1- Menstrual disorders (irregular periods)

Question 1

Primary amenorrhoea is defined as not starting menstruation:

Answer 1

• By 13 years when there is no other evidence of pubertal development
• By 15 years of age where there are other signs of puberty, such as breast bud development

Question 2

normal puberty in girls

Answer 2

starts age 8 – 14

Question 3

normal puberty in boys

Answer 3

9-15

Question 4

how long does puberty take

Answer 4

4 years

Question 5

in girls puverty start with the devlopment of

Answer 5

1) Breast buds
2) Pubic hairs
3) menstrual periods (about two years from the start of puberty)

Question 6

Oligomenorrhoea

Answer 6

Infrequent menstrual periods (fewer than 6 to eight periods per year)

Question 7

causes of primary amenorrrhea

Answer 7

1) Genitourinary malformation
* imperforate hymen
* vaginal septum
* absent vagina
* absent uterus

2) Genetic
* Turners syndrome 45XO
* Congenital adrenal hyperplasia
* Kallmans
* Androgen insensitivity syndrome

3) Endocrine disorder (hypothalamic pituitary dysfunction)
* hypogonadotropic hypogonadism (e.g. kallmans)
* hypergonadotropic hypogonadism
* hypothalamic- underweight

Question 8

what is hypogonadism

Answer 8

lack of oestrogen and testosterone which rise before puberty

Question 9

causes of hypogonadism

Answer 9

1. • Hypogonadotropic hypogonadism: a deficiency of LH and FSH
2. • Hypergonadotropic hypogonadism: a lack of response to LH and FSH by the gonads (the testes and ovaries)

Question 10

Hypogonadotropic hypogonadism

Answer 10

involves deficiency of LH and FSH, leading to deficiency of the sex hormones (oestrogen).

Question 11

causes of hypogonadotropic hypogonadism

Answer 11

• Hypopituitarism (under production of pituitary hormones)
• Damage to the hypothalamus or pituitary, for example, by radiotherapy or surgery for cancer
• Significant chronic conditions can temporarily delay puberty (e.g. cystic fibrosis or inflammatory bowel disease)
• Excessive exercise or dieting can delay the onset of menstruation in girls
• Constitutional delay in growth and development is a temporary delay in growth and puberty without underlying physical pathology
• Endocrine disorders such as growth hormone deficiency, hypothyroidism, Cushing’s or hyperprolactinaemia
• Kallman syndrome

Question 12

Hypergonadotropic hypogonadism

Answer 12

is where the gonads fail to respond to stimulation from the gonadotrophins (LH and FSH). Without negative feedback from the sex hormones (oestrogen), the anterior pituitary produces increasing amounts of LH and FSH. Consequently, you get high gonadotrophins (“hypergonadotropic”) and low sex hormones (“hypogonadism”).

Question 13

causes of hypergonadotropic hypogonadism

Answer 13

is the result of abnormal functioning of the gonads. This could be due to:

• Previous damage to the gonads (e.g. torsion, cancer or infections such as mumps)
• Congenital absence of the ovaries
• Turner’s syndrome (XO)

Question 14

kallmans

Answer 14

is a genetic disorder that prevents a person from starting or fully completing puberty. Kallmann syndrome is a form of a group of conditions termed hypogonadotropic hypogonadism. To distinguish it from other forms of hypogonadotropic hypogonadism, Kallmann syndrome has the additional symptom of a total lack of sense of smell (anosmia) or a reduced sense of smell

Question 15

turners syndrome

Answer 15

45XO
a genetic condition in which a female is partially or completely missing an X chromosome.[2] Signs and symptoms vary among those affected.[1] Often, a short and webbed neck, low-set ears, low hairline at the back of the neck, short stature, and swollen hands and feet are seen at birth.[1] Typically, those affected do not develop menstrual periods and breasts without hormone treatment and are unable to have children without reproductive technology.[1] Heart defects, diabetes, and low thyroid hormone occur in the disorder more frequently tha

Question 16

congenital adrenal hyperplasia

Answer 16

• autosomal recessive
• deficiency in 21-hydroxylase enzyme
• causes underproduction of cortisol and aldosterone and an overproduction of androgens from birth

presentation
- can be unwell after birth due to electrolyte disturbance and hypoglycaemia

Question 17

typical feature of CAH due to high androgens

Answer 17

Tall for their age
Facial hair
Absent periods (primary amenorrhoea)
Deep voice
Early puberty

Question 18

Androgen insensitivity syndrome

Answer 18

is a condition where the tissues are unable to respond to androgen hormones (e.g. testosterone), so typical male sexual characteristics do not develop.
- It results in a female phenotype, other than the internal pelvic organs.
- Patients have normal female external genitalia and breast tissue.
- Internally there are testes in the abdomen or inguinal canal, and an absent uterus, upper vagina, fallopian tubes and ovaries.

