The Urinary Tract and the Reproductive System E-book

Question 1

Testosterone produced during

Answer 1

Testosterone produced during foetal development then for the first few months.
The testes then remain dormant until puberty.

Question 2

GnRH) are released from

Answer 2

Pulses of gonadotrophin releasing hormone (GnRH) are released from the hypothalamus which stimulates follicle stimulating hormone (FSH) and luteinizing hormone (LH) release from the pituitary

Question 3

LH stimulates the

Answer 3

LH stimulates the testes to secrete androgens, primarily testosterone from the Leydig cells.

Question 4

FSH stimulates the

Answer 4

FSH stimulates the Sertoli cells in the seminiferous tubules in the testes to secrete androgen-binding protein (ABP).

Question 5

When does Testosterone stimulate spermatogenesis.

Answer 5

Only in the presence of ABP

Question 6

Sertoli cells release

Answer 6

Sertoli cells release inhibin, a protein hormone that inhibits FSH secretion by the anterior pituitary. If spermatogenesis is proceeding too slowly, less inhibin is released, which permits more FSH secretion and an increased rate of spermatogenesis.

Question 7

Testosterone inhibits

Answer 7

Testosterone inhibits GnRH secretion by the hypothalamus and decreases the sensitivity of the pituitary to GnRH. This negative feedback mechanism
decreases during puberty.

Question 8

Testosterone stimulates

Answer 8

Testosterone stimulates the development of secondary sex characteristics

Question 9

Dihydrotestosterone (DHT) stimulates

Answer 9

Dihydrotestosterone (DHT) stimulates the development of pubic, axillary and facial hair

Question 10

Testosterone causes.. to enlarge

Answer 10

Testosterone causes ducts and glands of reproductive system to enlarge

Question 11

Testosterone stimulates a

Answer 11

Testosterone stimulates a growth spurt leading to increased muscle mass, increased basal metabolic rate and a larger larynx

Question 12

why males have a higher haematocrit and RBC than females.

Answer 12

Testosterone stimulates erythropoiesis which is

Question 13

What leads to increased libido

Answer 13

Testosterone stimulates the brain leading to increased libido

Question 14

As a man ages,

Answer 14

As a man ages, testosterone levels drop from a peak of approximately 7mg/day at 20 years of age to 1/5 of this aged 80. Feedback inhibition of the pituitary decreases and levels of FSH and LH increase.

Question 15

Prostate gland

Answer 15

 Located immediately below the bladder and immediately in front of the rectum.
 Consists of between 30 and 50 tubulacinar glands in fibrous capsule.
 These produce a thin, milky secretion which empties through approximately 20 poresin the urethral wall.
 Secretion makes up approximately 30% of semen.
 Position in front of the rectum means that it can be palpated through the rectal wall - digital rectal examination (DRE).

Question 16

Benign Prostate Enlargement (BPE) / Benign Prostatic Hyperplasia (BPH)

Answer 16

BPE/BPH is the most common disorder of the prostate responsible for LUTS. It is a condition that is common in older men.

Question 17

Pathophysiology: BPE

Answer 17

BPE/BPH occurs when there is hyperplasia of the epithelial and stromal components of the prostate gland, which leads to progressive obstruction of urine flow and increased activity of the detrusor muscle (Berry et al (1984) cited by Wilt and N’Dow 2008).
 Pathogenesis thought to be androgen/oestrogen imbalance.
 DHT thought to be the main stimulator of the growth of prostatic glands.

Question 18

Symptoms: BPE

Answer 18

 Frequency of urination is a common early symptom.
 Difficulty or delay in initiating urination with variability and reduced forcefulness of urinary stream and post-void dribbling often present.
 Acute urinary retention or retention with overflow incontinence may occur.
 Digital rectal examination (DRE) – smooth enlarged prostate = benign hyperplasia.

Question 19

BPE/BPH – Differential diagnoses:

Answer 19

/BPH – Differential diagnoses:
 Poorly controlled diabetes
 Neurological disorders
 UTIs
 Chronic bacterial prostatitis
 Overactive bladder
 Medication: diuretics, anticholinergics,antidepressants
 Lifestyle factors: caffeine, alcohol, excess intake of liquids

Question 20

not routinely required for diagnosis as BPE/BPH is not a risk factor for prostate cancer

Answer 20

Prostate specific antigen (PSA) and DRE

Question 21

BPE/BPH – management

Answer 21

 Observation (watchful waiting) if only growing slowly
 Lifestyle management
 Modification of existing medication and/or management of co-existing medical conditions
 Prostate and bladder specific drug treatment
 Surgical treatments

Question 22

BPE lifestyle

Answer 22

 Reassurance
 Reduce fluid or diuretic intake
 Avoid excess or night-time fluid intake
 Avoid caffeine
 Avoid alcohol
 Void bladder before long trips, meetings or bed time

Question 23

BPE Co-morbidities

Answer 23

 Review control ofdiabetes

 Review any diuretic therapies

Question 24

BPE drug therapy

Answer 24

• α-blockers
• 5α-reductase
• Antimuscarinics

Other adjunct drug treatments include:
 Diuretics, desmopressin

Question 25

α-blockers

Answer 25

 Improve bladder and prostate smooth muscle tone.

