Androgens and poor responders: are we ready to take the plunge into clinical therapy?

Fanchin, Rénato; Frydman, Nelly; Even, Marc; Silva, Ana Luisa Berwanger da; Grynberg, Michaël; Ayoubi, Jean-Marc

doi:10.1016/j.fertnstert.2011.09.050

Cited by 16 publications

(18 citation statements)

References 58 publications

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“…It is characterized by excessive AFCs, which have been positively correlated with circulating androgen concentrations ( Jonard et al, 2003 ; Pigny et al, 2003 ). In case of congenital adrenal hyperplasia or some virilizing tumors, which exposed women to androgen for long duration, comparable ovarian morphologies in PCOS were observed ( Fanchin et al, 2011 ). After high doses testosterone taken by noncastrated female to male transsexuals, multifollicular ovarian pattern like PCOS was observed by some investigators ( Futterweit & Deligdisch, 1986 ; Pache et al, 1991 ).…”

Section: Discussionmentioning

confidence: 90%

“…Several strategies have not fulfilled to increase reproductive outcomes for these poor responders, and commonly used approach is to make a high androgen intra-ovarian environment. So, dehydroepiandrosterone (DHEA), transdermal testosterone, aromatase inhibitor or recombinant luteinizing hormone (LH) was commonly administered in clinical practice ( de los Santos et al, 2013 ; Fanchin et al, 2011 ). The roles of androgens in ovarian folliculogenesis have been proposed, and basically androgens are essential substrates for ovarian steroidogenesis according to 2-cell two- gonadotropin theory ( Ryan et al, 1968 ).…”

Section: Discussionmentioning

confidence: 99%

“…When high dose of androgens were used for 5 days before and continuing through out FSH and LH treatment, antagonistic actions to gonadotropin stimulation were observed ( Zeleznik et al, 2004 ). Furthermore intra-ovarian bioavailability of androgens administered systemically at nonvilrilzing dose needs further investigation ( Fanchin et al, 2011 ). The proper duration of androgen pretreatment should be taken into consideration also.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Ovarian Features after 2 Weeks, 3 Weeks and 4 Weeks Transdermal Testosterone Gel Treatment and Their Associated Effect on IVF Outcomes in Poor Responders

Kim¹,

Ahn²,

Moon³

et al. 2014

Development &Amp; Reproduciton

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This study was performed to investigate the effect of of transdermal testosterone gel (TTG) on controlled ovarian stimulation (COS) and IVF outcomes and ovarian morphology according to pretreatment duration in poor responders. A total of 120 women were recruited for this pilot study. They were randomized into control, 2 weeks, 3 weeks or 4 weeks TTG treatment groups. For three TTG treatment groups, 12.5 mg TTG was applied daily for 2 weeks, 3 weeks or 4 weeks in preceding period of study stimulation cycle. After 3 weeks of TTG pretreatment, significant increase of antral follicle count (AFC) and significant decreases of mean follicular diameter (MFD) and resistance index (RI) value of ovarian stromal artery were observed (p=0.026, p<0.001, p<0.01, respectively). The total dose of rhFSH administered for COS significantly decreased after 3 and 4 weeks TTG treatment both compared with control group (p<0.001, p<0.001). The numbers of oocytes retrieved and mature oocytes were significanty higher in 3 and 4 weeks TTG treatment groups than control group (p<0.001, p<0.001 in the number of oocytes retrieved; p<0.001, p<0.001 in the number of mature oocytes). The clinical pregnancy rate and live birth rate were increased only in 4 weeks TTG treatment group compared with control group (p=0.030 and p=0.042, respectively). These data demonstrated that TTG pretreatment for 3 to 4 weeks increases AFC and ovarian stromal blood flow, thereby potentially improving the ovarian response to COS and IVF outcome in poor responders undergoing IVF/ICSI.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Ovarian Features after 2 Weeks, 3 Weeks and 4 Weeks Transdermal Testosterone Gel Treatment and Their Associated Effect on IVF Outcomes in Poor Responders

Kim¹,

Ahn²,

Moon³

et al. 2014

Development &Amp; Reproduciton

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“…Androgens are considered to be detrimental to ovarian function, and sufficient androgen actions through the AR are necessary for normal follicle development and function. 21,25 AR expression can be found in GC of mostly immature preantral and early-antral follicles; thereafter, they decrease with advancing follicle maturation, suggesting the importance of androgens mainly in the early stages of follicle maturation 21,22,26 (Figure 1). Many studies demonstrate androgens as essential for follicular recruitment, follicular growth, and reduction in GC apoptosis leading to an increase in the number of growing follicles.…”

Section: Discussionmentioning

confidence: 99%

The Benefits of Testosterone Therapy in Poor Ovarian Responders Undergoing In Vitro Fertilisation (IVF)

