Development Of Hormonal Contraceptives Research Articles

Hormonal male contraception.

Male contraception with exogenously administered hormones suppresses both luteinizing hormone and follicle stimulating hormone leading to low intratesticular testosterone concentration. This results in reversible suppression of spermatogenesis and marked decrease in sperm output in the ejaculate and preventing pregnancy in the female partner. Studies of testosterone administered alone or in combination of another gonadotropin suppressive agent such as a progestin or gonadotropin releasing hormone (GnRH) analog showed decisively that the exogenous hormone administrations are effective in suppressing sperm output with few adverse events that are not anticipated. In contraceptive efficacy studies, testosterone alone or combined with a progestin are as effective in preventing pregnancies as female contraceptive methods. Hormone combinations for male contraception are in late-phase clinical trials and hold the promise of being the new, reversible contraception method for men in over half a century. Lessons learned from the male hormonal contraceptive development pave the way for new targeted approached to regulate male fertility.

A global grounded theory exploration of investigators’ perspectives on male hormonal contraceptive development and acceptability

ABSTRACT While best practices have been proposed on how to engage men in family planning (FP), the limited options of male hormonal contraceptives (MHC) are a barrier to reaching men as clients of FP programs. The lack of alternative MHC is preventing the global health community from providing holistic reproductive healthcare. A qualitative grounded theory study was conducted in 2020 to explore MHC experts’ perceptions around the development and theoretical acceptability of MHCs. Individual in-depth interviews were conducted with 15 key informants. The informants cited evidence that there is a demand for MHC. The inability to access this data by the pharmaceutical industry was acknowledged. Many informants expressed concern of the possibility for MHC to increase male power in a predominantly patriarchal world. To most informants, at least for the initial introduction of MHC, fertility sharing is something that will largely happen among couples alone rather than individually. There is proven demand among women and men for MHC, however industries may still be reluctant to invest. Effort is needed by the sexual and reproductive health and rights community to include male engagement in FP and to advocate for the development and use of MHC as a tool for women’s empowerment.

The other sexual revolution: hormonal control of family planning in plants

The development of hormonal contraceptives stands out as a key contribution of biochemistry to the 20th century, part of the wider ‘sexual revolution’ that dramatically changed society in many Western countries. But unbeknown to them, the pioneers of the contraceptive pill had been beaten to the idea by a few hundred million years, by a rather unlikely group of organisms that have been using hormones as contraceptives since their own sexual revolutions back in the swinging Palaeozoic. Since their successful conquest of land in the Ordovician, land plants had been restricted in the genetic mixing and expansion of populations by their relative immobility. A series of key innovations in the seed plant group, and in particular in flowering plants, enabled plants to mate and to disperse their offspring over much longer distances, by harnessing the wind or animals to provide mobility. However, all this ‘outsourcing’ created new challenges; coordinating and optimizing reproductive effort is not straightforward when it depends on a third party. Here, I discuss some of the key signalling molecules – sex hormones, as it were – that plants use to plan their families and manage their fertility, and why this matters to us, now more than ever.

Conhecimentos dos Médicos Residentes de Ginecologia e Obstetrícia sobre Contracepção Hormonal em Situações Especiais

