Menstrual Cycle and Its Disorders

Question 1

Define primary amenorrhea.

Answer 1

Absence of menstruation despite signs of puberty

o Primary = no menstruation before 16 years of age
- May be manifestation of delayed puberty – no secondary sexual characteristics by
age 14
- Menstrual outflow more likely if primary amenorrhoea in girl with secondary sexual
characteristics

Question 2

Define secondary amenorrhea

Answer 2

Absence of menstruation for 6 months in a woman who has previously menstruated. Most common = pregnancy. Other causes include high/low BMI, stress, exercise, prolactinom

Question 3

Define dysfunctional uterine bleeding.

Answer 3

Irregular bleeding due to anovulation or an anovulatory cycle (may be anatomical e.g. uterine fibroids)

Question 4

Define oligomenorrhea.

Answer 4

Menstrual cycle >35days (PCOS = most common cause)

Question 5

Define menorrhagia

Answer 5

Regular menstrual intervals, excessive flow and duration

Clinical Definition: Excessive menstrual blood loss that interferes with a woman’s physical, emotional, social and material quality of life, and which can occur alone or in a combination of other symptoms

Objective Definition: Blood loss >80ml in otherwise normal menstrual cycle. Value corresponds to the amount that a woman on a normal diet can lose per cycle without becoming iron deficient

Question 6

Define metorrhagia

Answer 6

Irregular menstrual intervals, excessive flow and duration

Question 7

Define anovulation/anovulatory menses

Answer 7

Menstrual cycle without ovulation (often very light due to absence of progesterone)

Question 8

Define dysmenorrhea.

Answer 8

Menstrual cramping/pain

Question 9

How common is menorrhagia?

Answer 9

⅓ of women experience heavy periods, but most do not seek medical help

Question 10

Describe the aetiology of menorrhagia.

Answer 10

• Most women with regular cycles are ovulatory
• Menorrhagia may result from subtle abnormalities of endometrial haemostasis or uterineprostaglandin levels
• Uterine fibroids = 30% women with HMB
• Polyps = 10% women with HMB
• Chronic pelvic infection, ovarian tumours and endometrial/cervical malignancy usually cause irregularbleeding
• Thyroid disease, haemostatic disorders (vWD) and anticoagulant therapy are rarer causes of menorrhagia

Question 11

Describe the clinical features of menorrhagia.

Answer 11

• History

o Amount and timing of bleeding

o Flooding and passage of large clots = excessive loss

o Method of contraception should be ascertained

• Examination

o Anaemia = common

o Irregular enlargement of uterus = fibroids

o Tenderness with/without enlargement = adenomyosis

Question 12

What are the investigations for menorrhagia?

Answer 12

• Hb
• Coagulation and TFTs
• TVUS: local organic causes
  
  • Endometrial thickness
  • Exclude fibroid
  • >10mm endometrial thickness or polyp in woman >40 years old with recent onset menorrhagia or IMB → endometrial biopsy (hysteroscopy or pipelle)
    
    • Exclude malignancy or premalignancy
• Hysteroscopy: allows inspections of uterine cavity and detection of polyps and submucous fibroid

Question 13

How should we think of managing menorrhagia?

Answer 13

• Consider referral
• For women with no identified pathology, fibroids less than 3 cm in diameter, or suspected or diagnosed adenomyosis - tx specific
• For women with fibroids of 3 cm or more in diameter - tx specific

Question 14

When should we consider a referral for menorrhagia?

Answer 14

• Urgently if physical examination identifies ascites and/or a pelvic or abdominal mass (which is not obviously due to uterine fibroids).
• Using a suspected cancer pathway referral (for an appointment within 2 weeks) if she has a pelvic mass associated with any other features of cancer (such as unexplained bleeding or weight loss)
• Also refer if
  
  • Complications such as compressive symptoms of large fibroids (e.g. dyspareunia, pelvic pain, discomfort, constipation or urinary symptoms)
  • Iron deficiency anaemia which does not respond to tx
  • No improvement in menorrhagia after inital tx
• Consider referring - women with fibroids > 3 cm or more in diameter to specialist acre for ix

Question 15

How should we manage women with no identified pathology, fibroids less than 3 cm in diameter, or suspected or diagnosed adenomyosis?