Question 19

structural pathology cause amenorrhea

Answer 19

Structural pathology in the pelvic organs can prevent menstruation. If the ovaries are unaffected, there will be typical secondary sexual characteristics, but no menstrual periods. There may be cyclical abdominal pain as menses build up but are unable to escape through the vagina. Structural pathology that can cause primary amenorrhoea include:

• Imperforate hymen
• Transverse vaginal septae
• Vaginal agenesis
• Absent uterus
• Female genital mutilation

Question 20

investigations for primary amenorrhea

Answer 20

Full examiantion and history

Initial investigations
* Full blood count and ferritin for anaemia
* U&E for chronic kidney disease
* Anti-TTG or anti-EMA antibodies for coeliac disease

Hormonal blood tests
* FSH and LH will be low in hypogonadotropic hypogonadism and high in hypergonadotropic hypogonadism
* Thyroid function tests
* Insulin-like growth factor I is used as a screening test for GH deficiency
* Prolactin is raised in hyperprolactinaemia
* Testosterone is raised in polycystic ovarian syndrome, androgen insensitivity syndrome and congenital adrenal hyperplasia

Genetic testing with microarray
- turners

Imaging
* Xray of the wrist to assess bone age and inform a diagnosis of constitutional delay
* Pelvic ultrasound to assess the ovaries and other pelvic organs
* MRI of the brain to look for pituitary pathology and assess the olfactory bulbs in possible Kallman syndrome

Question 21

management of primary amenorrhoea: due to hormones

Answer 21

Where necessary, replacement hormones can induce menstruation and improve symptoms.

Question 22

management of primary amenorrhoea: constiutitonal dely in growth and develp

Answer 22

may only require reassurance and observation.

Question 23

management of primary amenorrhoea: In patients with hypogonadotrophic hypogonadism, such as hypopituitarism or Kallman syndrome,

Answer 23

• Pulsatile GnRH can be used to induce ovulation and menstruation. This has the potential to induce fertility.
• Alternatively, where pregnancy is not wanted, replacement sex hormones in the form of the combined contraceptive pill may be used to induce regular menstruation and prevent the symptoms of oestrogen deficiency.

Question 24

secondary amenorrhea

Answer 24

no menstruation for more than three months after previous regular menstrual periods. Consider assessment and investigation after three to six months. In women with previously infrequent irregular periods, consider investigating after six to twelve months.

Question 25

causes of secondary amenorrhea

Answer 25

* Pregnancy is the most common cause * Menopause and premature ovarian failure * Hormonal contraception (e.g. IUS or POP) * Hypothalamic or pituitary pathology * Ovarian causes such as polycystic ovarian syndrome * Uterine pathology such as Asherman’s syndrome * Thyroid pathology * Hyperprolactinaemia

Question 26

hypothalamic amenorrhea

Answer 26

The hypothalamus reduces the production of GnRH in response to significant physiological or psychological stress. This leads to hypogonadotropic hypogonadism and amenorrhoea. The hypothalamus responds this way to prevent pregnancy in situations where the body may not be fit for it, for example: * * Excessive exercise (e.g. athletes) * Low body weight and eating disorders * Chronic disease * Psychological stress *

Question 27

Pituitary causes of secondary amenorrhoea include:

Answer 27

- Pituitary tumours, such as a prolactin-secreting prolactinoma - Pituitary failure due to trauma, radiotherapy, surgery or Sheehan syndrome

Question 28

hyperprolactinaemia

Answer 28

high prolactin levels prevent GnRH release from the hypothalamus- causes hypogonadotropic hypogonadism - cause: pituitary adenoma - treatment- often no treatment. Dopamine agonists can be used to reduce prolactin production

Question 29

assessment for secondary amenorrhea

Answer 29

* Detailed history and examination to assess for potential causes * Hormonal blood tests * Ultrasound of the pelvis to diagnose polycystic ovarian syndrome

Question 30

tests for ammenorhhea

Answer 30

**Beta human chorionic gonadotropin (HCG)** urine or blood tests are required to diagnose or rule out pregnancy. **Luteinising hormone and follicle-stimulating hormone:** - High FSH suggests primary ovarian failure - High LH, or LH:FSH ratio, suggests polycystic ovarian syndrome **Prolactin** can be measured to assess for hyperprolactinaemia, followed by an MRI to identify a pituitary tumour. **Thyroid stimulating hormone (TSH)** can screen for thyroid pathology. This is followed by T3 and T4 when the TSH is abnormal. - Raise TSH and low T3 and T4 indicate hypothyroidism - Low TSH and raised T3 and T4 indicate hyperthyroidism Raised **testosterone** indicates polycystic ovarian syndrome, androgen insensitivity syndrome or congenital adrenal hyperplasia.

