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BIOM2015 Physiology And Pharmacology Of Human Disease

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BIOM2015 Physiology And Pharmacology Of Human Disease

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BIOM2015 Physiology And Pharmacology Of Human Disease

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Course Code: BIOM2015
University: The University Of Queensland

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Country: Australia

Question: 
Review literature on the new contraceptives for men and their effects on health and reproduction.
Answer: 

Introduction:
Male contraceptives also referred to as male birth control are ways of averting pregnancy that mainly manipulates the male physiology. The commonly used kind of male contraception includes vasectomy, the withdrawal method, and condoms which are not suitable for all men. This is because the majority of the men find using a condom cumbersome while vasectomy requires surgery that is irreversible and the pullout method is not efficient enough to control pregnancy (Roth & Amory, 2016). Although contraceptives are mostly associated with women and are useful in ensuring that there are no unwanted pregnancies, some women are unable to use them due to adverse health effects and health conditions leaving them with no effective contraception methods. Also, the majority of the men desire to take responsibility for family planning. This explains why there is a great need for the invention of male contraceptives (Amory, 2016).
Although men want the invention of more birth control options, it has taken too long to get them. A lot of reasons have been given concerning the long time that has been taken to come up with male contraceptives. Men have partly been blamed for this and the fact that most women continue to bear the burden of using birth control methods. In late 2016, a huge clinical trial of a male hormonal contraceptive was stopped due to the side effects it had, and the men who undertook in the study were accused of being too inadequate in handling the side effects that women undergo as a result of pills every day (Antonietta, Giulia, Marta & Cristina, 2014).
It has proven very difficult to find new methods of contraception, and one of the primary challenges is dealing with male biology. The male produces approximately 250 million sperms during ejaculation while women produce one or two eggs every month making it easier to generate female contraceptives than the male contraceptives. Another challenge is ensuring that the birth control methods are as effective and safe as the ones used by women. This reason has made the majority of pharmaceutical companies quit the quest to identify new male contraceptives. Despite these problems, however, there has been some progress (Cheng & Mruk, 2013).
An estimated 80–90 million unintended pregnancies occur annually. The emergence of new male contraception has helped solve this problem. A study undertaken by Eppin Pharma and Oregon Health and Sciences University has identified a compound called EPO55 that has the potential of slowing the mobility of the sperm without interfering with the hormones. The compound works by binding to the sperm proteins and hence reducing the ability of the sperm to swim remarkably hindering fertilization. This makes this compound ideal for the non-hormonal male contraception method (Chao, Page & Anderson, 2014).
The study on compound EPO55 has been conducted on male rhesus macaques, a species of monkeys indigenous to northern India. According to medical daily, the monkeys were injected with a high-dose infusion, and after 30 hours, their sperm was unable to move. The sperms were able to regain their motility 18 days later. It is difficult to predict the effects of the compound since human trials have not been performed yet. The researchers are currently working on an oral pill and have stressed on the fact that more effort is needed to ensure that they are effective in preventing pregnancy.  
There has been the development of a daily gel which has both progestin and testosterone. The progestin present in the gel is meant to be injected to both the arms and shoulders daily with the aim of reducing the level of gonadotropin hormones which stimulate the production of testosterone in the testes. Since the production of sperms relies on high levels of testosterone in the testes, a blocking the gonadotropins reduces the production of sperms. Lowering the testosterone levels in the testes results in decreased levels in the blood to, and this can have severe side effects such as problems with ejaculation and reduced libido. This explains why the gel is substituted with testosterone to ensure that the normal functioning but hindering the production of sperms again (Costantino, Gava, Berra & Meriggiola, 2014).
