Menstruation can be postponed by giving oral norethisterone 5 mg t.d.s., starting 3 days before the expected onset; bleeding occurs 2-3 days after withdrawal. Users of the combined oral contraceptive pill (having a 7-day break) can simply continue with active pills where they would normally stop for 7 days.
Although there is no evidence that harm follows such manoeuvres, it is obviously imprudent to practise them frequently.
Note. These uses of progestogen should not be undertaken if there is any possibility of pregnancy.
Endometriosis. Medical treatments for endometriosis have focused on the hormonal alteration of the menstrual cycle in an attempt to produce a pseudo-pregnancy, pseudo-menopause, or chronic anovulation. Each of these situations is believed to cause a suboptimal milieu for the growth and maintenance of endometrium and, by extension, of implants of endometriosis. Danazol 600 to 800 mg per day causes anovulation by attenuating the midcycle surge of luteinising hormone secretion, inhibiting multiple enzymes in the steroidogenic pathway, and increasing serum free testosterone concentrations.
Medroxyprogesterone causes the decidualisation of endometrial tissue, with eventual atrophy. Adverse effects occur at low (20-30 mg) or high (100 mg/day) dose including abnormal uterine bleeding, nausea, breast tenderness, fluid retention, and depression. These resolve after the discontinuation of the drug. Gestrinone 5-10 mg/week is an antiprogestational steroid that causes a decline in the concentrations of oestrogen and progesterone receptors, and a 50% decline in serum oestradiol concentrations. Androgenic side effects, such as a deepening of the voice, hirsutism, and clitoral hypertrophy, are potentially irreversible.
A combination of an oestrogen and a progestogen induces a hormonal pseudo-pregnancy. The oral contraceptive is used either continuously or cyclically (21 active pill followed by 7 days of placebo). Both regimens are effective; the amenorrhea of continuous administration is advantageous for women with dysmenorrhea. Gonadotropin-releasing hormone (GnRH) agonists diminish the secretion of follicle-stimulating hormone and luteinising hormone, resulting in hypo-gonadotropic hypogonadism, endometrial atrophy and amenorrhea. The GnRH agonist can be given intranasally, subcutaneously, or intramuscularly, with a frequency of administration ranging from twice daily to every three months. The side effects are the menopausal-type symptoms of hypoestrogenism (such as transient vaginal bleeding, hot flushes, vaginal dryness) and can be prevented by concurrent administration of HRT in postmenopausal doses.
Although most treatments for endometriosis are directed at the implant themselves, the symptoms can be also treated directly. Nonsteroidal antiinflammatory drugs (NSAID) such as diclofenac, ibuprofen, mefenamic acid, are often given to relieve the pain associated with endometriosis. These drugs are frequently the first-line treatment in women with pelvic pain whose cause has not yet been proved to be endometriosis.
Dysmenorrhoea is due to uterine contractions resulting from excess prostaglandins in the uterus during ovulatory cycles. It can be treated by suppressing ovulation (using the combined pill or norethisterone); also by using inhibitors of prostaglandin synthesis, e.g. aspirin, indometacin, naproxen. The analgesic prostaglandin synthase inhibitor (NSAID) may need to be given for several days before menstruation or only at the time of the pain.
Premenstrual tension syndrome may be due to an imbalance of natural oestrogen and progesterone secretion but knowledge of the syndrome remains imprecise. Psychosocial factors can be important. Placebo effects are strong. Drugs are not necessarily the preferred treatment. There is evidence for and against:
• Restriction of salt and fluid plus a thiazide diuretic in the second half of the menstrual cycle where symptoms suggest fluid retention
• Pyridoxine (vitamin B6, a coenzyme): try 100 mg/d orally (not more) for 3 months and abandon if there is no benefit. It may help depression and irritability particularly
• Oestrogen-progestogen oral contraceptive combination
• Bromocriptine, especially where there is breast pain
• Prostaglandin synthase inhibition, e.g. mefenamic acid.
Cyclical breast pain or mastalgia, when severe, may respond to continuous use of gamolenic acid (Efamast) (orally); it is an essential unsaturated fatty acid for cell membranes (patients have low concentrations); it may act by reducing cellular uptake of prolaction and ovarian hormones. Danazol and bromocriptine also help.
Oxytocics, i.e. drugs that hasten childbirth, and prostaglandins induce uterine contractions. They are used to induce abortion, to induce or augment labour, and to minimise blood loss from the placental site.
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