 Review patient 4 – 6 weeks after starting therapy then annually thereafter.

Question 26

5α-reductase inhibitors

Answer 26

 Can be used alone or in combination with an α-blocker dependent on symptoms, results and prostate size
 Reduce prostate size.
 Sexual function side effects.
 Improvement in symptoms generally seen within 3 - 6 months of starting treatment
 Review patient 3 - 6 months after starting therapy then every 6 - 12 months thereafter

Question 27

Antimuscarinics

Answer 27

 Decrease hypercontractility of detrusor muscle.

 Useful for symptoms of overactive bladder.

Question 28

BPE Surgical options

Answer 28

The standard surgical option is transurethral resection of prostate (TURP):
“This involves endoscopic removal of the inner (paraurethral) zones of the enlarged prostate using a diathermy loop.” (Wilt TJ, N’Dow J, 2008)
This is a highly effective procedure and is the gold standard. The associated risks are those of the general anaesthetic itself and severe haemorrhage
- Transurethral incision of the prostate (TUIP), Laser prostatectomy.

Question 29

Surgical options risks

Answer 29

 impotence
 incontinence
 need for further treatment due to stricture formation, urinary retention or disease relapse

Question 30

Erection mechanism

Answer 30

draw

Question 31

ED Possible causes:

Answer 31

 Ageing
 Cardiovascular disease
 Neurological disease
 Diabetes mellitus
 Medication i.e. drug induced prescription or non prescription
 Fear of failure
 Hormonal
 Depression

Question 32

ED Co-morbidities

Answer 32

 ED may be the first symptom of diabetes mellitus in approximately 20% of cases of ED
 Risk factors for ED are very similar to those for cardiovascular disease
 ED itself is a risk factor for cardiovascular disease
(equivalentto moderate smoking)
 Risk factors:
 Sedentary lifestyle
 Obesity
 Smoking
 Hypercholesterolaemia
 Metabolic syndrome
 ED in an otherwise asymptomatic man could be a marker for underlying cardiovascular disease.
 Hyperthyroidism may cause ED as there is increased SHBG production leading to
o decreased free testosterone levels. Successful treatment of hyperthyroidism may resolve co-existing ED.
 Thiazides and non-selective beta-blockers may cause ED.

Question 33

Treatment of ED 1st and 2nd line

Answer 33

 Identification and treatment of reversible lifestyle factors.
 Identification and treatment of reversible hormone imbalances.
 Review of drug therapies for co-existing diseases.
 Psychosexual/relationship therapy

First-line treatment:
-Phosphodiesterase type-5 inhibitors
 sildenafil (Viagra)
 tadalafil (Cialis)
 vardenafil (Levitra)
 avanafil (Spedra)
-Vacuum erection devices

Second-line treatments:
- Intracavernous injection therapy
 alprostadil (Caverject, Viridal Duo)
- Intraurethral alprostadil
 medicated pellet (MUSE)
- Topical (tip of penis)
 Alprostadil (Vitaros)

Question 34

Unlicensed ED treatments

Answer 34

 Papaverine, phentolamine

 Third-line treatments: Penileprosthesis

Question 35

Prostatitis - acute or chronic

Answer 35

BPE/BPH and prostate cancer are relatively common pathologies of the prostate, but a rarer condition of the prostate is prostatitis, which is an inflammation of the prostate.
The main symptoms are:
 pelvic pain
 pain on urination
 pain on ejaculation.

A man who presents with these symptoms should be referred immediately to his GP. If prostatitis has been caused by a bacterial infection then it needs urgent treatment with antibiotics; early treatment will prevent damage to the prostate gland and halt the spread of infection to the surrounding urinary tract

Question 36

The Cycle - Female

Answer 36

Each month after puberty until menopause, gonadotrophins, follicle stimulating hormone (FSH) and luteinising hormone (LH) are secreted by the anterior pituitary.
Each oocyte is surrounded by a single layer of follicular cells – called primordial follicles.
FSH and LH stimulate the development of several primordial follicles which start to grow into primary follicles. One of these follicles develops further to a secondary follicle and eventually matures to a mature (graafian) follicle. Just before ovulation, the diploid primary oocyte undergoes first phase meiosis. This produces two haploid cells, each with 23 chromosomes but unequal in size. The smaller cell produced by meiosis is called the first polar body and contains discarded nuclear material. The larger cell, known as the secondary oocyte, receives most of the cytoplasm. Once a secondary oocyte is formed it begins meiosis II but then stops in metaphase. The mature graafian follicle then ruptures releasing the secondary oocyte – ovulation. Meiosis II only continues if sperm is present in the fallopian tubes and fertilisation occurs. Otherwise all cells degenerate.

