Menstrual Cycle

Question 1

What are the two phases of the uterine cycle?

Answer 1

The menstrual cycle can be described by referring to either the uterus or the ovary. Endometrial cycle results from growth and shedding of the uterine lining – the endometrium. Two phases to the uterine cycle:
• Proliferative: At the end of the menstrual phase, the endometrium thickens again
• Secretory: after ovulation, endometrial growth stops and the glands become more active and full of secretions

Question 2

What happens in the proliferative phase of the uterine cycle?

Answer 2

• Proliferative: At the end of the menstrual phase, the endometrium thickens again
• Secretory: after ovulation, endometrial growth stops and the glands become more active and full of secretions

Question 3

What happens in the secretory phase of the uterine cycle?

Answer 3

• Proliferative: At the end of the menstrual phase, the endometrium thickens again
• Secretory: after ovulation, endometrial growth stops and the glands become more active and full of secretions

Question 4

What are the three phases of the ovarian cycle?

Answer 4

• Follicular phase
• Ovulation
• Postovulatory or luteal phase – always remains constant – 14 days.

Question 5

What is the average duration of the ovarian cycle?

Answer 5

The average duration of the ovarian cycle is 28 days (range from 23-35 days)
If the cycle is prolonged, the follicular phase lengthens (i.e. longer time to ovulation), but the luteal phase remains constant at 14 days.

Question 6

What three things are Fundamental to the normal menstrual cycle?

Answer 6

Fundamental to the normal menstrual cycle are:
• Intact hypothalamo-pituitary-ovarian endocrine axis
• Presence of responsive follicles in the ovaries
• Functional uterus

Question 7

How many days is a normal menstrual cycle? How much blood loss is normal?

Answer 7

Loss → 2-8 days (5)
Cycle → 23-35 days (29)
Blood loss → <60-80mls

Question 8

What is the Endocrine control of the menstrual cycle?

Answer 8

• Hypothalamus controls the cycle: can be influenced by higher centers in the brain i.e. anxiety and stress can affect the cycle
• Hypothalamus acts on pituitary gland by secreting pulses of GnRH
• GnRH travels through small vessels in pituitary portal system to the anterior pituitary where it acts to stimulate synthesis and release of FSH and LH (gonadotrophins)

Question 9

What is the role of FSH in the menstrual cycle?

Answer 9

• FSH stimulates:
• The growth of follicles during the “follicular phase” of the cycle
• Sex hormone secretion, predominately oestradiol, by the granulosa cells of the mature ovarian follicle.

Question 10

What is the role of LH in the menstrual cycle?

Answer 10

• LH stimulates:
• Sex hormone production in thecal cells (Cells in the ovarian follicles): testosterone, which is subsequently converted by the action of FSH into oestrodiol
• Plays an ESSENTIAL ROLE in ovulation
• Mid cycle surge of LH triggers rupture of the mature ovarian follicle with release of the oocyte
• Postovulatory production of progesterone by the corpus luteum is under the influence of LH
• Cyclical activity within the ovary which constitutes the ovarian cycle is maintained by feedback mechanism which operate between the ovary, hypothalamus and the pituitary

Question 11

What occurs in Day 1-8 of the ovarian cycle?

Answer 11

Follicular Phase
• Day 1 is the first day of menstruation, endometrium is shed. Myometrial contraction causes pain.
• At the start of the cycle, FSH and LH levels rise in response to a fall in oestrogen and progesterone at menstruation.
• This stimulates the development of 10-20 follicles
• The follicle that is most sensitive to FSH is the dominant follicle – destined for full maturation and ovulation
• This dominant follicle appears during mid-follicular phase, the others undergo atresia
• With the growth of the dominant follicle, oestrogen levels increase

Question 12

What occurs in Day 9-14 of the ovarian cycle?

Answer 12

Follicular Phase
• Maturation of the follicle occurs as there is an increase in oestrogen by the granulosa cells of the developing follicle.
• As oestrogen levels rise, the release of FSH is suppressed (negative feedback) which prevents hyperstimulation of the ovary and maturation of multiple follicles.
• Granulosa cells also produce inhibin: said to restrict number of follicles undergoing maturation
• Oestrogen causes proliferation of the endometrium

Question 13

What occurs in Day 14 of the ovarian cycle?

