1
Q
What does the female pelvic viscera consist of?
A
ovary, uterine tube, uterus and cervix
and vagina plus urethra
2
Q
What does the ovary look like? Where is it located?
A
almond-shaped structure, with one on each side on lateral pelvic wall in ovarian fossa between internal and external iliac vessels
- immediately medial to obturator nerve and thin wall of acetabulum
- hangs off posterior aspect of broad lig on mesovarium and supported by ovarian lig and suspensory lig (truly intraperitoneal)
3
Q
What may central dislocation of the hip injure?
A
The ovary
4
Q
What is the function of the ovaries?
A
- produce an ovum monthly in response to FSH and LH from pituitary gland
- also produces oestrogen and progesterone to maintain uterine cycle
5
Q
What clinical pathology can occur as the ovum is secreted into the peritoneal cavity?
A
Ectopic pregnancy may occur in peritoneal cavity or in uterine tube
6
Q
(i) What is at risk during surgical procedures on the ovary? (ii) Where can ovarian disease cause referred pain to?
A
(i) The ureter as it lies posteriorly
(ii) medial thigh since the obturator nerve lies laterally
7
Q
What is the (i) arterial (ii) venous supply of the ovary?
A
(i) ovarian artery from Ao at L1/2
(ii) ovarian vein initially forms a plexus which coalesces into ovarian vein - the left drains to left renal and right to IVC
8
Q
What is the (i) lymph drainage (ii) nerve supply (iii) referred pain of the ovary?
A
(i) para-aortic (lateral) nodes
(ii) sympathetic nerves derived from T10/11
(iii) peri-umbilical region
9
Q
What are the various sections of the uterine tube?
A
- ostium surrounded by fimbriae (w/in peritoneal cavity)
- infundibulum
- ampulla (where fetilisation occurs)
- isthmus
- intramural part through uterine wall
10
Q
Where does the uterine tube lie within the body?
A
in upper free edge of broad ligament (mesosalpinx)
11
Q
What is its blood supply? Where is pain?
A
BS = anastomosis between ovarian and uterine arteries
- pain = lower abdominal
12
Q
What is the function of the uterine tube?
A
fertilisation of ovum and transport to uterus
13
Q
What is the uterus like? What is its function?
A
- pear shaped, thick walled, muscular
- central pelvic organ for implantation of fertilised ovum and growth of foetus and placenta
14
Q
How is the uterus supported?
A
- levator ani, perineal body and membrane
- fascial thickenings on pelvic floor that pass from uterus and cervix to sacrum which are the supportive uterine ligaments
15
Q
What are the supportive uterine ligaments derived from? Mention how the Tendinous Arch of Pelvic Fascia arises.
A
- membranous fascia that covers the organs (visceral) as well as pelvic floor (parietal),a s well as any intervening connective tissue
- visceral and parietal fasciae meet and fuse as organs pierce pelvic floor, forming Tendinous Arch of Pelvic Fascia, adjacent to organs and running from pubis to sacrum
16
Q
What may weakness of ligaments and of pelvic floor muscles lead to?
A
prolapse
17
Q
(i) What is the broad ligament (ii)What is the round ligament (iii) What is the function of these 2 ligaments?
A
(i) Peritoneum drapes over the bladder, then like a sheet over the uterus, uterine tube and ovarian ligaments to form the Broad Ligament from uterus to lateral pelvic wall
(ii) passes in broad ligament from uterus to deep inguinal ring and down inguinal canal to fuse with the labia
(iii) hold uterus anteflexed and anteverted over bladder
18
Q
The cervix of the uterus pushes into the vagina forming anterior and posterior fornices, why are they important?
A
- they are distensible and foreign bodies may get lost
- peritoneal cavity may be accessed via posterior fornix
19
Q
What should the relationship/angulation between uterine cervix to vagina and between cervix and body be? What happens to cause back-ache and difficulty in conception?
A
- should be anteverted and anteflexed
- retroversion and/or retroflexion
20
Q
What 2 surfaces does the uterus have?
A
- vesical
- intestinal
21
Q
What are the (i) internal features (ii) blood supply of the uterus and vagina?
A
(i) uterus has thick muscular wall and relatively narrow cavity. Vagina has distensible wall for intercourse and childbirth
(ii) by anastomosing uterine and vaginal arteries (vesical arteries are involved too)
22
Q
What is the shape of the vagina? Where is it located within the body?
A
- angled up and back, passing from cervix to vestibule, between labia minora
- anterior and posterior wall are in contact with each other, taking an H shape
- lies anterior to rectum but behind bladder and urethra
23
Q
Where does the ureter pass in relation to uterine artery?
A
- inferior to artery, adjacent to lateral fornicles
24
Q
What is the arterial supply of the (i) ovary (ii) vagina (iii) urethra?
A
(i) ovarian artery from aorta at L1/2
(ii) superior vesical, vaginal, int.pudendal and uterine artery
(iii) vaginal and internal pudendal
** venous drainage mirrors arteries
25
What is the urethra like in females?
