Contraceptive efficacy of testosterone-induced azoospermia in normal men
Abstract
A multicentre study (ten centres) in seven countries was done to assess the contraceptive efficacy of hormonally-induced azoospermia in 271 healthy fertile men. Each subject received 200 mg testosterone enanthate weekly by intramuscular injection. 157 men (cumulative rate at 6 months 65%) became azoospermic in three consecutive semen samples. These men entered a 12-month efficacy phase during which continuing testosterone injections were the only form of contraception. There was 1 pregnancy during 1486 months of the efficacy phase (0·8 conceptions [95% confidence interval 0·02-4·5] per 100 person- years). Discontinuations from the study were mainly because azoospermia was not achieved within 6 months and because of dislike of the injection schedule. The mean time to become azoospermic was 120 days (SD 40); reappearance of spermatozoa was detected in 11 men and in no case led to discontinuation from the study or to pregnancy. After the testosterone injections had been stopped, the estimated median time from azoospermia to recovery (sperm concentration of at least 20 million/ml) was 3·7 months (3·6-3·9) and to the subject's mean baseline sperm concentration was 6·7 months (6·2-8·7). Hormonal regimens that induce azoospermia can provide highly effective, sustained, and reversible male contraception with minimum side-effects.
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Fertility Management in Cystinosis: A Clinical Perspective
2024, Kidney International ReportsCystinosis is a rare, inherited, lysosomal storage disorder characterized by the progressive accumulation of intralysosomal cystine and subsequent organ and tissue damage. The kidneys are the first and most severely impacted organ. Although cystinosis was once considered a fatal pediatric disease, patients with cystinosis are living well into adulthood with advances in medical care, including kidney transplant and early and continuous use of cysteamine therapy. This increase in life expectancy has revealed an extrarenal phenotype of cystinosis that emerges in adolescence and adulthood, affecting nearly all body systems, including the endocrine and reproductive systems. As individuals with cystinosis are planning for the future, reproductive health and fertility have become areas of increased focus. This narrative review aims to summarize the current understanding of reproductive health and fertility in patients with cystinosis and discuss practical considerations for monitoring and managing these complications.
Male contraception
2023, Progres en UrologieLa contraception est un enjeu important de santé mondiale, qui demeure dominée par les contraceptions féminines. Des évolutions concernant les contraceptions masculines pourraient permettre de redistribuer la charge contraceptive.
Une recherche bibliographique a permis de faire l’état des lieux sur les options existantes en rappelant les critères d’une contraception optimale, d’établir les principes d’une consultation pré-contraception masculine et de faire l’état des lieux sur les différentes voies de recherche avec leurs avantages et inconvénients.
Les nouvelles options de contraception masculine sont détaillées, qu’elles soient hormonales (androgénothérapies, association de progestatifs et de testostérone) ou non, notamment thermiques, avec les résultats actuels et les voies d’amélioration. Le préservatif et la vasectomie demeurent les 2 seules options validées. Le développement récent de la vasectomie mini-invasive sans scalpel et de techniques d’occlusion permettent de simplifier le geste, de minimiser le risque de complications (douleurs, hématomes, syndrome douloureux post-vasectomie) et d’améliorer l’efficacité. Les questions du regret et des possibilités de reperméabilisation sont également évoquées.
La question de la contraception masculine va de plus en plus s’imposer en consultation chez l’urologue. Celui-ci devra informer le patient comme le prévoit le cadre légal avant vasectomie, et le conseiller au mieux concernant la technique qui sera souvent mini-invasive sans scalpel ; de nouvelles options réversibles devraient également élargir l’éventail des options disponibles en routine, pour aller progressivement vers une équité contraceptive.
Contraception is a major global health issue, which is still dominated by female contraception. Developments in male contraception could help redistribute the contraceptive burden.
A literature search was carried out to review the existing options and the criteria for optimal contraception, to establish the principles of a male pre-contraception consultation, and to review the various research avenues with their advantages and disadvantages.
The new male contraception options are detailed, whether hormonal (androgen therapy, combination of progestins and testosterone) or non-hormonal, particularly thermal, with current results and avenues for improvement. Condom use and vasectomy remain the only 2 validated options. The recent development of minimally invasive vasectomy without the need for a scalpel and of occlusion techniques has simplified the procedure, minimised the risk of complications (pain, haematomas, post-vasectomy pain syndrome) and improved efficacy. The issues of regret and the possibility of repermeabilisation are also raised.
