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      Male contraception: where are we going and where have we been?

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          Abstract

          Progress in developing new reversible male contraception has been slow. While the hormonal approach has been clearly shown to be capable of providing effective and reversible contraception, there remains no product available. Currently, trials of a self-administered gel combination of testosterone and the progestogen Nestorone® are under way, complementing the largely injectable methods previously investigated. Novel long-acting steroids with both androgenic and progestogenic activity are also in early clinical trials. The non-hormonal approach offers potential advantages, with potential sites of action on spermatogenesis, and sperm maturation in the epididymis or at the vas, but remains in preclinical testing. Surveys indicate the willingness of men, and their partners, to use a new male method, but they continue to lack that opportunity.

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          First-in-human testing of a wirelessly controlled drug delivery microchip.

          The first clinical trial of an implantable microchip-based drug delivery device is discussed. Human parathyroid hormone fragment (1-34) [hPTH(1-34)] was delivered from the device in vivo. hPTH(1-34) is the only approved anabolic osteoporosis treatment, but requires daily injections, making patient compliance an obstacle to effective treatment. Furthermore, a net increase in bone mineral density requires intermittent or pulsatile hPTH(1-34) delivery, a challenge for implantable drug delivery products. The microchip-based devices, containing discrete doses of lyophilized hPTH(1-34), were implanted in eight osteoporotic postmenopausal women for 4 months and wirelessly programmed to release doses from the device once daily for up to 20 days. A computer-based programmer, operating in the Medical Implant Communications Service band, established a bidirectional wireless communication link with the implant to program the dosing schedule and receive implant status confirming proper operation. Each woman subsequently received hPTH(1-34) injections in escalating doses. The pharmacokinetics, safety, tolerability, and bioequivalence of hPTH(1-34) were assessed. Device dosing produced similar pharmacokinetics to multiple injections and had lower coefficients of variation. Bone marker evaluation indicated that daily release from the device increased bone formation. There were no toxic or adverse events due to the device or drug, and patients stated that the implant did not affect quality of life.
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            Contraceptive efficacy of testosterone-induced azoospermia and oligozoospermia in normal men.

            (1996)
            To determine contraceptive efficacy of hormonally induced sperm suppression to severe oligozoospermia or azoospermia. Prospective, noncomparative contraceptive efficacy study. Multicenter study in 15 centers in nine countries. Three hundred ninety-nine normal, healthy, fertile men requesting a male contraceptive method. Weekly IM injection of 200 mg T enanthate. Incidence of pregnancies in efficacy when couples relied on T injections alone for contraception. Four pregnancies occurred during 49.5 person-years involving men with oligozoospermia (0.1 to 3 x 10(6)/mL) and none during 230.4 person-years in azoospermic men: pregnancy rates 8.1 (95 percent confidence interval [CI] 2.2 to 20.7) and 0.0 (95 percent CI, 0.0 to 1.6) per 100 person-years, respectively, or 1.4 (95 percent CI, 0.4 to 3.7) per 100 person-years for oligozoospermia and azoospermia (O to 3 x 10(6)/mL) combined. Pregnancy rates were related to sperm concentration. Inadequate suppression of spermatogenesis occurred in eight men and escape from suppression occurred in four. Discontinuations were due to personal reasons (50 men, cumulative annual life-table rate 12.2 percent [95 percent CI, 9.1 percent to 16.1 percent]) and dislike of the injection schedule (21 men, 5.1 percent [95 percent CI, 3.2 percent to 7.9 percent]). Thirty-five men discontinued for medical reasons (9.4 percent [95 percent CI, 6.7 percent to 13.2 percent]), with no serious treatment-related side effects. After stopping injections, sperm output recovered; additionally, fertility was demonstrated in 33 couples. Suppression of spermatogenesis to azoospermia or severe oligozoospermia (< or = 3 x 10(6)/mL) induced by weekly T enanthate injections results in sustained, reversible contraception with good efficacy and minimal short-term side effects. New hormonal regimens with more convenient delivery and improved spermatogenic suppression would provide practical male contraception.
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              Contraceptive efficacy of testosterone-induced azoospermia in normal men

              (1990)
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                Author and article information

                Journal
                BMJ Sex Reprod Health
                BMJ Sex Reprod Health
                familyplanning
                bmjsrh
                BMJ Sexual & Reproductive Health
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2515-1991
                2515-2009
                October 2019
                19 September 2019
                : 45
                : 4
                : 236-242
                Affiliations
                [1] departmentMRC Centre for Reproductive Health , The Queen's Medical Research Institute, University of Edinburgh , Edinburgh, UK
                Author notes
                [Correspondence to ] Dr John Joseph Reynolds-Wright, MRC Centre for Reproductive Health, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh EH16 4TJ, UK; john.reynolds-wright@ 123456nhs.net
                Author information
                http://orcid.org/0000-0001-6597-1666
                Article
                bmjsrh-2019-200395
                10.1136/bmjsrh-2019-200395
                6892591
                31537614
                5b00a8d8-3d1b-4d14-8fd6-f310261cc37d
                © Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See:  https://creativecommons.org/licenses/by/4.0/.

                History
                : 08 May 2019
                : 13 August 2019
                : 30 August 2019
                Funding
                Funded by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD);
                Funded by: MRC Centre for Reproductive Health;
                Award ID: MR/N022556/1
                Categories
                Review
                1506
                Custom metadata
                unlocked

                hormonal contraception,male contraception,review
                hormonal contraception, male contraception, review

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