DISUSUN OLEH:
NPM : 183112540120561
Kelas : B5 Kebidanan
UNIVERSITAS NASIONAL
JAKARTA
2019
ii
KATA PENGANTAR
Puji dan syukur penyusun panjatkan kepada Tuhan Yang Maha Esa atas
selesainya tugas Individu II mata kuliah Asuhan Kebidanan Terkini dengan judul
“Jurnal Kontrasepsi Pria di Indonesia dan Luar Negeri”. Makalah ini dapat
begitupun tugas yang telah penyusun buat, baik dalam hal isi maupun
karena itu, saran dan kritik yang membangun dari rekan-rekan sangat dibutuhkan
makalah ini dapat bermanfaat sebagai sumbangan pemikiran kecil bagi kemajuan
Penyusun
iii
DAFTAR ISI
JUDUL ...........................................................................................................................i
BAB I PENDAHULUAN
B. Tujuan ..................................................................................................3
A. Kesimpulan ...........................................................................................40
B. Saran ......................................................................................................40
DAFTAR PUSTAKA
BAB I
PENDAHULUAN
A. Latar Belakang
sel telur yang dilepaskan dari indung telur wanita pada masa suburnya.
vasektomi).
untuk didapatkan dan digunakan. Selain itu, harganya murah dan minim
efek samping. Bentuk kondom berupa selubung tipis yang elastis, dan
vasektomi, tidak ada lagi sperma di dalam air maninya. Jadi meskipun
B. Tujuan
Untuk Menganalisis secara ilmiah terkait isi jurnal terapi Kontrasepsi
BAB II
ANALISIS JURNAL
A. Judul Jurnal
2. Male Contraception.
B. Pengarang
& Suprayetno
2007).
vasektomi dari seluruh dunia, negara Cina dan India saja sudah
2015).
mengatakan pria ber KB itu lucu dan aneh, KB itu kan hanya
cara:
14
nonhormonal eksperimental).
oleh karena itu dianggap sebagai alat kontrasepsi wanita yang lebih
baik, sehingga mereka tidak akan dibahas lebih lanjut dalam ulasan
reproduksi wanita.
& Suprayetno
Analisis Univariat
1. Karakteristik Responde
a. Umur
Kabupaten Bengkalis
(67,9 %).
16
b. Pekerjaan
(75,6%).
c. Pendidikan
d. Jumlah Anak
orang (55,1%).
f. Sumber Informasi
Tabel Distribusi Frekuensi Responden
6.
Berdasarkan Sumber Informasi Di Desa Mentayan
Wilayah Kerja UPT Puskesmas Selatbaru Kecamatan
Bantan Kabupaten Bengkalis Tahun
2016
18
2 Negatif 50 64,1
Jumlah 78 100
19
4. Penggunaan KB Vasektomi
Tabel 9. Distribusi Frekuensi Penggunaan KB Vasektomi Di Desa
Analisa Bivariat
Analisis bivariat adalah analisis yang digunakan untuk melihat
KB Vasektomi
Pengeta Penggunaan KB P
pengetahuannya kurang.
Moti Penggunaan KB
Vasi Vasektomi Total P value
Suami Tidak Ya OR
N % N % N %
Negatif 4 98 1 2 5 100 0,000
9 0
21
Unintended pregnancy
Method 1992 1995 2002 2008 rate per year (%)
Vasectomy 11 11 9 10 0.1
Condoms 12 20 18 16 15–20
Withdrawal 2 3 4 5 25–30
Total 25 34 31 31
(
operasi, dan infeksi yang jarang. Meskipun sebagian besar nyeri pasca
lamanya waktu antara vasektomi dan vas ovasostomi karena dua alasan.
23
patensi vas, terutama jika> 8 tahun telah berlalu sejak vasektomi asli
Kedua, 20% -30% pria tetap infertil meskipun telah dipatenkan vas, seperti
vasektomi adalah sangat efektif dan sangat aman. Kelemahan utama adalah
diinginkan.