Answer 13

Ovulation
• Associated with a rapid enlargement of the follicle. Sometimes short-lived pain in one of the other iliac fossa “mittelschmerz” pain
• The final rise in oestradiol concentration is thought to be responsible for the mid-cycle surge of LH. Immediately before ovulation there is a fall in oestradiol levels and an increase in progesterone production.
• Ovulation follows within 36 hours of the mid-cycle surge of LH

Question 14

What occurs in Day 15-28 of the ovarian cycle?

Answer 14

Luteal Phase
• Remainder of the follicle which is retained in the ovary is penetrated by capillaries and fibroblasts from the theca. The granulosa cells undergo luteinization and these structures collectively form the corpus luteum (major source of sex steroid hormones, oestrogen and progesterone, secreted by the ovary in the postovulatory phase)
• Establishment of CL results in an increase in progesterone secretion and a second rise in oestradiol levels i.e. CL produces progesterone and oestradiol
• Progesterone levels peak 1 week after ovulation (day 21-28 of the cycle). Tests of serum progesterone at this time may be used in fertility investigations to confirm the occurrence of ovulation.
• Higher progesterone level cause inhibition of LH and FSH so that no more follicles develop and over time the low levels of FSH and LH will mean that the corpus luteum breaks down
• Progesterone transforms the endometrium from proliferative to secretory
• FSH and LH remain low until the regression of the CL (days 26-28)  corpus albicans
• If conception and implantation occur the CL does not regress because it is maintained by hCG secreted by the trophoblast (hCG is detected via. pregnancy tests)
• If conception does not occur the CL regresses, progesterone levels fall, menstruation insues
• The consequent fall in sex hormones allows FSH and LH to rise and initiate the next cycle

Question 15

Where does FSH and LH come from?

Answer 15

Anterior Pituitary

Question 16

Where does oestrogen come from?

Answer 16

From oocyte (size dependant)

Question 17

Where does progesterone come from?

Answer 17

Corpus lutuem

Question 18

What is the endometrium?

Answer 18

• The endometrium is composed of 2 layers:
• Superficial layer which is shed in menstruation
• Basal layer which does not take part in this process by which regenerates the superficial layer during the subsequent cycle
• The junction between these layers is marked by the change in the character of the arterioles supplying the endometrium.

Question 19

What happens in the Proliferative Phase?

Answer 19

• In the follicular phase the rising levels of oestrogen causes the endometrium to proliferate
• The lining changes from a single layer of columnar cells to a pseudostratified epithelium which frequently undergoes mitosis
• 0.5mm-3.5-5mm

Question 20

What happens in the Secretory Phase?

Answer 20

• Corresponds to luteal phase of cycle
• After ovulation, progesterone production induces secretory changes in the endometrial glands, preparing the endometrium for implantation:
• Growth of the spiral arteries
• Fluid secretion
• Formation of a temporary layer called the decidua in the endometrial stroma
• Reducing the contractility of smooth muscle
• Side effect: raising body temperature

Question 21

What happens in the Menstrual Phase?

Answer 21

• Luteal phase lasts for 14 days at the end of which regression of the CL is associated with a decline in oestrogen and progesterone production
• This fall is followed by an intense, spasmodic contraction of the spiral section of the endometrial arterioles, giving rise to ischaemic necrosis, shedding of the superficial layer of the endometrium and bleeding.

Other changes: progesterone thickens cervical mucus, breast changes (more sensitive so swell etc), and mood during cycle fluctuates due to falling levels in progesterone.

Question 22

Overview of menstrual cycle?

