Encourage weight loss

• This recommendation is based on expert advice in a non-systematic review [Balen and Anderson, 2007].
• If more than 5% of body weight can be lost, there is an excellent chance of restoring menstrual regularity [Balen and Anderson, 2007].

Risk of endometrial cancer

• Severe oligomenorrhoea and amenorrhoea in the presence of premenopausal levels of oestrogen can lead to endometrial hyperplasia, which in some women could develop into endometrial cancer [RCOG, 2007]. Inter-menstrual intervals of more than 3 months may be associated with endometrial hyperplasia [RCOG, 2007].
• The true risk of endometrial cancer in women with polycystic ovary syndrome (PCOS) is unknown. Studies are small or have been done on women with infertility, including those with causes of infertility other than PCOS [Balen, 2001]. Other studies have been uncontrolled, and their interpretation is complicated by the variety of diagnostic criteria used to define the syndrome [Hardiman et al, 2003]. There are anecdotal reports of endometrial cancer developing in teenagers with amenorrhoea [Wild, 2002a].
• Endometrial cancer has a mean age of occurrence of 61 years in the UK. Cases in women younger than 35 years of age are exceptionally rare and usually occur when anovulation is secondary to PCOS or oestrogen-secreting tumours [Balen, 2000].

Induce withdrawal bleeding and then refer for ultrasonography to assess endometrial thickness

• These recommendations are based on expert opinion in a review article [Balen, 2000] and advice from CKS expert reviewers.

Prescribe treatment to induce withdrawal bleeding

• These recommendations are based on guidance from the Royal College of Obstetricians and Gynaecologists [RCOG, 2007] and expert opinion in a review article [Hardiman et al, 2003].
• Although evidence is lacking about the risk of endometrial cancer in women with oligomenorrhoea or amenorrhoea, expert opinion is that there is little option other than to advise women to take treatment to induce regular bleeding, at least every 3 months [RCOG, 2007].
• Another option is a progestogen-secreting intrauterine system, such as the levonorgestrel-releasing intrauterine system [Balen and Glass, 2005].
• Cyclical progestogen treatment using less-androgenic progestogens, such as medroxyprogesterone acetate, can be used to induce withdrawal bleeding [Balen, 2000]. However, evidence is lacking about the optimal progestogen, dosage, or treatment regimen [Hardiman et al, 2003]. Guidelines from the Royal College of Obstetricians and Gynaecologists recommend at least a 12-day course of progestogens each month. Medroxyprogesterone is recommended because it is licensed for endometrial protection from oestrogenic hormone replacement therapy as a 14-day course within each 28-day oestrogen hormone replacement therapy cycle.

Women unwilling to take cyclical hormone treatment

• These recommendations are based on expert advice in a non-systematic review [Balen, 2001].

Women who are amenorrhoeic do not need osteoporosis prophylaxis

• Women with PCOS have some ovarian activity [Crosignani and Vegetti, 1996]. Follicular development and oestrogen production continue but are arrested at some stage short of full maturation of an ovulatory follicle. Therefore, although these women are anovulatory, they do not show signs of oestrogen deficiency [Baird, 1997].
• A small case-controlled study of 45 adolescent women with amenorrhoea or oligomenorrhoea (14 had polycystic ovaries) matched with 45 women with regular menstruation found that, although overall the women with amenorrhoea or oligomenorrhoea had lower bone mineral density than those with regular menstruation, those with polycystic ovaries had a bone mineral density similar to that of the control group [To and Wong, 2005].
• A subgroup of 51 women with PCOS in a case-controlled study found that amenorrhoeic women with PCOS had only a marginal decrease in bone mass. Bone protection was thought to be due to adequate oestrogen production and overproduction of androgenic steroids [Adami et al, 1998].