Summary
The complex mechanism concerned with the initiation and establishment of a pregnancy involves ovulation, the adequate access to the egg by ‘active’ spermatozoa followed by the transport of the zygote to the uterine cavity where it can imbed and grow in the suitably prepared endometrium. The sites within a woman vulnerable to the action of contraceptive agents are therefore the hypothalamic-pituitary axis, the ovary, the fallopian tubes, the endometrium and the cervix.
Hormonal steroid contraceptives in common use consist of synthetic oestrogens (ethinyloestradiol or mestranol) and progestagens derived from 19-nortestosterone or 17α-hydroxy progesterone.
The mechanism of action of contraceptive drugs is complex because closely related compounds may have different pharmacological effects which will also vary with dose levels and combination with other steroids.
Suppression of ovulation may be achieved by oestrogens reducing the release of FSH and the progestagens suppressing the peak of LH release. Some contraceptive steroids may also exert a direct effect upon the ovary, influencing steroidgenesis. Contraception may be achieved without ovulation-suppression, due to the disturbance of the normal luteal phase of the endometrium, and possibly by interfering with tubal transport, although this later inference is based almost solely on animal studies. Progestagens produce changes in the physico-chemical structure of the cervical mucus making it ‘hostile’ to sperm penetration, but an appreciation of the full effects of progestagens on sperm activity must await the resolution of the role of sperm capacitation in the human.
Although there have been reports of masculinisation of the female fetus following the use of large doses of certain progestational steroids for non-contraceptive purpose, there is no evidence that the inadvertent use of hormonal steroids at oral contraceptive dosage during early pregnancy, causes abnormal development of the external genitalia in the newborn.
It is possible that some contraceptive steroids may interfere with lactation once it has become firmly established and oestrogen-containing preparations are best avoided early in the puerperium because of the associated increased risk of thromboembolism.
Return of fertility after oral steroidal contraception is usually prompt and although the statistical evidence is not certain there is a strong clinical impression that a ‘rebound’ of increased fertility may occur. However, there is an undetermined small minority of women who remain infertile due to a continued failure of ovulation. Some of these women have had menstrual disturbance before contraception and most respond favourably to ovulationstimulation therapy.
Steroid contraceptive compounds not only affect the physiology and structure of most of the reproductive organs but may affect systems remote from those immediately concerned with reproduction. A reduction of BSP excretion by the liver occurs in 10 to 50 % of women and the rare cases of jaundice may have previously revealed their particular susceptibility to the C-17 substituted testosterone compounds by suffering from cholestatic jaundice or pruritus in late pregnancy. Glucose tolerance is impaired, especially in those predisposed to diabetes. The oestrogen fraction in combined or sequential oral preparations increases the thyroxine-binding globulin and cortisol-binding globulin thereby raising the levels of serum PBI and serum cortisol, but without interfering with the functional state of the thyroid or the pituitary-adrenal response to stressful situations.
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Seddon, R.J. Hormonal Steroid Contraceptives I: Physiological and Pharmacological Considerations. Drugs 1, 399–420 (1971). https://doi.org/10.2165/00003495-197101050-00003
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DOI: https://doi.org/10.2165/00003495-197101050-00003