Answer 22

• At the start of the cycle, levels of FSH rise and stimulate the development of 10-20 follicles. A single dominant follicle matures, secretes oestrogen and the remainder undergo atresia. As the oestrogen levels rise, the release of FSH is suppressed (negative feedback which serves to prevent multiple follicles maturing).
• The very high preovulatory oestradiol level stimulates positive feedback and a mid-cycle surge of LH occurs = triggers ovulation. The remainder of the ruptured follicle becomes the corpus luteum which secretes progesterone
• Progesterone brings about secretory changes in the endometrium that are necessary for successful implantation
• If conception and implantation occur the CL is maintained by hCG secreted by the trophoblast. If however, these do not occur then the CL regresses and the levels of sex hormone fall and menstruation ensues. Process starts again!
Overview of menstrual cycle –
- Consists of uterine and ovarian cycles.
Uterine cycle (referring to uterine lining, the endometrium):
• Proliferative phase
• Secretory phase
• Menstrual phase
Ovarian cycle (controls uterine cycle): Av. duration = 28 days.
• Follicular phase
• Ovulation
• Postovulatory / Luteal phase
- If cycle prolonged, follicular phase lengthens but luteal phase remains constant at 14 days.
- Fundamental to normal menstrual cycle:
• Intact hypothalamo-pituitary-ovarian endocrine axis
• Presence of responsive follicles in ovaries
• Functional uterus

Question 23

What is menorrhagia?

Answer 23

Heavy menstrual bleeding

Question 24

What are irregular periods?

Answer 24

Periods outside the range of 23-35 days with a variability of >7 days between the shortest and longest cycle.

Question 25

What is primary amenorrhea?

Answer 25

Periods never start

Question 26

What is secondary amenorrhea?

Answer 26

Periods stop for 6m or more

Question 27

What is oligomenorrhea?

Answer 27

Infrequent periods (every 35 days-6months)

Question 28

What is dysmenorrhoea?

Answer 28

Painful periods

Question 29

What is premenstrual syndrome?

Answer 29

Psychological and physical symptoms worse in the luteal phase

Question 30

What is the Endocrine Control of the Menstrual Cycle?

Answer 30

• Controlled by hypothalamo-pituitary-ovarian axis.
• It acts on pituitary gland by secreting gonadotrophin-releasing hormone (GnRH), a decapeptide that is secreted in a pulsatile manner by hypothalamus.
• GnRH travels through small blood vessels of pituitary portal system to anterior pituitary, where it acts on pituitary gonadotrophs to stimulate synthesis and release of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).
• FSH, a glycoprotein stimulates follicular maturation during follicular phase of cycle. It also, along with LH, stimulates steroid hormone secretion (predominately oestrogen) from granulosa cells of mature ovarian follicle.
• LH is also a glycoprotein. In addition to its contribution in steroidogenesis in follicle, it plays essential role in ovulation, as this is dependent on mid-cycle surge of LH. Production of progesterone by corpus luteum is also under influence of LH.
• Cyclical activity maintained by feedback mechanisms, which operate between ovary, hypothalamus and pituitary.

Question 31

What is Polymenorrhoea?

Answer 31

Form of abnormal uterine bleeding/ menstrual cycle that is shorter than 21 days.
• Often coexists with excessive blood loss
• More common at extremes of reproductive age (Very young of very old)

Question 32

What are the causes of Polymenorrhoea?

Answer 32

• Anovulatory cycles – During which ovulation does not occur in the cycle.
- Common in younger women and near the climacteric (menopause)
• Local anatomical disorder
- Non-malignant causes:
o Fibroids, uterine and cervical polyps, adenomyosis, endometriosis, chronic pelvic infection
- Malignant causes:
o In older women
o Especially if recent change
o Ovarian, cervical and particularly endometrial

Question 33

What are the clinical features of Polymenorrhoea?

Answer 33

• Assess as for menorrhagia – Lots of bleeding:
o Amount and timing of bleeding (menstrual calendar)
o Flooding and passage of large clots indicate excessive loss
o Severe dysmenorrhoea suggest anatomical cause
o Any contraception?

• Examination:
o Anaemia
o Pelvic signs often absent – pain, abnormal vaginal discharge/ bleeding, skin changes
o Irregular enlargement of uterus suggests fibroids
o Tenderness suggests adenomyosis - inner lining of the uterus (the endometrium) breaks through the muscle wall of the uterus (the myometrium).
o An ovarian mass may be felt
o Tenderness and immobile pelvic organs are common with endometriosis and infection
o Cervical polyps may be seen on speculum examination

Question 34

What are the investigations for Polymenorrhoea?