2020

EMJ

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Introduction: Poor ovarian responders are the most challenging patients in reproductive medicine and no successful treatment has been proposed. Androgens are thought to play an important role during early folliculogenesis and diminished levels are associated with decreased ovarian sensitivity to follicle-stimulating hormone. This study aimed to determine whether pretreatment with testosterone improves the results in poor responders undergoing in vitro fertilisation (IVF). Materials and methods: This observational pilot study enrolled 33 poor responders undergoing IVF. Eleven patients were pretreated with 250 mg intramuscular testosterone and compared to a control group of 22 patients. The participants were tested for free testosterone, dehydroepiandrosterone sulfate, sex hormone binding globulin, and anti-mullerian hormone (AMH). Results: The two groups had similar baseline characteristics. Significant improvement was reached in the hormones free testosterone, dehydroepiandrosterone sulfate, and sex hormone binding globulin in the testosterone-pretreatment group. No difference was detected in antral follicle count (5.06 versus 4.24); AMH (0.51 versus 0.53), mature oocytes (2.2 versus 2.32), and the number of embryos (1.2 versus 1.33) between the study and control groups, respectively. There was a slow improvement in fertilisation rate but without any significance (62.97% versus 57.61%). However, the cancellation rate of the ovarian stimulation was much greater in the control group (18.18%) in comparison with the study group (0.0%). Pregnancy rate (PR) in the testosterone group was higher than controls (PR per cycle: 27.3% versus 4.6; p=0.09). Conclusion: Based on the limited number of patients studied, pretreatment with testosterone seems to improve PR and cancellation rate in poor responders but failed to affect antral follicle count, AMH, and the number of mature oocytes and embryos. Given these results, further research would provide more certainty.

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“…Albeit still controversial [ 4 , 5 ], these observations have led to androgen supplementation in women with hypoandrogenic LFOR [ 6 ], and to the suggestion that pregnancy success with in vitro fertilization (IVF) in hypoandrogenic LFOR directly correlates with improvements in patients’ testosterone levels [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

The importance of adrenal hypoandrogenism in infertile women with low functional ovarian reserve: a case study of associated adrenal insufficiency

Gleicher

Kushnir

Weghofer

et al. 2016

Reprod Biol Endocrinol

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BackgroundLow testosterone (T), whether due to ovarian and/or adrenal insufficiency, usually results in poor follicle maturation at small growing follicle stages. The consequence is a phenotype of low functional ovarian reserve (LFOR), characterized by poor granulosa cell mass, low anti-Müllerian hormone and estradiol but rising follicle stimulating hormone. Such hypoandrogenism can be of ovarian and/or adrenal origin. Dehydroepiandrosterone sulfate (DHEAS) is exclusively produced by adrenals and, therefore, reflects adrenal androgen production in the zona reticularis. We here determined in a case study of infertile women with LFOR the presence of adrenal hypoandrogenism, its effects on ovarian function, and the possibility of presence of concomitant adrenal insufficiency (AI), thus reflecting insufficiency of all three adrenal cortical zonae.MethodsWe searched our center’s anonymized electronic research database for women with LFOR, who were also characterized by peripheral adrenal hypoandrogenemia (total testosterone < 16.9 ng/dL) and low DHEAS (<76.0 μg/dL). Among 225 women with LFOR, we identified 29 (12.9 %). The adrenal function of so identified women were further investigated with morning cortisol and ACTH levels and/or standard ACTH stimulation tests. We also determined the prevalence of classical AI (insufficiency glucocorticoid production by zona fasciculata) in hypoandrogenic women with LFOR, and impact of adrenal hypoandrogenism on ovaries.ResultsAmong 14/28 women with adrenal hypoandrogenism due to insufficiency of the zona reticularis available for follow up, 4 (28.6 %) also demonstrated previously unrecognized classical primary, secondary or tertiary AI due to insufficiency of the zona fasciculata. An additional patient with presenting diagnosis of seemingly primary ovarian insufficiency (POI), demonstrated extremely low T and DHEAS levels, a diagnosis of Addison’s disease, and was on glucocorticoid but not androgen supplementation. As her dramatic improvement in ovarian function criteria after androgen supplementation confirmed, her correct diagnosis, therefore, was actually secondary ovarian insufficiency (SOI) due to adrenal hypoandrogenism.ConclusionsWomen with LFOR, characterized by low T and DHEAS, are also at risk for AI, while women with AI may be at risk for adrenal induced hypoandrogenism and, therefore, SOI. A currently undetermined percentage of POI patients actually are, likely, affected by SOI, a for prognostic reasons highly significant difference in diagnosis.

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Androgens and poor responders: are we ready to take the plunge into clinical therapy?

Cited by 16 publications

References 58 publications

Ovarian Features after 2 Weeks, 3 Weeks and 4 Weeks Transdermal Testosterone Gel Treatment and Their Associated Effect on IVF Outcomes in Poor Responders

Ovarian Features after 2 Weeks, 3 Weeks and 4 Weeks Transdermal Testosterone Gel Treatment and Their Associated Effect on IVF Outcomes in Poor Responders

The Benefits of Testosterone Therapy in Poor Ovarian Responders Undergoing In Vitro Fertilisation (IVF)

The importance of adrenal hypoandrogenism in infertile women with low functional ovarian reserve: a case study of associated adrenal insufficiency

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