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A Practical Guide to the Diagnosis and Management of Amenorrhoea

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Summary

For women of reproductive age, pregnancy and lactation are the two most common physiological causes of amenorrhoea. This article concentrates on pathological causes of amenorrhoea. Primary amenorrhoea refers to the absence of menarche at the age of 16 and secondary amenorrhoea is the cessation of menses for at least 6 months in already cycling women.

Amenorrhoea is not a diagnosis but a symptom indicating anatomical, genetic and neuroendocrine abnormalities. It can be determined by two different groups of causes: (a) anatomical defects of the genital organs; (b) endocrine dysfunctions.

Both congenital and acquired anomalies in the structure of the uterus and vagina could produce amenorrhoea; nevertheless, in the vast majority of patients, amenorrhoea is related to an ovarian malfunction. Diagnostic work-up includes history, physical examination, laboratory data and imaging.

Amenorrhoea resulting from ovarian malfunction is associated with 4 distinct endocrine conditions. Hyperprolactinaemic amenorrhoea is often associated with a pituitary adenoma. Prolactin-lowering drugs, cyclical progestogen and hormone replacement therapy (HRT) are the different choices of treatment for cycle disturbance; a contraceptive pill can be used to ensure contraception, while prolactin-lowering drugs induce fertility in patients who desire pregnancy.

Hypogonadotrophic amenorrhoea is frequently associated with stress and nutritional deficiency. If this is the case the patient should simply be counselled. A sequential use of estrogen and progestogen can be suggested to prevent estrogen deficiency or for psychological reasons. If contraception is needed, oral contraception may be the choice for both cycle and fertility control. If the patient desires pregnancy, ovulation may be induced with pulsatile gonadotrophin-releasing hormone (GnRH) in patients with hypothalamic disfunction and with gonadotrophins in patients with pituitary failure.

Hypergonadotrophic amenorrhoea is the result of an ovarian failure. There is no curative therapy for these amenorrhoeas. However, a long term hypoestrogenic condition should be treated with estrogen to cure symptoms and to prevent an increased risk of cardiovascular disease and osteoporosis.

Normogonadotrophic amenorrhoea is caused by some disturbance in the pattern of pulsatile GnRH secretion. Since these women have some ovarian activity, they are not hypoestrogenic and will bleed in response to progestogen withdrawal. Most of these patients are likely to have polycystic ovarian disease (PCO). Menstrual bleeding can be induced in these women by cyclical progestogen administration or the sequential use of estrogen plus progestogen. Oral contraception is indicated not only in patients who desire to be protected against pregnancy but also in women with acne and hirsutism. These frequently present signs of hyperandrogenism are consistently improved by the ovarian suppression induced by the contraceptive pill. The beneficial effect of the pill can be reinforced by the simultaneous use of antiandrogens. Women with normogonadotrophic amenorrhoea and desiring pregnancy have a less favourable response to all forms of ovulation induction (antiestrogen, GnRH and gonadotrophin preparations).

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Crosignani, P.G., Vegetti, W. A Practical Guide to the Diagnosis and Management of Amenorrhoea. Drugs 52, 671–681 (1996). https://doi.org/10.2165/00003495-199652050-00005

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