Abnormal menstruation, PCOS Flashcards
Abnormal menstruation is an umbrella term that describes amenorrhea, oligomenorrhoea, dysmenorrhoea, and menorrhagia. Learning the differential diagnoses for each menstrual problem will be very helpful.
What are the differential diagnoses for:
a) . Amenorrhoea and oligomenorrhoea
b) . Dysmenorrhoea
c) . Menorrhagia
Causes of menorrhagia:
- Structural
- Leiomyomata (uterine fibroids)
- Endometrial cancer - tho more likely initially to cause irregular bleeding
- Adenomyosis (associated with a uniformly enlarged tender uterus, HMB and dysmenorrhoea)
- Endometrial polyps (can also cause IMB)
- Endometrial hyperplasia (maybe associated with irregular, anovulatory cycles)
- Non-structural
- PCOS
- Hypothyroidism
- IUD (copper coil)
- Dysfunctional uterine bleeding: this describes menorrhagia in the absence of underlying pathology.
Causes of primary amenorrhoea (failure to start menstruation by age 16):
- Turner’s syndrome
- Androgen insensitivity syndrome
- Congenital adrenal hyperplasia
- Congenital malformations of the genital tract
Causes of secondary amenorrhoea (cessation of established, regular menstruation for 6 months or longer) and oligomenorrhoea:
- Physiological e.g. pregnancy, lactation (account for most cases of amenorrhoea)
- Pathological:
- Functional hypothalamic disorders
- Weight loss-related amenorrhoea
- Stress-related amenorrhoea
- Exercise-related amenorrhoea
- Anterior pituitary disorders (most commonly caused by high prolactin levels)
- Prolactinoma (micro/macroadenoma) –> hyperprolactinaemia
- Drugs (anti-dopaminergic effects) that cause hyperprolactinaemia include phenothiazines, antihistamines, butyrophenones, metoclopramide, cimetidine, methyldopa
- Sheehan’s syndrome (postpartum necrosis of the anterior pituitary from severe obstetric haemorrhage and hypotension)
- Disorders of the genital tract
- Premature ovarian failure (POF)
- PCOS
- Uterine causes
- Surgical removal of the uterus
- Conditions that scar the endometrium and cause intrauterine adhesions and loss of menses - TB, Asherman’s syndrome
- Cryptomenorrhoea (‘hidden menstruation’)
- Cervical stenosis from surgical procedures or infection can cause blockage of menses through obstruction of outflow
- Thyrotoxicosis, hypothyroidism
- Functional hypothalamic disorders
Causes of dysmenorrhoea (the most common gynaecological symptom)
- Primary dysmenorrhoea - occurs in the absence of any pelvic pathology and is caused by excessive myometrial contractions producing uterine ischaemia in response to local release of prostaglandins from the endometrium
- Secondary or acquired dysmenorrhoea - occurs in association with pelvic pathology e.g. endometriosis, fibroids, adenomyosis, pelvic infections, adhesions and developmental anomalies
What is polycystic ovary syndrome (PCOS)?
Polycystic ovary syndrome is the most common endocrine disorder in women of reproductive age. It appears to emerge at puberty and is characterized by features such as hyperandrogenism (oligomenorrhea, hirsutism, and acne), anovulatory infertility, and polycystic ovarian morphology
The clinical features vary widely, with symptoms of hyperandrogenism and severe menstrual disturbances at one end of the spectrum (previously known as Stein-Leventhal syndrome), and mild symptoms at the other.
a) . What is the cause of PCOS?
b) . Describe its pathogenesis
a) . The cause is unknown but strong genetic component
b) . Pathogenesis:
-
Insulin resistance and resulting compensatory hyperinsulinaemia
- This leads to reduced production of sex hormone-binding globulin (SHBG) in the liver, causing more biologically active free testosterone in the blood
- Excess androgens stop follicular development and therefore causes anovulation and menstrual disturbance/ irregularity. It also results in symptoms of hyperandrogenism (hirsutism, acne)
- Hyperinsulinaemia affects liver production of lipoprotein, resulting in hyperlipidaemia. Hence, women with PCOS are prone to developing T2DM and obesity and are at greater risk of metabolic syndrome (which describes a combination of diabetes, HTN and obesity)
-
Hormonal imbalance (hypothalamic-pituitary-ovarian dysfunction)
- In PCOS, follicles do not ovulate. This means that there is no corpus luteum to secrete progesterone. Without progesterone, there is nothing to inhibit GnRH secretion from the anterior pituitary. As a result, there is an increase in the pulse frequency of GnRH secretion in PCOS. This increase in GnRH leads to an increase in LH relative to the FSH, since LH-secreting cells are more responsive to a faster pulse frequency of GnRH release –> an increase in the LH: FSH ratio
- Progesterone normally exerts a negative feedback on the secretion of oestrogen, so without progesterone, there will be a rise in oestrogen level –> endometrial hyperplasia –> endometrial cancer!