Many small mucous glands and lacunae, para-urethral glands and ducts near orifice
- passes through deep perineal pouch with external sphincter and then perineal membrane
- external sphincter signet ring, marked anteriorly, other muscle longitudinal to make shorter wider urethra during micturition
26
What is the lymph drainage of the (i) bladder and urethra (ii) ovary (iii) uterus and prox. vagina (iv) uterine tube (v) distal vagina and urethra?
(i) ext. and int. iliac nodes
(ii) para-aortic
(iii) int. iliac nodes
(iv) para-aortic but may also pass to superficial inguinal
(v) deep and superficial inguinal nodes
27
What is the nerve supply, and referred pain of the ovary (and distal uterine tube)?
Mainly supplied via pre-aortic sympathetics derived from T10/11
- pain referred to peri-umbilical region
28
What is the nerve supply, and referred pain, of the uterine body (and prox. uterine tube)?
Branches of pelvic plexus with sympathetics mainly from T12 and L1
- pain = suprapubic
29
What is the nerve supply, and referred pain of the uterine cervix and proximal vagina?
P'symp pelvic splanchnics (and pelvic plexuses)
| - pain = deep in pelvis
30
What muscles make up the levator ani (pelvic floor)?
Iliococcygeus
| Pubococcygeus (puborectalis and pubovaginalis)
31
What is the nerve supply of the distal vaginal (somatic)?
pudendal
32
What does WHO define infertility as?
- a disease of the reproductive system defined by the failure to achieve a clinical pregnancy after 12 months or more of regular, unprotected sexual intercourse
33
For surrogacy, who is the (i) legal mother (ii) legal father?
(i) person who gave birth
| (ii) genetic father
34
Describe (i) screening tests (ii) diagnostic tests done during pregnancy
(i) offered to all pregnant women - assess chance of you/baby having particular health problem/disability. Usually simple tests (blood test, USS, questionnaire). Don't provide definite diagnosis but help you and your midwife decide whether you need further tests to make that diagnosis
(ii) the follow on tests carried out to find out whether baby does have a particular condition. Offered to women who have 'higher-chance' result from screening May involve chorionic villus or amniocentesis, can be associated with increased risk miscarriage. Or may be detailed USS
35
What are the 5 reasons we carry out screening and testing?
1. To reassure parents (not straightforward)
2. To inform and prepare parents for birth of an affected parent
3. To allow in utero treatment, or delivery at specialist centre for immediate postnatal treatment
4. To allow termination of an affected foetus
5. To provide info so that parents may choose between 2,3 or 4 (key issue here = choice)
36
What prenatal testing is done for (i) natural conception (ii) IVF?
(i) non invasive screening (USS, serum test)
invasive prenatal diagnostic (PND) testing e.g. CVS, amniocentesis
NIPT sometimes (non invasive pre natal testing)
(ii) preimplantation genetic diagnosis (PGD)
37
When is ultrasound used in pregnancy? Why is it used? What are the ethical issues arising?
- dating scan 12 weeks (8-14)
- anomaly scan 20 weeks (18-20 w and 6 days)
- anomaly done for physical abnormalities e.g. spina bifida
- ethical issues = everyone offered anomaly scan but not everyone chooses to take it
38
What does Down's syndrome screening consist of? When is it done?
Combo of USS (nuchal translucency) and serum test (analyse markers in blood - PAPP-A, free beta-hCH)
- done between weeks 10 and 13
39
Why is Down's syndrome screening done? What are the ethical issues arising regarding this screening?
- measures the CHANCE of DS, it is not a diagnostic test (can also detect Edward's syndrome T18)
- ethical = risk (low v high) if greater than 1:150 then there's the option to take diagnostic test (amniocentesis or CVS)
40
How good is the 'combined' screening test for DS?
FALSE +VE = test abnormal but foetus not affected
FALSE -VE = test normal, but foetus affected
COMBINED TEST: FN 16% FP 2.2%
41
What is the quadruple test used for DS screening? What is the percentage of false positives and negatives with this test?
- used if a woman presents later (14 weeks 2 days+)
- blood test = alpha-fetoprotein (AFP), total human chorionic gonadotrophin (hCG), unconjugated oestriol, inhibin-A
FN 20% FP 3.5%
42
What is amniocentesis? When is it done? Why is it done?
- a needle inserted through abdomen and into amniotic fluid
- done at 15+ weeks (15-18)
- done for prev pregnancy with foetal problems, family history, over 35 years, antenatal screening result suggests a problem
- looks for DS, other chromosomal disorders, blood disorders (sickle cell), other genetic disorders, (sex)
43
What are the ethical issues surrounding amniocentesis?
- 0.5 to 1% risk of miscarriage (also, delay in getting results), infection, injury
- FP 0.1 to 0.6% and FN 0.6%
44
What is chorionic villus sampling? When is it done? Why is it done?
- fine needle inserted through abdomen and into uterus, or through cervix and small piece of developing placenta removed
- done at 11 weeks (11-14)
- tests for inherited disorders (CF, sickle cell, thalassemias, muscular dystrophy) and chromosomal disorders, (sex) earlier in pregnancy
45
What are the ethical issues surrounding CVS?
- 1-2% risk of miscarriage (also, delay in getting results), infection, heavy bleeding
- FP 1-2%, FN 2%
46
What are 6 examples of diseases for which DNA tests are available?