selama beberapa ratus tahun. Sejak 1920, sebagian besar kondom terbuat
dari lateks. Kondom lateks unik di antara alat kontrasepsi karena kondom
yang sebagian besar merupakan hasil dari penggunaan atau kerusakan yang
tidak tepat atau tidak konsisten, yang terjadi pada 4% kasus . Tingkat
dengan kesuburan spontan tinggi . Selain itu, beberapa pria tidak menyukai
FSH dari hipofisis melalui umpan balik negatif (Gbr. 1B). Konsentrasi LH
dan FSH yang rendah menghilangkan testis dari sinyal yang diperlukan
pada sebagian besar, tetapi tidak semua, pria setelah 3-4 bulan pemberian
yang berasal dari hormon akan disambut oleh sebagian besar pria dan, yang
25
ejakulasi dari 15 hingga 150 juta sperma per mililiter ejakulasi. Tidak
mereka menjadi <15 juta per mililiter, yang disebut oligospermia, tanpa
menjadi <1% per tahun . Oleh karena itu, penekanan 100% pria yang
diobati dengan konsentrasi sperma <1 juta sperma per mililiter dianggap
hormonal pria. Relawan studi di Asia lebih rentan terhadap penekanan sper-
kisaran 90% -100%, sedangkan pria yang belajar di Eropa, Amerika Utara,
rejimen yang sama . Tidak ada penjelasan yang jelas untuk perbedaan ini.
Namun demikian, ini penting dalam interpretasi hasil uji coba dan
terdegradasi oleh hati. Oleh karena itu, sebagian besar rejimen kontrasepsi
lebih lama seperti testosteron enanthate (TE) yang diberikan dengan cara
injeksi intramuskular setiap minggu. Dua uji coba multisenter dari suntikan
Dunia (WHO). Studi pertama mendaftarkan 271 subyek yang diberi dosis
mereka selama 1 tahun. Selama periode itu, hanya satu kehamilan terjadi,
pria yang menjadi azoospermic atau oligo-sperma hingga <3 juta sperma
dalam penelitian ini. Tiga ratus sembilan puluh satu (98%) pria menjadi
PEMBAHASAN
faktor umur yang masih dewasa muda (21-40 tahun) dan jumlah
Suparyanto, 2010).
gagal menekan hingga <3 juta sperma per mili liter dan karenanya
kesehatan prostat dan hati serta suasana hati dan perilaku tidak
diketahui.
suntikan bulanan 500 atau 1.000 mg TU. Sembilan puluh persen pria
dan efek sampingnya minimal; namun, untuk alasan yang tidak jelas
lebih unggul dari TE saja dalam hal azoospermia (67% vs 33%), dan
rejimen LNG-TE termasuk kenaikan berat badan yang lebih besar dan
yang sangat tinggi tetapi hanya dalam uji coba kecil pada 10-15 pria
.dan dalam uji coba kontrasepsi pria 6 bulan . Dalam studi terakhir,
1 juta sperma per mililiter. Yang penting, sebagian besar subyek pada
sampai saat ini tidak ada generasi kandidat yang saat ini telah diuji
189453 adalah panantagonis RAR yang aktif secara oral. Pada dosis
mata pelajaran. Senyawa ini, atau antagonis alfa asam reti-asam yang
Sejak awal 1990-an, upaya telah dilakukan di India dan Cina untuk
klinis kecil pada pria telah dilakukan dengan menggunakan teknik ini
Suprayetno
kategori rendah.
penggunaan KB vasektomi.
penggunaan KB vasektomi.
BAB III
PENUTUP
A. KESIMPULAN
Untuk waktu yang lama, pria hanya bergantung pada dua metode
tabung yang membawa sperma ke penis. Sementara, pil KB pria dan gel
suntikan dan implan; cincin; dan suntikan dan spons. Waktu dan sikap
berubah secara global. Salah satu alasan pria tidak terlibat dalam
B. SARAN
melakukan vasektomi dan tidak bisa memiliki anak lagi. Oleh karena
41
Pria sebagai suami dapat mencari informasi lebih banyak dari tenaga
digunakan.
42
DAFTAR PUSTAKA
_______, 2009. Peningkatan Partisipasi Pria dalam KB dan KR. Jakarta :BKKBN
:Genta Jalsus.
_______ Riau, 2016. Data Cakupan Peserta KB Vasektomi Provinsi Riau Tahun
2015-2016.
Skripsi,UniversitasAirlangga,Yogyak arta.Repository.unair.ac.id/.FKM.%2
43
Becker KL, ed-itor. Principles and practice of endocrinology and metabolism. 2nd
absence of the vas deferens. The fertilizing capacity of human epididymal sperm.
