearance by liver
198
What are the 3 common synthetic derivatives of progesterone (called progestins)?
1. Medroxyprogesterone
2. Hydroxyprogesterone
3. Norethisterone (weak androgen)
199
What are the therapeutic uses of progestogens?
- Main: oral contraceptive pill alone or combo with estrogen
- Progesterone only injectable/implantable contraception or part of an intrauterine contraceptive
- Combine with estrogen for estrogen replacement therapy
200
What 3 things does estrogen replacement therapy prevent in a women with an intact uterus?
1. Endometrial hyperplasia
2. Carcinoma
3. Endometriosis
201
What is Danazol?
Modified progestogen used to treat sex- hormone dependent conditions (endometriosis, breast dysplasia & gynaecomastia)
202
How does Danazol work?
- Acts via the progesterone receptor to inhibit gonadotrophin production
- Reduces estrogen synthesis in women & androgen synthesis in men
- Androgenic activity so virilizing when given to women
203
What are the unwanted side effects associated with Danazol?
- GI disturbances
- Weight gain
- Fluid retention
- Dizziness
- Headaches
- Menopausal symptoms
204
What are the adverse effects of progestins?
- Acne
- Fluid retention
- Weight gain
- Depression
- Change in libido
- Breast discomfort
- Menstrual cycle irregularity
- Increased risk of thromboembolism
205
What is the anti-progestogen, Mifepristone, in combo with prostaglandin analogues used for?
Chemical abortion up to 9 weeks
206
Describe the different forms of estrogen & progestogen in the combined contraceptive pill?
- Estrogen is: ethinyloestradiol or mestranol
| - Progestogen is: norethisterone, levonorgestrel, ethynodiol, desogestrel or gestodene
207
How much estrogen is in the combined contraceptive pill?
20 – 50 ug
208
How is most combined pills taken?
- 21 consecutive days followed by 7 days pill free to allow a withdrawal bleed
- Menstrual cycles return quickly after discontinuation
209
What is the mode of action of the combined contraceptive pill?
- Estrogen inhibits FSH via negative feedback on anterior pituitary & suppresses ovarian follicle development
- Progestin inhibits LH & prevents ovulation.
- Estrogen & progestin alter the endometrium to discourage implantation
- Interfere with the coordinated contractions of the cervix, uterus & fallopian tubes
210
What are the adverse effects of the combined contraceptive pill?
- Mild nausea, flushing, dizziness, and bloating.
- Weight gain, skin changes, depression or irritability.
- Amenorrhea (variable duration) after stop taking the pill
- Small number of women develop reversible hypertension
- Small increase in risk of thromboembolism
211
What do the progestin only contraceptive pills include?
Norethisterone, levonorgestrel or ethynodiol diacetate
212
How is the progestin only contraceptive pill taken?
Daily without interruption
213
What is the mode of action of the progestin only contraceptive pill?
- Cervical mucous made inhospitable to sperm
| - Hinders implantation through effects on the endometrium & motility & secretions of fallopian tubes
214
Describe post-coital (emergeny) contraception?
Oral levonogestrel alone or in combo with estrogen is effective if taken within 72hrs & repeated 12hrs later
215
Describe long-acting progestogen only contraception?
- Medroxyprogesterone acetate intramuscularly
as a contraceptive (effective & safe)
- Levonorgestrel implanted subcutaneously. The capsules release progestogen slowly over 5yrs
216
How long can a levonorgestrel impregnated intrauterine device can last for?
35yrs
217
What are the symptoms of menopause?
- Headaches & hot flushes
- Teeth loosen & gums recede
- Risk of cardiovascular disease
- Backaches
- Body & pubic hair becomes thicker & darker
- Boens lose mass
- Vaginal dryness, itching , shrinking
- Stress/urge incontinence
- Skin & mucous membranes become drier, rougher
- Nipples smaller & flatten
- Breasts droop
- Hair thinning
218
Describe Postmenopausal hormone replacement therapy?