Question 37

The process of ovulation

Answer 37

 In the adult female, higher brain centres impose a menstrual cycle of 28 days upon the activity of hypothalamic GnRH
 Pulses of GnRH, at about 2-hour intervals, stimulate the release of pituitary LH and FSH
 LH stimulates ovarian androgen production by ovarian theca cells
 FSH stimulates follicular development and aromatase activity (an enzyme required to convert ovarian androgens to oestrogens) in the ovarian granulosa cells. FSH also stimulates release of inhibin from ovarian stromal cells, which inhibits FSH release. Activin counteracts inhibin

Question 38

Secretion and physiological effects of oestrogens, progesterone, relaxin, and inhibin in the female reproductive cycle

Answer 38

 Oestrogens show a double feedback action on the pituitary, initially inhibiting gonadotrophin secretion (negative feedback), but later high-level exposure results in increased GnRH secretion and increased LH sensitivity to GnRH (positive feedback) which leads to the mid-cycle LH surge including ovulation from the leading follicle

Question 39

High levels of oestrogens exert a positive feedback effect

Answer 39

 The follicle then differentiates into a corpus luteum, which secretes both progesterone and oestradiol during the second half of the cycle (luteal phase).
 Oestrogen initially and then progesterone, cause uterine endometrial proliferation in preparation for possible implantation; if implantation does not occur, the corpus luteum regresses and progesterone secretion and inhibin levels fall so that the endometrium is shed (menstruation) allowing increased GnRH and FSH secretion
 If implantation and pregnancy follow, human chorionic gonadotrophin (hCG) production from the trophoblast maintains corpus luteum function until 10-12 weeks of gestation, by which time the placenta will be making sufficient oestrogen and progesterone to support itself

Question 40

Menorrhagia

Answer 40

Normal menstrual flow is around 35-80ml; menorrhagia can be defined as a menstrual flow of 80ml or more. NICE guidance CG44 defines it as “as excessive menstrual blood loss which interferes with the woman’s physical, emotional, social and material quality of life, and which can occur alone or in combination with other symptoms. Any interventions should aim to improve quality of life measures.” For the majority of women, there is no obvious cause for heavy periods, but it may also be a symptom of an underlying disease. Conditions such as polyps, endometriosis, fibroids, pelvic inflammatory disease or polycystic ovary disease can also resultin heavy periods.
Copper intrauterine devices (IUDs) are associated with heavy menstrual flow. Certain endocrine disorders such as hypothyroidism may also disrupt the menstrual cycle and result in heavy menstrual periods.

Question 41

Dysmenorrhoea

Answer 41

Dysmenorrhoea describes painful periods associated with low abdominal cramping pain which may also spread to the back and thighs.

Primary dysmenorrhoea: no underlying pelvic disease. Pain is caused by increased endometrial production of prostaglandins that facilitate smooth muscle contraction in the uterus.

Secondary dysmenorrhoea is caused by some underlying pelvic disease such as endometriosis, fibroids, pelvic inflammatory disease or adenomyosis. Dysmenorrhoea is also associated with IUD, especially in the first few months after insertion. Secondary dysmenorrhoea is more common in women aged between 30 and 45. Any woman of this age group presenting with dysmenorrhoea for the first time, or with severe or worsening pain, should be encouraged to further investigate their symptoms.

Question 42

Amenorrhoea

Answer 42

This is defined as an absence of periods or markedly irregular infrequent periods (oligomenorrhoea). Polycystic ovary syndrome (PCOS) is the most common cause.

Weight-related amenorrhoea – a minimum body weight is necessary for regular menstruation and may be seen at weights within “normal” range. Restoration of body weight to above 50th centile for height is usually effective in restoring menstruation but oestrogen replacement is often necessary.

Hypothalamic amenorrhoea – low oestrogen and gonadotrophin levels in the absence of organic pituitary disease, weight loss or excessive exercise. It may be related to stress, weight loss or stopping the contraceptive pill, but some patients can have defective cycling mechanisms without explanation.

Hypothyroidism- oligomenorrhoea and amenorrhoea are common in severe hypothyroidism in young women.

Question 43

Polycystic Ovary Syndrome (PCOS)

Answer 43

PCOS is characterised by multiple small cysts in the ovaries (which represent follicles under arrested development), excess androgen production from the ovaries (and to a lesser extent the adrenal glands). Levels of androgens vary from patient to patient.
SHBG levels are often low due to high insulin levels leading to high free androgen levels.
Hair follicle response to circulatory androgens is very variable, even with identical clinical and biochemical features therefore it is very difficult to predict symptomology

Question 44

Examples of clinical features of PCOS:

Answer 44

 Amenorrhoea/ oligomenorrhoea
 Hirsutism
 Acne

Question 45

Hirsutism

Answer 45

Begins around the time of menarche and increases slowly and steadily over the teens and twenties. It may be severe and affect all androgen-dependent areas on face and body. Male pattern baldness may occur in women, particularly if there is a familial tendency for premature hair loss.