The question of male contraception will become increasingly important in consultations with urologists. The urologist will have to inform the patient, as required by law, before the vasectomy is performed, and provide the best possible advice on the technique, which will often be minimally invasive without the need for a scalpel. New reversible options should also broaden the range of options available on a routine basis, with a view to gradually moving towards contraceptive equity.
Design of an international male contraceptive efficacy trial using a self-administered daily transdermal gel containing testosterone and segesterone acetate (Nestorone)
2023, ContraceptionInjectable male hormonal contraceptives are effective for preventing pregnancy in clinical trials; however, users may prefer to avoid medical appointments and injections. A self-administered transdermal contraceptive gel may be more acceptable for long-term contraception. Transdermal testosterone gels are widely used to treat hypogonadism and transdermal administration may have utility for male contraception; however, no efficacy data from transdermal male hormonal contraceptive gel are available. We designed and are currently conducting an international, multicenter, open-label study of self-administration of a daily combined testosterone and segesterone acetate (Nestorone) gel for male contraception. The transdermal approach to male contraception raises novel considerations regarding adherence with the daily gel, as well as concern about the potential transfer of the gel and the contraceptive hormones to the female partner. Enrolled couples are in committed relationships. Male partners have baseline normal spermatogenesis and are in good health; female partners are regularly menstruating and at risk for unintended pregnancy. The study’s primary outcome is the rate of pregnancy in couples during the study’s 52-week efficacy phase. Secondary endpoints include the proportion of male participants suppressing sperm production and entering the efficacy phase, side effects, hormone concentrations in male participants and their female partners, sexual function, and regimen acceptability. Enrollment concluded on November 1, 2022, with 462 couples and enrollment is now closed. This report outlines the strategy and design of the first study to examine the contraceptive efficacy of a self-administered male hormonal contraceptive gel. The results will be presented in future reports.
The development of a safe, effective, reversible male contraceptive would improve contraceptive options and may decrease rates of unintended pregnancy. This manuscript outlines the study design and analysis plan for an ongoing large international trial of a novel transdermal hormone gel for male contraception. Successful completion of this and future studies of this formulation may lead to the approval of a male contraceptive.
Male contraception development: monitoring effective spermatogenesis suppression utilizing a user-controlled sperm concentration test compared with standard semen analysis
2023, Fertility and SterilityTo determine whether a user-controlled sperm concentration test compared with standard semen analysis can effectively monitor spermatogenesis suppression for male contraception.
Single center, prospective sub study of the ongoing clinical trial: “Study of daily application of Nestorone and testosterone combination gel for male contraception.”
Research institute at an academic medical center.
Couples participating in the male contraceptive clinical trial.
None.
The ability by participants to monitor sperm suppression to a threshold compatible with contraceptive efficacy utilizing a user-controlled test verified by sperm concentration determined by standard laboratory methods.
Thirty-eight men participating in a hormonal male contraceptive clinical trial provided multiple samples during spermatogenesis suppression for this substudy. Participants, employing a user-controlled test, correctly identified the absence of sperm (a negative test) in 100% of their laboratory-confirmed azoospermic samples (n = 122). Participants also identified 100% of samples (n = 73) with sperm >0.2 million/mL as positive. Sperm counts between 0.01 and 0.2 million/mL were identified as negative in 96% of samples. Trial participants noted the overall ease of using the test with respect to sample preparation, test timing, and result interpretation, and that they could accurately use this test at home without difficulty.
Participants undergoing spermatogenesis suppression in a hormonal male contraceptive trial performed user-controlled test to determine whether their semen sperm concentration was ≤ or >0.2 million/mL. Compared with standard semen analyses, participants correctly identified 100% of samples with sperm counts >0.2 million/mL as positive (Sensitivity 100%). A positive result when the couple is using a male contraceptive method triggers the need for semen analysis by a laboratory while the couple uses another method of contraception. Participants correctly diagnosed samples ≤0.2 million sperm/mL as negative in 99% of samples (specificity 99%). A negative result indicates a sperm concentration ≤0.2 million/mL, well below the threshold of ≤1 million/mL offering contraceptive efficacy demonstrated by prior studies. At-home sperm concentration test would minimize the need for users to return to the clinic to monitor suppression of spermatogenesis, decreasing cost and burden of male contraception trials and increasing practicality of the method.
