Contraception technology: past, present and future

Abstract

Steady progress in contraception research has been achieved over the past 50 years. Hormonal and non-hormonal modern contraceptives have improved women’s lives by reducing different health conditions that contributed to considerable morbidity. However the contraceptives available today are not suitable to all users and the need to expand contraceptive choices still exists. Novel products such as new implants, contraceptive vaginal rings, transdermal patches and newer combinations of oral contraceptives have recently been introduced in family planning programs and hormonal contraception is widely used for spacing and limiting births. Concerns over the adverse effects of hormonal contraceptives have led to research and development of new combinations with improved metabolic profile. Recent developments include use of natural compounds such as estradiol (E2) and estradiol valerate (E2V) with the hope to decrease thrombotic risk, in combination with newer progestins derived from the progesterone structure or from spirolactone, in order to avoid the androgenic effects. Progesterone antagonists and progesterone receptor modulators are highly effective in blocking ovulation and preventing follicular rupture and are undergoing investigations in the form of oral pills and in semi long-acting delivery systems. Future developments also include the combination of a contraceptive with an antiretroviral agent for dual contraception and protection against sexually transmitted diseases, to be used before intercourse or on demand, as well as for continuous use in dual-protection rings. Alhough clinical trials of male contraception have reflected promising results, limited involvement of industry in that area of research has decreased the likelihood of having a male method available in the current decade. Development of non-hormonal methods are still at an early stage of research, with the identification of specific targets within the reproductive system in ovaries and testes, as well as interactions between spermatozoa and ova. It is hoped that the introduction of new methods with additional health benefits would help women and couples with unmet needs to obtain access to a wider range of contraceptives with improved acceptability.

A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrine-disrupting chemicals

“…Somewhat surprisingly, the types of effects caused by several synthetic progesterone receptor agonists (norethindrone, levonorgestrel, gestodene, desogestrel) in the FSTRA resemble those observed for known AR agonists, including masculinization of females, reductions in plasma concentrations of sex steroids and VTG in females, and reduced fecundity ( Table 5). This is consistent with the fact that some progesterone receptor agonists bind to and activate mammalian ARs [40][41][42] and consequently can cause, for example, masculinization in women [49,50]. In this context, data from the FSTRA provide novel insights as to an endocrine pathway (AR activation) of potential concern relative to fish exposed to progestins in the environment [48].…”

A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrine-disrupting chemicals

“…Somewhat surprisingly, the types of effects caused by several synthetic progesterone receptor agonists (norethindrone, levonorgestrel, gestodene, desogestrel) in the FSTRA resemble those observed for known AR agonists, including masculinization of females, reductions in plasma concentrations of sex steroids and VTG in females, and reduced fecundity ( Table 5). This is consistent with the fact that some progesterone receptor agonists bind to and activate mammalian ARs [40][41][42] and consequently can cause, for example, masculinization in women [49,50]. In this context, data from the FSTRA provide novel insights as to an endocrine pathway (AR activation) of potential concern relative to fish exposed to progestins in the environment [48].…”

Risks of Malignant and Non-Malignant Tumours in Tall Women Treated with High-Dose Oestrogen during Adolescence

“…The first combined contraceptive pill introduced in 1960 contained 150 μg of mestranol which is equivalent to 100 μg of ethinyloestradiol. The doses of ethinyloestradiol in use have since then gradually decreased to 20-30 μg [13,14]. A possible explanation to our results is, of course, that the difference in our study occurred by chance.…”

Influence of Menstrual Cycle and Oral Contraceptive Phase on Spinal Excitability

“…We hypothesized that the elevated levels of estradiol in nonusers would enhance spinal excitability, but that the users would have stable hormonal concentrations and spinal excitability. Our hypothesis was based on the fact that the exogenous hormones in the OCPs result in negative feedback to the hypothalamic–pituitary–ovarian axis, resulting in low stable concentrations of endogenous estrogen and progesterone [37]. However, our results show that OCPs do not mitigate cyclic changes in sex hormones, as the users demonstrated a trend similar to that in the nonusers, with a significantly higher peak of endogenous estradiol during the second testing session.…”