Question 46

Long-term health risks for patients with PCOS:

Answer 46

 Multiple risk factors for diabetes
 Obesity
 Family history of type-2 diabetes
 Abnormalities in insulin action (both resistance and β-cell dysfunction)
 Women with PCOS 3-7 times more at risk of developing type 2 diabetes
 Increased risk of CVD
 Increased risk of dyslipidaemia

Question 47

PCOS - Explain that weight loss may:

Answer 47

• Reduce hyperinsulinism and hyperandrogenism.
• Reduce the risk of type 2 diabetes and CVD.
• Result in menstrual regularity.
• Improve the chance of pregnancy (if it is desired

Question 48

Oligomenorrhoea or amenorrhoea - If the woman has prolonged amenorrhea (less than one period every three months), abnormal vaginal bleeding, or excess weight:

Answer 48

• Prescribe a cyclical progestogen (such as medroxyprogesterone 10 mg daily for 14 days) to induce a withdrawal bleed, then
• Refer for a transvaginal ultrasound to assess endometrial thickness.

Question 49

Acne - pcos

Answer 49

Offer a COC as a first-line treatment, provided there are no contraindications

Question 50

Drugs used in the treatment of overactive bladder

Answer 50

Darifenacin	
Fesoterodine	
Oxybutynin	
Propiverine	
Solifenacin	
Tolterodine	
Trospium

Question 51

Desmopressin

Answer 51

1-desamino-8-D-arginine vasopressin (demopressin) is a synthetic vasopressin analogue that has strong antidiuretic effects without altering blood pressure. It has been used primarily in the treatment of nocturia and nocturnal enuresis in children and adults

Question 52

Which medications should not be offered to women to treat urinary incontinence or overactive bladder.

Answer 52

Do not offer women flavoxate, propantheline or imipramine to treat urinary incontinence or overactive bladder.

Question 53

Testing for UI

Answer 53

Undertake a urine dipstick test in all women presenting with UI to detect the presence of blood, glucose, protein, leucocytes and nitrites in the urine.

Question 54

When is Mirabegron given

Answer 54

Mirabegron is recommended as an option for treating the symptoms of overactive bladder only for people in whom antimuscarinic drugs are contraindicated or clinically ineffective, or have unacceptable side effects.

Question 55

Under active bladder (UAB) is usually observed when the following mechanisms are damaged

Answer 55

Bladder peripheral afferent pathways

Bladder peripheral efferent pathways

Lumbosacral spinal cord (spinal micturition center)

Myogenic failure

Question 56

Treatment Options for Underactive Bladder

Answer 56

Physiotherapy - Double void, straining to void, indwelling, or intermittent catheterization

Drug

• α-adrenoceptor antagonists
• Muscarinic receptor agonists (bethanechol, carbachol)
• Acethylcholinesterase (distigmine)
• Prostaglandin E2
• 4 types of EP2 receptors
• Stem cell therapy
• Gene therapy - HSV-rhNGF

Question 57

first-line option in children who require a rapid response or short-term control of bedwetting

Answer 57

desmopressin

Prescribe a low dose of oral desmopressin (Desmotabs® 200 micrograms or sublingual DesmoMelt® 120 micrograms) initially, at bedtime.

• If there is a response to desmopressin, continue short-term treatment.
• If there is no response consider advising the parents to increase the dose of desmopressin (Desmotabs® 400 micrograms or DesmoMelt® 240 micrograms).
• Consider starting a trial of desmopressin at least 1 week before the school trip or sleepover to determine the effectiveness of treatment.

Question 58

What advice can I give parents or carers regarding desmopressin

Answer 58

• Desmopressin should be taken at bedtime. It works by reducing the amount of urine the body produces at night. This mimics the action of the body’s own naturally occurring antidiuretic hormone (ADH). In most children levels of ADH rise overnight and reduce the volume of water excreted by the kidneys compared with during the daytime.
• Many children, but not all, will experience a reduction in wetness.
• Many children, but not all, will relapse when treatment is withdrawn.
• If the child relapses, repeated courses may be used.
• Fluid intake should be restricted to sips only, from 1 hour before taking desmopressin until 8 hours afterwards (a total of one regular glass of water may be drunk in this time). Fluid restriction is required to avoid the potential for fluid overload and hyponatraemia (low sodium levels in the blood) which can lead to hyponatraemic convulsions. In addition:
• Children should avoid swallowing water when swimming (to avoid fluid overload).
• Over the counter nonsteroidal anti-inflammatories such as ibuprofen should be avoided. They can cause water retention and increase the risk of hyponatraemia.
• Desmopressin should be stopped if the child has vomiting or diarrhoea until fluid balance is normal.