5. Roth MY, Page ST, Lin K, Anawalt BD, Matsumoto AM, Snyder
6. Haws JM, Morgan GT, Pollack AE, Koonin LM, Magnani RJ,
12. McMahon AJ, Buckley J, Taylor A, Lloyd SN, Deane RF, Kirk D.
13. Myers SA, Mershon CE, Fuchs EF. Vasectomy reversal for
15. Belker AM, Thomas AJ, Fuchs EF, Konnak JW, Sharlip ID.
17. Peterson HB, Howards SS. Vasectomy and prostate cancer: the
C, et al. Fac-tors associated with condom use problems during vaginal sex with
new estimates from the 1995 National Survey of Family Growth. Fam Plann
Fertility, contra-ception, and fatherhood: data on men and women from cycle 6
(2002) of the 2002 National Survey of Family Growth. Vital Health Stat 23
2006;26: 1–142.
22. Newby KV, Brown KE, French DP, Wallace LM. Which outcome
25. Walsh TL, Frezieres RG, Peacock K, Nelson AL, Clark VA,
Alini1, Suprayetno2
1
Dosen Universitas Pahlawan Tuanku Tambusai
2
Mahasiswa Program Studi Sarjana Keperawatan Universitas Pahlawan Tuanku Tambusai
Email : Alini_09@yahoo.com
ABSTRAK
Vasektomi merupakan kontrasepsi yang memiliki efektifitas tinggi (98,85%) untuk dapat
mencegah kehamilan. Data kantor BPP dan KB Kabupaten Bengkalis menyebutkan bahwa
akseptor KB vasektomi pada tahun 2016 berjumlah 8 akseptor, mengalami penurunan
dibandingkan tahun 2014 sebanyak 43 akseptor. Tujun penelitian ini untuk mengetahui
hubungan pengetahuan dan motivasi suami tentang vasektomi dengan penggunaan KB
vasektomi. Desain penelitian yang digunakan adalah kuantitatif dengan pendekatan cross
sectional study. Populasinya adalah KK pria sudah menikah di Desa mentayan, pengambilan
sampel secara purposive sampling berjumlah 78 KK pria menikah memenuhi syarat vasektomi.
Hasil analisa univariat diketahui pengetahuan responden tentang vasektomi sebagian besar
kurang (60,3%), motivasi suami untuk melakukan vasektomi sebagian besar negatif (64,1%).
Hasil analisa bivariat menggunakan uji chi square menunjukkan ada hubungan antara
pengetahuan dan motivasi suami dengan penggunaan KB vasektomi di Desa Mentayan
wilayah kerja UPT Puskesmas Selatbaru Kecamatan Bantan, diperoleh nilai p value=0,000 ≤
(0,05). Diharapkan kepada pihak BPP dan KB Kabupaten Bengkalis agar dapat memberikan
informasi secara luas dan terbuka sehingga masyarakat termotivasi untuk menggunakan KB
vasektomi.
Kata Kunci: Pengetahuan, Motivasi, Vasektomi
ABSTRACT
Vasectomy is a contraceptive that has a high effectiveness (98.85%) in order to prevent
pregnancy. BPP and Bengkalis District office data stated that the acceptors of KB vasectomy
in 2016 amounted to 8 acceptors, decreased compared to 2014 as many as 43 acceptors. The
purpose of this study to determine the relationship of knowledge and motivation of husbands
about vasectomy with the use of KB vasectomy. The research design used was quantitative
with cross sectional study approach. The population is KK married man in Desa mentayan,
sampling by purposive sampling amounting to 78 KK married man eligible vasectomy. The
result of univariate analysis is known that the respondent's knowledge about vasectomy is
mostly (60,3%), husband's motivation to do vasectomy is mostly negative (64,1%). The result
of bivariate analysis using chi square test showed that there was a relationship between
husband's knowledge and motivation with the use of KB vasectomy in Mentayan village
working area of UPT Puskesmas Selatbaru Subdistrict of Bantan, obtained p value = 0,000 ≤
(0,05). It is expected that the BPP and KB Bengkalis regency in order to provide information
widely and openly so that people are motivated to use KB vasectomy.
