PCOS Flashcards
PCOS - Mx
Polycystic ovarian syndrome: management
Polycystic ovarian syndrome (PCOS) is a complex condition of ovarian dysfunction thought to affect between 5-20% of women of reproductive age. Management is complicated and problem based partly because the aetiology of PCOS is not fully understood. Both hyperinsulinaemia and high levels of luteinizing hormone are seen in PCOS and there appears to be some overlap with the metabolic syndrome.
General
weight reduction if appropriate
if a women requires contraception then a combined oral contraceptive (COC) pill may help regulate her cycle and induce a monthly bleed (see below)
PCOS - Mx of Hirsutism and Acne
Hirsutism and acne
a COC pill may be used help manage hirsutism. Possible options include a third generation COC which has fewer androgenic effects or co-cyprindiol which has an anti-androgen action. Both of these types of COC may carry an increased risk of venous thromboembolism
if doesn’t respond to COC then topical eflornithine may be tried
spironolactone, flutamide and finasteride may be used under specialist supervision
PCOS and Mx of Infertility
Infertility
weight reduction if appropriate
the management of infertility in patients with PCOS should be supervised by a specialist. There is an ongoing debate as to whether metformin, clomifene or a combination should be used to stimulate ovulation
a 2007 trial published in the New England Journal of Medicine suggested clomifene was the most effective treatment. There is a potential risk of multiple pregnancies with anti-oestrogen* therapies such as clomifene. The RCOG published an opinion paper in 2008 and concluded that on current evidence metformin is not a first line treatment of choice in the management of PCOS
metformin is also used, either combined with clomifene or alone, particularly in patients who are obese
gonadotrophin
*work by occupying hypothalamic oestrogen receptors without activating them. This interferes with the binding of oestradiol and thus prevents negative feedback inhibition of FSH secretion
PCOS and Hirsutism - Example Question
A 19-year-old woman comes to the endocrine clinic for review. She has problems with hirsutism and irregular periods, and troublesome weight gain. Her GP has just stressed the need to lose weight and offered no pharmacological intervention. She takes no medication from the doctor and is currently studying law. Examination reveals a blood pressure of 135/85 mmHg, pulse is 65 beats per minute and regular. body mass index is 32kg/m². You confirm extensive hirsutism affecting the beard line, upper lip and the nipples. there is acne over the face and the upper chest. Relevant bloods include:
testosterone 4.8 nmol/l (upper limit of normal 2.1 nmol/l)
LH:FSH ratio 2.1
fasting glucose 5.0 mmol/l
Her main concern is hirsutism.
Which of the following is the most appropriate intervention?
> Co-cyprindiol Clomiphene Levonorgestrel Metformin Pioglitazone
Co-cyprindiol contains both cyproterone, an anti-androgen, and ethinylestradiol, (a synthetic oestrogen). In combination, used for the treatment of polycystic ovarian syndrome, the most likely diagnosis here, co-cyprindiol significantly reduces symptoms of hirsutism and acne, both related to androgen excess.
Clomiphene is the preferred option for inducing ovulation, and is preferred to metformin for this purpose, although the two are sometimes used in combination in the obese population. Pioglitazone is also effective in reducing ovarian insulin resistance, and inducing ovulation, but is not used due to its adverse event profile. Progesterone, (levonorgestrel), is ineffective in managing hirsutism.
PCOS and Conception - Example Question
A 32-year-old female presents to the infertility clinic with an inability to conceive. She is overweight, with a body-mass index of 32 kg/m², and has noticed increased hair growth over her face and chest over the last 12 months. Her periods are irregular and she has also noticed a deepening of her voice. An ultrasound of the pelvis has revealed the presence of multiple cysts in both ovaries. She has been treated with cyproterone acetate for her hirsutism but was informed that she should not attempt conception whilst on the drug. She now wishes to conceive.
On examination, she has a cushingoid appearance, with abdominal striae and her blood pressure is 140/85 mmHg.
Laboratory investigations reveal:
9:00 am Cortisol 710 nmol/l (170 700 nmol/l) LH 28 iU/l (1 20 iU/l) Basal FSH 4.7 iU/l (1.0 8.8 iU/l) DHEAS 509 µg/dl (31 228 µg/dl) Prolactin 602 mU/l (<360 mU/l) 17 OH Progesterone 54 ng/dl (<80 ng/dl)
Which of the following treatment options would be most appropriate for the treatment of infertility?
Metformin Spironolactone Reverse circadian rhythm steroids > Clomiphene citrate Cabergoline
The Rotterdam criteria for the diagnosis of PCOS requires at least two of the following
Clinical or biochemical evidence of hyperandrogenism.
Evidence of oligo- or anovulation.
Presence of polycystic ovaries on ultrasound.
Multiple clinical trials have been conducted to assess which drug is the most appropriate in aiding fertility. An article published in the New England journal of Medicine entitled Clomiphene, Metformin, or Both for Infertility in the Polycystic Ovary Syndrome concluded that Clomiphene is superior to metformin in achieving live birth in infertile women with the polycystic ovary syndrome, although multiple birth is a complication(N Engl J Med 2007; 356:551-566 February 8, 2007).