-There is no evidence of adverse effects if desmopressin is used long term.

Question 59

How should I manage children with primary bedwetting and daytime symptoms?

Answer 59

Refer all children with primary bedwetting and daytime symptoms

Question 60

Desmopressin should not be used for children:

Answer 60

With heart failure.
With hypertension (controlled or uncontrolled).
Taking diuretics.
With psychogenic polydipsia or alcohol misuse.

Question 61

Desmopressin - adverse effects

Answer 61

Fluid retention and hyponatraemia can occur, leading to:
Headache.
Nausea and vomiting.
Weight gain.
Convulsions (in serious cases).
Headache, nausea, stomach pain, allergic reactions and emotional disorders (very rare) such as aggression have also been reported.

Question 62

Desmopressin Key drug interactions

Answer 62

Drugs that cause water retention and increase the risk of hyponatraemia — may have an additive effect when taken concomitantly and cause water overload and/or hyponatraemia.
Examples of drugs that can cause water retention and increase the risk of hyponatraemia include nonsteroidal anti-inflammatory drugs, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), chlorpromazine, lamotrigine, and carbamazepine.
Concomitant use should be avoided.
Loperamide — concomitant use with loperamide may increase the plasma levels of desmopressin which could lead to an increased risk of water retention and/or hyponatraemia. Avoid concomitant use.
Furosemide — desmopressin should not be used concurrently with furosemide because of the risk of hyponatraemia.

Question 63

Urine-testing strategies for children 3 years or older

Answer 63

If both leukocyte esterase and nitrite are positive - The child should be regarded as having UTI and antibiotic treatment should be started. If a child has a high or intermediate risk of serious illness and/or a past history of previous UTI, a urine sample should be sent for culture.

If leukocyte esterase is negative and nitrite is positive - Antibiotic treatment should be started if the urine test was carried out on a fresh sample of urine. A urine sample should be sent for culture. Subsequent management will depend upon the result of urine culture.

If leukocyte esterase is positive and nitrite is negative - A urine sample should be sent for microscopy and culture. Antibiotic treatment for UTI should not be started unless there is good clinical evidence of UTI (for example, obvious urinary symptoms). Leukocyte esterase may be indicative of an infection outside the urinary tract which may need to be managed differently.

If both leukocyte esterase and nitrite are negative - The child should not be regarded as having UTI. Antibiotic treatment for UTI should not be started, and a urine sample should not be sent for culture. Other causes of illness should be explored.

Question 64

Pyuria positive and Bacteriuria positive

Answer 64

The infant or child should be regarded as having UTI

Question 65

Pyuria positive and Bacteriuria negative

Answer 65

Antibiotic treatment should be started if clinically UTI

Question 66

Pyuria negative and Bacteriuria positive

Answer 66

The infant or child should be regarded as having UTI

Question 67

Pyuria negative and Bacteriuria negative

Answer 67

The infant or child should be regarded as not having UTI

Question 68

Bacteriuria

Answer 68

Bacteria in the urine with or without urinary tract infection.

Question 69

Pyuria

Answer 69

White cells in the urine.

Question 70

Clinical features UTI

Answer 70

Lower UTI can be defined as evidence of UTI with symptoms suggestive of cystitis (dysuria, or increased urinary frequency without fever, chills or back pain), while upper UTI can present with symptoms suggestive of pyelonephritis (loin pain, flank tenderness, fever, rigors, or other manifestations of systemic inflammatory response)

Question 71

Optimisation of antimicrobials for UTI in elderly patients

Answer 71

• Do not start antibiotics for asymptomatic bacteriuria in the elderly or in catheterised patients;
• Always send a sample for culture before starting antibiotic therapy;
• Check previous culture and sensitivity results before prescribing;
• Use local guidelines when deciding which antibiotic to give;
• Ensure the correct course length is prescribed (i.e. seven days for a man, or minimum of seven days for a CAUTI);
• Ensure the patient completes the full course (even if symptoms improve).

Question 72

SIGN Guidelines for UTI recommend

Answer 72

three-day course of trimethoprim tablets 200mg twice a day, or nitrofurantoin modified release capsules 100mg twice a day for non-pregnant women of any age, who have signs or symptoms of an acute lower UTI.

Question 73

Nitrofurantoin is contraindicated in

Answer 73

patients with an estimated glomerular filtration rate (eGFR) of less than 45ml/min/1.73m2

Question 74

For treatment of acute pyelonephritis, PHE recommend

Answer 74

empirical treatment with ciprofloxacin 500mg twice daily or co-amoxiclav 500/125mg three times a day, for a minimum of seven days.

Question 75

If the man has moderate-to-severe voiding symptoms offer

Answer 75

an alpha-blocker (alfuzosin, doxazosin, tamsulosin, or terazosin).