- Involves cyclic or continuous administration of low dose estrogens (estradiol, estriol) with/without progestogens
- Improves symptoms cause by reduced estrogen
- Prevents and treats osteoporosis.
219
What are the drawbacks with using hormone replacement therapy?
- Withdrawal bleeding
- Increased risk of breast cancer & endometrial cancer
- Increased risk of thromboembolism
220
What are the influences of testosterone?
- Hair growth
- Synthesis of serum proteins in liver
- Penile growth
- Spermatogenesis
- Prostate growth
- Libido
- Aggression
- Increased strength & volume of muscle
- Stimulation of erythropoietin in kidney
- Stimulation of bone marrow stem cells
- Accelerated linear growth closure of epiphyseal plates
221
What are intramuscular depot injections/patches of testosterone esters used for?
- Replacement therapy in male hypogonadism
| - Female hypo sexuality following ovariectomy
222
Give 2 examples of Antiandrogens?
- Flutamide
| - Cyproterone
223
What can anti androgens be used for?
Part of treatment of prostatic cancer
224
What can Dihydrotestosterone synthesis inhibitors (finasteride) be used to treat?
Benign prostatic hypertrophy
225
How/why can androgens be modified?
- Alter balance of anabolic & other effects
| - Nandrolone, for example, increase protein synthesis & muscle development
226
What are anabolic steroids used for?
- Aplastic anaemia
| - Abused by athletes
227
What are the potential side effects of anabolic steroids?
- Infertility
- Salt & water retention
- Coronary heart disease
- Liver disease
228
What is Gonadotrophin-releasing hormone & what are analogs of it used for?
- Decapeptide
| - Analogs used to manipulate reproductive axis
229
Give 2 examples of Gonadotrophin-releasing hormone analogs?
- Gonadorelin
| - Nafarelin (more potent)
230
What are the 2 different mode of action & uses of GnRH analogues?
- Pulsatile fashion will stimulate gonadotrophins (FSH and LH) & induce ovulation, used in the treatment of infertility
- Continuous regimen will induce gonadal suppression, used in sex hormone-dependent conditions (e.g. prostate and breast cancers, endometriosis & large uterine fibroids)
231
What are gonadotropins (FSH & LH) used to treat?
Infertility in both male & female
232
How are gonadotropins made?
- Recombinant DNA technology
| - Extracted from urine of pregnant or post-menopausal women
233
What does puberty involve?
- Growth in stature
- Change in body composition
- Development of secondary sexual characteristics
- Achievement of fertility
234
What are primary sexual characteristics?
- Reproductive organs
| - Present at birth
235
What are secondary sexual characteristics?
- Develop during puberty
| - Not directly part of reproductive system
236
What is Adrenarche?
- Hypothalamic-pituitary-adrenal axis
- Maturational increase in adrenal androgen (DHEA-S) production
- Around 6yrs in boys & girls
- Occurs in conjunction with gonadal maturation
237
What is the primary stimulus of adrenarche?
Enhanced adrenal sensitivity to ACTH
238
What are increased androgen levels responsible for?
- Development of pubic & axillary hair (pubarche)
- Development of pilosebaceous unit in skin (acne)
- Increases cortical bone density
239
Describe puberty in females (lasting 4.5yrs in total)?
- 1st sign: breast development (8.5-12.5yrs)
- Pubic hair growth & rapid height spurt
- Menarche (~13yrs, 2.5yrs after start of puberty, signals end of growth)
240
What is the normal amount of height gain remaining after female menarche?
5cm remaining
241
What is Thelarche?
Female breast budding during puberty
242
What is underlying the external female secondary sexual characteristic developments?
Endocrine axis controlling increased adrenal androgen production (adrenarche) & increased gonadal steroid production (gonadarche)
243
Describe the 5 Tanner stages for female puberty?
- Stage I: prepubertal
- Stage II: breast & papilla elevated as small mound, areolar diameter increase. Sparse, light pubic hair
- Stage III: further enlargement of breast bud. Darker, beginning to curl pubic hair
- Stage IV: areola & papilla form secondary mound. Increased coarse, curly pubic hair
- Stage V: mature areola. Adult feminine triangle pubic hair with spread to medial thigh
244
When does menarche occur in females?