NCT: 03452111.
Desarrollo de la contracepción masculina: monitorización efectiva de la supresión de la espermatogénesis utilizando una prueba de concentración de espermatozoides controlada por el usuario en comparación con un análisis de semen estándar.
Determinar como un test de concentración de espermatozoides controlado por el usuario en comparación con un análisis de semen estándar puede monitorizar eficazmente la supresión de la espermatogénesis para la contracepción masculina.
Un centro, subestudio prospectivo del ensayo clínico en marcha: “Estudio de la aplicación diaria de Nesterona y testosterona combinada en gel para la contracepción masculina”.
Instituto de investigación en un centro médico académico.
Parejas participantes en el ensayo clínico de contracepción masculina.
Ninguna.
La capacidad de los participantes para monitorizar la supresión de la espermatogénesis hasta un umbral compatible con la eficacia contraceptiva utilizando una prueba controlada por el usuario verificada por la concentración de esperma determinada por métodos de laboratorio estándar.
Treinta y ocho hombres participantes en un ensayo clínico de contracepción hormonal masculina proporcionaron múltiples muestras durante la supresión de la espermatogénesis para este subestudio. Los participantes, empleando un test controlado por el usuario identificaron correctamente la ausencia de esperma (test negativo) en el 100% de sus muestras azoospérmicas confirmadas en el laboratorio (n=122). Los participantes también identificaron el 100% de las muestras (n=73) con espermatozoides <0.2 millones / mL como positivas. Recuentos espermáticos entre 0.01 y 0.02 millones/mL fueron identificados como negativos en el 96% de las muestras. Los participantes del ensayo señalaron la facilidad de usar el test para la preparación de la muestra, tiempo del test, e interpretación de resultados y que ellos pudieron utilizar de forma precisa el test en casa sin dificultad.
Participantes sometidos a supresión de la espermatogénesis en un ensayo de contracepción hormonal masculina realizaron un test controlado por el usuario para determinar si la concentración de espermatozoides en semen era ≤ o > 0.2 millones/mL. En comparación con el análisis de semen estándar, los participantes identificaron correctamente el 100% de las muestras con recuento de espermatozoides > 0.2 millones/mL como positiva (Sensibilidad 100%). Un resultado positivo cuando la pareja está usando un método de contracepción masculino desencadena la necesidad de análisis de semen en un laboratorio mientras la pareja usa otro método de anticoncepción. Los participantes diagnosticaron correctamente muestras ≤ 0.2 millones/mL como negativas en el 900% de las muestras (especificidad 99%). Un resultado negativo indica una concentración de espermatozoides ≤ 0.2 millones/mL, muy por debajo del límite de ≤ 1 millón/mL ofreciendo eficacia anticonceptiva demostrada por estudios previos. La prueba de concentración de espermatozoides en casa podría minimizar la necesidad de los usuarios de volver a la clínica para monitorizar la supresión de la espermatogénesis, disminuyendo el coste y la carga de los ensayos de contracepción masculina y aumentando la practicidad del método.
Prescriptions for testosterone therapy (TT) to treat testosterone deficiency have increased in recent years. The purpose of this review was to evaluate the risks of several treatment modalities to better counsel patients. Both short-acting and long-acting TT has been shown to restore normal serum testosterone levels and improve symptoms of testosterone deficiency. Short-acting pharmacology mimics normal physiology more closely than long-acting TT but requires multiple doses per day. Long-acting TT has a higher rate of patient adherence but is more likely to create supraphysiologic serum testosterone and pathologic sequelae.
Male contraceptive development: A medicinal chemistry perspective
2022, European Journal of Medicinal ChemistryThere is a need for non-hormonal contraceptives. One area that needs further investigation is the development of male contraceptives. Comparatively little is understood about potential drug targets in men to achieve a reversible contraceptive effect. In this article, we review the need for male contraceptives and some thoughts around the characteristics of a male contraceptive and the potential development pathway. We then discuss different potential approaches to discovering male contraceptives and then highlight potential targets that have been discussed in the literature.