Keywords: Knowledge, Motivation, Vasectomy
Responden yang memiliki pengetahuan mengikuti pola hidup yang sehat dan
baik tentang vasektomi lebih besar melakukan pemeriksaan kesehatan rutin.
kemungkinannya untuk menggunakan KB Hasil penelitian ini juga didukung oleh
vasektomi. Pengetahuan dapat membentuk penelitian Surinati dkk (2014) di Banjar
keyakinan tertentu sehingga seseorang Karang Sewung Denpasar, dari hasil
berperilaku sesuai keyakinan tersebut. penelitian diketahui bahwa dari 123
Sedangkan responden yang memiliki responden, yang memiliki pengetahuan
pengetahuan kurang tentang vasektomi baik (51,2%) sebagian besar (91,9%) tidak
cenderung akan menolak untuk menggunakan KB vasektomi dengan hasil
menggunakan KB vasektomi, kecuali ada uji statistik p value=0,002 yang artinya
faktor eksternal yang membuat responden terdapat hubungan yang signifikan antara
tersebut menggunakan KB vasektomi. pengetahuan dengan penggunaan KB
Menurut Notoatmodjo (2007) vasektomi.
pengetahuan merupakan hasil dari tahu dan Penelitian lain yang dilakukan Prasetyo
ini terjadi setelah orang melakukan (2014) di Kabupaten Karanganyar, hasil
penginderaan terhadap suatu objek tertentu penelitian pada chi square memiliki angka
melalui panca indera manusia yaitu 0,951 yang menunjukkan bahwa ada
penglihatan, pendengaran, penciuman, perbedaan yang bermakna antara tingkat
rasa, dan raba. Sebagian pengetahuan pengetahuan suami tentang vasektomi
manusia diperoleh melalui mata dan dengan keikutsertaan dalam program KB
telinga. pengetahuan baik dipengaruhi oleh vasektomi.
pendidikan yang tinggi yang artinya 2. Hubungan Motivasi Suami Dengan
bimbingan yang diberikan seseorang Penggunaan KB Vasektomi Di Desa
kepada orang lain terhadap suatu hal agar Mentayan Wilayah Kerja UPT
mereka dapat memahami. Tidak dapat Puskesmas Selatbaru Kecamatan
dipungkiri bahwa semakin tinggi Bantan Kabupaten Bengkalis Tahun
pendidikan seseorang semakin mudah pula 2016
mereka menerima informasi dan pada Berdasarkan hasil penelitian diketahui
akhirnya semakin banyak pula ada hubungan yang signifikan antara
pengetahuan yang dimilikinya. motivasi suami dengan penggunaan KB
Menurut Wawan dan Dewi (2011), vasektomi, di peroleh hasil uji statistik p
bertambahnya umur seseorang akan value=0,000.
mengalami perubahan aspek fisik dan Menurut asumsi peneliti bahwa
psikologis (mental). Usia mempengaruhi responden yang memiliki motivasi negatif
terhadap daya tangkap dan pola fikir tetapi menggunakan KB vasektomi bisa
seseorang, semakin bertambah usia akan disebabkan karena faktor sumber informasi
semakin berkembang pula daya tangkap yang didapat hanya dari kader posyandu
dan pola fikirnya. Makin tua umur sehingga responden mempunyai persepsi
seseorang maka proses perkembangan yang salah tentang KB vasektomi, faktor
mentalnya bertambah baik. Dari uraian jumlah anak yang sudah cukup banyak
diatas dapat dilihat bahwa dengan yaitu 4 orang dan istri mengalami
bertambahnya umur seseorang dapat gangguan kesehatan sehingga tidak bisa
berpengaruh pada pertambahan menggunakan KB hormonal. Sedangkan
pengetahuan yang diperolehnya, pada usia responden yang memiliki motivasi positif
dewasa cenderung lebih berhati-hati dalam tetapi tidak menggunakan KB vasektomi
melakukan tindakan terhadap kesehatan disebabkan karena faktor umur responden
mereka. Secara umum tingkat kedewasaan masih kelompok dewasa muda (21–40 thn)
pada usia tua lebih mungkin untuk dan faktor jumlah anak yang masih 2
melakukan berbagai perilaku sehat seperti orang.