1. cystic fibrosis
2. phenylketonuria
3. tay-sachs
4. duchenne muscular dystrophy
5. huntington's disease
5. inherited breast and ovarian cancers
47
What is the new non-invasive prenatal genetic testing (NIPT)?
Cell-free foetal DNA (DNA from placenta which is v similar to DNA from foetus)
- used as early as 9-10 weeks
- risk of chromosomal abnormalities w more accuracy than other non-invasive methods (invasive still required for definitive result)
- definitive diagnosis of some conditions (cf, achondroplasia)
- can determine gender
48
What is preimplantation genetic diagnosis? Who is it offered to? What does it involve? What disorders is it acceptable for?
- not common and £££
- offered to couples at risk of passing on a genetic disorder
- involves removing 1 cell from early embryo (4-8 cell embryo)
- used for disorders that may affect capacity for live birth, risk of child be born with/developing serious disability (genetic, chromosomal, mitochondrial)
- if gender related disorder, can use to select gender
49
How serious is "serious"?
Difficult, but code of practice gives guidance
- take into consideration the views of those seeking treatment
- availability of effective treatment
- speed of degeneration
= extent of intellectual impairment
- social support available
- family circumstances
50
What is huntington's disease? What is its inheritence
- inherited, late onset, degenerative condition
| - 50/50 chance of inheriting from affected pt
51
What are the 2 ethical issues for prenatal testing of HD?
1) Prenatal genetic testing for HD
– If seek testing, do so on understanding that they will terminate if test positive
– Why? Testing is only available to adults, and not all at risk choose to take it; prenatal testing means that the parents know something about the child’s future that the child has not elected to know
2) PGD for HD
– Thus select an embryo that does not carry the inherited HD gene
52
What is/are saviour sibling?
- create an embryo (using PGD) which will be a tissue match for an existing child who has a condition which requires e.g. bone marrow transplant
????
53
What are the 3 examples of saviour sibling?
1. Hashmi Famil
2. Whittaker
3. fletcher family
54
Is a saviour sibling wthical?
Is the saviour sibling being“used”as a means (to help the other child) rather than an end in themselves (just for being them)?
– But people have children for all kinds of reasons..
What is the psychological effect on the saviour sibling (and the existing child) and their resultant relationship?
– But then, what of the impact of bereavement on a family?
55
What is CRISPR? What does it do?
gene editing technology
56
Where is the urogenital triangle located skeletally?
between pubic symphysis and ischiopubic ramus
| - anterior to ischial tuberosities
57
How is the UG triangle divided into a superior deep pouch and an inferior superficial pouch? What does the deep pouch consist of?
By the perineal membrane
| - external urethral sphincter and deep transverse perineal muscles, with the urethra and vagina passing through
58
What is the (i) inferior boundary (ii) upper boundary of the male deep pouch? What does it contain?
(i) thick perineal membrane
(ii) thinner fascia covering superior surface of ext. urethral sphincter and deep transverse perineal muscles
- also contains urethra and bulbo-urethral glands
59
What does the superficial pouch contain?
The genitalia
- penis and scrotum
- clitoris, labia minora and majora forming vulva and vaginal vestibule in female
60
What are the comparable features of the penis and clitoris?
2 crura - which are attached to ischiopubic rami and become corpora cavernosa which fill with blood to produce erection
- one central bulb that's split in female as bulb of vestibule but in male becomes corpus spongiosum (houses urethra to prevent compression during erection)
- the crura and bulb form the root
61
What is the body of the penis split into? What is the skin like on the penis? How is foreskin formed?
- 3 corpora = 2 dorsal cavernosa and ventral spongiosum
- skin = loose no fat, superficial dartos fascia surrounds whole penis
- skin doubles back on itself to form prepuce/foreskin that's continuous with glans at the corona
62
Describe the corpora of the penis.
1) CORPORA CAVERNOSA
- divided by a septum that's complete proximally, but pectiniform distally (to stay straight)
- corpora cavernosa of penis each surrounded by thick tunica albuginea and deep fascia surrounds them all
2) CORPUS SPONGIOSUM
- transmits urethra and forms the glans as a cap over corpora cavernosa
63
Describe the muscles and ligaments of the penis.
- ischiocavernosus muscle surrounds each crus and bulbiospongiosus surrounds the bulb
- the muscles support penis and contribute to erection
- bulbospongiosus also compresses urethra during ejaculation or to expel urine
- supportive ligaments = Fundiform and Triangular from the linea alba and pubic symphysis
64
Describe the foreskin and glans of the penis.
Foreskin = fold of skin continuous with the glans and => also with mucous membrane of urethra
- sebaceous glands form smegma
- there's a v small frenulum, ventrally between foreskin and glans, with increased sensation either side
- skin and glans show a ventral, midline raphe
65
Describe the membranous part of the male urethra.
- the narrowest part apart from ext orifice
- a tube of fibro-elastic and smooth muscle within the striated external sphincter & pubo-urethral or puboprostatic part of levator ani to resist surges of raised intra-abdominal pressure
- ext sphincter shaped like an inverted pear, with its base on the perineal membrane and apex pushing up into prostatic urethea
66
Describe the spongy (bulbar and penile) part of the male urethra.