Answer 34

• Full blood count: anaemia
• Investigations should exclude malignancy (except in younger women) and exclude local treatable pathology
o Cervical smear
o USS examination of cavity if >35 years with irregular or IMB or if <35 years and medical treatment has failed
o Endometrial biopsy
- At hysteroscopy
- If endometrium thickened, polyp suspected or ablative surgery or the IUS are to be used
o Diagnostic laparoscopy
- If endometriosis or chronic pelvic infection are suspected

Question 35

What is the treatment for Polymenorrhoea?

Answer 35

Medical treatment:
• Where no anatomical cause is detected: cycles are considered anovulatory
• Combine oral contraceptive usually induces regular and lighter menstruation
o Complications more common in older patients
• Cyclical progestogens
o Cause amenorrhoea, but bleeding follows withdrawal: mimic normal menstruation
• HRT: may regulate erratic dysfunctional uterine bleeding during the climacteric
• Mirena coil (Intrauterine device)
• Also: antifibrinolytics and NSAIDs

Surgical treatment
• Cervical polyp can be avulsed and sent for histological examination
• Also endometrial resection and diathermy or hysterectomy

Question 36

What is Amenorrhoea?

Answer 36

• Absence of menstruation
• Primary amenorrhoea - failure of menses to occur by age 16 years
o May be a manifestation of delayed puberty: when secondary sex characteristics are not present by 14 years
o May also occur in girls with otherwise normal secondary sexual characteristics (pubic hair, enlarged breasts and widened hips of females) - problem of menstrual outflow is likely

• Secondary amenorrhoea - Previously normal menstruation ceases for 6+months

Question 37

What is Oligomenorrhoea?

Answer 37

• When menstruation occurs less frequently than every 32 days
• Transient oligomenorrhoea – ‘stress’ or emotional related, usually self-limiting.

Question 38

What are the causes of Amenorrhoea?

Answer 38

See pic
Classification of causes of amenorrhea -
Common causes – pregnancy, lactation and menopause, iatrogenic causes – progestagenic contraception

Question 39

What is the treatment for Amenorrhoea?

Answer 39

Must be guided by the diagnosis and fertility wishes-
Options include:
• Treat any underlying causes
• Attain normal BMI
• COCP/cyclical progestogens – e.g. for PCOS
• HRT for premature ovarian failure
• Relief of genital tract obstruction

Question 40

What is Menorrhagia?

Answer 40

• >80mL menstrual loss or subjectively unacceptable loss to the woman
• Irregular menstruation and intermenstrual bleeding (IMB) often occur in conjunction
• Irregular periods are more likely to be anovulatory, and are more commonly associated with malignancy (especially in older women)
• Very common: 1/20 women between 30-49years will seek help
*Ask how many times they need to change their pads/ tampons – quantify loss.

Question 41

What are the clinical features of Menorrhagia?

Answer 41

• Soaking through one or more sanitary pads or tampons every hour for several consecutive hours
• Flooding/needing to use double sanitary protection to control your menstrual flow
• Needing to wake up to change sanitary protection during the night
• Bleeding for longer than a week
• Passing blood clots larger than a quarter
• Restricting daily activities due to heavy menstrual flow
• Symptoms of anemia, such as tiredness, fatigue or shortness of breath
• Contraception?

Question 42

What are the causes of Menorrhagia?

Answer 42

1. Hormonal imbalance
   - number of conditions can cause hormone imbalances, including polycystic ovary syndrome (PCOS), obesity, insulin resistance and thyroid problems.
2. Unexplained (60% of cases)
   - Dysfunctional Uterine Bleeding: subtle abnormalities of endometrial haemostasis or uterine prostaglandin levels
3. Systemic (rare)
   - Thyroid disease
   - Haemostatic disorder e.g. von Willebrand’s disease – hereditary blood clotting disorder. Abnormality in quantity or quality of VW factor, needed for platelets to bind to endothelium suggested by easy bruising/excessive bleeding after surgery/trauma
   - Anticoagulant therapy
4. Local anatomical disorder
   - Uterine fibroids (30%)
   - Uterine and cervical polyps (10%)
   - Adenomyoisis
   - Endometriosis
5. Other
   - Pregnancy complications
   - Intrauterine devices – well known side effect is menorrhagia
   - Inherited bleeding disorders
   - Medication – anticoags, hormonal medication and anti inflammatory medication
   Complications –
   Anaemia - signs and symptoms include pale skin, weakness and fatigue
   Severe pain – dysmenorrhea

Question 43

What are the investigations for Menorrhagia?