- Chronically elevated LH means that there is no LH surge –> anovulation
- A low FSH results in follicles not maturing enough to become a full functional Graafian follicle that can ovulate. The follicles that don’t ovulate are the cysts that form on the ovary in PCOS. Multiple cysts on the ovary represent past failed follicular ovulation events.
- Excessive LH stimulate the thecal cells to produce more androgens, which further contribute to symptoms of hyperandrogenism
Epidemiology of PCOS:
How common is PCOS in women?
Affects which ethnicity more?
PCOS is one of the most common endocrine disorders *affecting women of reproductive age
Lowest prevalence in Chinese women and highest prevalence in Black women
Give 4 complications of PCOS
-
Metabolic syndrome
- Insulin resistance has been shown to worsen reproductive and metabolic features and T2DM in PCOS, which is further exacerbated by obesity
- The prevalence of impaired glucose tolerance and type 2 diabetes are significantly increased in PCOS
-
Cardiovascular disease
- Women with PCOS have more risk factors for CVD e.g. central obesity, hypertriglyceridaemia, decreased HDL, hypertension and T2DM (major risk factor)
-
Infertility
- PCOS is the single most common cause of infertility in young women
-
Pregnancy complications
- PCOS pregnancies are more at risk of gestational diabetes, pregnancy-induced HTN, pre-eclampsia, and premature delivery
- They are also more at risk of caesarean delivery, miscarriage, and hypoglycaemia (which can cause seizures, coma, and death)
-
Endometrial cancer
- Due to prolonged oligomenorrhoea/ amenorrhoea and an increased prevalence of obesity
-
Obstructive Sleep Apnoea
- The prevalence of obstructive sleep apnoea is increased in obese women with PCOS
What is the outlook for PCOS?
PCOS is a chronic condition that needs lifelong control! There is no cure. Treatment aims at reducing signs and symptoms and preventing the development of complications
What are the clinical features of PCOS?
Presentations:
Features of hyperandrogenism and menstrual irregularity +/- FHx of PCOS
Symptoms
-
Oligomenorrhoea, amenorrhoea, or subfertility/ infertility
-
Oligomenorrhoea (irregular menstrual cycles) are defined as:
- Normal in the 1st year post-menarche as part of the pubertal transition
- 2 years of irregular cycles (> 45 days or < 21 days) after the onset of menarche
- > 3 years of irregular cycles (> 35 days or < 21 days, or < 8 cycles every year) post menarche to perimenopause
- > 1 year of irregular cycles (> 90 days for any one cycle) post menarche
- Primary amenorrhoea by age 15 or > 3 years of irregular cycles post thelarche (breast development)
-
Oligomenorrhoea (irregular menstrual cycles) are defined as:
- Hirsutism, acne (due to hyperandrogenism)
- Obesity
- Obstructive Sleep Apnoea
- Anxiety/ depression
Signs
-
Acanthosis nigricans (due to insulin resistance) - see image
- Grey-brown pigmentation that is palpably thickened and covered by a papillomatous elevation (giving it a velvety texture). The condition commonly affects the axillae, perineum, or extensor surfaces of the elbows and knuckles. When the neck is affected, there is often a thin necklace of warty fissures that can spread as a wide band
Give 4 differential diagnoses of PCOS
Differential diagnoses of PCOS
-
Simple obesity
- High BMI
- Raised androgen levels
-
Cushing’s syndrome
- Symptoms include hypertension, striae, and easy bruising
- Elevated 24-hour urinary free cortisol levels
-
Primary hypothyroidism
- Goitre
- Elevated TSH and low T4
-
Androgen-secreting tumour (virilizing adrenal or ovarian neoplasm)
- Extremely elevated plasma androgen
-
Non-classic congenital adrenal hyperplasia (autosomal recessive)
- FHx of infertility, hirsutism, or both; common in Ashkenazi Jewish people