- narrowest part at ext orifice
| - bulbo-urethral glands, plus many scattered glands, especially in navicular fossa
67
Where are the 2 right angle bends in the male urethra?
1) between membranous and bulbar urethra
| 2) in spongy urethra as it becomes pendulous
68
What is the epithelium in the male urethra?
Urothelium until ejaculatory ducts, then psuedostratified columnar, before stratified squamous in distal urethra, keratinised at external orifice
69
What is Episiotomy? How must it be done?
- a surgical cut in the muscular area between the vagina and the anus (the area called the perineum) made just before delivery to enlarge your vaginal opening.
- must be back and angled laterally (usually right) to avoid cutting anal sphincter
70
Describe the female external genitalia - the vulva.
- labium majus laterally, then labium minus
- vagina and urethra opening in vestibule between labia minora, which divide into medial and lateral folds to form prepuce of clitoris
- labia majora meet anteriorly to form mons pubis, while posteriorly they form the posterior commissure or fourchette
71
What is the significance of the greater vestibular or Bartholin's glands?
they may be the site of painful cyst or abscess formation
72
What is the clitoris made up of?
- body is essentially 2 crura
| - while the bulb contributes minimally as a little cap over the highly sensitive glans
73
What is the bulb of erectile tissue divided by? Covered by? What is the function of said covering?
- divided by vagina
| - covered by bulbospongiosus that aids the pubovaginalis part of levator ani in its sphincteric effect
74
What does the internal pudendal supply? (ensuring to mention any significant branches)
- supplies perineum in both sexes
- gives arteries to urethra, post 2/3 scrotum/labia, cavernous tissue of penis or clitoris, skin of shaft and glans of penis/clitoris.
75
What artery supplies the anterior 1/3 of the scrotum or labia?
External pudendal from femoral
76
What is the venous drainage of the penile skin and foreskin?
- superficial dorsal veins to external pudendals
77
What is the venous drainage of the penile glans and shaft?
- deep dorsal vein to prostatic plexus and then internal iliac
78
Where do prostatic and vesical plexuses drain to?
internal iliac vein
79
What is the perineal lymph drainage of the following; (i) deeper structures (corpora, corpus, bulb and vestibule, prox vagina and urethra) (ii) sup penis, scrotum + labia (iii) glans of penis and clitoris?
(i) int iliac nodes
(ii) superficial inguinal nodes
(iii) deep inguinal (cloquet) and ext iliac
80
What do perineal nerves require? What are they derived from?
1) somatic motor for control of striated muscle - ext urethra and anal sphincters, bulbospongiosus and ischiocavernosus, perinei
2) sensation - urethra, glans of penis + clitoris
3) Autonomic both symp and p'symp, afferent and efferent
- derived from S2,3,4 - pudendal nerves and pelvis plexuses
81
Describe the nerve supply of the pudendal nerve and what are the various somatic motor and sensory branches it gives.
- muscular branches to bulbospongiosus, ischiocavernosus and ext urethral sphincter
- dorsal nerve of penis/clitoris, sensory as far as glans
- perineal nerve giving post scrotal/labial nerves
82
Describe the pelvic plexus; when is it at risk?
- initially symp, but joined by p'symp pelvis splanchnic, nervi erigentes from S2,3,4
- branches tend to join and be distributed with branches of pudendal nerve
- cavernous nerve passes directly to prostate, urethra, corpus spongiosum and erectile tissue of corpora cavernosa - penis and clitoris
- at risk in rectal and prostatic surgery
83
What is the function of the rectum? What does it look like?
- the storage of faeces prior to defecation
- follows the sacral curve and also has lateral curvature/concavities seen externally which form the left, right, left rectal folds/valves that are seen internally
84
What is the lower, slightly dilated part of the rectum called?
the rectal ampulla
85
What is the mesorectum/where is it located? What does it contain?
posterior, between reflecting peritoneum, containing superior rectal artery and vein, plus lymph nodes & nerves
86
What nerves are at risk in rectal surgery?
Urogenital nerves and vessels - pelvic plexus
87
Where is the recto-anal junction?
At the pelvic floor - puborectalis, and behind the perineal body
88
What is the changes in epithelium from the rectum to anal canal?
- from columnar to stratified squamous, and eventually skin
89
What is the pectinate line in the anal canal?
Embryological and afferent nerve supply changes
| - sensitive to pain below line
90
Name and describe the sphincters of the anal canal.
INTERNAL - smooth muscle, autonomic, derived from circular muscle layer, ends at intersphincteric groove
EXTERNAL - striated muscle, deep superficial and subcutaneous parts
91
What does the external anal sphincter fuse with in females?
puborectalis, the trans perinei, the anococcygeal ligament and the perineal body
92
What is the anococcygeal ligament formed by? What is its purpose?
the fused levator ani
| - attaches anal canal to the coccyx
93
Describe the internal features of the anal canal.
Anal columns, valves, pectinate line, anal cushions (mucous membrane, 3,7,11 oclock), anal sinuses and glands
- mucous membrane and submucosa are loose mobile and distensible to allow expansion for defecation, there's a rich underlying vasculature
- anal cushions and internal sphincter maintain anal closure when there is no pressure or content from the rectum
94
Describe the recto-anal arteries.