Answer 15

1. Consider a levonorgestrel intrauterine system (LNG-IUS) as the first-line treatment.
2. 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). - be aware progestogen only contracpetion may supress menstruation
   • If treatment is unsuccessful, the woman declines pharmacological treatment, or symptoms are severe, consider referral to a specialist for:
     
     • Ix for diagnosis
     • Alternative tx choices: including pharmacological options not already tried and surgical options (second-generation endometrial ablation and hysterectomy).

Question 16

How should we manage women with fibroids of 3cm or more in diameter?

Answer 16

1. Consider specialist referral for additional investigations and consideration of treatment options
2. If pharmacological treatment is needed while the woman is awaiting treatment or referral appointment, offer tranexamic acid and/or an NSAID. Advise women to continue using tranexamic acid and/or NSAIDs for as long as they are found to be beneficial.
3. Secondary acre tx options include:
   
   • Pharmacological treatment — hormonal (LNG-IUS, CHC, or cyclical oral progestogens) or non-hormonal (NSAIDs or tranexamic acid).
   • Uterine artery embolization.
   • Surgery — myomectomy, hysterectomy, or second-generation endometrial ablation (considered for women with menorrhagia and fibroids of 3 cm or more in diameter who meet the criteria specified in the manufacturers’ instructions).

Question 17

How should we counsel a patient with menorrhagia?

Answer 17

• Discuss the natural variability and range of menstrual blood loss with the woman. For some women, reassurance may be all that is required, and treatment may not be needed.
• If the woman feels that she does not fall within the normal ranges, provide information on the possible treatment options and discuss these with the woman. Discussions should cover the benefits and risks of the various options, suitable treatments if she is trying to conceive, and whether she wants to retain her fertility and/or her uterus.
• Provide written information, such as patient information leaflets, to explain the condition and treatment options.
  
  • The NHS website (www.nhs.uk) has patient information on Heavy periods.

Question 18

When should we do an endometrial biopsy?

Answer 18

1. Endometrial thickness >10mm in premenopausal; >4mm in postmenopausal
2. Age >40 years
3. Menorrhagia with IMB
4. US suggests polyp
5. Before insertion of IUS if cycle irregular
6. Prior to endometrial ablation/diathermy as tissue will not be available for biopsy
7. Abnormal uterine bleeding  acute admission\

Question 19

What causes irregular menstruation and intermenstrual bleeding?

Answer 19

• Anovulatory cycles
  
  • Common in early and late reproductive years
• Pelvic pathology
  
  • Non malignant: fibroids, uterine/cervical polyps, adenomyosis, ovarian cysts, chronic pelvic infection
  • Older women with recent change: malignancy (ovarian, cervical and endometrial)

Question 20

How should we investigate irregular menstruation and intermenstrual bleeding?

Answer 20

• Hb
• Exclude malignancy
  o Smear
  o US of cavity for women >35 years with irregular/IMB, also for younger women where medical
  tx has failed
• Endometrial biopsy, preferably at hysteroscopy, used if endometrium thickened, polyp suspected,
  woman >40 or if ablative surgery/IUS to be used

Question 21

How can we manage irregular menstruation and intermenstrual bleeding?

Answer 21

• Drugs
  o Used for anovulatory cycles
  o IUS or COCP
  o High dose progestogens can be used → mimic normal menstruation if given cyclically
• Surgery
  o Cervical polyp – histology
  o Same surgery options as menorrhagia → may still get irregular but light bleeding if some
  endometrium remains

Question 22

What are the causes of amenorrhea and oligomenorrhea?

