A 32 year Old woman presents with absent periods for 3 months......

A 32-year-old woman complains that she has not had a period for 3 months. Four home pregnancy tests have all been negative. She started her periods at the age of 15 years and until 30 years she had a normal 27-day cycle. She had one daughter by normal delivery 2 years ago, following which she breast-fed for 6 months. After that she had normal cycles again for several months and then her periods stopped abruptly. She was using the progesterone only pill for contraception while she was breast-feeding and stopped 6 months ago as she is keen to have another child. She reports symptoms of dryness during intercourse and has experienced sweating episodes at night as well as episodes of feeling extremely hot at any time of day.

There is no relevant gynaecological history.

The only medical history of note is that she has been hypothyroid for 10 years and takes thyroxine 100 μg per day.

She does not take any alcohol, smoke or use recreational drugs.

Examination findings are unremarkable

Investigations:
Haemoglobin  = 12.2 g/dL (normal = 11.7–15.7 g/dL)
Thyroid-stimulating hormone = 3.6 mu/L (normal = 0.5–7 mu/L)
Free thyroxine = 28 pmol/L (normal =  11–23 pmol/L)
Follicle-stimulating hormone = 45 IU/L
Luteinizing hormone = 30 IU/L
Prolactin  = 401 mu/L (normal = 90–520 mu/L)

Questions
• What is the diagnosis?
• What further investigations should be performed?
• What are the important points in the management of this woman?

Answers and Discussion


This woman has symptoms of amenorrhoea as well as hypo-oestrogenic vasomotor symptoms and vaginal dryness.
The diagnosis is of premature menopause, confirmed by the very high gonadotrophin levels. High levels occur because the ovary is resistant to the effects of gonadotrophins, and negative feedback to the hypothalamus and pituitary causes increasing secretion to try and stimulate the ovary.

Sheehan’s syndrome (pituitary necrosis after postpartum haemorrhage) would also cause amenorrhoea but would have inhibited breast-feeding and all menstruation since delivery.

Premature menopause (before the age of 40 years) occurs in 1 per cent of women and has significant physical and psychological consequences. It may be idiopathic but a familial tendency is common. In some cases it is an autoimmune condition (associated with hypothyroidism in this case). Disorders of the X chromosome can also be associated.

Effects of premature menopause
• Hypo-oestrogenic effects:

•  vaginal dryness
•  vasomotor symptoms (hot flushes, night sweats)
•  osteoporosis
•  increased cardiovascular risk

• Psychological and social effects:

•  infertility
•  feeling of inadequacy as a woman
•  feelings of premature ageing and need to take hormone-replacement therapy (HRT)
•  impact on relationships

Further investigations

• Repeat gonadotrophin level is required to confirm the result and exclude a midcycle gonadotrophin surge or fluctuating gonadotrophins. 
• Bone scan is necessary for baseline bone density and to help in monitoring the effects of hormone replacement. 
• Chromosomal analysis identifies the rare cases of premature menopause due to fragile X syndrome or Turner’s syndrome mosaicism.

Management

Osteoporosis may be prevented with oestrogen replacement, with progesterone protection of the uterus. Traditional HRT preparations or the combined oral contraceptive pill are effective, the latter making women feel more ‘normal’, with a monthly withdrawal bleed.

Her options are adoption, accepting childlessness and in vitro fertilization (IVF) with donor oocytes.

Occasionally premature menopause is a fluctuating condition (resistant ovary syndrome) whereby the ovaries may function intermittently. 

Patient support organizations are a good source for women experiencing such an unexpected and stigmatizing diagnosis.