The gel can suppress the level of sperms in an estimated 90 percent of men to one million millimeters or less which is the amount required in preventing unwanted pregnancy with fewer side effects. The gel is undergoing the clinical trials involving 420 couples in the UK, US, Kenya, Italy, and Chile where the couples are required to use the gel until their sperm count is low enough. They are expected to rely on this gel for contraception for a year. If the gel is proven effective and safe, they will move to the third phase where a large number of couples will be used (Colagross et al., 2017).
Researchers have come up with male birth control which is still undergoing clinical studies. The quest in coming up with the male pill has been quite challenging due to the sperm suppressing hormone which keeps changing such that the drug induces rapidly clears the body and hence requiring more than a once-daily dose. However, researchers are working towards coming up with a pill that overcomes the problem. Studies from a 100-person randomized controlled trial indicate that dimenthondrolone undecanoate also referred to as DMAU is safe when taken daily for an amount. The effects from the drug remain in the blood for an estimated 18hours suggesting that one will need to take it once a day (Ayoub, Page, Swerdloff, Liu, Amory, Leung & Bremner, 2017).
DMAU functions the same way as the birth control gel. This is because it is a steroid molecule containing the properties of progestin and testosterone. Researchers reveal that the pill can reduce sperm production. They have also shown that the drug was well tolerated and hence enhancing the drug development. The introduction of the female pill was accompanied by high doses than they are currently and the side effects were much higher. Recently, the medicine has mild side effects for the majority of the women setting the bar higher for researchers working on the introduction of male pills (Ayoub et al., 2017). Researchers are in the process of recruiting volunteers to aid in the testing of the injectable form of DMAU. Research undertaken in animals indicate that the injectable form can suppress the production of sperms for some months at a time and that they return to the usual levels once the dosage wears off (Kanakis & Goulis, 2015).
Researchers are in the process of coming up with the nonsurgical vasectomy which seems optimistic in animal studies. Vasectomy is the type of surgery that entails tying or cutting the vas deferens to prevent the sperm from moving into the urethra and getting into a female. Researchers in India have come up with a type of nonsurgical vasectomy called Reverse Inhibition of Sperm under Guidance. It entails administering a polymer gel into the vas deferens to block the sperm. This treatment can be reversed by injecting a sit that destroys the gel. This treatment will be introduced in India in the next couple of years. The treatment is 98% effective in preventing pregnancy. Approximately 540 men have received the treatment in India which continues to stop pregnancies in their partners for 13 years. The fact that India has a high number of married women with an unfulfilled need for birth control methods compared to any other country as well as increased social stigma and the absence of privacy in stores has made use of condoms to stand at less than 6% (Wang, Sitruk?Ware & Serfaty, 2016).
Researchers have also introduced Vasalgel that is the preclinical phase of testing. Although their human trails have not been scheduled yet, the results from the testing performed on rabbits and monkeys are quite promising (Waller, Bolick, Lissner, Premanandan & Gamerman, 2017). Researchers have also come up with Gossypol which is currently being studied as a male contraceptive. It is extracted from cotton and works by reducing the production of sperms. Women use it to treat disorders present in the uterus such as endometriosis, cancer, and abnormal bleeding (Colagross-Schouten, Lemoy, Keesler, Lissner & VandeVoort, 2017). When taken, Gossypol can reduce the sperm function and count in an estimated 60% to 100% of men. Stopping the treatment in 3-24 months can result in sperm recovery in 50% to 77% of men. Approximately 10% of men may experience very low sperm counts for about 4.5 years. While the continual use of Gossypol may lead to permanent loss of the ability to get children (Nya-Ngatchou & Amory, 2013).
Trestolone is a medication that is under development for future use as a way of non-hormonal birth control for men. For a man to be considered infertile, a non-hormonal birth control method should hinder spermatogenesis by interfering with the production of gonadotrophins. Trestolone can interrupt the release of follicle stimulating hormones, gonadotropins and luteinizing hormone even in low doses Spermatogenesis depends on the presence of testosterone and follicle stimulating hormone and hence interfering with the production of follicle stimulating hormone, trestolone provides an endocrine environment where spermatogenesis cannot occur (Kanakis & Goulis, 2015).