Although female contraceptives are very effective at preventing unintended pregnancy, some women can not use them because of
health conditions or side-effects, leaving some couples without effective contraceptive options. In addition, many men wish to take
active responsibility for family planning. Thus, there is a great need for male contraceptives to prevent unintended pregnancies, of
which 80–90 million occur annually. At present, effective male contraceptive options are condoms and vasectomy, which are not ideal
for all men. Therefore, efforts are under way to develop novel male contraceptives. This paper briefly reviews the advantages and dis-
advantages of condoms and vasectomies and then discusses the research directed toward development of novel methods of male contra-
ception. (Fertil SterilÒ 2016;106:1303–9. Ó2016 by American Society for Reproductive Medicine.)
Key Words: Spermatogenesis, testes, condoms, vasectomy, unintended pregnancy, spermatozoa, novel male contraceptives
Discuss: You can discuss this article with its authors and with other ASRM members at https://www.fertstertdialog.com/users/16110-
fertility-and-sterility/posts/12470-22685
OVERVIEW OF MALE sperm production and maintains sexual This last category of contraceptives,
REPRODUCTIVE function as well as muscle and bone such as spermicides, are usually in-
PHYSIOLOGY mass (4). Testosterone is produced by tended to be used intravaginally by
Leydig cells in the interstitium of the the female and are therefore more
Production of mature sperm in the hu-
testes when stimulated by LH. Sperm properly considered female contracep-
man testes takes 72 days (1). After pu-
production occurs in the seminiferous tives, so they will not be discussed
berty, sperm production is continuous
tubules, where the sperm are nurtured further in this review. Instead, the pre-
and occurs in four distinct phases: 1)
by Sertoli cells stimulated by FSH and sent article will describe the efficacy of
a mitotic phase in which the stem cells,
high concentrations of intratesticular existing methods of male contraception
the spermatogonia, give rise to diploid
testosterone (Fig. 1A) (5). Given the and then discuss the research directed
spermatocytes; 2) a meiotic phase in
physiology of sperm production, a toward development of novel methods
which spermatocytes double their chro-
male contraceptive can work in one of of male contraception that function
mosome complement and undergo two
several ways: either by inhibiting sperm production
cycles of cell division resulting in
or by preventing sperm from reaching
haploid spermatids; 3) spermiogenesis, 1. By preventing sperm from reaching the female reproductive tract.
which involves spermatid nuclear the egg by physical barriers (con-
condensation and flagellum formation; doms, vasectomy, and experimental
and 4) spermiation, which involves vas occlusion methods).
CURRENTLY AVAILABLE
release of the spermatozoa into the 2. By preventing sperm production
tubular lumen (2). Storage and further (experimental hormonal and
MALE CONTRACEPTIVE
maturation of sperm take place in the nonhormonal methods). METHODS
epididymis. Sperm aspirated from the 3. By killing or inhibiting the function Vasectomy
cauda epididymis are capable of fertil- of sperm or the sperm's ability to Vasectomy is a simple outpatient sur-
izing an egg in vitro (3). The testes bind the egg after ejaculation (sper- gery performed under local anesthesia,
also synthesize testosterone, a steroid micides, experimental antimotility in which the vas deferens is surgically
hormone. Testosterone is necessary for agents). interrupted bilaterally through a small
scrotal incision. There are 500,000
Received June 28, 2016; revised August 4, 2016; accepted August 17, 2016; published online vasectomies performed in the United
September 24, 2016. States yearly and worldwide >50
J.K.A. has received research funding from Clarus Therapeutics.
Supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Develop-
million men have undergone the pro-
ment, a division of the National Institute of Health through cooperative agreement U54 cedure (6), although there are signifi-
HD04245 and K24 HD082231 (J.K.A.). cant cultural differences in the
Reprint requests: John K. Amory, M.D., M.P.H., University of Washington, Box 356429, 1959 NE Pacific
St., Seattle, Washington 98195 (E-mail: jamory@u.washington.edu). acceptability of this procedure in
different settings. Vasectomies are
Fertility and Sterility® Vol. 106, No. 6, November 2016 0015-0282/$36.00
Copyright ©2016 American Society for Reproductive Medicine, Published by Elsevier Inc.
highly effective, with a failure rate
http://dx.doi.org/10.1016/j.fertnstert.2016.08.036 <1% and a low rate of complications
FIGURE 1
(A) Normal function of the hypothalamic-pituitary-testicular axis, with FSH and LH stimulating the testes to produce sperm and testosterone, and
testosterone providing feedback regulation of FSH and LH production in the pituitary. (B) Suppression of FSH and LH production by exogenously
administered androgens and progestins, which lowers FSH and LH concentrations, depriving the testes of the signals required for sperm production
and leading to contraception.