Another article Status of clomiphene citrate and metformin for infertility in PCOS (Trends Endocrinol Metab. 2012 Oct;23(10):533-43) published the following results:
‘Though widely used, there is uncertainty about the effectiveness and adverse effects of metformin and clomiphene citrate (CC) for infertility in polycystic ovary syndrome (PCOS). A systematic review (SR) of the best available evidence suggests that both CC and metformin are better than placebo for increasing ovulation and pregnancy rates, but CC is more effective than metformin for ovulation, pregnancy and live-birth rates, in PCOS patients with body mass index (BMI) >30.’
In PCOS, serum prolactin may also be marginally raised, but the levels seldom exceed 1500 mU/l.
Reverse circadian rhythm steroids are used in the treatment of congenital adrenal hyperplasia, whilst cabergoline is used for the medical management of hyperprolactinemia.
Spironolactone has antiandrogenic activity and can cause improvements in hirsutism in PCOS but has no bearing on fertility.
PCOS - Features
Polycystic ovary syndrome (PCOS) is a complex condition of ovarian dysfunction thought to affect between 5-20% of women of reproductive age. The aetiology of PCOS is not fully understood. Both hyperinsulinaemia and high levels of luteinizing hormone are seen in PCOS and there appears to be some overlap with the metabolic syndrome.
Features
•subfertility and infertility
•menstrual disturbances: oligomenorrhea and amenorrhoea
•hirsutism, acne (due to hyperandrogenism)
•obesity
•acanthosis nigricans (due to insulin resistance)
PCOS - Ix
Investigations
•pelvic ultrasound: multiple cysts on the ovaries
•FSH, LH, prolactin, TSH, and testosterone are useful investigations: raised LH:FSH ratio is a ‘classical’ feature but is no longer thought to be useful in diagnosis. Prolactin may be normal or mildly elevated. Testosterone may be normal or mildly elevated - however, if markedly raised consider other causes
•check for impaired glucose tolerance
PCOS - Ix - Example Question
A 22-year-old Asian woman with a body mass index of 24 kg/m² presents with new onset acne, hirsutism, and weight gain. Upon further questioning, it is found that she has had irregular periods for the last two years. On examination, there is mild acne and thick hair growth on her chin and areola region. Abdominal exam is unremarkable.
What are the most likely biochemical results given the clinical findings?
Raised testosterone, low LH/FSH ratio, insulin resistance
Low testosterone, low LH/FSH ratio, insulin resistance
Low testosterone, raised LH/FSH ratio, insulin resistance
Raised testosterone, raised LH/FSH ratio, increased insulin sensitivity
> Raised testosterone, raised LH/FSH ratio, insulin resistance
The clinical description is consistent with polycystic ovary syndrome (PCOS). This presents with hirsutism, acne, oligo/amenorrhoea and subfertility. Biochemical findings in PCOS include insulin resistance, raised testosterone, raised LH/FSH ratio, raised prolactin and low HDL.
Clitoromegaly
Seen occasionally in PCOS but is normally assoc with V High androgen levels
If clitoromegaly is found then further Ix to exclude an ovarian or adrenal androgen secreting tumour are required
Mechanism of action of Metformin in PCOS?
Increases peripheral insulin sensitivity
Majority of patients with PCOS have a degree of insulin resistance which in turn can lead to complicated changes in the hypothalamic-pituitary-ovarian axis
Hirsutism Mx
Assessment = Ferriman-Gallway Scoring System:
9 body areas are assigned a score of 0-4, a score >15 is considered to indicate moderate or severe hirsutism
Mx:
- advise weight loss if overweight
- cosmetic techniques eg waxing/bleaching - not available on NHS
- consider COCP e.g. Co-cyprindiol (Dianette - cannot be used long term as risk of VTE) or ethinylestradiol and drospirenone (Yasmin)
- facial hirsutism - topical eflornithine - CI in pregnancy and breast feeding
Hirsutism vs Hypertrichosis
Hirsutism = ANDROGEN DEPENDENT - often used to describe androgen-dependent hair growth in women
Hypertrichosis = ANDROGEN-INDEPENDENT hair growth
Causes of Hirsutism:
- PCOS = primary cause
- congenital adrenal hyperplasia
- androgen therapy
- obesity = peripheral conversion of oestrogen to androgens
- adrenal tumour
- androgen secreting ovarian tumour
- Drugs - PHENYTOIN
Causes of Hypertrichosis:
- Drugs - Minoxidil, CYCLOSPORIN, Diazoxide
- Congenital hypertrichosis lanuginosa
- Congenital hypertrichosis terminalis
- Porphyria cutanea tarda
- Anorexia nervosa
PCOS: Biochemical profile
Biochemical findings in PCOS include insulin resistance, raised testosterone, raised LH/FSH ratio, raised prolactin (but not over 1000) and low HDL.
Rotterdam Criteria - PCOS Diagnosis
The Rotterdam criteria for the diagnosis of PCOS requires at least two of the following
Clinical or biochemical evidence of hyperandrogenism.
Evidence of oligo- or anovulation.
Presence of polycystic ovaries on ultrasound.