- Elevated basal 17-hydroxyprogesterone levels in the morning or on stimulation
-
Premature ovarian failure
- Normal androgen levels
- Elevated plasma FSH levels and normal or subnormal estradiol levels
-
Acromegaly
- Symptoms include enlargement of the extremities, coarse features, and prognathism
- Increased plasma insulin-like growth factor (IGF) levels
-
Raised prolactin/ prolactinoma
- Galactorrhoea
- Elevated plasma prolactin levels
-
Drug-induced hyperandrogenism
-
Androgenic drugs that may cause hirsutism include:
- Testosterone
- ACTH
- High-dose corticosteroids and anabolic steroids
- Androgenic progestogens in oral contraceptives
- Non-androgenic drugs that may cause hirsutism include:
- Ciclosporin
- Phenytoin
- Minoxidil (rogaine)
-
Androgenic drugs that may cause hirsutism include:
Give 3 medications that can cause hirsutism in females
Testosterone
ACTH
High-dose corticosteroids or anabolic steroids
Androgenic progestogens in oral contraceptives
Ciclosporin
Minoxidil
Phenytoin
What investigations would you want to carry out in patients with PCOS?
Ix: (To confirm the diagnosis and to exclude other conditions that present similarly to PCOS)
- Measure total testosterone: normal to moderately elevated in women with PCOS
- If significantly raised, consider other causes e.g. androgen-secreting tumour (virilizing adrenal or ovarian neoplasm)
- Measure sex hormone-binding globulin (SHBG): normal to low in women with PCOS
- Calculate free androgen index (100 x total testosterone level/ SHBG) to assess the amount of biologically active free testosterone: normal or elevated in women with PCOS
- Measure the following to rule out other causes of oligomenorrhoea and amenorrhoea (e.g. premature ovarian failure, hypothyroidism, and hyperprolactinaemia, Cushing’s syndrome, acromegaly)
-
Measure LH and FSH: raised LH: FSH ratio in women with PCOS
- Elevated FSH and normal or subnormal estradiol levels in premature ovarian failure
- Decreased LH and FSH in hypogonadotropic hypogonadism
- Measure prolactin: maybe normal or mildly elevated in PCOS
- Measure TSH and T4 to rule out hypothyroidism
- Measure 24-hour urinary free cortisol levels to rule out Cushing’s syndrome
- Measure plasma IGF to rule out acromegaly
-
Measure LH and FSH: raised LH: FSH ratio in women with PCOS
- Check fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), and HbA1c for impaired glucose tolerance and T2DM
- _Refer *adults* (not adolescents) for a pelvic USS_: shows multiple cysts on the ovaries
- Polycystic ovaries on USS are defined as the presence of >/= 12 follicles in at least one ovary (measuring 2-9 mm in diameter) or increased ovarian volume (> 10 cm3)
- Note that polycystic ovaries do NOT have to be present to make the diagnosis of PCOS, and the finding of polycystic ovaries does NOT alone establish the diagnosis
- _******USS should NOT be used to diagnose PCOS in adolescent females_
In adolescents, consider Ix after only 1 year of irregular cycles if COCP is about to be started, as COCPs will mask the diagnosis of PCOS by suppressing hyperandrogenaemia
Should you use USS to diagnose PCOS in adolescent females?
NOOOO!
USS is NOT part of the diagnostic criteria for PCOS in adolescent females, it’s only used in adults
What diagnostic criteria are used to diagnose PCOS in adults?
The Rotterdam criteria
PCOS is diagnosed in adults if two of three of the following criteria are present:
- Infrequent or no ovulation (i.e. oligomenorrhoea or amenorrhoea)
- Clinical and/or biochemical signs of hyperandrogenism (such as hirsutism, acne, or raised total or free testosterone levels)
- Polycystic ovaries on USS - defined as the presence of >/= 12 follicles (measuring 2-9 mm in diameter) in one or both ovaries and/or increased ovarian volume (> 10 cm3)
What are the diagnostic criteria for PCOS in adolescents?
