A Combined Regimen of Cyproterone Acetate and Testosterone Enanthate as a Potentially Highly Effective Male Contraceptive

Meriggiola, Maria Cristina; Bremner, William J.; Paulsen, C. Alvin; Valdiserri, Alessandro; Incorvaia, Loredana; Motta, Roberto; Pavani, A; Capelli, M.; Flamigni, Carlo

doi:10.1097/00006254-199803000-00020

Cited by 24 publications

(43 citation statements)

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“…It is therefore not unexpected that gonadotropin suppression by T treatment alone in the clinical male contraception studies has not been able to bring about complete suppression of spermatogenesis. In fact, one of the most effective contraceptive regimens has been the combination of T with the antiandrogen cyproterone acetate (43). The men achieving azoospermia with this regimen may in fact have been hypogonadal which explains the efficacy.…”

Section: Discussionmentioning

confidence: 99%

Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception

et al. 2014

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Testosterone (T), alone or in combination with progestin, provides a promising approach to hormonal male contraception. Its principle relies on enhanced negative feedback of exogenous T to suppress gonadotropins, thereby blocking the testicular T production needed for spermatogenesis, while simultaneously maintaining the extragonadal androgen actions, such as potency and libido, to avoid hypogonadism. A serious drawback of the treatment is that a significant proportion of men do not reach azoospermia or severe oligozoospermia, commensurate with contraceptive efficacy. We tested here, using hypogonadal luteinizing hormone/choriongonadotropin receptor (LHCGR) knockout (LHR−/−) mice, the basic principle of the T-based male contraceptive method, that a specific T dose could maintain extragonadal androgen actions without simultaneously activating spermatogenesis. LHR−/− mice were treated with increasing T doses, and the responses of their spermatogenesis and extragonadal androgen actions (including gonadotropin suppression and sexual behavior) were assessed. Conspicuously, all dose responses to T were practically superimposable, and no dose of T could be defined that would maintain sexual function and suppress gonadotropins without simultaneously activating spermatogenesis. This finding, never addressed in clinical contraceptive trials, is not unexpected in light of the same androgen receptor mediating androgen actions in all organs. When extrapolated to humans, our findings may jeopardize the current approach to hormonal male contraception and call for more effective means of inhibiting intratesticular T production or action, to achieve consistent spermatogenic suppression.—Oduwole, O. O., Vydra, N., Wood, N. E. M., Samanta, L., Owen, L., Keevil, B., Donaldson, M., Naresh, K., Huhtaniemi, I. T. Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception.

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Section: Discussionmentioning

confidence: 99%

Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception

et al. 2014

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“…First, we treated 10 normal men with cyproterone acetate and testosterone (which causes a reduction in gonadotropins below the sensitivity of the RIA assay after 16 weeks of treatment). 21 This treatment caused a significant reduction in circulating INSL3 (from 693.3 ± 131.8 to 139.8 ± 64.9 pg/mL, P <.001) (FIG. 3A).…”

Section: Figurementioning

confidence: 92%

“…We selected the following groups of subjects: 40 normal adult men, 10 normal adult women at different times in the menstrual cycle, 5 untreated orchiectomized men, 9 untreated men with 47,XXY Klinefelter's syndrome and azoospermia, 32 severely infertile men with high FSH levels and severe hypospermatogenesis, 22 6 men with HH at basal conditions at the time of the first visit (untreated) and after a 4-wk period of treatment with hCG (2,000 IU twice per week, im), 10 normal adult men before and after 16 weeks of treatment with cyproterone acetate (CPA, 50 mg twice a day, orally) plus testosterone enanthate (TE, 100 mg/wk, im) in a male contraception program, 21 and 2 infertile men before and after 30 days from administration of the GnRH analogue leuprolide (3.75 mg, im) and during the following 2 months of therapy with r-hFSH (100 IU every day, im) and hCG (2,000 IU twice per week, im). Serum concentrations of INSL3 were measured in duplicate by RIA using a novel INSL3 RIA kit (Phoenix Pharmaceuticals, Belmont, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