Question 76

If the man has an enlarged prostate and is considered to be at high risk of progression offer

Answer 76

a 5-alpha reductase inhibitor (dutasteride or finasteride).

Question 77

If the man has bothersome moderate-to-severe voiding symptoms and prostatic enlargement, consider offering

Answer 77

combination of an alpha-blocker and a 5-alpha reductase inhibitor.

Question 78

If the man has a mixed picture with storage symptoms and voiding symptoms which persist after treatment with an alpha-blocker alone, consider

Answer 78

adding an antimuscarinic (anticholinergic) drug.
- Oxybutynin (immediate release), tolterodine (immediate release), or darifenacin (once daily preparation) can be used first line.

Question 79

Do not offer oxybutynin (immediate release) to

Answer 79

frail older men due to the risk of impairment of daily functioning, chronic confusion, or acute delirium (less common).

Question 80

How should I manage a man with overactive bladder as the predominant symptom?

Answer 80

If symptoms persist, offer an antimuscarinic (anticholinergic) drug.
Oxybutynin (immediate release), tolterodine (immediate release), or darifenacin (once daily preparation) can be used first line.

Question 81

How should I manage nocturnal polyuria as the predominant symptom?

Answer 81

Exclude or manage treatable causes of nocturnal polyuria.
Advise the man to limit his fluid intake in the late afternoon and evening, and offer information on self-help resources.
If limiting fluid intake in the late afternoon and evening is ineffective, consider offering a loop diuretic to be taken in the late afternoon. For example, furosemide 40 mg (off-label use).
For detailed prescribing information, see the section on Furosemide.
If nocturnal polyuria remains bothersome, refer the man or seek specialist advice about switching to oral desmopressin to be taken at bedtime.
Start treatment with the lowest dose of 50 micrograms.

Question 82

If the man has recurrent acute retention, or acute-on-chronic urinary retention:

Answer 82

An alpha-blocker (modified-release alfuzosin 10 mg a day) — licensed for use in acute urinary retention associated with benign prostatic hyperplasia in men over 65 years of age. Start at least 24 hours before attempting to remove the catheter. After removing the catheter, confirm over several hours that the man can void freely. The licensed duration of use is for 2–3 days during catheterization, and for 1 day after removal (maximum 4 days). However, some experts recommend that the alpha-blocker should be continued until the man has been fully investigated to determine the cause and to assess renal function. For detailed prescribing information, see Alpha-blockers.
Intermittent urethral catheterization — refer the man or his carer to a continence nurse for training in catheterization.
A long-term indwelling catheter

Question 83

Alpha-blocker eg

Answer 83

alfuzosin
tamsulosin
doxazosin
terazosin

Question 84

5-alpha reductase inhibitors eg

Answer 84

Finasteride — prescribe 5 mg once a day.

Dutasteride — prescribe 500 micrograms once a day.

Question 85

Antimuscarinics (anticholinergics) eg

Answer 85

Oxybutynin
Darifenacin 
Fesoterodine 
Propiverine
Solifenacin
Tolterodine
Trospium

Question 86

Unlicensed ED treatments

Answer 86

 Papaverine, phentolamine

 Third-line treatments: Penileprosthesis

Question 87

First pharmacological treatment for premature ejaculation to be licensed in the UK

Answer 87

Dapoxetine - a short-acting selective serotonin-reuptake inhibitor (SSRI)

Question 88

How should I manage a woman with suspected endometriosis? If the woman does not wish to conceive

Answer 88

consider prescribing a 3–6 month trial of hormonal contraception (off-label use):

• Monophasic combined oral contraceptive (COC) preparations containing 30–35 micrograms of ethinylestradiol and norethisterone, norgestimate, or levonorgestrel are usually first choice. Advise the woman to start a 3–month trial of a conventional regimen, then switch to tricycling or continuous use if this does not control symptoms.
• Oral (desogestrel 75 micrograms), depot (Depo-Provera® or SAYANA PRESS®), subdermal implant (Nexplanon®), and intrauterine progestogen-only (Mirena®) contraceptives may also be considered, after a full discussion of the advantages and disadvantages.

Question 89

How should I manage a woman with suspected endometriosis? If the woman does not wish to conceive and does not want to take hormonal contraception

Answer 89

offer an oral progestogen, such as:

- Medroxyprogesterone or norethisterone.