Both hyperandrogenism and irregular menstrual cycles (oligomenorrhoea or amenorrhoea) are required for a diagnosis of PCOS
How do you manage PCOS in adults/ adolescents?
Mx:
- Inform women with PCOS about the possible long-term complications of PCOS, including T2DM and cardiovascular disease
-
Encourage a healthy lifestyle i.e. healthy diet, regular exercise, weight loss, and optimise modifiable cardiovascular risk factors
- Explain that weight loss may reduce hyperinsulinaemia and hyperandrogenism, reduce the risk of T2DM and CVD, result in menstrual regularity, and improve the chance of pregnancy
- Orlistat can be given for severe obesity
- Consider referral to a dietician
-
Offer screening for impaired glucose tolerance and T2DM + assess for cardiovascular risk factors
- Offer OGTT and regular monitoring for weight change
- Annual BP checks
- Offer screening for depression and anxiety
- Each patient should receive counselling from a medical professional. The nature of PCOS and potential implications on fertility and cardiovascular health should be explained
- Managing clinical features of PCOS:
-
Oligomenorrhoea/ amenorrhoea
- In adults with prolonged amenorrhoea (< 1 one period every 3 months), abnormal vaginal bleeding, or excess weight –> prescribe a cyclical progestogen to induce a withdrawal bleed + referral for a transvaginal USS to assess endometrial thickness
- If endometrial thickening is present (> 10 mm) or the endometrium has an unusual appearance –> referral for endometrial sampling to exclude endometrial hyperplasia or cancer
- If endometrium is of normal thickness and appearance –> advise treatment to prevent endometrial hyperplasia.
- Options include:
- Cyclical progestogen (e.g. medroxyprogesterone 10 mg daily for 14 days every 1-3 months) to induce regular withdrawal bleeds
- COCP
- Levonorgestrel-releasing intrauterine system (LNG-IUS)
- If unwilling to take cyclical hormone treatment or use LNG-IUS - refer to specialist care and arrange regular transvaginal USS (every 6-12 months) to assess the endometrial thickness and appearance
- Options include:
- In adults with prolonged amenorrhoea (< 1 one period every 3 months), abnormal vaginal bleeding, or excess weight –> prescribe a cyclical progestogen to induce a withdrawal bleed + referral for a transvaginal USS to assess endometrial thickness
-
Oligomenorrhoea/ amenorrhoea
(To protect the endometrium from hyperplasia, it’s advised to induce withdrawal bleeds for at least 3 times a year!)
- Hirsutism
* Prescribe a COCP
* If doesn’t respond to COCP, give topical eflornithine
* Anti-androgen medications e.g. cyproterone, spironolactone, or finasteride can be used under specialist supervision
* Discuss methods of hair reduction and removal (such as shaving and waxing)-
Acne
- Prescribe a COCP
-
Infertility
- REFERRAL TO FERTILITY SERVICES!
- Give advice on weight loss and smoking cessation
- Exclude other causes of infertility
- Clomifene (anti-oestrogen therapy) +/- metformin to help induce ovulation - it works by blocking hypothalamic oestrogen receptors This interferes with the binding of oestradiol and thus prevents negative feedback inhibition of FSH secretion.
-
Acne
- Hirsutism
(NICE guidelines recommend Metformin for women trying to conceive with a BMI >25)
- Pregnancy
- Consider referring the woman to be screened for gestational diabetes
- Offer OGTT to women planning pregnancy. If already pregnant, it should be offered before 20 weeks gestation
- Pregnant women should have an OGTT again at 24-28 weeks gestation
Why is it important for women with PCOS to induce withdrawal bleeds at least every 3-4 months?
How does COCP help induce withdrawal bleeds and lower the risk of endometrial cancer?
This is because women with PCOS are at an increased risk for developing endometrial cancer due to prolonged unopposed oestrogen exposure without progesterone surge in the second half of the cycle. This chronic exposure to the high oestrogen level results in endometrial hyperplasia which can become endometrial cancer!
COCP is useful in PCOS because progesterone inhibits the release of GnRH (restoring the normal menstrual cycle) and oestrogen helps with the acne and hirsutism