Insulin‐Like Factor 3: A Novel Circulating Hormone of Testicular Origin in Humans

Ferlin

2005

Annals of the New York Academy of Sciences

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Insulin-like factor 3 (INSL3) affects testicular descent. Mutations in the INSL3 gene or its receptor, LGR8/GREAT, can cause cryptorchidism. Expression of LGR8/GREAT in different tissues and production of INSL3 by adult-type Leydig cells suggest additional roles for this hormonal system in adults. We used a novel radioimmunoassay kit to measure INSL3 concentrations in the serum of normal men and those with different testicular pathologies. We demonstrate that INSL3 circulates in adult men and is almost exclusively of testicular origin. Subjects with severe testicular damage (infertility) produce small amounts of INSL3, and concentrations of this hormone seem to reflect the functional status of the Leydig cells. Analysis of men treated with different combinations of hormones of the hypothalamus-pituitary-testis axis suggests that the production of INSL3 is related to the luteinizing hormone.

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“…Assays for glucose, total cholesterol, HDL, and triglycerides levels were performed in the hospital's chemistry laboratory according to validated procedures. All blood samples were immediately assayed using established commercial assays by the hospital laboratory, which is routinely monitored by participation in external quality control programs [28].…”

Section: Anthropometric Measures and Laboratory Analysesmentioning

confidence: 99%

Prevalence of Sexual Dysfunction Among Postmenopausal Women with and Without Metabolic Syndrome

Martelli

Valisella

Moscatiello

et al. 2012

The Journal of Sexual Medicine

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Introduction The metabolic syndrome (MetS) is a multifactorial disease characterized by the co-occurrence of impaired glucose tolerance/diabetes, central obesity, high levels of triglycerides, low levels of high-density lipoprotein, and hypertension. Its prevalence is higher in menopausal women. We, and others, have recently shown that female sexual dysfunction (FSD) affects menopausal women. Whether the presence of MetS may be linked to a higher risk of FSD in menopausal women is unknown. Aims The aims of our study were: (i) to evaluate the prevalence of FSD in women with MetS (based on National Cholesterol Education program-Adult Treatment Panel III 2009 criteria) in comparison with healthy controls and (ii) to evaluate the influence of singular components of MetS on female sexual function. Methods The Female Sexual Function Index (FSFI) questionnaire, the Female Sexual Distress Scale (FSDS), and The Middlesex Hospital Questionnaire were administered to 103 postmenopausal women with MetS and 105 healthy postmenopausal controls (HC). Female sexuality was defined as dysfunctional when FSFI score was <23 and FSDS was >15. Main Outcome Measures FSFI and FSDS were completed by women with and without MetS. Results The prevalence of women with sexual dysfunction was higher in MetS women than HC (39/103 [37.9%] vs. 20/105 [19%], P = 0.003). The prevalence of both pathological scores in every FSFI domain and FSDS score was higher in MetS women than HC. The logistic regression, considering age and the length of relationship as a common starting point, shows that higher levels of triglycerides are linked to a higher risk of presenting FSD (odds ratio = 2.007 95% confidence interval [1.033–3.901]) in the whole population. Conclusions Our preliminary results suggest that prevalence of FSD is higher in women with MetS in comparison with healthy controls. Higher levels of triglycerides are linked to a higher risk of presenting FSD.

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A Combined Regimen of Cyproterone Acetate and Testosterone Enanthate as a Potentially Highly Effective Male Contraceptive

Cited by 24 publications

References 0 publications

Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception

Overlapping dose responses of spermatogenic and extragonadal testosterone actions jeopardize the principle of hormonal male contraception

Insulin‐Like Factor 3: A Novel Circulating Hormone of Testicular Origin in Humans

Prevalence of Sexual Dysfunction Among Postmenopausal Women with and Without Metabolic Syndrome

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