Question 90

For women with moderate PMS

Answer 90

offer lifestyle advice and consider:

• A new-generation combined oral contraceptive (COC), especially if the woman requires contraception (off-label use if used solely to treat PMS symptoms). There is more evidence to support the use of Yasmin® (drospirenone 3 mg and ethinylestradiol 0.030 mg). However, other new-generation COCs may also be effective, especially if they have been used before and have been found to be of benefit.
  The COC can be used cyclically or continuously.
• Paracetamol or a nonsteroidal anti-inflammatory drug (ibuprofen, naproxen, or mefenamic acid) if the predominant problem is pain (for example headache or generalized aches and pains).
• Referral for CBT

Question 91

For women with severe PMS

Answer 91

A selective serotonin reuptake inhibitor (SSRI, off-label use). The SSRI can be taken either continuously or just during the luteal phase (for example days 15–28 of the menstrual cycle, depending on its length).
Do not prescribe an SSRI if there is doubt about the diagnosis or a lack of experience in prescribing them.
In people younger than 18 years of age, prescribe an SSRI only on the advice of a specialist.
Inform the woman that the use of an SSRI to treat PMS symptoms is an off-label use.
Give an initial trial of 3 months’ treatment; if there is benefit, continue treatment for 6 months to 1 year. Suggested doses are fluoxetine 20 mg a day, sertraline 50 mg to 100 mg a day, citalopram 20 mg a day, escitalopram 20 mg a day, or paroxetine 20 mg a day.
Monitor the woman’s response to treatment closely, including asking about any thoughts of self harm.

Question 92

Treatments which are not recommended for initiation in primary care for premenstrual syndrome (PMS) are:

Answer 92

Progesterone or progestogens used alone.
Antidepressants other than selective serotonin reuptake inhibitors (SSRIs).
Alprazolam.
Diuretics.
Danazol.
Transdermal oestrogen.
Gonadotrophin releasing hormone analogues.
Complementary therapies and dietary supplements (such as vitamin B6, calcium and vitamin D, magnesium, evening primrose oil, and agnus castus).

Question 93

How should I manage women with menorrhagia in primary care?

Answer 93

• Consider a levonorgestrel intrauterine system (LNG-IUS) as the first-line treatment.
• If an LNG-IUS is declined or unsuitable, consider the following pharmacological treatments:
• Non-hormonal: tranexamic acid or a non steroidal anti-inflammatory drug (NSAID).
• Hormonal: combined hormonal contraception (CHC) or a cyclical oral progestogen (such as oral norethisterone).

Question 94

How should I manage primary dysmenorrhoea?

Answer 94

• Offer NSAID, unless contraindicated.
• If the woman does not wish to conceive, consider prescribing a 3–6 month trial of a hormonal contraceptive as an alternative first-line treatment.
• Monophasic combined oral contraceptive (COC) preparations containing 30–35 micrograms of ethinylestradiol and norethisterone, norgestimate, or levonorgestrel are usually first choice.
• Oral (desogestrel 75 micrograms), parenteral (Depo-Provera® or Sayana Press®, and Nexplanon®), and intrauterine progestogen-only (Mirena®) contraceptives may also be considered after a full discussion of the advantages and disadvantages.

Question 95

Pharmacological treatment of fibroids

Answer 95

•Levonorgestrel-releasing intrauterine system (where at least 12 months’ treatment is expected)
• Combined oral contraceptives or, for women in whom hormonal treatments are not acceptable, tranexamic acid or NSAID
drugs
• Norethisterone or injected progestogen

Question 96

Drugs used to shrink fibroids or used pre-operatively include

Answer 96

GnRH analogues (goserelin, leuprorelin, triptorelin) and selective progesterone receptor modulator (ulipristal).

Question 97

Overactive bladder (OAB) is considered to be caused by

Answer 97

overactivity of the detrusor muscles in the bladder wall.

Question 98

Risk factors OAB

Answer 98

Caucasians, people with insulin-dependent diabetes and
those who are depressed are over three times more likely
to develop OAB.

Other risk factors include arthritis,
hormone replacement therapy and being overweight.

The physiological changes associated with ageing may
also lead to changes in muscle tone and bladder function,
which may explain the increased incidence of OAB in
people aged over 75 years.

For postmenopausal women, OAB may be associated with oestrogen deficiency and vaginal atrophy

Question 99

Medicines that can cause OAB

Answer 99

● Angiotensin-converting enzyme inhibitors — coughing, a common adverse effect, can induce stress incontinence
● Alpha-adrenoceptor antagonists — relaxation of smooth muscle can induce stress incontinence
● Alpha-adrenoceptor agonists — constriction of smooth muscle can induce urinary retention and overflow incontinence
● Antipsychotics — anticholinergic activity can induce urinary retention and overflow incontinence
● Cholinesterase inhibitors — can increase strength and frequency of bladder contractions
● Diuretics — increase urine production, increasing frequency, urgency and overflow incontinence
● Opioids — can induce urinary retention and overflow incontinence
● Sedating antihistamines — promote urinary retention and overflow incontinence
● Sedatives and hypnotics — can affect a patient’s awareness of needing to urinate
● Tricyclic antidepressants — relax smooth muscle and constrict muscles in the bladder neck, inducing urinary retention and overflow incontinence

Question 100

OAB diagnosis

Answer 100

● Midstream urine sample
● Ultrasound to determine the residual volume of the
bladder
● Abdominal X-ray to detect bladder stones
● Flexible cystoscopy
● Cystometrography to measure any sudden changes
in bladder pressure that relate to involuntary detrusor contractions