RESUMO Introdução Os anticoncepcionais hormonais (ACH) vêm sendo utilizados e difundidos desde a década de 1960. Sua importância atualmente é inegável, pois eles são responsáveis pelo tratamento e prevenção de várias doenças ginecológicas. A evolução dos ACH consistiu na implantação de uma ampla variedade de contraceptivos, de diferentes dosagens, combinações e formas de administração. Com o intuito de orientar sobre a segurança dos vários métodos contraceptivos em contextos específicos, a Organização Mundial da Saúde (OMS) lançou o guia Critérios de Elegibilidade para o Uso de Contraceptivos. Objetivo Este estudo objetiva avaliar o conhecimento dos residentes de Ginecologia e Obstetrícia de Goiânia a respeito da contracepção hormonal, de acordo com o guia Critérios de Elegibilidade para o Uso de Contraceptivos da OMS. Métodos Foi realizado um estudo transversal, descritivo, com residentes de Ginecologia e Obstetrícia de dois hospitais de Goiânia (GO), um filantrópico e outro da Secretaria Estadual de Saúde de Goiás. Foi aplicado um questionário com perguntas de cunho epidemiológico e perguntas técnicas sobre indicações e contraindicações de determinados métodos contraceptivos nas seguintes situações especiais: cefaleias, hipertensão arterial sistêmica, tabagismo, tromboembolismo, trombose arterial e embolia pulmonar. Foi realizada análise univariada, e os dados foram dispostos em tabelas de frequência. Resultados Os questionários foram respondidos por 33 residentes, com média de idade de 29,2 anos, dos quais 61% afirmaram ter formação adequada sobre contracepção; 63% se sentiam aptos a prescrevê-los; e os residentes dos dois últimos anos se sentiram mais seguros (82,4%) do que o grupo de recém-chegados à residência e os residentes do primeiro ano (75%), porém não foi obtida diferença significativa entre eles. Conclusão Os anos de residência médica não foram suficientes para melhorar significativamente os conhecimentos a respeito dos critérios de elegibilidade da OMS entre os grupos iniciais e finais do curso de residência, apesar de oferecerem maior segurança na prescrição.

Contraception: an ongoing study in misinformation and misunderstanding

The last six decades have witnessed the birth and development of hormonal contraception, a truly monumental milestone in human history given its profound impact on women’s health, wellbeing and sex...

Physiologic role and regulation of intratesticular sex steroids

To summarize recent advances in our understanding of the role and regulation of intratesticular androgens, and their metabolites, in human spermatogenesis. Over the last few years, a number of studies have been published examining intratesticular sex steroid concentrations in normal men following gonadotropin manipulation and in the setting of impaired fertility. Advances in the field have been facilitated by the availability of more sensitive and specific assays for intratesticular sex steroid quantification. High levels of intratesticular androgens are required for normal spermatogenesis in men. However, the quantitative relationship between intratesticular testosterone concentrations and male fertility is not fully understood. In the setting of impaired spermatogenesis, intratesticular metabolites of testosterone may play a role in initiating or maintaining fertility. Advances in the precision of androgen measurements and recent studies examining intratesticular responses to hormonal manipulation have advanced our understanding of the testicular microenvironment. These advances have set the stage for future studies in this area which will be important for moving forward male hormonal contraceptive development and furthering our understanding of male reproductive pathology. Whether 'gonadotropin-independent' intratesticular androgen synthesis plays a role in human spermatogenesis will likely be a focus of investigation in the coming years.

Efficacy, safety, and patient acceptability of the combined chlormadinone acetate-ethinylestradiol oral contraceptive

Efficacy, safety, and patient acceptability of the combined chlormadinone acetate-ethinylestradiol oral contraceptive Serena Ferrari, Marianna Cannoletta, Matteo Generali, Lucia Cazzato, Angelo CagnacciDepartment of Obstetrics, Gynecology, and Pediatrics, Azienda Ospedaliero, Universitaria di Modena, ItalyAbstract: Since their introduction in 1959, development of hormonal contraceptives has been ongoing, with the ultimate aim of creating not only an effective and safe contraceptive method, but also a drug able to meet the need for treatment of other conditions, such as acne, seborrhea, and hirsutism, with few or no side effects. With this objective, a new progestin, chlormadinone acetate (CMA), has been developed as a derivative of progesterone for ­contraception. This new molecule has been introduced in combination with ethinylestradiol (EE) 30 µg as a safe ­contraceptive with antiandrogenic properties. Many clinical studies have investigated this new oral combination and found it to be safe, with a Pearl Index similar to that of other combined hormonal contraceptives. CMA, because of its antiandrogenic properties, has been also considered effective for resolution of acne, seborrhea, and hirsutism. The data show it to be a safe molecule in terms of glucose and lipid metabolism. No major weight changes have been linked with its use, and it seems to be the only progestin able to reduce fat mass during use. The CMA-EE combination is well tolerated and acceptable to women. Adverse events related to its use are similar to those reported with other third-generation ­contraceptives. We can conclude that CMA-EE is an effective, safe, and well tolerated ­antiandrogenic hormonal contraceptive.Keywords: chlormadinone acetate, acne, weight, metabolism, safety, hormonal contraceptive

