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Selected Topics in WOMEN’S HEALTH

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Selected Topics in WOMEN’S HEALTH www.bpac.org.nz keyword: womenshealth Selected topics in WOMEN’S HEALTH Laboratory investigation of amenorrhoea Polycystic ovary syndrome An overview of dysfunctional uterine bleeding Perimenopause and menopause Sexual dysfunction - loss of libido 8 | September 2010 | best tests Amenorrhoea Amenorrhoea is the absence of menstruation flow. It can Causes of primary amenorrhoea2 be classified as either primary or secondary,1 relative to menarche: ■ Hypergonadotropic hypogonadism/primary hypogonadism/gonadal failure: ■ Primary amenorrhoea: absence of menses by age 16 years in a female with appropriate development – Abnormal sex chromosomes e.g. Turner of secondary sexual characteristics; or absence syndrome of menses by age 13 years and no other pubertal – Normal sex chromosomes e.g. premature maturation2 ovarian failure ■ Secondary amenorrhoea: lack of menses in a ■ Hypogonadotropic hypogonadism/secondary previously menstruating, non-pregnant female, for hypogonadism: 2 greater than six months – In many cases this may be due to a familial delay in puberty and growth. Other causes include congenital abnormalities Primary amenorrhoea e.g. isolated GnRH deficiency, acquired Key messages: lesions, endocrine disturbance, tumour, systemic illness or eating disorder. ■ The most common cause of primary amenorrhoea in a female with no secondary sexual characteristics ■ Eugonadism: is a constitutional delay in growth and puberty. – Anatomic e.g. congenital absence of the In the first instance, watchful waiting is the most uterus and vagina, intersex disorders appropriate course. or inappropriate endocrine feedback ■ For females with primary amenorrhoea but who mechanisms have secondary sexual characteristics, pelvic ultrasound is indicated. In a large case series of primary amenorrhoea, the most common aetiologies were:2 Evaluation of primary amenorrhoea ■ Chromosomal abnormalities causing gonadal Causes of primary amenorrhoea should be evaluated dysgenesis (ovarian failure due to the in the context of the presence or absence of secondary premature depletion of all oocytes and follicles) 2 sexual characteristics. – 50% ■ Hypothalamic hypogonadism including Absence of secondary sexual characteristics functional hypothalamic amenorrhoea – 20% The most common cause of primary amenorrhoea in ■ Absence of the uterus, cervix and/or vagina, a female with no secondary sexual characteristics is Müllerian agenesis – 15% hypogonadotropic (i.e. low LH and FSH) hypogonadism, ■ Transverse vaginal septum or imperforate often due to a constitutional delay in growth and puberty. hymen – 5% A detailed family history may reveal a familial aspect to ■ Pituitary disease – 5% this. If there is a positive family history, watchful waiting is appropriate in the first instance, although the time will depend upon the age of the patient at presentation. Testing LH and FSH is unhelpful in determining constitutional delay of puberty as low levels can be due to a delay but also a number of other conditions (Figure 1). best tests | September 2010 | 9 Primary amenorrhoea in females with no secondary sexual where a person has a female external appearance despite a characteristics may also be caused by hypergonadotropic 46XY karyotype and undescended testes. It can also be due (i.e. high LH and FSH) hypogonadism. This is usually caused to Müllerian ageneis which is a congenital malformation by premature ovarian failure, or gonadal dysgenesis – the characterised by a failure of the Müllerian ducts to develop, most common form of female gonadal dysgenesis is Turner resulting in a missing uterus and variable malformations syndrome (45X0 karyotype). of the vagina. If the uterus is normal, outflow tract obstruction should Presence of secondary sexual characteristics be considered. An imperforate hymen or a transverse It is recommended that a female aged 16 years or over vaginal septum can cause outflow obstruction. This is with secondary sexual characteristics, presenting with most often associated with cyclic lower abdominal pain primary amenorrhoea, is referred for a pelvic ultrasound from blood accumulation in the uterus and vagina. If there to determine if the uterus is present. Absence of the uterus is no evidence of outflow obstruction, investigate as for may be the result of androgen insensitivity syndrome, secondary amenorrhoea (Table 1). Diagnostic pathway for primary amenorrhoea History and physical examination completed for a patient with primary amenorrhoea Secondary sexual characteristics present? Perform ultrasonography Consider watchful waiting NO YES of the uterus Measure FSH and LH levels Uterus absent or FSH and LH < 5 IU per L FSH > 20 IU per L Uterus present and LH > 40 IU per L