Answer 43

• FBC, TFTs, clotting (coagulation disorders)
• Cervical smear – infection, inflammation, pre-malignant changes
• Transvaginal ultrasound – looks at endometrial thickness, fibroids, polyps or ovarian masses
• Hysteroscopy + endometrial biopsy – if endometrial thickness >10mm, suspected polyp, >40yrs with recent onset menorrhagia, IMB, or no response to Rx to exclude malignancy

Question 44

What is the treatment for Menorrhagia?

Answer 44

Conservative – iron supplements + analgesia (if anaemic + painful)

Medications – after excluding pathology
Medical therapy for menorrhagia may include:
• First line
o Hormonal IUS (Liletta, Mirena) – releases levonorgestrel, which makes the uterine lining thin and decreases menstrual blood flow and cramping
• Second line (tranexamic acid + mefenemic acid 1st-line if don’t want coil)
o Tranexamic acid – antifibrinolytics taken during menstruation only, reduce blood loss, few S/E
o NSAIDS – (e.g. mefenamic acid) help reduce menstrual blood loss by inhibiting prostaglandin secretion, and pain relief
o COCP – help regulate menstrual cycles and reduce episodes of excessive or prolonged menstrual bleeding
 Limited role as avoided in older pts due to complications
• Third line
o Oral/IM progestogens – cause amenorrhoea but withdrawal bleed
o GnRH analogues – produce amenorrhoea with withdrawal bleed, only 6 month use unless addback HRT is used
Procedures
• Hysteroscopic
o Polyp resection/transcervical resection of fibroid
o Endometrial ablation/resection – reduce fertility
• Radical
o Myomectomy - This procedure involves surgical removal of uterine fibroids
o Hysterectomy - surgery to remove your uterus and cervix — is a permanent procedure that causes sterility and ends menstrual periods
o Uterine artery embolization – for women whose menorrhagia is caused by fibroids, the goal of this procedure is to shrink any fibroids in the uterus by blocking the uterine arteries and cutting off their blood supply

Question 45

What is Premenstrual syndrome?

Answer 45

Premenstrual syndrome –
• is when women experience distressing psychological, physical and or behavioural symptoms before their period, symptoms which usually occur during the period. E.g. cramps, breast tenderness and mood changes. May be due to the hormonal changes leading up to a period.
• Also, involving significant regression of symptoms with onset of or during the period.

Question 46

What are the causes of Premenstrual syndrome?

Answer 46

• Cyclical ovarian activity is likely to be the central component (ovarian ‘trigger’, such as ovulation, may initiate a cas- cade of events).
• A central increased responsiveness to a combination of steroids, chemical messengers (E2/serotonin, progesterone/GABA), and psychological sensitivity may play a part.

Question 47

What are the investigations for Premenstrual syndrome?

Answer 47

Detailed history can help diagnosis
But only a prospective symptoms diary can be used to establish the true nature of the condition
DSM 4 criteria

Question 48

What is the treatment for Premenstrual syndrome?

Answer 48

Conservative –
• Dietary alterations – less fat, sugar, salt caffeine and alcohol
• Dietary supplements – Vitamin B6, Vitamin E, Magnesium good for PMS anxiety, primrose oil for mastalgia
• Exercise
• Stress reduction
• Cognitive behavioural therapy
Hormonal
• Ovulation suppression agents
o COCP: useful for some women. However, some women
have PMS-type progestagenic side effects or symptoms during the pill-free interval.
o Danazol (androgenic): 4 RCTs report benefit for PMS, but there are significant masculinizing side effects. Treatment in luteal phase only is effective for breast tenderness
o GnRH analogues ± addback HRT: are of proven benefit for moderate to severe PMS, but with a licence for 6mths treatment only due to bone loss. Usually given with addback tibolone (fewer side effects and bone loss). ‘GnRH test’ useful for those considering hysterectomy and bilateral salpingo-oophrectomy (BSO) for severe symptoms

Question 49

What is PCOD?