Demographic effects of the introduction of steroid contraception in developed countries

The use of the contraceptive pill increased very rapidly in the 1970s in many developed countries, and fertility almost simultaneously started to decline. We discuss here the possibility of a causal link between these two major changes. We first provide evidence for a relationship between the spread of oral contraceptive use and the change in fertility in many European countries over the last three or four decades. The situation of specific countries is examined more in depth on the basis of available literature. We then review the various theories attempting to explain these trends and see how the family planning variables are treated in these approaches. At the country level, the conclusion is unambiguous: within individual countries, there is no systematic negative correlation between fertility and contraceptive pill use. The development of hormonal contraception cannot be considered as responsible for either starting or the size of the fertility decline. A more subtle chain of causality must be considered, but there is no agreement on a general theory of fertility changes. Most authors, however, agree that the diffusion of modern contraception has certainly contributed to the reduction in the number of unwanted pregnancies and has also facilitated and favoured the adoption of new (more restrictive) norms for the ideal family size.

Future developments in hormonal contraception

The range of contraception options has recently increased to include long-term, reversible, and highly effective methods. Several new oral contraceptive (OC) formulations are now available in the United States, where OCs are the most popular reversible method. Long-term contraceptive systems that deliver hormones via subdermal implants, vaginal ring, intrauterine system, and transdermal patch afford convenient and effective alternatives to OCs. Contraceptives using hormone combinations appear to be especially effective with safety profiles comparable to OCs. All recently approved in the United States, the transdermal contraceptive patch offers once-weekly dosing with an improved compliance profile, the monthly vaginal ring has the convenient advantage of being user-controlled; a monthly combination injectable provides good pregnancy protection and improved bleeding control compared with the progestin-only formulatin; and the 5-year the levonorgestrel-releasing intrauterine system significantly diminishes menstrual blood loss. A single subdermal implant has been approved for use in Europe. With 60% of all unintended pregnancies occurring in women using birth control, it is anticipated that this increasing range of options will enhance compliance and provide more effective contraception suitable for the individual user.

Regulation of testicular function in men: implications for male hormonal contraceptive development

In the adult male, the testes produce both sperm and testosterone. The function of the testicles is directed by the central nervous system and pituitary gland. Precise regulation of testicular function is conferred by an elegant feedback loop in which the secretion of pituitary gonadotropins is stimulated by gonadotropin hormone-releasing hormone (GnRH) from the hypothalamus and modulated by testicular hormones. Testosterone and its metabolites estradiol and dihydrotestosterone (DHT) as well as inhibin B inhibit the secretion of the gonadotropins both directly at the pituitary and centrally at the level of the hypothalamus. In the testes, LH stimulates testosterone synthesis and FSH promotes spermatogenesis, but the exact details of gonadotropin action are incompletely understood. A primary goal of research into understanding the hormonal regulation of testicular function is the development of reversible, safe and effective male hormonal contraceptives. The administration of exogenous testosterone suppresses pituitary gonadotropins and hence spermatogenesis in most, but not all, men. The addition of a second agent such as a progestin or a GnRH antagonist yields more complete gonadotropin suppression; such combination regimens effectively suppress spermatogenesis in almost all men and may soon bring the promise of hormonal male contraception to fruition.

Recent developments in hormonal contraception.

Recent developments in hormonal contraception.

Identification of specific sites of hormonal regulation in spermatogenesis in rats, monkeys, and man.