Phenoxybenzamine has been identified as a method of birth control that works by blocking ejaculation which makes it an effective way of contraception. Studies indicate that the medication does not affect the quality of semen and is easily reversible through terminating the treatment (Nieschlag, 2013). Adjudin and Gamendazole have been identified to cause infertility in rats. They are derived from Lonidamine and function by interfering with the functioning of the Sertoli cells and hence leading to decreased amounts of inhibin B. The sperms produces are premature and thus preventing pregnancy. This makes the use of Adjudin and Gamendazole more effective.
Researchers have come up with the clean sheet pill which is nonhormonal and works by hindering the releasing of the sperm.  It also reduces the spread of sexually transmitted infections. The clean sheet pill has only been tested in animals, and it has produced promising results, but the development has failed to progress due to lack of adequate finances.  The clean sheet pill results in the relaxation of muscles, leading to long contractions through vas deferens indicating that men will be able to attain orgasm but at the same time the production of semen will be inhibited (Michael, Silva & Hamil, 2016).
Nifedipine, an example of a calcium channel blocker can be used as a male contraceptive by changing the lipid metabolism of the sperm making it unable to fertilize an egg. Several tests have been conducted on the mice, and no side effects have been identified. The birth control method has also been found to be very useful in controlling pregnancy. The medication works by interfering with the ability of sperms to move and hence making it difficult for it to reach and fertilize an egg (Roth, Page & Bremner, 2016).
Researchers are investigating the immunocontraception method of birth control that has been proved to be successful in primates. Generally, immunocontraception entails the introduction of vaccines that result in an adaptive immune system which result in short term infertility. Extensive innovations have to be done for it to be used by human beings. This method of contraception is better than the existing methods of contraception. This is because it does need surgery unlike methods such as tubal ligation and vasectomy. This type of birth control can be given once annually as opposed to the daily pills (Murdoch & Goldberg, 2014).
Researchers have also come up with the combination of Depo-Provera injections to hinder spermatogenesis as well as the application of the testosterone gel on the skin to enhance the hormones. They have also invented a similar method to this which includes the use of a subdermal implant injecting the compound 7α-methyl-19-nortestosterone as well as the Depo-Provera which is to be administered annually. The Depo-Provera injection has shown the ability to decrease the sperm count if used at a higher dosage (Roth et al., 2016).
Research indicates that the testosterone undecanoate injection can also prevent unwanted pregnancy in men. This injection has successfully passed the Phase III trial in China. Testosterone is important in enhancing the growth and development of male features as well as their sex organs (Wang, Festin & Swerdloff, 2016). Male hormonal contraception. Research shows that the blocking of chromatin remodeling by binding to BRDT can cause changeable infertility in male mice. Currently, there is the development if JQ1, which is a nonhormonal birth control method that can effectively inhibit the testes from producing the sperms. This type of contraception does not have the side effects like the initially researches hormonal birth control methods for men (Kogan & Wald, M. (2014).
Effects of male contraceptives on health and reproduction
Male contraceptives can cause adverse health effects on the health and the male reproduction. Majority of this birth control methods can increase the risk of developing cardiovascular diseases (Zitzmann, 2018). Gossypol is considered very harmful for use without the supervision of a healthcare professional. When ingested through the mouth, the effects remain uncertain and may lead to a permanent inability to bear children in men is used for an extended period. When ingested by women, it may result in the interruption of the regular functioning of the ovaries. It can also result in loss of appetite, decreased sex drive, reduced potassium levels, loss of energy and the disruption of the functioning of the digestive tract. High doses can result in problems in the circulation of blood, malnutrition and other issues. It is also unsafe to apply Gossypol directly on the skin as it may cause itching and burning sensation. It may also worsen existing conditions such as urinary tract infections. It may also worsen conditions such as hypokalemia (Keshmiri-Neghab & Goliaei, 2014).