Free anastomosis, especially of superior and inf rectals
- superior rectal from inf mesenteric (usually main supply)
- middle rectal from int. iliac, highly variable and often absent
- inf rectal from int pudendal
- may be contribution from median sacral which may cause bleeding during surgery
95
Describe the recto-anal veins.
Mirror the arteries, but also form external and internal submucosal venous plexuses = porto-systemic anastomosis
- superior rectal veins to inf mesenteric to portal vein
- middle and inf rectal veins to internal iliac veins, systemic
96
What is the recto-anal lymph drainage?
initially to nodes adjacent to the rectum and then to:
- inf mesenteric for superior rectum
- int. iliac nodes for lower rectum and prox anal canal
- superficial inguinal for distal anal canal
97
What is the recto-anal nerve supply?
- p'symp pelvic splanchnics going to pelvic plexus
- int pudendal nerve from S2,3,4 giving inf rectal branches to supply external anal sphincter, adjacent pelvic floor muscles and sensation to distal anal canal
98
What do the pelvic plexuses do to the rectum and anal canal?
- pelvic plexuses carry recto-anal sensation and also control the internal sphincter
99
How is normal continence upheld in anal canal?
Normal continence: levator ani and puborectalis, making recto-
anal angle more acute; internal and external sphincters; abdominal pressure flattens anterior wall of lower rectum over upper anal canal; anal cushions close the canal
100
When is defecation allowed? Describe.
- cortical inhib rleeased via corticospinal tracts (micturition)
- abdo pressure increased
- puborectalis relaxes, allowing recto-anal angle to straighten, ext sphincter relaxes (somatic S2,3,4)
- lower colon & rectum contract, while internal sphincter relaxes - p'symp - pelvic splanchnics (s2,3,4)
101
What are the reflexes of defecation?
- at S2,3,4
- incontinence may follow the loss of control following cortical or cord lesions above S2,3,4 or damage to ext sphincter during obstetric or perineal procedures, or entrapment of pudendal nerve
102
What are the various changes that occur at the pectinate line in the anal canal?
Arteries: from IMA to inf rectal
Veins: from portal circulation to inf rectal (systemic)
Lymph: int iliac to superf. inguinal
Innervation: from autonomic to somatic
103
What is the ischio-anal fossa? What is its function?
- fat filled pyramidal region below levator ani and either side of anal canal to allow its distension during defecation
104
Where does the (i) pudendal NVB (ii) inf rectal NVB lie?
(i) laterally in Alcock's canal (obturator fascia)
| (ii) passes across apex to supply the ext. sphincter and anal canal sensation
105
What are 2 clinical conditions of the anal canal and ischio-anal fossa?
1) dilation of venous plexuses giving haemorrhoids/piles
| 2) ischio-anal abscess caused by a sinus from the anal canal
106
What are the dermatomes suppling the peri-anal skin? When would it be important to know this?
S4,5
| - when assessing possible spinal cord or nerve root injury
107
Where is peritoneum on the (i) upper 1/3 (ii) middle 1/3 and (iii) lower 1/3 in the rectum?
(i) front and sides
(ii) front only
(iii) none
108
With regards to male puberty, what happens to the feedback mechanism of testosterone?
Decreasing sensitivity
109
What are the 3 main causes of hypogonadism?
1. Temporary delay of puberty
2. Hypogonadotrophic hypogonadism
3. Hypergonadotrophic hypogonadism
110
What things can cause a temporary delay in puberty?
- constitutional delay in puberty (familial, sporadic)
- chronic illness e.g. malabsorption, malnutrition, malignancy
- hormonal disturbance e.g. GH deficiency, hypothyroidism
111
What things can cause hypogonadotrophic hypogonadism?
- Kallman's Syndrom (with anosmia)
| - Hypopituitarism e.g. trauma, tumour
112
What things can cause hypergonadotrophic hypogonadism?
- Klinefelter's syndrome (XXY)
- Anorchia
- Orchitis (e.g. mumps)
- radiation treatment and/or cytotoxic chemotherapy (e.g. leukaemia)
- surgical or traumatic castration
113
What is the treatment for Kallman's syndrome (hypogonadotrophic hypogonadism)? What treatment is necessary for someone with Kallman's syndrome to be able to father a child?
- monthly testosterone injections
| - if he wanted to be a father he would need exogenous GnRH to promote spermatogenesis
114
How is someone with Klinefelter's syndrome treated?
1) testosterone replacement
2) biphophonates and calcium (if signs of OP from long term testosterone deficiency)
3) reduction mammoplasty (for gynecomastia)
115
What are the symptoms/consequences of male hypogonadism? (HINT: there's 6)
1. sexual dysfunction
2. fatigue
3. depressed mood
4. osteoporosis
5. decrease in muscle mass and strength
6. loss of facial and body hair
116
What are the current therapies for testosterone replacement?
- IM injection every 2-3 weeks
- Oral 3 to 4 times day
- SC pellets every 4-6 months
- transdermal
- buccal
117
Where are estrogens synthesised in the body?
- by the ovary and placenta and in small amounts in adrenal cortex and testis
118
What are the 3 main endogenous estrogens in humans? Which is the most potent and princple one to be secreted by ovary?