A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrine-disrupting chemicals

“…Somewhat surprisingly, the types of effects caused by several synthetic progesterone receptor agonists (norethindrone, levonorgestrel, gestodene, desogestrel) in the FSTRA resemble those observed for known AR agonists, including masculinization of females, reductions in plasma concentrations of sex steroids and VTG in females, and reduced fecundity ( Table 5). This is consistent with the fact that some progesterone receptor agonists bind to and activate mammalian ARs [40][41][42] and consequently can cause, for example, masculinization in women [49,50]. In this context, data from the FSTRA provide novel insights as to an endocrine pathway (AR activation) of potential concern relative to fish exposed to progestins in the environment [48].…”

Risks of Malignant and Non-Malignant Tumours in Tall Women Treated with High-Dose Oestrogen during Adolescence

“…The first combined contraceptive pill introduced in 1960 contained 150 μg of mestranol which is equivalent to 100 μg of ethinyloestradiol. The doses of ethinyloestradiol in use have since then gradually decreased to 20-30 μg [13,14]. A possible explanation to our results is, of course, that the difference in our study occurred by chance.…”

Influence of Menstrual Cycle and Oral Contraceptive Phase on Spinal Excitability

“…We hypothesized that the elevated levels of estradiol in nonusers would enhance spinal excitability, but that the users would have stable hormonal concentrations and spinal excitability. Our hypothesis was based on the fact that the exogenous hormones in the OCPs result in negative feedback to the hypothalamic–pituitary–ovarian axis, resulting in low stable concentrations of endogenous estrogen and progesterone [37]. However, our results show that OCPs do not mitigate cyclic changes in sex hormones, as the users demonstrated a trend similar to that in the nonusers, with a significantly higher peak of endogenous estradiol during the second testing session.…”

A novel framework for interpretation of data from the fish short-term reproduction assay (FSTRA) for the detection of endocrine-disrupting chemicals

“…Somewhat surprisingly, the types of effects caused by several synthetic progesterone receptor agonists (norethindrone, levonorgestrel, gestodene, desogestrel) in the FSTRA resemble those observed for known AR agonists, including masculinization of females, reductions in plasma concentrations of sex steroids and VTG in females, and reduced fecundity ( Table 5). This is consistent with the fact that some progesterone receptor agonists bind to and activate mammalian ARs [40][41][42] and consequently can cause, for example, masculinization in women [49,50]. In this context, data from the FSTRA provide novel insights as to an endocrine pathway (AR activation) of potential concern relative to fish exposed to progestins in the environment [48].…”

Risks of Malignant and Non-Malignant Tumours in Tall Women Treated with High-Dose Oestrogen during Adolescence

“…The first combined contraceptive pill introduced in 1960 contained 150 μg of mestranol which is equivalent to 100 μg of ethinyloestradiol. The doses of ethinyloestradiol in use have since then gradually decreased to 20-30 μg [13,14]. A possible explanation to our results is, of course, that the difference in our study occurred by chance.…”

Influence of Menstrual Cycle and Oral Contraceptive Phase on Spinal Excitability

“…We hypothesized that the elevated levels of estradiol in nonusers would enhance spinal excitability, but that the users would have stable hormonal concentrations and spinal excitability. Our hypothesis was based on the fact that the exogenous hormones in the OCPs result in negative feedback to the hypothalamic–pituitary–ovarian axis, resulting in low stable concentrations of endogenous estrogen and progesterone [37]. However, our results show that OCPs do not mitigate cyclic changes in sex hormones, as the users demonstrated a trend similar to that in the nonusers, with a significantly higher peak of endogenous estradiol during the second testing session.…”