Nestorone®: a progestin with a unique pharmacological profile

Kumar, Narender

doi:10.1016/s0039-128x(00)00119-7

Cited by 162 publications

(110 citation statements)

References 30 publications

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“…Very small structural changes in the parent molecule may induce considerable differences in the progestin activity. 19 The effects of progestins are related to interactions not only with progesterone receptors but also with other steroid hormone receptors. Norpregnane derivatives, including nomegestrol acetate and promegestone, appear to have a very high progestational activity, and unlike nortestosterone derivatives, they do not possess androgenic, estrogenic, or glucocorticoid activity.…”

Section: Discussionmentioning

confidence: 99%

Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

et al. 2007

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After adjustment for potential confounding factors, odds ratios (ORs) for VTE in current users of oral and transdermal estrogen compared with nonusers were 4.2 (95% CI, 1.5 to 11.6) and 0.9 (95% CI, 0.4 to 2.1), respectively. There was no significant association of VTE with micronized progesterone and pregnane derivatives (OR, 0.7; 95% CI, 0.3 to 1.9 and OR, 0.9; 95% CI, 0.4 to 2.3, respectively). In contrast, norpregnane derivatives were associated with a 4-fold-increased VTE risk (OR, 3.9; 95% CI, 1.5 to 10.0). Conclusions-Oral but not transdermal estrogen is associated with an increased VTE risk. In addition, our data suggest that norpregnane derivatives may be thrombogenic, whereas micronized progesterone and pregnane derivatives appear safe with respect to thrombotic risk. If confirmed, these findings could benefit women in the management of their menopausal symptoms with respect to the VTE risk associated with oral estrogen and use of progestogens. (Circulation.

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Section: Discussionmentioning

confidence: 99%

Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

et al. 2007

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“…The potency of these two drugs in terms of an endometrial response has been reported to be similar [76,77]. However, there has been no specific study comparing the efficacy of these two oral agents in fertility-sparing therapy.…”

Section: Preferred Progestinsmentioning

confidence: 99%

Progestins in the Fertility-Sparing Treatment and Retreatment of Patients With Primary and Recurrent Endometrial Cancer

Nam

2015

The Oncologist

109

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Endometrial cancer is the most common gynecologic cancer in developed countries. Approximately 3%-14% of endometrial cancers are diagnosed in young women under 40 who want to preserve their fertility. The incidence of endometrial cancer in this age group is increasing, for which fertility-sparing therapy is increasingly used because it is one of the most important quality of life issues in these women. Progestin therapy is the most common type of fertility-sparing therapy. In this review, the most up-to-date findings regarding fertility-sparing progestin therapy for young women with primary and recurrent endometrial cancer is addressed in terms of diagnosis, treatment, follow-up, and oncologic and reproductive outcomes. Fertility-sparing progestin therapy is highly effective in selected young women with primary and recurrent endometrial cancer. The selection of appropriate patients through comprehensive pretreatment evaluation is of paramount importance to achieve the best outcomes without compromising survival. Because of the high rate of recurrence after successful fertility-sparing therapy, close surveillance is mandatory, and prophylactic hysterectomy is the best option for patients who have completed family planning. Pregnancy outcomes are very promising with the aid of assisted reproductive technologies. Continuous daily oral medroxyprogesterone acetate and megestrol acetate are the preferred progestins for fertility-sparing therapy, but future studies should be performed to determine the optimal dose and treatment duration of these agents. The Oncologist 2015; 20:270-278 Implications for Practice: In young women with endometrial cancer, the cure rate is very high.Therefore, the efficacy of treatment should not be limited to the oncologic outcomes.The quality-of-life issue is as important as oncologic outcomes in these patients. Fertility preservation is one of the most important quality-of-life issues. Based on the results of numerous studies, fertility-sparing progestin therapy can be safely performed in endometrioid adenocarcinoma confined to the endometrium. It also can be reasonably recommended to selected women with more advanced disease and recurrent disease. However, careful follow-up is important because of the high rate of recurrence.

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“…They exert rapid non-genomic effects on Leydig cells, spermatozoa and affect sperm function (Lishko et al, 2011;Strunker et al, 2011) such as motility, capacitation, acrosome reaction and the ability to bind to zona proteins (Baldi et al, 1995(Baldi et al, , 1999. Some progestins, like LNG, also bind to androgen receptors (Phillips et al, 1990;Kumar et al, 2000) and exert androgenic activities such as decreasing blood sex hormone binding globulin and HDL-cholesterol levels. Clinical studies showed that combining progestins with androgens lead to an enhanced suppression of gonadotropins and spermatogenesis by inhibiting spermatogonial proliferation and spermiation in the human testes (McLachlan et al, 2002).…”

Section: Discussionmentioning

confidence: 99%

Functional role of progestin and the progesterone receptor in the suppression of spermatogenesis in rodents

et al. 2013

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SUMMARYSynthetic progestins such as levonorgestrel (LNG) are used in combination with testosterone (T) in male contraceptive clinical trials to suppress gonadotropins secretion, but whether progestins have additional direct effects on the testis are not known. This study aimed to examine the effect of a potent progestin, (LNG), alone or in combination with testosterone (T) on spermatogenesis in adult rats, and to evaluate the functional role of the progesterone receptors (PRs) in the testis. In comparison with a low dose of LNG treatment in adult rats for 4 weeks, T and T + LNG treatment decreased testicular sperm count to 64.1 and 40.2% of control levels respectively. LNG induced germ cell apoptosis at stages I-IV and XII-XIV; T increased apoptosis at stages VII-VIII; LNG + T treatment induced greater germ cell apoptosis at a wider range of seminiferous epithelial stages. RT-PCR and Western Blots showed that PR was present in testes and up-regulated during suppression of spermatogenesis induced by testicular hormonal deprivation. PR knockout (PRKO) mice had larger testes, greater sperm production, increased numbers of Sertoli and Leydig cells. Suppression of gonadotropin and intratesticular T by GnRH-antagonist treatment induced PR promoter driven LacZ expression in Leydig cells of PRKO mice. This suggests that GnRH-antagonist treatment while inducing germ cell apoptosis also up-regulates PR. We conclude that (i) LNG + T induced greater suppression of spermatogenesis through increase in germ cell apoptosis involving a wider range of seminiferous epithelial stages than either treatment alone, (ii) up-regulation of PR was associated with inhibition of spermatogenesis, (iii) PR knockout mice showed increased sperm production suggesting that testicular PR activated events play a physiological and pharmacological inhibitory role in the testis. These data support the hypothesis that in addition to its known suppressive effects on gonadotropins, progestins may have direct inhibitory actions on the testis.

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Nestorone®: a progestin with a unique pharmacological profile

Cited by 162 publications

References 30 publications

Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

Hormone Therapy and Venous Thromboembolism Among Postmenopausal Women

Progestins in the Fertility-Sparing Treatment and Retreatment of Patients With Primary and Recurrent Endometrial Cancer

Functional role of progestin and the progesterone receptor in the suppression of spermatogenesis in rodents

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