Question 101

OAB pharmacological management

Answer 101

NICE recommends that immediate-release oxybutynin, immediate-release tolterodine or modifiedrelease darifenacin be tried first

Question 102

NICE does not recommend the use of … for the treatment of OAB

Answer 102

flavoxate, propantheline and imipramine

Question 103

Oxybutynin - OAB

Answer 103

Oxybutynin acts on the muscarinic receptor
subtypes M1, M2 and M3 and has a mild antispasmodic
effect at higher doses. Treatment begins at 5mg two or
three times a day and increases to a maximum of 5mg four
times a day. Treatment adherence can be affected by
adverse effects, such as dry mouth, dry eyes, constipation
and confusion (see Box 2, p16) — particularly in elderly
patients. Therefore, immediate-release oxybutynin must
be avoided in older patients.
8
Using a modified-release preparation may improve the
tolerability of oxybutynin, yet this effect has not been
proven. Patients are prescribed 5mg daily of the
modified-release preparation, increasing each week by 5mg
to a maximum of 20mg daily. This approach is considerably
more expensive than using immediate-release preparations
of oxybutynin and is not recommended by NICE first line.
A transdermal patch is available for patients who
benefit from oxybutynin, but who cannot tolerate the
adverse effects or for whom the oral route is not suitable.
One patch releases 3.9mg over 24 hours. Patches are
applied to clean, dry and intact skin on the abdomen,
buttock or hip and are replaced twice a week.

Question 104

Tolterodine - OAB

Answer 104

Tolterodine acts on the muscarinic receptor
subtypes M2 and M3. It is generally better tolerated than oxybutynin and does not require dose titration. Although
discontinuation rates were found to be lower with
tolterodine treatment compared with oxybutynin in metaanalysis studies by NICE (5.3% versus 11%, respectively, at
week 4), patients taking tolterodine were less likely to be
continent after four weeks (25.1% versus 28.2%,
respectively).
6 It is prescribed at 2mg twice a day; 1mg twice
a day is suggested for patients with impaired liver function,
those with severe renal impairment, elderly patients and
those who experience unacceptable adverse effects.
An extended-release preparation is available that
appears to offer a lower incidence of dry mouth and may
be suitable for patients who require once-daily
preparations. However, this preparation is not considered
cost-effective by NICE and is not recommended first line

Question 105

Darifenacin - OAB

Answer 105

Darifenacin is a selective antimuscarinic
medicine that acts on the muscarinic receptor subtype M3.
Doses of the modified-release product start at 7.5mg daily
increasing to 15mg daily after two weeks, if required.
Darifenacin is recommended as a first-line treatment
choice and is the most cost-effective once-daily
preparation available. It is better tolerated than
immediate-release oxybutynin (discontinuation rate for
darifenacin 4%). The safety and efficacy of using
darifenacin to treat patients with neurogenic causes of
detrusor overactivity have not yet been established.
Solifenacin is structurally similar to darifenacin and has
the same mechanism of action but is more expensive

Question 106

Second line OAB treatment

Answer 106

Mirabegron
Desmopressin
Oestrogen

Question 107

What should not be offered for stress urinary incontinence

Answer 107

Duolextine

Question 108

What may be considered specifically to reduce nocturia in women with UI or OAB who find it a troublesome symptom.

Answer 108

desmopression

• Use particular caution in women with cystic fibrosis and avoid in those over 65 years with cardiovascular disease or hypertension.

Question 109

LUTS treatment

Answer 109

• Offer drug treatment only to men with bothersome LUTS when conservative management options have been unsuccessful or are not appropriate
• Offer an alpha blocker (alfuzosin, doxazosin, tamsulosin or terazosin) to men with moderate to severe LUTS
• Offer an anticholinergic to men to manage the symptoms of OAB.
• Offer a 5‑alpha reductase inhibitor to men with LUTS who have prostates estimated to be larger than 30 g or a PSA level greater than 1.4 ng/ml, and who are considered to be at high risk of progression (for example, older men).
• Consider offering a combination of an alpha blocker and a 5‑alpha reductase inhibitor to men with bothersome moderate to severe LUTS and prostates estimated to be larger than 30 g or a PSA level greater than 1.4 ng/ml.
• Consider offering an anticholinergic as well as an alpha blocker to men who still have storage symptoms after treatment with an alpha blocker alone.
• Consider offering a late afternoon loop diuretic to men with nocturnal polyuria.
• Consider offering oral desmopressin to men with nocturnal polyuria if other medical causes have been excluded and they have not benefited from other treatments. Measure serum sodium 3 days after the first dose. If serum sodium is reduced to below the normal range, stop desmopressin treatment.
• Do not offer phosphodiesterase‑5‑inhibitors solely for the purpose of treating lower urinary tract symptoms in men, except as part of a randomised controlled trial.