Answer 22

• Physiological
  o Pregnancy
  o Post-menopausal
  o Lactation
  o Constitutional delay is common and often familial
• Pathological
  o Can be due to an issue at any level at the
  • Hypothalamus
  • Pituitary
  • Thyroid
  • Adrenals
  • Ovary
  • Uterus
  • Outflow tract
• o Drugs: progestogens, GnRH anaologues, antipsychotics (increase prolactin)
  o Primary amenorrhoea
  
  • Rare congenital abnormality
  • Acquired disorders that arise before commencement of puberty
• Secondary amenorrhoea
  
  • POF
  • PCOS
  • $Hyperprolactinaemia

Question 23

Summarise the investigations and management of amenorrhea and oligomenorrhea?

Answer 23

Question 24

How should we assess primary amenorrhea?

Answer 24

• Hx
  
  • Sexual hx/contracpetion
  • cyclical abdominal pain
  • stress, depression, WL …
  • Headache, visual disturbances, galactorrhea - prolactinoma
  • Age at menarche for mother and sisters
  • FH of genetic anomalies
• Examiantion
  
  • Height and weight
  • Top to toe - syndromes
• Consider
  
  • pelvic US - confirm presence of vagina and uterus (if cannot be done by pelvic exam)
  • Serum prolactin
  • TSH
  • FSH and LH
  • Testosterone
  • Other Ix suggested by hx and clinical findings

Question 25

How should we assess secondary amenorrhea?

Answer 25

• Hx
  
  • Exclude physiological causes, including pregnancy, lactation, and menopause (in women 40 years of age or older).
  • Contraceptive use
  • Hot flushes and vaginal dryness
  • Headaches, visual disturbances, or galactorrhoea
  • Acne, hirsutism, and weight gain
  • Stress, depression, weight loss, disturbance of perception of weight or shape, level of exercise, and chronic systemic illness
  • Symptoms of thyroid and other endocrine disease.
  • A history of obstetric or surgical procedures (such as endometrial curettage) that may have resulted in intrauterine adhesions.
  • A history of chemotherapy and pelvic radiotherapy (which can cause POI); and cranial radiotherapy, head injury, or major obstetric haemorrhage (which can cause hypopituitarism).
  • Drugs (such as antipsychotics, which can cause increased prolactin levels) and illicit drug use (in particular cocaine and opiates, which can cause hypogonadism).
  • A family history of cessation of menses before 40 years of age (suggesting POI).
• Examination
  
  • Height and weight
• Examine for features of:
  
  • Cushing’s syndrome (striae, buffalo hump, significant central obesity, easy bruising, hypertension, and proximal muscle weakness).
  • Thyroid disease. See the CKS topics on Hyperthyroidism and Hypothyroidism for more information.
  • Excess androgens (hirsutism, acne) or virilization (hirsutism, acne, deep voice, temporal balding, increase in muscle bulk, breast atrophy, and clitoromegaly).
  • Decreased endogenous estrogen (reddened or thin vaginal mucosa).
  • If appropriate, examine for galactorrhoea (suggesting raised prolactin levels).
  • Assess visual fields (if a pituitary tumour is suspected).
• Ix
  
  • Follicle-stimulating hormone and luteinizing hormone.
  • Prolactin level.
    
    • Do not examine the breasts before taking blood for prolactin levels, as this may then be falsely elevated. If the breasts have been examined, delay the blood test for at least 48 hours.
    • Total testosterone.
    • Thyroid-stimulating hormone.
    • Ultrasound scan (if PCOS is suspected).
    • Other investigations as suggested by clinical findings.

Question 26

How should we manage primary amenorrhea?

Answer 26

• Treat cause
• Refer:
  
  • Girls who have no secondary sexual characteristics who have not started menstruating by 13 years of age.
  • Girls with normal secondary sexual characteristics who have not started menstruating by 15 years of age.
• Refer is parents very concerned or an abnormality is suspected
  
  • • Growth retardation.
      