A detailed understanding of the hormonal regulation of spermatogenesis is required for the informed assessment and management of male fertility and, conversely, for the development of safe and reversible male hormonal contraception. An approach to the study of these issues is outlined based on the use of well-defined in vivo models of gonadotropin/androgen deprivation and replacement, the quantitative assessment of germ cell number using stereological techniques, and the directed study of specific steps in spermatogenesis shown to be hormone dependent. Drawing together data from rat, monkey, and human models, we identify differences between species and formulate an overview of the hormonal regulation of spermatogenesis. There is good evidence for both separate and synergistic roles for both testosterone and follicle-stimulating hormone (FSH) in achieving quantitatively normal spermatogenesis. Based on relatively selective withdrawal and replacement studies, FSH has key roles in the progression of type A to B spermatogonia and, in synergy with testosterone, in regulating germ cell viability. Testosterone is an absolute requirement for spermatogenesis. In rats, it has been shown to promote the adhesion of round spermatids to Sertoli cells, without which they are sloughed from the epithelium and spermatid elongation fails. The release of mature elongated spermatids from the testis (spermiation) is also under FSH/testosterone control in rats. Data from monkeys and men treated with steroidal contraceptives indicate that impairment of spermiation is a key to achieving azoospermia. The contribution of 5alpha-reduced androgens in the testis to the regulation of spermatogenesis is also relevant, as 5alpha-reduced androgens are maintained during gonadotropin suppression and may act to maintain low levels of germ cell development. These concepts are also discussed in the context of male hormonal contraceptive development.

Would Women Trust Their Partners to Use a Male Pill?

Despite a renewed interest in the development of hormonal contraceptives for men, many discussions about the potential acceptability of a 'male pill' end by speculating whether women would trust their partners to use the method reliably. To determine the views of women, we undertook a survey of 1894 women attending family planning clinics in Scotland (450), China (900) and South Africa (544). In all centres over 65% of women thought that the responsibility for contraception falls too much on women. More than 90% in South Africa and Scotland thought that a 'male pill' was a good idea, with Chinese women (71% in Hong Kong and 87% in Shanghai) only slightly less positive. Only 13% of the total sample did not think that hormonal male contraception was a good idea and only 36 women (2% of the total) said that they would not trust their partner to use it. 78% of Scottish women, 71% of Shanghai women, and 78% of white women and 40% of black and coloured women in Cape Town thought that they would use the method. This survey should dispel the myth that women would not trust their partners to use a 'male pill' reliably and illustrates the potential market for the method.

Would women trust their partners to use a male pill?

Despite a renewed interest in the development of hormonal contraceptives for men, many discussions about the potential acceptability of a 'male pill' end by speculating whether women would trust their partners to use the method reliably. To determine the views of women, we undertook a survey of 1894 women attending family planning clinics in Scotland (450), China (900) and South Africa (544). In all centres over 65% of women thought that the responsibility for contraception falls too much on women. More than 90% in South Africa and Scotland thought that a 'male pill' was a good idea, with Chinese women (71% in Hong Kong and 87% in Shanghai) only slightly less positive. Only 13% of the total sample did not think that hormonal male contraception was a good idea and only 36 women (2% of the total) said that they would not trust their partner to use it. 78% of Scottish women, 71% of Shanghai women, and 78% of white women and 40% of black and coloured women in Cape Town thought that they would use the method. This survey should dispel the myth that women would not trust their partners to use a 'male pill' reliably and illustrates the potential market for the method.

How the Oral Contraceptives Came to be Developed

IT IS an appealing and romantic notion to think that great discoveries spring fullblown from the brow of genius, catalyzed by trivial events such as an overflowing bathtub or a falling apple; indeed, some great discoveries may have happened in this way. However, in today's world, with its virtually instant information access and the living presence of nine tenths of all the scientists who ever existed, discoveries are more likely to arise from a coincidence of information, technological advances, intellectual and societal timeliness, and financial support. The development of hormonal contraceptives is one of the epochal events of the 20th century. Its direct and remote effects on moral, social, and other cultural values; on the interaction of population, resources, and environment; and thus on the ultimate state of the human condition remain for future historians to assess. The Idea It has been said that every idea has a pedigree. The