- oestriol
- oestrone
- oestradiol = most potent and principle oestrogen secreted by ovary
119
What is the MoA of oestrogens?
- involves interaction with nuclear receptors in target tissues to regulate gene transcription
- pharmacological effects on repro system depend upon sexual maturity of recipient
120
What are the different ways estrogens can be used?
- given cyclically in female adult to induce artificial menstrual cycle or can be used for contraception
- given at/after menopause as they prevent menopausal symptoms and protect against OP but increase risk of thromboembolism
121
What are the therapeutic uses of estrogens?
1. replacement therapy in primary ovarian failure (Turner's) to promote sexual maturation
2. replacement therapy for menopausal symptoms e.g. flushing, vaginal dryness and OP
3. in contraception they are used in combo with progestins
4. prostate and breast cancer
5. when administered to males they cause feminisation
122
Name examples of (i) natural (ii) synthetic estrogens?
(i) estradiol, estriol
| (ii) mestranol, ethinylestradiol, diethylstilbestrol
123
What are estrogens bound to in blood?
- bound to albumin and to a sex hormone-binding globulin
124
What can a change in the levels of binding proteins modulate?
the level of active estrogens
| - i.e. estrogens in the unbound state
125
What are SERMs?
- competetive antagonists or partial antagonists of estrogens = selective estrogen receptor modulators
- drugs that are selective estrogen agonists in some tissues but antagonists in others are being developed
126
What is the uses of (i) clomiphene (ii) tamoxifen (iii) raloxifene?
(i) acts as an estrogen antag in the hypothalamus and ant. pituitary to inhibit negative feedback effect to induce ovulation
(ii) used in estrogen-dependent breast cancer (anti-estrogenic action on mammary tissue)
(iii) used to treat and prevent osteoporosis (estrogenic action on bone)
127
Why is progesterone not used therapeutically?
due to rapid clearance, instead synthetic derivative called progestins are used
128
What are some common synthetic derivatives of progestins?
- medroxyprogesterone
- hydroxyprogesterone
- norethisterone (weak androgen)
129
What are the therapeutic uses of progestogens?
- main uses in oral contraceptive pill alone or in combo with estrogen
- used as progesterone only injectable or implantable contraception or part of an intrauterine contraceptive
- combined with estrogen for estrogen replacement therapy in women, with an intact uterus, to prevent endometrial hypoplasia, carcinoma, endometriosis
130
What is danazol? What is its MoA? What does it do? What are the various side effects?
- modified progestogen used to treat sex-hormone dependent conditions including endometriosis, breast dysplasia and gynaecomastia
- acts via progesterone receptor to inhibit gonadotrophin production
- reduces estrogen synthesis in women and androgen synthesis in men
- SE = GI disturbances, weight gain, fluid retention, dizziness, headaches and menopausal symptoms
- has androgenic activity so is virilizing when given to women
131
What are the adverse effects of progestins?
- acne
- fluid retention
- weight gain
- depression
- change in libido
- breast discomfort
- menstrual cycle irregularity and increased thromboembolism
132
What is mifepristone? What is it used for?
Anti-progestogen
- in combination with prostaglandin analogues is an effective medical alternative to surgical termination of early pregnancy (up to 9 wks)
133
What is the (i) estrogen (ii) progestogen used in the combined contraceptive pill?
(i) ethinyloestradiol or mestranol
(ii) norethisterone, levonorgestrel, ethynodiol or in 3rd generation pills desogestrel or gestodene (more potent and have less androgenic actions)
134
What is the normal estrogen content in the combined pill?
Generally 20-50 micrograms
135
What is the mode of action of the combined pill?
- estrogen inhibits secretion of FSH via negative feedback on anterior pituitary and => suppresses development of ovarian follicle
- progestin inhibits LH secretion and prevents ovulation
- act in concert to alter the endometrium in such such a way as to discourage implantation
- may also interfere with coordinated contractions of cervix, uterus and fallopian tubes that facilitate fertilisation and implantation
136
What are the adverse effects of the combined contraceptive pill?
- mild nausea, flushing, dizziness and bloating
- weight gain, skin changes (acne or pigmentation) depression or irritability
- amenorrhea of variable duration after cessation of taking the pill
- serious withdrawal effects are rare
- a small no. women develop reversible hypertension
- small increase in risk of thromboembolism
137
What is the MoA of the progestin only pill? Why is it used instead of the combined pill sometimes?
- primarily on cervical mucous which is made inhospitable to sperm and probably also hinders implantation through its effect on the endometrium and on the motility and secretions of fallopian tubes
- offer a suitable alternative to women in whom estrogen-containing pills are contraindicated and suitable for those whose BP rises too much with combined pill
138
What are the other types of drug regimens for contraception?
1) Post-coital (emergency) contraception
- oral administration of levonogestrel alone or in combo with estrogen is effective if taken w/in 72 hours and repeated 12 hrs later
2) Long-acting progestogen only contraception
- medroxyprogesterone acetate can be given IM as a contraceptive, This is effective and safe
- levonorgestrel implanted subcutaneously is used by 3 million women worldwide. The capsules release their progestogen slowly over 5 years
- a levonorgestrel impregnated intrauterine device can last for 35 yrs
139
What are the other types of drug regimens for contraception?