Ovaries mature becoming more sensitive to gonadotropin & release more steroid hormones exerting negative feedback on gonadotropin secretion = cycle will develop & menarche
245
Describe what happens at male puberty?
- 1st sign: Testicular enlargement (>4mls vol) at 10-15yrs
- Pubic hair growth & penile growth
- Spermarche (sperm in seminal fluid) mean age 13.4
- Growth spurt when testicular vol 12-15mls
246
Why are males, on average, taller than females?
Male growth spurt is later & of greater magnitude (they achieve more growth before peak velocity)
247
What is the normal time interval between onset of pubic hair & axillary & facial hair?
2yr
248
What are androgen-dependent secondary sexual characteristics?
- Facial, underarm, pubic hair
- Deepening of voice (growth of larynx)
- Thick secretion of skin oil glands
- Masculine pattern of fat
- Bone growth via GH secretion then termination via closure of epiphyseal plates
- Stimulating of muscle protein synthesis
- Erythropoietin stimulations giving higher haematocrit
249
What initiates puberty?
Gonadotropin (FSH/LH) release by hypothalamic-pituitary-gonadal axis
250
What suppresses gonadotropin (FSH/LH) release?
Continuous infusion of GnRH
251
When are pulses of GnRH most detectible?
Childhood yrs during sleep & low frequency & amplitude therefore don't stimulate gonadotropin release
252
What are the 4 phases of human growth?
1. Fetal- uterine environment, fastest, 30% of eventual height determined
2. Infantile- nutrition, happiness & thyroid (birth-18months), rapid but decreasing, 15%
3. Childhood- thyroid hormones, GH, health & happiness, genetics. Slow
4. Pubertal- sex hormones (testosterone/oestrogen), GH & insulin-like growth factor
253
What is the peak height velocity in boys & girls?
- BOYS: 10cm/yr (13.5 mean age)
| - GIRLS: 9cm/yr (11.5 mean age)
254
How does puberty limit adult height?
Gonadal steroids lead to epiphyseal closure of long bones
255
When do changes in body composition begin in males & females?
- MALE: ~9yrs
| - FEMALE: ~6yrs
256
What are factors contributing to earlier puberty?
- Genetics (mother & sister)
- Lower social class = obesity = earlier menarche
- Close to equator, lower altitudes, urban setting
- Endocrine disrupting chemicals ie. plastics, agriculture, fuels
- Afro-carribean & African-american earlier
257
How much can nutritional status in childhood explain puberty timing?
25% of variation in timing of puberty
258
What is the relationship between increase in body fat & time of puberty onset?
- Increase body fat may play critical role in turning on adrenal androgen secretion & adrenarche
- Leptin may be link between adipose tissue, energy homeostasis centres in hypothalamus & reproductive system
259
What is the relationship between reduced body fat & puberty onset?
- Athletes often have delayed maturation & menarche
| - Malnutrition/anorexia cause delay
260
What is "critical fat mass"?
Girls will reach menarche as they reach body weight of ~47kg (55kg in boys)
261
How much is FSH & LH increased in menopause due to lack of negative feedback?
- FSH= 10-20x (excreted in urine)
| - LH = 3x
262
What are the consequences/symptoms of menopause?
- Vascular instability
- Atrophy of all oestrogen dependant tissues
- Rise in adrenal androgens may lead to hirsutism
- Loss of libido
- Depression, anxiety, mental confusion
263
What does vascular instability in menopause cause?
- Night sweats
| - Hot flushes
264
What are the oestrogen dependant tissues which become atrophied in menopause?
- Breast, uterus, vagina, urethra
- Skin collagen loss
- Bone catabolism with loss of Ca2+ leads to osteoporosis
- LDL rises increasing risk of coronary thrombosis
265
What does hormone replacement therapy replace when used for menopause?
- Steroids
- Maintains oestrogen dependent tissues
- Delays osteoporosis
MD3002
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