Question 31

manageemnt of secondary amenorrhea

Answer 31

depends on cause Where necessary, replacement hormones can induce menstruation and improve symptoms.

Question 32

polycystic ovarian syndrome characteristics

Answer 32

multiple ovarian cysts, infertility, oligomenorrhea, hyperandrogenism and insulin resistance.

Question 33

rotterdam criteria

Answer 33

The Rotterdam criteria are used for making a diagnosis of polycystic ovarian syndrome. A diagnosis requires at least two of the three key features: * Oligoovulation or anovulation, presenting with irregular or absent menstrual periods * Hyperandrogenism, characterised by hirsutism and acne * Polycystic ovaries on ultrasound (or ovarian volume of more than 10cm3)

Question 34

DD of hirsutism

Answer 34

* Medications, such as phenytoin, ciclosporin, corticosteroids, testosterone and anabolic steroids * Ovarian or adrenal tumours that secrete androgens * Cushing’s syndrome * Congenital adrenal hyperplasia

Question 35

insulin resisrance and PCOS

Answer 35

Insulin resistance is a crucial part of PCOS. When someone is resistant to insulin, their pancreas has to produce more insulin to get a response from the cells of the body. Insulin promotes the release of androgens from the ovaries and adrenal glands. Therefore, higher levels of insulin result in higher levels of androgens (such as testosterone). Insulin also suppresses sex hormone-binding globulin (SHBG) production by the liver. SHBG normally binds to androgens and suppresses their function. Reduced SHBG further promotes hyperandrogenism in women with PCOS. The high insulin levels contribute to halting the development of the follicles in the ovaries, leading to anovulation and multiple partially developed follicles (seen as polycystic ovaries on the scan). Diet, exercise and weight loss help reduce insulin resistance.

Question 36

hormonal blood test findings for PCOS

Answer 36

* Raised luteinising hormone * Raised LH to FSH ratio (high LH compared with FSH) * Raised testosterone * Raised insulin * Normal or raised oestrogen levels

Question 37

investigations for PCOS

Answer 37

Blood tests * Testosterone * Sex hormone-binding globulin * Luteinizing hormone * Follicle-stimulating hormone * Prolactin (may be mildly elevated in PCOS) * Thyroid-stimulating hormone US (transvaginal) screening for diabetes using OGTT

Question 38

OGTT

Answer 38

An OGTT is performed in the morning prior to having breakfast. It involves taking a baseline fasting plasma glucose, giving a 75g glucose drink and then measuring plasma glucose 2 hours later. It tests the ability of the body to cope with a carbohydrate meal. The results are: * Impaired fasting glucose – fasting glucose of 6.1 – 6.9 mmol/l (before the glucose drink) * Impaired glucose tolerance – plasma glucose at 2 hours of 7.8 – 11.1 mmol/l * Diabetes – plasma glucose at 2 hours above 11.1 mmol/l

Question 39

general management of PCOS

Answer 39

* Weight loss- can result in ovulation * Low glycaemic index, calorie-controlled diet * Exercise * Smoking cessation * Antihypertensive medications where required * Statins where indicated (QRISK >10%)

Question 40

Why are people with PCOS at risk of endometrial cancer

Answer 40

Under normal circumstances, the corpus luteum releases progesterone after ovulation. Women with PCOS do not ovulate (or ovulate infrequently), and therefore do not produce sufficient progesterone. They continue to produce oestrogen and do not experience regular menstruation. Consequently, the endometrial lining continues to proliferate under the influence of oestrogen, without regular shedding during menstruation. This is similar to giving unopposed oestrogen in women on hormone replacement therapy. It results in endometrial hyperplasia and a significant risk of endometrial cancer. also have risk factors such as - obesity - diabetes - insulin reistance - amenorrhea

Question 41

Options for reducing the risk of endometrial hyperplasia and endometrial cancer in those with PCOS

Answer 41

1) Mirena coil for continuous endometrial protection 2) Inducing a withdrawal bleed at least every 3 – 4 months with either: - Cyclical progestogens (e.g. medroxyprogesterone acetate 10mg once a day for 14 days) - Combined oral contraceptive pill

Question 42

PCOS: managing inferility

Answer 42

Weight loss is the initial step for improving fertility. Losing weight can restore regular ovulation. A specialist may initiate other options where weight loss fails. These include: * * Clomifene * Laparoscopic ovarian drilling * In vitro fertilisation (IVF)

Question 43

PCOS: managing hirsutism

Answer 43

- weight loss - COCP - topical eflornithine