Answer 49

Metabolic condition that may or may not come with having polycystic ovaries

Question 50

What are the causes of PCOD?

Answer 50

• Causes: exact cause is unknown but thought to be related to abnormal hormone levels.
  o High insulin levels due to insulin resistance- body doesn’t respond to normal levels of insulin, so compensates by making more
• Weight gain furthers this risk
  o Hormone imbalance- raised testosterone, LH, oestrogen and prolactin, and decreased levels of sex hormone- binding globulin (SHBG)
  o Genetics
  o Stress coupled with hormonal imbalances are thought to be some reasons that give rise to PCOS as well.

Question 51

What are the clinical features of PCOD?

Answer 51

o Oligomenorrhoea (<9 periods/yr); irregular periods
o Infertility/subfertility
o Acne
o Hirsutism
o Alopecia
o Abdominal obesity – adds to effect of insulin resistance
o Psychological Sx – mood swings, depression, anxiety
o Sleep apnoea
o Acanthosis nigricans
o Clitoromegaly, increased muscle mass, deep voice (if severe)

Question 52

What is the diagnostic criteria for PCOD?

Answer 52

Criteria for diagnosis – Need to have at least 2 of the below:
- Polycystic ovaries appear on ultrasound – small follicular cysts developed due to hormonal imbalances. These cysts are usually immature eggs that could not be expelled out of the ovary
- Oligo-ovulation or anovulation (oligomenorrhoea/irregular periods)
- Increased testosterone in blood or associated symptoms e.g. extra hair growth or acne
*So women can have PCOS without having polycystic ovaries (have the two other criteria met)
Women can have polycystic ovaries and not have PCOS (just have cysts and no irregular periods or increased testosterone)

Question 53

What are the investigations for PCOD?

Answer 53

o Total (normal) and free (raised) testosterone, low/normal SHBG, elevated LH with normal FSH
- ?POF if both LH+FSH raised, hypogonadotropic hypogonadism if both reduced
o USS for characteristic ovaries (3x normal volume if polycystic)
o Other bloods to exclude differentials – TFTs (hypothyroidism), 17-hydroxyprogesterone (CAH), DHEA-S and free androgen index (androgen-secreting tumours), prolactin (hyperprolactinaemia), 24-hour cortisol (Cushing’s)
o Fasting glucose, OGTT, fasting lipid levels

Question 54

What is the treatment for PCOD?

Answer 54

• PCOS can’t be cured but the symptoms can be managed
  o Lifestyle changes
• Weight loss
• Healthy eating to aid with weight loss
  o Improving menstrual regularity
   Weight loss. • COCP
• Metformin
  o Controlling symptoms of hyperandrogenism
   Cosmetic (depilatory cream, electrolysis, shaving, plucking)
   Antiandrogens such as eflornithine facial cream, finasteride, or spironolactone:
  o can be used to help with acne and hirsutism 

  o can take 6–9mths to improve hair growth 

  o avoid pregnancy (feminizes a male fetus) 

   COCP:
  o reduces serum androgen levels by increasing SHBG levels (so androgen binds to SHBG)
  o co-cyprindiol combines ethinylestradiol and cyproterone acetate, providing a regular monthly withdrawal bleed and beneficial antiandrogenic effects. 

  o Subfertility
   Weight loss alone may achieve spontaneous ovulation
   Ovulation induction with antioestrogens or gonadotrophins
   Laparoscopic ovarian diathermy
   IVF if ovulation cannot be achieved or does not succeed in pregnancy
  o Insulin sensitizers
   Metformin combined with ovulation induction with clomifene citrate increases ovulation and pregnancy rates, but may not significantly improve live birth rate. 

   Does not significantly improve hirsutism, acne, or weight loss, despite lowering androgen levels and improving insulin sensitivity 


Question 55

What is Menopause?

Answer 55

median age: 51 years (premature if <40yrs – e.g. no cause, infections, autoimmune, chemotherapy, metabolic, ovarian dysgenesis Rx: HRT until 51 + oocyte donation for fertility)

• Permanent cessation of menstruation that results from loss of ovarian follicular activity.
• Last menstrual period: diagnosed retrospectively 12 months after

Question 56

What are the clinical features of Menopause?