      • Symptoms and signs of androgen excess (such as hirsutism) or thyroid disease.
      • Galactorrhoea.
      • Suspected genital tract malformation, intracranial tumour (for example prolactinoma), chromosomal anomaly (for example Turner’s syndrome or androgen insensitivity), or anorexia nervosa.
      • Puberty lasting 5 years without menarche (for example presenting at 15 years of age when pubic hair and breast development started at 10 years of age).
  • Referral to a gynaecologist (preferably with a special interest in adolescent gynaecology) is appropriate for most people.
  • Referral to an endocrinologist is recommended for those with hyperprolactinaemia, thyroid disease, or features of androgen excess (such as hirsutism, acne, and virilization).
• If caused by WL, excessive exercise, stress, chronic illness → endocrinology or dietician or psychiatry

Question 27

How should we manage secondary amenorrhea?

Answer 27

• Treat cause:
  
  • PCOS
  • Hypothyroidism
  • Menopause
  • Pregnancy
• Refer all other to specialist
  
  • Persistently elevated follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels, which suggests premature ovarian insufficiency in women younger than 40 years of age.
  • Recent history of uterine or cervical surgery (such as endometrial curettage, Caesarean section, or myomectomy) or severe pelvic infection (endometritis), which suggests Asherman’s syndrome or cervical stenosis.
  • Infertility.
  • Suspected PCOS, if diagnosis and management are not feasible in primary care.
  • Hyperprolactinaemia: serum prolactin level greater than 1000 mIU/L, or 500–1000 mIU/L on two occasions. This includes those taking drugs that are known to increase prolactin levels.
  • Low FSH and LH levels (to exclude hypopituitarism or a pituitary tumour, although stress, excessive exercise, or weight loss are more likely causes).
  • An increased testosterone level that is not explained by PCOS (suggesting an androgen-secreting tumour, late-onset congenital adrenal hyperplasia, or Cushing’s syndrome).
  • Other features of Cushing’s syndrome or late-onset congenital adrenal hyperplasia (besides an increased testosterone level).
• If WL, stress, chronic illness related - psych, dietician, endo
• Offer contraceptive advice to women who do not wish to become pregnant, as a small number of women with secondary amenorrhoea will become pregnant.

Question 28

Define post-coital bleeding.

Answer 28

Defined as vaginal bleeding following intercourse that is not menstrual loss. Except for first intercourse, this is
always abnormal and cervical carcinoma must be excluded.

Question 29

What are the possible causes of post-coital bleeding?

Answer 29

Benign conditions

• Urogenital atrophy
• Benign vascular tumours of the genital tract, e.g. haemangiomas, A-V malformation
• Cervical or endometrial polyps
• Cervical ectropion
• Cervical endometriosis

Infection

• Vulvovaginitis secondary to candidiasis or trichomonas
• Cervicitis secondary to chlamydia or gonorrhoea
• Endometritis in presence of intrauterine coil device (IUCD)

Vulval

• Vulval dermatoses, e.g. lichen sclerosus
• Genital warts
• Genital ulcers, e.g. herpes, chancroid
• Syphilis
• Lymphogranuloma venereum

Malignancy

• Vulval cancer
• Vaginal cancer
• Cervical cancer
• Endometrial cancer

Other

• Trauma and genital piercings
• Bleeding disorders
• Foreign bodies
• Sexual abuse
• Pregnancy-related
• Female genital mutilation (FGM)

Question 30

How should we assess post-coital bleeding?

Answer 30

History

A thorough clinical history and examination can help to elicit risk factors and signs suggestive of underlying pathology. The history should enquire about:

• The patient’s age
• The duration, frequency and amount of bleeding
• Menstrual history, including normal bleeding pattern and last menstrual period
• The presence of other gynaecological symptoms, such as vaginal discharge, pelvic pain and dyspareunia
• Contraceptive history and use of other hormonal therapy (for example, hormone replacement therapy, tamoxifen)
• History of human papilloma virus (HPV) immunisation
• Cervical screening history, including date and result of last screening test
• Details of any previous colposcopy and treatment
• Sexual history, including any previous history of sexually transmitted infections (where appropriate)
• Relevant past medical and surgical history, including bleeding disorders
• Current medications, particularly use of anticoagulants
• Other relevant risk factors, such as smoking status.