abnormal or normal Hypogonadotrophic Hypergonadotrophic hypogonadism hypogonadism Karyotype analysis Outflow obstruction? NO Karyotype analysis YES 46, XY 46, XX Imperforate hymen or transverse Androgen 46, XX 45, XO Müllerian vaginal septum insensitivity agenesis syndrome Premature Turner Evaluate for secondary ovarian failure syndrome amenorrhoea Figure 1: Investigations for primary amenorrhoea (adapted from Master-Hunter, 2006)3 10 | September 2010 | best tests Secondary amenorrhoea Secondary amenorrhoea is defined as a lack of menses for Causes of secondary amenorrhoea six months in a non-pregnant patient who was previously After excluding pregnancy (and breast feeding), menstruating. the most common causes of secondary amenorrhoea are:4,5 Key messages: ■ Ovarian disease (40%) – ovarian failure ■ Exclude pregnancy as it is the most common cause due to normal or early menopause, of secondary amenorrhoea hyperandrogenism e.g. PCOS, testosterone ■ Other than pregnancy , most cases of secondary supplementation amenorrhoea are caused by menopause, polycystic ■ Functional hypothalamic anovulation ovary syndrome (PCOS) or functional anovulation (35%) – due to excessive exercise, e.g. excessive exercise, eating disorder, stress or eating disorders, stress or some certain medicines medicines e.g. oral contraceptives, depot ■ FSH, TSH and prolactin measurements will help medroxyprogesterone identify most causes of secondary amenorrhoea. If ■ Pituitary disease (19%) – has a similar there is suspicion of pituitary disease, FT4 should presentation to functional hypothalamic also be tested. amenorrhoea except for the occasional additional finding of galactorrhoea in some Diagnostic evaluation of secondary women. Rare causes are sellar masses, amenorrhoea other disease of the pituitary and primary Pregnancy should be first excluded by either urine hypothyroidism. pregnancy test or a serum hCG, rather than relying solely ■ Uterine disease (5%) – Asherman’s on history. syndrome is the only uterine cause of secondary amenorrhoea. This syndrome The history, physical examination and measurement results from acquired scarring of the of FSH, TSH and prolactin will help identify the most endometrial lining, usually secondary to common causes of amenorrhoea. In addition, for women postpartum hemorrhage or endometrial with evidence of hyperandrogenism e.g. assessment of infection following instrumental procedure hirsutism and acne, and measurement of testosterone such as a dilatation and curettage. would also be indicated. Results can often be difficult to interpret (Table 1) therefore review or advice from a relevant specialist may be appropriate. Table 1: Laboratory findings in common causes of secondary amenorhoea6 Condition FSH Prolactin Testosterone Hyperprolactinaemia Normal/low High Normal Polycystic Ovary Syndrome Normal Normal/slightly increased Normal/moderately increased in 5–30% Free androgen index increased Ovarian failure High Normal Normal Hypothalamic e.g. weight loss, Low/normal Normal Normal excessive exercise, or stress best tests | September 2010 | 11 Polycystic ovary syndrome polycystic ovaries on ultrasound will satisfy the current diagnostic criteria (Table 2). Other tests that should be Polycystic ovary syndrome (PCOS) is reported to affect considered when investigating PCOS include FSH, TSH and between 5–10% of women of reproductive age.2, 3 prolactin levels. As well as taking a full history, examination of a woman Once the diagnosis of PCOS is established, fasting glucose with suspected PCOS should include an assessment of: and lipids are recommended. For women with fasting ■ Weight (both BMI and hip/waist ratio) glucose >5.5 mmol/L an oral glucose tolerance test (OGTT) is indicated. In addition, some clinicians recommend that ■ Acne and hirsutism OGTT should be done for all women with PCOS who have ■ Blood pressure a BMI > 30 and for all women aged over 40 years even if of normal weight. Diagnostic criteria have been developed for PCOS For more information about investigating PCOS see PCOS is a syndrome, so there is no single diagnostic test. “Understanding polycystic ovary syndrome” BPJ 12, April There are several definitions of PCOS, but generally PCOS 2008. is defined by the presence of hyperandrogenism (clinical or biochemical), ovarian dysfunction (oligo-anovulation or Limited role of LH/FSH ratio8 7 polycystic ovaries), and the exclusion of related disorders. In the past, the diagnosis of PCOS was often based Table 2 compares diagnostic criteria for PCOS. upon the finding of an elevated ratio of LH to FSH in serum. Women with PCOS tend to have elevated Investigation of PCOS LH concentrations, with normal to low FSH. However, while some clinicians still test LH and FSH, this is not A clinical or biochemical finding of increased androgen required for a diagnosis of
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