Androgen actions in the ovary: balance is key

Prizant, Hen; Gleicher, Norbert; Sen, Aritro

doi:10.1530/joe-14-0296

Cited by 116 publications

(93 citation statements)

References 105 publications

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“…Since then, low FOR has been defined as a relatively hypoandrogenic condition in need of androgen supplementation (Gleicher et al 2013), and various animal models established the importance of appropriate testosterone levels for normal growth and maturation of small growing follicles (recently reviewed in this journal by Prizant et al 2014). DHEA effects have been attributed to its conversion to testosterone, which synergistically enhances FSH effects on GCs through the androgen receptor (reviewed in Prizant et al 2014, Shohat-Tal et al 2015.…”

Section: Androgen Supplementation Of Women With Low Formentioning

confidence: 99%

“…DHEA effects have been attributed to its conversion to testosterone, which synergistically enhances FSH effects on GCs through the androgen receptor (reviewed in Prizant et al 2014, Shohat-Tal et al 2015.…”

Section: Androgen Supplementation Of Women With Low Formentioning

confidence: 99%

“…For that reason, meta-analyses either had to conclude that not enough data existed to reach conclusions or that no treatment effects were apparent. Small as well as large animal studies, however, repeatedly demonstrated highly significant effects (animal as well as human studies are in detail reviewed in Prizant et al 2014).…”

Section: Androgen Supplementation Of Women With Low Formentioning

confidence: 99%

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Improvements in IVF in women of advanced age

Gleicher

Kushnir

Albertini

et al. 2016

Journal of Endocrinology

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Women above age 40 years in the US now represent the most rapidly growing age group having children. Patients undergoing in vitro fertilization (IVF) are rapidly aging in parallel. Especially where egg donations are legal, donation cycles, therefore, multiply more rapidly than autologous IVF cycles. The donor oocytes, however, are hardly ever a preferred patient choice. Since with use of own eggs, live birth rates decline with advancing age but remain stable (and higher) with donor eggs, older patients always face the difficult and very personal choice between poorer chances with own and better chances with donor oocytes. Physician contribution to this decision should in our opinion be restricted to accurate outcome information for both options. Achievable pregnancy and live birth rates in older women are, however, frequently underestimated, thereby mistakenly biasing fertility providers, private insurance companies and even regulatory government agencies. Restriction on access to IVF for older women is then often the consequence. In this review, we summarize the limited published data on best treatments of ‘older’ ovaries, while also addressing treatment approaches that should be avoided in older women. This focused review, therefore, to a degree is subjective. Research addressing aging ovaries in IVF has been disappointingly sparse, and has in our opinion too heavily concentrated on methods of embryo selection (ES), which, especially in older women, not only fail to improve IVF outcomes, but actually, negatively affect live birth chances. We conclude that, aside from breakthroughs in gamete creation, only pharmacological interventions into early (small growing follicle stages) follicle maturation will offer new potential to positively impact oocyte and embryo quality and, therefore, IVF outcomes. Research, therefore, should be accordingly redirected.

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Section: Androgen Supplementation Of Women With Low Formentioning

confidence: 99%

Section: Androgen Supplementation Of Women With Low Formentioning

confidence: 99%

Section: Androgen Supplementation Of Women With Low Formentioning

confidence: 99%

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Improvements in IVF in women of advanced age

Gleicher

Kushnir

Albertini

et al. 2016

Journal of Endocrinology

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“…Therefore, androgen excess or deficiency is likely to have impact on the rate of follicle transition during fetal and postnatal life. Due to negligible role of gonadotropins during fetal stage of folliculogenesis, androgens are probably responsible for changes in the expression of the set of genes crucial for the development of ovarian follicles [14].…”

Section: Introductionmentioning

confidence: 99%

TGFβ (transforming growth factor β) superfamily members and their receptors in the fetal porcine ovaries: effect of prenatal flutamide treatment

Knapczyk-Stwora

Grzesiak

Duda

et al. 2015

Folia Histochem Cytobiol.