Question 31

Define dysmenorrhea.

Answer 31

• Painful menstruation associated with high prostaglandin levels in endometrium
• Due to contraction and uterine ischaemia

Question 32

What are the 2 types of dysmenorrhea?

Answer 32

• Primary dysmenorrhoea occurs in young females in the absence of any identifiable underlying pelvic pathology. It usually occurs 6–12 months after the menarche, once cycles are regular, and is thought to be caused by the production of uterine prostaglandins during menstruation
• Secondary dysmenorrhoea often starts after several years of painless periods and is caused by an underlying pelvic pathology (such as endometriosis, adenomyosis, fibroids, endometrial polyps, or pelvic inflammatory disease) or by intrauterine device (IUD) insertion.

Question 33

What is the assessment of dysmenorrhea?

Answer 33

• Take a history.
• Examine the woman.
  
  • Perform an abdominal examination in all women — to assess for large fibroids and other masses.
  • Perform a pelvic examination (including a speculum examination of the cervix), except in young women who are not sexually active if the symptoms are suggestive of primary dysmenorrhoea.
• Consider arranging the following investigations:
  
  • An ultrasound scan — to rule out fibroids, adnexal pathology, and endometriosis, or to assess an intrauterine contraceptive device.
  • High vaginal and endocervical swabs — if the woman is at risk of a sexually transmitted infection, especially if pain is associated with vaginal discharge and abnormal vaginal bleeding.
  • Pregnancy test — to exclude an ectopic pregnancy.

Question 34

When is primary dysmenorrhea going to be the more likely diagnosis?

Answer 34

• Menstrual pain starts 6–12 months after the menarche, once cycles are regular.
• Pain, usually cramping in nature, occurs in the lower abdomen but may radiate to the back and inner thigh.
• Pain starts shortly before the onset of menstruation and lasts for up to 72 hours, improving as the menses progresses.
• Non-gynaecological symptoms, such as nausea, vomiting, diarrhoea, fatigue, irritability, dizziness, bloating, headache, lower back pain, and emotional symptoms, are present.
• Other gynaecological symptoms are not present.
• Pelvic examination is normal.

Question 35

When is secondary dysmenorrhea going to be the more likely diagnosis?

Answer 35

• Pain starts after several years of painless periods.
• Pain is not consistently related to menstruation alone and may persist after menstruation finishes or may be present throughout the menstrual cycle but is exacerbated by menstruation.
• Other symptoms are present, including:
  
  • Other gynaecological symptoms, such as dyspareunia, vaginal discharge, menorrhagia, intermenstrual bleeding, and postcoital bleeding.
  • Non-gynaecological symptoms, such as rectal pain and bleeding (which may be associated with endometriosis).
• Pelvic examination is abnormal, although the absence of abnormal findings does not exclude secondary dysmenorrhoea.

Question 36

Define precocious puberty.

Answer 36

Menstruation before age of 10 years or secondary sexual characteristics present before 8 years

• Very rare
• Growth spurt occurs early, but final height is reduced due to early fusion of the epiphyses

Question 37

What causes precocious puberty? How can treat it?

Answer 37

90% of the time, no cause is found

• GnRH agonists – inhibit sex hormone secretion → regression of secondary sexual characteristics and
  cessation of menstruation
• Central causes
  o Increased GnRH secretion
  o Meningitis, encephalitis, CNS tumours, hydrocrephaly and hypothyroidism → prevent normal prepubertal inhibition of hypothalamic GnRH release
• Ovarian/adrenal causes
  o Increased oestrogen secretion
  o Hormone-producing tumours of the ovary or adrenal glands
  o Regression occurs after removal
  o McCune-Albright syndrome: bone and ovarian cysts, café au lait spots and precocious
  puberty – tx with cyproterone acetate (an antiandrogenic progestogen)

Question 38

What are causes of ambiguous development? What is the tx?

