Female Reproduction Contraception
There are many oral contraceptive preparations on the market and a choice should be made to prescribe the one with the lowest estrogen and progesterone concentrations that give good cycle control. Combined oral contraceptives (COCs) can also be used to treat a number of gynaecological conditions involving irregular cycles, menorrhagia or dysmenorrhoea. In addition to progesterone only pills (POPs), intrauterine devices which release progesterone locally to the endometrium are available (Mirena Intrauterine Systems, Schering Health) and are used both for contraception and for the treatment of endometriosis and other painful disorders of menstruation.
COCs are contraindicated in women who are pregnant, or who have a history of various forms of cardiovascular disease, cerebrovascular problems, certain liver disorders and undiagnosed gynaecological problems. COCs influence blood coagulation and there is a small increased risk of deep vein thrombosis, pulmonary embolism, stroke and myocardial infarction. This is slightly higher in women taking COCs containing third-generation progestagens (desogestrel, gestodene), particularly when there are other risk factors such as obesity, smoking and older age (>35 years). COCs should not be prescribed to women with known clotting abnormalities or a history of hemiplegic migraine. Side-effects should be monitored including regular blood pressure readings.
Oral contraception is fertility control using orally active synthetic sex hormone derivatives (Fig. 30a).
Combined oral contraceptives (COCs) represent the most widely used form of estrogens and progestagens, and constitute the most reliable and effective method for preventing pregnancy in countries where they are widely available. COCs act by preventing ovulation through negative-feedback inhibition of gonadotrophin release. Women taking COCs do not show the early follicular rise of follicle-stimulating hormone (FSH), nor the midcycle rises in FSH and luteinizing hormone (LH). The COC is taken daily for 21 days and withheld for seven, to induce withdrawal bleeding. The COC may also act directly on the uterus and cervix. Cervical mucus becomes more viscous, presumably inhibiting penetration by sperm, and the endometrium does not develop into a suitable matrix for implantation.
Sequential COCs are prescribed so that the user takes estrogen alone daily for 14–16 days, then estrogen and progestagen together for 5–6 days, then 7 days without any pills; this aims to mimic the natural cycle.
Advantages of COC use. COCs provide reliable, reversible contraception and have a number of other advantages such as reduced dysmenorrhoea and menorrhagia, less benign breast disease and a reduced risk of ovarian and endometrial cancer.
Disdvantages of COC use. There is a small increase in the rate of venous thromboembolism in all women taking COCs and a history of thromboembolic disease or other risk factors for thromboembolism, such as obesity, immobility or a family history, are contraindications to this form of contraception. Likewise, there is an increased risk of arterial vascular disease and the COC should be avoided for older women, particularly smokers with obesity and/or hypertension. Other relative contraindications include migraine and a number of rare liver disorders. COCs should not be given to women with a history of breast or genital tract cancer.
Progestagen only pills (POPs; mini-pills) were introduced to eliminate the adverse effects reported with estrogen use. The progestagen does inhibit FSH and LH release but a major component of action is due to the thickening of cervical mucus, and endometrial atrophy. The method is not as reliable as COCs, the success rate being 97–98%, as opposed to 99% for combination OC use. Adverse effects reported with progestagen only OCs are: amenorrhoea; changes in plasma high-density lipoprotein (HDL) and low-density lipoprotein (LDL) – HDL decrease and LDL increase in concentration in plasma; breakthrough bleeding and ‘spotting’; and abnormal responses to glucose tolerance tests.
Emergency contraception is prescribed as levonorgestrel and is effective if the first dose is taken within 72 hours of unprotected intercourse. The treatment creates an endometrial environment hostile to the blastocyst and is followed by a withdrawal bleed that may be heavy.
Other uses of estrogens
Hormone replacement therapy (HRT) describes the use of sex hormones to replace the lack of endogenous hormones resulting from the cessation of cyclicity of ovarian function at the menopause or in women who have developed hypogonadism for other reasons. HRT is administered in the form of sequential daily doses of estrogen, coupled with progesterone in women with an intact uterus to prevent the risk of endometrial hyperplasia and malignancy. There are numerous HRT preparations in the form of tablets, transdermal patches and creams. The benefit versus risk of HRT should be calculated in all symptomatic menopausal women and it should not be prescribed for longer than 5–10 years, following which the risks from breast cancer and cardiovascular disease increase. In the absence of good data to the contrary, hypogonadal women should be treated up until the expected age of the menopause.