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Introduction. We have recently demonstrated that antiandrogen treatment during fetal life resulted in delayed folliculogenesis. The aim of the present study was to investigate the effect of androgen deficiency induced by flutamide on the expression of TGFb superfamily members and their receptors which are involved in follicle formation and its transition to the primary stage. Material and methods. Pregnant gilts were injected with flutamide (for seven days, 50 mg/day/kg b.w.) or corn oil (controls) starting at 43 (GD50), 83 (GD90) or 101 (GD108) gestational day. The expression in fetal ovaries of selected TGFb superfamily members (AMH, BMP4, GDF9), their receptors (AMHR-II, BMPR-IB, BMPR-II), and Smad1 and Smad3 proteins involved in signal transduction were investigated by real-time PCR and/or immunohistochemistry. Results. Flutamide treatment increased the expression of BMP4 mRNA on GD50 and GD108 and BMPR-IB mRNA on GD50. The expression of BMPR-II was decreased at mRNA level and lower immunostaining intensity was observed after flutamide administration only on GD50. GDF9 and AMHR-II mRNA expression levels were significantly downregulated in both GD90 and GD108 groups. However, AMHR-II was immunolocalized only on GD108 and less positively stained oocytes were found after flutamide treatment. AMH mRNA level was diminished in the GD90 group, while it was elevated in the GD108 group. Moreover, the higher amounts of positively stained oocytes for phosphorylated form of Smad1 were observed following flutamide administration on GD108. Conclusions. Experimentally-induced androgen deficiency during fetal development deregulates the expression level of some of TGFb superfamily members and their receptors which may affect primordial follicle assembly. Our findings further underline the role of androgens in the early stages of follicle development.

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“…Thus, although not reported by the authors, the positive impacts of DHEA on pregnancy rates described in this study may be due to an impact of DHEA on the endometrium. An important consideration, highlighted by Prizant and coworkers in a recent review, is that not all women respond equally well to DHEA supplementation due to inadequate conversion of DHEA to testosterone (Prizant et al 2014). Thus, 'non-responders' may not benefit from DHEA supplementation but require direct supplementation with testosterone; however, whether this would be effective in improving pregnancy outcomes in such patients remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

Regulation of androgen action during establishment of pregnancy

Gibson¹,

Simitsidellis²,

Saunders³

2016

Journal of Molecular Endocrinology

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During the establishment of pregnancy, the ovarian-derived hormones progesterone and oestradiol regulate remodelling of the endometrium to promote an environment that is able to support and maintain a successful pregnancy. Decidualisation is characterised by differentiation of endometrial stromal cells that secrete growth factors and cytokines that regulate vascular remodelling and immune cell influx. This differentiation process is critical for reproduction, and inadequate decidualisation is implicated in the aetiology of pregnancy disorders such as foetal growth restriction and preeclampsia. In contrast to progesterone and oestradiol, the role of androgens in regulating endometrial function is poorly understood. Androgen receptors are expressed in the endometrium, and androgens are reported to regulate both the transcriptome and the secretome of endometrial stromal cells. In androgen-target tissues, circulating precursors are activated to mediate local effects, and recent studies report that steroid concentrations detected in endometrial tissue are distinct to those detected in the peripheral circulation. New evidence suggests that decidualisation results in dynamic changes in the expression of androgen biosynthetic enzymes, highlighting a role for pre-receptor regulation of androgen action during the establishment of pregnancy. These results suggest that such enzymes could be future therapeutic targets for the treatment of infertility associated with endometrial dysfunction. In conclusion, these data support the hypothesis that androgens play a beneficial role in regulating the establishment and maintenance of pregnancy. Future studies should be focussed on investigating the safety and efficacy of androgen supplementation with the potential for utilisation of novel therapeutics, such as selective androgen receptor modulators, to improve reproductive outcomes in women.

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Androgen actions in the ovary: balance is key

Cited by 116 publications

References 105 publications

Improvements in IVF in women of advanced age

Improvements in IVF in women of advanced age

TGFβ (transforming growth factor β) superfamily members and their receptors in the fetal porcine ovaries: effect of prenatal flutamide treatment

Regulation of androgen action during establishment of pregnancy

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