Answer 38

• Increased androgen function in a genetic female
  
  • Congenital adrenal hyperplasia (CAH)
  • Autosomal recessive
  • Result of 21-hydroxylase deficiency
  • Increased ACTH → increased androgen production
  • Ambiguous genitalia at birth
  • Glucocorticoid deficiency can lead to Addisonian crisis
  • Occasionally presents at puberty with cliteromegaly and amenorrhoea
  • Tx involves cortisol and mineralocorticoid replacement
  • Androgen-secreting tumours and other causes of Cushing’s syndrome = rare
• Reduced androgen function in a genetic male
  
  • Androgen insensitivity syndrome
  • Receptor insensitivity to androgens → peripheral conversion to oestrogens
  • Appears female
  • Diagnosis when she presents with amenorrhoea
  • Uterus is absent and rudimentary testes present
  • Removed to due risk of possible malignant change
  • Oestrogen replacement therapy should be commenced

Question 39

Define premenstrual syndrome.

Answer 39

Encompasses psychological, behavioural and physical symptoms experienced on a regular basis during the luteal phase of the menstrual cycle

Often resolves by the end of menstruation

Question 40

How common is PMS?

Answer 40

Four in ten women (40%) experience symptoms of PMS and of these 5–8% suffer from severe PMS

Question 41

What are the clinical features of PMS?

Answer 41

History: vary, cyclical in nature
o Tension
o Irritability
o Aggression
o Depression
o Loss of control
o Bloatedness, GI upset and breast pain may occur

Question 42

What causes PMS?

Answer 42

Currently two theories predominate and appear interlinked. The first suggests that some women are ‘sensitive’ to progesterone and progestogens, since the serum concentrations of estrogen or progesterone are the same in those with or without PMS.

The second theory implicates the neurotransmitters serotonin and c-aminobutyric acid (GABA). Serotonin receptors are responsive to estrogen and progesterone, and selective serotonin reuptake inhibitors (SSRIs) are proven to reduce PMS symptoms. GABA levels are modulated by the metabolite of progesterone, allopregnanolone, and in women with PMS the allopregnanolone levels appear to be reduced.

Question 43

How is PMS diagnosed?

Answer 43

When clinically reviewing women for PMS, symptoms should be recorded prospectively, over two cycles using a symptom diary, as retrospective recall of symptoms is unreliable.

A symptom diary should be completed by the patient prior to commencing treatment.

Gonadotrophin-releasing hormone (GnRH) analogues may be used for 3 months for a definitive diagnosis if the completed symptom diary alone is inconclusive.

Question 44

When should PMS be referred to a gynaecologist?

Answer 44

Referral to a gynaecologist should be considered when simple measures (e.g. COCs, vitamin B6, SSRIs) have been explored and failed and when the severity of the PMS justifies gynaecological intervention

Question 45

How do we classify PMS?

Answer 45

Question 46

How do we manage PMS?

Answer 46

• Conservative – offer to all women regardless of severity

o Stress reduction

o Alcohol and caffeine limitation

o Smoking cessation

o Regular exercise

o Regular sleep

o Regular, frequent (2-3 hourly) small balanced meals (inc complex carbs)

o Offer pain relief if required - paracetamol or NSAIDs

• Moderate (some impact on personal, social and professional life)

o COCP Yasmin – has the best evidence base

Can be cyclical or continuous (current data prefers continuous use)

o Referral for CBT

• Severe (causes withdrawal from social and professional activities and prevents normal functioning)

o Same as moderate PMS

o SSRI Can be continuous or just during the luteal phase

Must monitor treatment response closely (esp regarding self-harm) and initially trial for 3 months