1) Post-coital (emergency) contraception
- oral administration of levonogestrel alone or in combo with estrogen is effective if taken w/in 72 hours and repeated 12 hrs later
2) Long-acting progestogen only contraception
- medroxyprogesterone acetate can be given IM as a contraceptive, This is effective and safe
- levonorgestrel implanted subcutaneously is used by 3 million women worldwide. The capsules release their progestogen slowly over 5 years
- a levonorgestrel impregnated intrauterine device can last for 35 yrs
140
What are the symptoms of menopause?
- headaches and hot flushes
- hair thinner and loses luster
- teeth loosen and gums recede
- breasts droop and flatten
- risk of CVD
- nipples smaller and flatten
- backaches
- skin and mucous membranes drier, skin develops a rougher texture
- body and pubic hair thicker and darker
- abdomen loses muscle tone
- stress or urge incontinence
- bone lose mass and become more fragile
- vaginal dryness, itching and shrinking
141
Describe postmenopausal hormone replacement therapy. What are the various side effects?
- at menopause ovarian function decreases and estrogen levels fall, can be treated with HRT
- it normally involves either cyclic or continuous administration of low dose estrogens with or w/out progestogens
- improves symptoms from reduced estrogen e.g. hot flushes, vaginal dryness
- prevents and treats osteoporosis
SE = withdrawal bleeding, increased risk of breast cancer, increased risk of endometrial cancer (if estrogens unopposed by progesterone), increased risk of thromboembolism
142
What is the main androgen? What stimulates androgen secretion?
Testosterone
| - LH stimulates androgen secretion
143
What is the MoA of testosterone receptors? What do the effects depend upon?
- via nuclear receptors and control of gene expression
- depend upon age/sex and include development of male secondary sex characteristics in pre-pubertal men and masculinisation of women
144
What is the function of (i) antiandrogens (ii) dihydrotestosterone synthesis inhibitors? Give 1/2 named examples for each.
(i) e.g. flutamide, cyproterone are used as part of treatment of prostatic cancer
(ii) e.g. finasteride being used in benign prostatic hypertrophy
145
What are anabolic steroids? When are they used? What are the side effects?
- androgens can be modified to alter balance of anabolic and other effects. Such steroids (nandrolone) increase protein synthesis and muscle development
- used in therapy of aplastic anaemia and abused by some athletes
- SE can be serious; infertility, salt + water retention, CHD, liver disease
146
What are gonadotrophin-releasing hormone analogues? Give some examples and when they are used.
Gonadorelin = same aa sequence as endogenous form but made synthetically
Nafarelin = more potent analogue
- given in pulsatile fashion will stimulate release of gonadotrophins and induce ovulation, used in treatment of infertility
- administration of GnRH is a continuous regimen will induce gonadal suppression. Used in sex-hormone dependent conditions e.g. prostate and breast cancers, endometriosis and large uterine fibroids
147
What are gonadotrophins used for?
- gonadotrophins preparations are used to treat infertility caused by lack of ovulation as a result of hypopituitarism following failure of treatment with clomiphene
- gonadotrophins are used to treat men with infertility due to hypogonadotropic hypogonadism
148
How are gonadotropins are made?
- made by recombinant DNA technology or extracted from urine of pregnant or post-menopausal women.
149
What is puberty? What does it involve?
- developmental stage during which adolescents reach sexual maturity and become capable of reproduction
- involves growth in stature, change in body composition, development of secondary sexual characteristics, achievement of fertility
150
What are the (i) primary (ii) secondary sexual characteristics?
(i) reproductive organs, present at birth
| (ii) develop during puberty, not directly part of the reproductive system
151
What is adenarche (hypothalamic-pituitary-adrenal axis)?
- maturational increase in adrenal androgen production
- around age 6
- occurs in conjunctional with gonadal maturation
- primary stimulus = enhanced adrenal sensitivity to ACTH
152
What are increased androgen levels responsible for?
1. development of pubic and axillary hair (pubarche)
2. development of pilosebaceous unit in the skin (acne)
3. increases cortical bone sensitivity
153
What is the first sign of puberty in females? What then follows?
- breast development between 8.5 and 12.5 yrs
- followed by pubic hair growth and rapid height spurt
- menarche 2.5 years after puberty and signals end of growth
154
What are the female secondary sexual characteristics?
- breast budding (therlarche)
- onset of pubic hair (pubarche)
- max growth velocity
- menarche
- development of axillary hair
- attainment of adult breast type
- adult hair pattern
155
How long, in total, does thelarche, growth spurt, pubarche and menarche require?
approx 4.5 years (range 1-6)
156
How long can it take regular ovulatory cycles to develop?
up to 18 months
157
What is the first sign of puberty in males? What age approx?
testicular enlargement to greater than 4mls volume
| - 10 to 15 yrs (mean 11)
158
When does (i) pubic hair and penile growth (ii) spermarche occur?
(i) normally 2 yr interval between onset of pubic hair and axillary and facial hair
(ii) mean age 13.4
159
When does a growth spurt occur in males?
- when testicular volume is 12 to 15 mls, after delay of around 18 months
- it is later and of greater magnitudes accounting for greater ave final height in males
160
What is an orchidometer used for?