Amory. Male contraception. Fertil Steril 2016.
(Table 1) (7, 8). The ‘‘no-scalpel technique,’’ developed in reversal, or vasovasostomy, restores fertility in most cases;
China (9) that relies on a single midline puncture in the however, rates of pregnancy vary from 50% to 75% depend-
scrotal raphe with the use of scissors, had been widely ing on the length of time between the vasectomy and the vas-
adopted (10, 11). Drawbacks to vasectomy include a delay ovasostomy for two reasons. First, in some men
in the onset of azoospermia of 3–4 months, postoperative vasovasostomy is unable to restore patency of the vas, espe-
pain, and rare infections. Although most postoperative pain cially if >8 years have elapsed since the original vasectomy
resolves quickly, 10%–15% of men experience chronic (15). Second, 20%–30% of men remain infertile despite
testicular discomfort (12). In one study of such men, 27 out restored patency of the vas, as documented by imaging tech-
of 33 had relief of their discomfort after reversal of the niques, probably because of the presence of antisperm anti-
vasectomy (13). bodies (16). For these reasons, vasectomy can not be
Vasectomies are most appropriate for men who do not recommended as a truly reversible method of contraception.
desire any future fertility. However, 3%–5% of men with va- Vasectomy is safe in terms of overall male health. Reports
sectomies do eventually request reversal, usually because of of associations between vasectomy and cardiovascular dis-
remarriage (14). For this reason, some urologists recommend ease and prostate cancer first reported in the 1980s have
freezing a semen sample before the procedure. Vasectomy proven to be incorrect (17, 18). In summary, vasectomy is
These studies demonstrated that testosterone injections has been published (45). A larger trial testing TU and nores-
are effective as a contraceptive in most men; however, a pro- thisterone enanthate to prevent pregnancy has been per-
portion of men fail to suppress to <3 million sperm per milli- formed but has not been published. Cyproterone acetate is a
liter and therefore remain potentially fertile. In addition, the unique progestin with antiandrogenic properties that has
necessity of weekly intramuscular injections was unpopular been studied in combination with weekly injections of TE,
with subjects, 12% of whom discontinued involvement owing showing very high efficacy but only in small trials of 10–15
to dislike of the injection schedule. Side-effects were fairly men (46, 47).
minimal, but notably, high-dose TE deceases serum high- Nestorone is a 19-norprogesterone–derived progestin
density lipoprotein (HDL) cholesterol, which might affect which can be applied as a transdermal gel (48). A combination
the development of atherosclerosis (33, 34); however, as is of Nestorone gel and testosterone transdermal gels were stud-
the case with any male hormonal contraceptive, the long- ied for gonadotropin suppression (49) and in a 6-month male
term effects on prostate and liver health as well as mood contraceptive trial (50). In the latter study, 89% of men
and behavior are unknown. achieved suppression of their sperm concentration to %1
Testosterone undecanoate (TU) is a long-chain ester that million sperm per milliliter. Importantly, a majority of sub-
normalizes serum testosterone concentrations in hypogona- jects on this regimen were very satisfied with the regimen,
dal men for 6–12 weeks after injection (35–37). A large trial stating that they would be likely to use it if it were commer-
of TU injections for male contraception was conducted in cially available (51). Ongoing studies are working to simplify
China (38). Volunteers received monthly injections of 500 the regimen into a single combination gel for phase II testing
or 1,000 mg TU. Ninety percent of the men had sperm at six international sites beginning in 2017.
concentrations of <1 million sperm/mL and used the Dimethandrolone undecanoate (DMAU) is a potent syn-
injections as their sole method of contraception for 1 year. thetic 19-norandrogen that acts as a ligand at both androgen
Only a few pregnancies were reported in treated men and and progesterone receptors, making DMAU a potential ‘‘sin-
side-effects were minimal; however, for unclear reasons the gle-agent’’ contraceptive (52). Studies in rodents and rabbits
method was not approved for use. have shown both reversible suppression of gonadotropins
In the hopes of achieving greater rates of azoospermia, and sperm with orally administered DMAU (53, 54). Phase I
several male contraceptive studies have combined testos- testing in humans has demonstrated short-term safety and
terone administration with administration of progestins, tolerability with reversible suppression of gonadotropins
which additively suppress FSH and LH from the pituitary (55), and phase II testing of this compound is underway. Inter-
and may have direct antisperm effects on the testes (39). Com- estingly, DMAU can be administered orally as well as by
binations of testosterone and depot injections of medroxy- intramuscular injection, making it a very exciting compound
progesterone acetate (DMPA) induced azoospermia in for male hormonal contraceptive development.