Trestolone can result in infertility in the majority of the men. However, this can be changed through the discontinuation of the drugs.  It can also lead to low estrogen levels and reduced sex drive as well as decreased bone mineral density. The side effects of Phenoxybenzamine the fatigue, nasal congestion, failure to ejaculate, nausea and vomiting, drowsiness and dryness of the mouth.  Nifedipine has numerous side effects such as redness of the skin, dizziness, constipation, nausea, and diarrhea. It can also cause a headache and low blood pressure. Immunocontraception can result in severe adverse effects such as autoimmunity as a result of the interruption of the immune system. The side effect of Testosterone undecanoate include loss of hair, pain at the injection site, increased weight gain, Acne, increased size of the breast in men, irritation, and dryness in the mouth and the gum and difficulty in sleeping (Chao et al., 2014).
In conclusion, the development of new male contraceptives is promising. This is a significant step in ensuring that there are reduced unplanned pregnancies and hence reducing human suffering and poverty. Although women are used to taking contraceptives, the introduction of male birth control methods will result in decreases unplanned pregnancies by 50%. Therefore, many efforts should be put towards ensuring that the development of the male contraceptives.
References:
Amory, J. K. (2016). Male contraception. Fertility and sterility, 106(6), 1303-1309.
Antonietta, C., Giulia, G., Marta, B., & Cristina, M. M. (2014). Advances in male hormonal contraception. The Indian Journal of Medical Research, 140(Suppl 1), S58.
Ayoub, R., Page, S. T., Swerdloff, R. S., Liu, P. Y., Amory, J. K., Leung, A., … & Bremner, W. J. (2017). Comparison of the single dose pharmacokinetics, pharmacodynamics, and safety of two novel oral formulations of dimethandrolone undecanoate (DMAU): a potential oral, male contraceptive. Andrology, 5(2), 278-285.
Chao, J., Page, S. T., & Anderson, R. A. (2014). Male contraception. Best Practice & Research Clinical Obstetrics & Gynaecology, 28(6), 845-857.
Cheng, C. Y., & Mruk, D. D. (2013). Why do we need male contraceptives?. Spermatogenesis, 3(3), e25888.
Colagross-Schouten, A., Lemoy, M. J., Keesler, R. I., Lissner, E., & VandeVoort, C. A. (2017). The contraceptive efficacy of intravas injection of Vasalgel™ for adult male rhesus monkeys. Basic and clinical andrology, 27(1), 4.
Costantino, A., Gava, G., Berra, M., & Meriggiola, C. M. (2014). Advances in male hormonal contraception. The Indian journal of medical research, 140(Suppl 1), S58-62.
Kanakis, G. A., & Goulis, D. D. (2015). Male contraception: a clinically-oriented review. Hormones (Athens), 14(4), 598.
Keshmiri-Neghab, H., & Goliaei, B. (2014). Therapeutic potential of gossypol: an overview. Pharmaceutical biology, 52(1), 124-128.
Kogan, P., & Wald, M. (2014). Male contraception: history and development. Urologic Clinics, 41(1), 145-161.
Michael, G. O., Silva, E. J., & Hamil, K. G. (2016). Non-hormonal male contraception: A review and development of an Eppin based contraceptive. Pharmacology & therapeutics, 157, 105-111.
Murdoch, F. E., & Goldberg, E. (2014). Male contraception: Another holy grail. Bioorganic & medicinal chemistry letters, 24(2), 419-424.
Nieschlag, E. (2013). Hormonal male contraception: end of a dream or start of a new era?. Endocrine, 43(3), 535-538.
Nya-Ngatchou, J. J., & Amory, J. K. (2013). New approaches to male non-hormonal contraception. Contraception, 87(3), 296-299.
Roth, M. Y., & Amory, J. K. (2016, May). Beyond the condom: frontiers in male contraception. In Seminars in reproductive medicine (Vol. 34, No. 3, p. 183). NIH Public Access.
Roth, M. Y., Page, S. T., & Bremner, W. J. (2016). Male hormonal contraception: looking back and moving forward. Andrology, 4(1), 4-12.
Waller, D., Bolick, D., Lissner, E., Premanandan, C., & Gamerman, G. (2017). Reversibility of Vasalgel™ male contraceptive in a rabbit model. Basic and clinical andrology, 27(1), 8.
Wang, C., Festin, M. P., & Swerdloff, R. S. (2016). Male hormonal contraception: where are we now?. Current obstetrics and gynecology reports, 5(1), 38-47.
Wang, C., Sitruk?Ware, R., & Serfaty, D. (2016). It is time for new male contraceptives!. Andrology, 4(5), 773-775.
Zitzmann, M. (2018). Would male hormonal contraceptives affect cardiovascular risk?. Asian journal of andrology, 20(2), 145.

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