To measure testicular volume in mL
161
What are male 2ndary sexual characteristics dependent upon? What are the androgen-dependent characteristics?
- on testosterone and its metabolite DHT
- facial, underarm + pubic hair, deepen voice, thick secretion oil glands, masculine pattern of fat distribution, bone growth via growth hormone secretion, stimulation of muscle protein synthesis, erythropoetin stimulation giving higher haematocrit in males
162
Describe how puberty is initiated (hypothalamic-pituitary-gonadal axis).
- gonadotrophin release (which was suppressed by continuous infusion of GnRH but pulsatile will lead to gonadal stimulation, maturation and production of steroid)
- pulses of GnRH are detectable in childhood years but mostly during sleep and of low frequency and amplitude therefore don't stimulate gonadotrophin release
- nocturnal secretion of GnRH pulses become more pronounced leading to gonadotrophin release
163
What are the 4 phases of human growth?
1. FETAL - uterine environment, fastest, 30% of eventual height determinedm
2. INFANTILE - nutrition, general health, happiness and thyroid function, rapid but decreasing growth rate, 15%
3. CHILDHOOD - dependent on thyroid hormones, growth hormone, general health and happiness, genetics. Slow steady prolonged
4. PUBERTAL - sex hormones esp testosterone and oestrogen, growth hormone and insulin-like growth factor
164
What is the peak velocity height age in (i) girls (ii) boys, and at what tanner stage?
(i) age 11.5 tanner stage 2-3
| (ii) age 13.5 tanner stage 3-4
165
When do changes in body composition begin?
about 6y in girls
| about 9y in boys
166
What factors contribute to earlier puberty? (HINT: there's 5)
1. Genetics - timing correlates w mother and sisters
2. Social factors - obestity = early menarche
3. Geographic factors - closer to equator, lower altitudes, urban settings
4. Enviro exposures - endocrine disrupting chemicals - industry uses e.g. plastics, agriculture, fuels
5. Race - onset earlier in afro-carribean/african american
167
What does obesity do to onset of puberty in boys and girls?
can accelerate in girls
| - but picture is less clear for boys, may delay onset
168
What does increased body fat do?
May play a critical role in turning on of adrenal androgen secretion and adrenarche
- leptin may link between adipose tissue, energy homeostasis centres in hypothalamus and the repro system
169
What happens to follicle cells during menopause?
- follicle sex cells gradually become insensitive to FSH and LH
- ovarian steroid levels fall
- no neg feedback to pituitary so dramatic increase in levels of FSH and LH
170
What are the consequences/symptoms of menopause?
1. vascular instability - night sweats and hot flushes
2. atrophy of oestrogen dependent tissues (breast, uterus, vagina, urethra, skin collagen loss, osteoporosis, LDL rises increasing risk of coronary thrombosis)
3. rise in adrenal androgens may lead to hirtuitism
4. loss of libido
5. depression, anxiety, mental confusion
171
What is chlamydia?
- common STD caused by chlamydia trachomatis
- can damage a woman's repro organs and symptoms of chlamydia usually mild or absent
- serious complications cause irreversible damage e.g. infertility, can occur silently before a woman ever recognises a problem
- chlamydia also can cause discharge from penis of an infected man
172
How do people catch chlamydia?
- during vaginal, anal or oral sex. Also from an infected mother to her baby during vaginal childbirth
- the greater the no sex partners the greater the risk of infection
- since cervix of teenage girls/young women is not fully matured, they're at particuarly high risk for infection if sexually active
173
What are the symptoms of chlamydia?
- known as 'silent' disease since 3/4 infected women and 1/2 infected men have no symptoms. If symptoms do occur, they appear w/in 1-3 weeks after exposure
WOMEN = abnormal vaginal discharge, pain when urinating. When spreads from cervix to fallopian tubes can either have 0 symptoms or lower abdo pain, low back pain, nausea, fever, pain during intercourse, bleeding between menstrual periods
MEN = discharge from their penis or a burning sensation when urinating. May also have burning and itching around opening of penis. pain and swelling in testicles (uncommon)
174
What are serious complications that can occur in women due to chlamydia?
- if untreated can spread to uterus or fallopian tubes and cause PID
- happens in up to 40% those with untreated can cause permanent damage to fallopian tubes, uterus and surrounding tissues
- damage can lead to chronic pelvic pain, infertility and potentially fatal ectopic pregnancy
- women with chlamydia are 5x more likely to become infected with HIV if exposed
175
What are serious complications that can occur in men due to chlamydia?
- complications are rare
- infections sometimes spreads to epididymis (tube which carries sperm from testis) causing pain, fever and rarely sterility
176
How do you test for chlamydia?
- physical examination for collection of samples from urethra
- urine testing using immunoassays (home testing)
177
What are the approaches to behaviour change that can be used for people who aren't attending screening?
1. Motivational interviewing - process of increasing motivation when people aren't thinking of change
2. Problem focused counselling - identifies cause of problems that prevent change
3. Modelling and rehearsal of change - improves skills and self efficacy to achieve change
178
What is more successful; motivational interviewing approaches or eduction?
motivational interviewing
MD3002
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