Answer 56

Short term consequences 
-	Vasomotor
o	Lasts 5-8 years....
o	Hot flushes, night sweats – commonest symptoms 
-	Periods changing
-	Insomnia
o	Tiredness, irritability, poor concentration
-	Mood swings
-	Cognitive function
-	Sexual dysfunction – reduced libido, anorgasmia, dyspareunia etc
-	Connective tissue / loss of collagen
o	Skin / hair
o	Joint / muscle aches
-	Fat redistribution

Medium

• Vaginal- dryness, itching, burning, soreness, dyspareunia
• Bladder- frequency, urgency, dysuria, UTI

Long term consequences
- Risk of osteoporosis
o Risk of fractures commonly – hip, vertebrae and lower end of radius
- Cardiovascular disease – MI and stroke
- (Urogenital atrophy – due to decrease in hormones so decrease in function of cells
o Symptoms of frequency, incontinence, nocturia, frequent infections, as well as vaginal symptoms such as itching, burning and dryness.)

Question 57

What are the investigations for Menopause?

Answer 57

• FSH – high FSH due to lack of oestrogen + inhibin production by unresponsive ovaries
  o Esp. helpful with women <45 yrs with menopausal FSH levels >30IU/L
• Anti-Müllerian hormone – produced by ovarian follicles as measure of ovarian reserve low
• TFTs – thyroid disease can cause hot flushes
• Catecholamines and 5-hydroxyindolacetic acid – raised in phaeochromocytoma and carcinoid syndrome
• LH, oestradiol and progesterone (low in anovulation – e.g. due to PCOS)
• DEXA scan – for bone density estimation of at-risk women
• Biochemical markers of bone metabolism – to monitor response to bisphosphonates

Question 58

What is the treatment for Menopause?

Answer 58

• Explanation
• Diet and lifestyle advice – avoid hot food, hot drinks
• HRT – if hysterectomy: oestrogen alone. If not: both o + p (to protect against unopposed oestrogen = endometrial hyperplasia/Ca)
  o Types
   Oestrogen – PO, TD (patch/gel), SC (implant) or PV (topical – e.g. for vaginal atrophy)
   Progestogens – PO, TD (patch) or IUS
   Tibolone – synthetic steroid converted to oestrogenic, progestogenic and androgenic compounds in vivo
   Androgens (e.g. testosterone) – patches/implants; for libido
  o Modes of administration
   Continuous combined – o+p together, back-to-back with no periods (most protective against endometrial Ca)
   Sequential cyclical – oestrogen every day for 1 month, progesterone 10-14 days at end of month
   Sequential long cyclical – oestrogen every day for 3 months, at end of last month, progesterone for 10-14 days
  o Benefits
   Reduces hot flushes, urovaginal Sx, sexual dysfunction – oestrogen does this
   Protects against osteoporosis – oestrogen does this (mandatory in HRT)
   Protects against colorectal cancer
  o Side effects
   GI, Headaches, Appetite/weight change, Anxiety, Acne, Oedema (fluid retention), Mastalgia, Skin changes
  o C/I – VTE, chronic kidney/liver disease…
  o Risks
   Increased breast Ca and endometrial (if unopposed oestrogen) Ca
   VTE (oral)
   Gallbladder disease (oral)
• Other non-oestrogen Rx
  o For hot flushes + night sweats give progestogens, clonidine, SSRIs or gabapentin
  o For vaginal atrophy give lubricants and moisturisers
  o Prevention and Rx of osteoporosis = bisphosphonates (e.g. alendronate – avoid in pregnancy), strontium ranelate, raloxifene (selective oestrogen receptor modulator), parathyroid hormone peptides (if severe/unresponsive to other Rx), denosumab (monoclonal Ab), calcium and vit D supplements
• Alternative/complementary therapies (not much evidence)
  o Phytoestrogens – isoflavones and lignans
  o Herbal remedies – black cohosh, kava kava, evening primrose, wild yam cream etc
  o Progesterone transdermal creams – no evidence

Question 59

What is Post-menopausal bleeding?

Answer 59

Vaginal bleeding occurring at least 12 months after the last menstrual period