Case one:

Liza, aged 33 years, is an administrator who presents with concerns about her periods. She decided 6 months ago to stop taking the OCP and has not had a proper period yet. She is now in a permanent relationship and wants to get pregnant before she turns 35.

HK Pract 2005;27:390-392

Further history

Liza had her menarche at age 15 years and had regular periods. At 19 years, she became pregnant and had a termination of pregnancy, following which she commenced the OCP. Liza remained on the OCP until 6 months ago. She has regular intercourse and 3 months ago began living with her partner. Two weeks ago, she had some spotting but no period followed.

Further history

Liza returns for review of the results. Liza's results are basically normal, but her oestradiol is in the lower range of normal (190) and follicle stimulating hormone (FSH) is very slightly elevated (12), but not diagnostic.

Further history

Three months later Liza revisits you with a history of a very light period 3 weeks after her last visit. However, since then she is feeling moody and depressed, her sleep patterns are erratic, and she is feeling hot throughout the night. You inform her that the repeat FSH was 35 and the oestradiol was 90, suggesting that she may be going through an early menopause. You suggest the tests be repeated again in 4-6 weeks

Further history

Liza comes back to you for her latest results that confirm an elevated FSH of 40. Other investigations are normal. Liza is devastated with the confirmed diagnosis of premature ovarian failure and cries inconsolably.

Answer 1

Liza has developed post-OCP amenorrhoea, therefore the information you require includes:

• age of menarche
• menstrual cycle pattern
• associated symptoms including pain, premenstrual symptoms such as headache, mood changes, acne, flushing, bloating and sleep disturbance
• previous pregnancies or gynaecological surgery.

Answer 2

The differential diagnoses are the causes of secondary amenorrhoea:

• pregnancy
• disorders of hypothalamic function such as emotional stress, weight loss, excessive physical exercise, medications, endocrine disorders, eg. hypothyroidism
• polycystic ovarian syndrome
• hyperprolactinaemia
• ovarian failure
• hyperandrogenaemia.

Answer 3

Further history should include:

• other signs or symptoms of pregnancy
• weight loss and present weight
• exercise program
• list of medications including vitamins, minerals and herbs
• androgen-like symptoms and signs, eg. acne,hirsuitism, alopecia
• galactorrhoea
• signs and symptoms of menopause, eg. hot flushes, night sweats, reduction in vaginal lubrication
• past history of infections, cancer, chemotherapy, and
• family history of autoimmune disease and early menopause.

Answer 4

General examination including:

• body mass index (BMI)
• thyroid
• breasts
• abdominal and gynaecological examination to exclude pelvic masses, enlarged ovaries and uterus
• Pap test.

Answer 5

Systemic disease needs to be excluded if indicated. Appropriate investigations at this stage include:

• TFT
• pregnancy test
• FSH, luteinising hormone (LH), oestradiol, prolactin
• testosterone (if possible sensitive testosterone)
• sex hormone binding globulin (SHBG), free testosterone
• vaginal ultrasound.

Answer 6

You suggest to Liza the hormone level tests may need to be repeated in a few months time and at this stage you are unable to diagnose her problem. You counsel her to wait and see, and to return in 2-3 months time after having a repeat of her hormone levels. You ask her to have the blood test on the third day of her period (if she bleeds) or in the week before she returns.

Answer 7

Further investigations would include:

· thyroid antibodies including antiperoxidaseantibodies· adrenal antibodies· karyotype

ovarian antibodies· dual energy X-ray absorptimetry (DEXA). In most cases, the cause of premature ovarian failure (POF) is not found. Some causes of POF include:· association with autoimmune disorders, eg. polyglandular failure syndrome, in particular, thyroid and adrenal autoimmune failure

chromosomal abnormalities such as: Turner syndrome and Turner's mosaic, fragile X syndrome, other X linked conditions including deletions, translocations and inversions and non-X chromosome conditions· chemotherapy and irradiation

familial, increased risk if there are family members with early menopause or infertility· enzyme defects/metabolic causes such as galactosaemia.

Answer 8

Premature ovarian failure is a devastating diagnosis for a young woman, especially if she wishes to have children. The patient requires careful and supportive ongoing counselling and follow up. Women experiencing early menopause experience a range of emotions including grief, depression, anger, resentment, fear of loss of fertility, change in body image, feelings of aging, and loss of femininity and sexuality. General practitioners can provide support in giving women permission to express their fears and emotions and to help them regain control over their lives. Occasionally, it may be necessary to refer patients for specialist counselling. A woman's family should also be involved in the counselling process. Discussion regarding the use of hormone therapy (HT) is also appropriate. Referral to a fertility specialist to discuss IVF possibilities (including donor egg) may be appropriate.

Answer 9

The Hormone Therapy Consensus Statement published by The Royal Australian and New Zealand College of Obstetricians and Gynaecologists in August 2004 states, 'There is no available evidence regarding the risks and benefits of long term use of HT in women who undergo an early menopause. Based on expert opinion, women who have undergone an early menopause are usually advised to use HT until they reach the age of natural menopause' (see Resources). High dose HT is recommended with oestrogen, cyclic progestin and possibly testosterone. Cyclic therapy is recommended. About 10% will ovulate and may therefore spontaneously become pregnant, so contraception is required for women who do not wish to conceive. The OCP is an alternative to HT.