one-half of study subjects and some degree of oligozoosper-
mia in most others. The contraceptive efficacy of these com-
binations, however, was poor, with several couples Nonhormonal Male Contraceptives
conceiving while receiving therapy despite simultaneous Several groups are examining approaches to ‘‘nonhormonal’’
use of other contraceptives (40). male contraception, although to date none of the current gen-
Several male contraceptive studies of the potent oral pro- eration of candidates has been tested in men. Nonhormonal
gestin levonorgestrel (LNG) have been performed. For male contraception does not involve the administration of
example, in one study, LNG (500 mg orally daily) was com- hormones or compounds that block hormone secretion or
bined with TE (100 mg intramuscularly per week) for hormone action. Nonhormonal contraception may be more
6 months. The LNG-TE combination was superior to TE alone appealing to men because it avoids any impact on testos-
in terms of azoospermia (67% vs. 33%), and 94% of the men terone concentrations or sexual function. In addition, the
had sperm concentrations of <1 million per milliliter use of testosterone or another anabolic steroid could lead to
compared with 61% of the TE-alone group (41). Drawbacks sports disqualification. Finally, nonhormonal contraceptives
to the LNG-TE regimen included greater weight gain and de- may be more easily dosed orally than steroid preparations
creases in HDL cholesterol compared with the TE-alone group. owing to rapid ‘‘first-pass’’ metabolism of testosterone in
Other progestins, such as desogestrel, have been tested in male the liver.
contraceptive regimens with similar results, but without An early example of a nonhormonal contraceptive candi-
causing weight gain or large reductions HDL cholesterol date is adjudin. Adjudin is an antisperm compound that dis-
(42). One large industry-sponsored study of testosterone dec- rupts the adhesion of spermatids to Sertoli cells, causing
anoate injections coupled with etonogestrel implants sup- premature spermiation and infertility. Administration of
pressed 80%–90% of men to a sperm concentration of <1 two doses of 50 mg/kg adjudin weekly induced 100% infer-
million per milliliter over 1 year (43). A follow-up study, tility after 5 weeks of treatment in adult rats without changes
one of the only placebo-controlled studies in the field, com- in serum testosterone, FSH, or LH concentrations (56).
bined etonorgestrel with TU with similar results in suppres- Because there was some liver inflammation observed in a
sion of spermatogenesis (44). Unfortunately, the companies 29-day study of adjudin administration (57), researchers con-
sponsoring these two studies have not pursued this work jugated adjudin to an FSH-b mutant specifically targeting it
further. Finally, only one study with 52 couples testing to Sertoli cells, thereby significantly reducing the dose neces-
androgen-progestin combinations for pregnancy prevention sary for contraception (58). Unfortunately, the cost of this
approach and the possibility of developing anti-FSH autoan- understanding of its mechanism of action. Our group
tibodies has stalled progress to human studies. demonstrated that WIN 18,446 suppresses spermatogenesis
H2-Gamendazole is an antisperm compound that impairs by inhibiting testicular retinoic acid biosynthesis via
the function of the apical ectoplasmic specialization (59). All inhibition of the testes-specific aldehyde dehydrogenase
male rats who received a single oral dose of 6 mg/kg ALDH1A2 (77, 78). With the use of a rabbit model, we
H2-gamendazole were infertile, but only 57% regained observed that oral administration of WIN 18,446 induced
fertility (60). Regarding toxicology, three out of five rats reversible azoospermia, and reductions in spermatogenesis
died after receiving a dose of 200 mg/kg H2-gamendazole; were preceded by a reduction in intratesticular retinoic acid.
however, no observable abnormalities, including liver inflam- These findings suggest that inhibition of the testicular
mation, necrosis, or hemorrhage, were detected at doses of retinoic acid biosynthesis is a promising target for male
<200 mg/kg. The investigators are hoping to move into hu- contraceptive development. Our group is focusing on the
man testing at lower doses to minimize the risk of toxicity. development of novel specific compounds that inhibit
Two other noteworthy approaches to nonhormonal male testicular retinoic acid biosynthesis via ALDH1A2 without
contraception have been published. The first study demon- interfering with alcohol metabolism. Hopefully, this work
strated that seven out of nine male nonhuman primates could will result in compounds that reversibly inhibit
be immunized against the semen protein Eppin and were un- spermatogenesis without significant side-effects.
able to father pregnancies, and the effect was reversible when
the immunizations were stopped (61). This research group is Vas Occlusion Methods
now working to develop small molecular inhibitors of Eppin
Since the early 1990s, efforts have been underway in India
binding as male contraceptives. A second high-profile paper
and China to develop a temporary plug for the vas deferens,
showed that the small molecule JQ1 could reversibly suppress
which could theoretically be removed or dissolved by an in-
spermatogenesis in mice by inhibiting the function of the pro-
jection at a later date to provide reversibility. The Indian
tein BRDT (62). Unfortunately, this compound also inhibits
vas occlusion device is called RISUG for ‘‘reversible inhibition
other similar proteins. Therefore, this group is attempting to
of sperm under guidance.’’ With the use of ultrasound guid-
develop a BRDT-specific inhibitor.
ance, sterile styrene maleic anhydrate is instilled into the
It has been known since 1925 that vitamin A (retinol) is
vas, bilaterally occluding it and preventing the passage of
required for normal spermatogenesis (63). Vitamin A and its
sperm. Several small clinical trials in men have been per-
active metabolite retinoic acid is required at puberty for the
formed with the use of this technique (79, 80), showing
initiation of spermatogenesis and for the maintenance of
excellent contraceptive efficacy over periods of up to
spermatogenesis in adults (64, 65). Retinoic acid produced
1 year. The procedure has been shown to be reversible in
from retinol in situ binds one of several retinoic acid
some nonhuman models (81), but data on efficacy and
receptors (RARs), which regulate gene expression. Because
reversibility from large-scale clinical trials are not available
male RAR-knockout animals are sterile owing to various
(82). Similar vas occlusion devices using medical-grade sili-
problems in spermatogenesis (66–69), blockade of retinoic
cone and polyurethane plugs were studied in China (83, 84).
acid function or biosynthesis is an appealing approach to
Unfortunately, both compounds had problems with time to
male nonhormonal contraceptive development.
sperm suppression and recovery of sperm counts after
BMS-189453 is an orally active RAR panantagonist. At
reversal, leading the investigators to abandon that approach.
daily oral doses of 15, 60, or 240 mg/kg for 1 month, BMS-
189453 produced marked testicular degeneration in rats, but
CONCLUSION
also led to increases in leukocyte counts and alkaline phos-
phatase and alanine aminotransferase levels (70). One group Contraception is essential for the prevention of unintended
has explored whether a lower dose of BMS-189453 might pregnancy. Approximately 30% of couples currently rely on
function as a contraceptive without the toxicity seen at higher male contraceptive methods, i.e., condoms and vasectomy.
doses (71). Two groups of 30 mice each were given BMS- Shortcomings of these methods have led to efforts to develop
189453 in oral doses of 5 mg/kg for 2 weeks and 2.5 mg/kg new types of male contraceptives. Hormone-based male con-
for 4 weeks. The study showed that the mice were completely traceptive regimens have undergone extensive clinical testing
sterile by 4 weeks after a dosing regimen of 5 mg/kg and by but suffer from incomplete suppression of spermatogenesis in
the end of treatment with a dose of 2.5 mg/kg for 4 weeks. all men and unknown long-term side-effect profiles. Nonhor-
By 12 weeks after treatment, fertility was completely restored monal methods in development appear promising in preclinical
in all of the subjects. This compound, or a more specific reti- studies, but extensive testing of these approaches will be
noic acid alpha antagonist (72, 73), holds promise for required before human studies can be performed to determine
nonhormonal contraception. their efficacy for the prevention of unintended pregnancy. In-
More than 50 years ago, the oral administration of WIN terest in the research community regarding these efforts is high,
18,446 was shown to completely and reversibly inhibit sper- as demonstrated by the recent creation of an International Con-
matogenesis in men (74–76). Unfortunately, subjects taking sortium for Male Contraception to promote this work.
WIN 18,446 experienced a ‘‘disulfiram reaction’’ consisting
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