The effect of selective estrogen receptor modulator administration on the hypothalamic-pituitary-testicular axis in men with idiopathic oligozoospermia

Tsourdi, Elena; Kourtis, Anargyros; Farmakiotis, Dimitrios; Katsikis, Ilias; Salmas, Marios; Panidis, Dimitrios

doi:10.1016/j.fertnstert.2008.06.002

Cited by 20 publications

(14 citation statements)

References 14 publications

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“…As a result, local testosterone production and spermatogenesis are increased [14]. Consequently, several prior studies have shown the beneficial effect on endocrine outcome of tamoxifen in the treatment of male infertility, namely, increased serum levels of FSH and testosterone after treatment with tamoxifen [4,11]. In line with prior findings, we revealed increased serum levels of testosterone, FSH and LH after 3 months of treatment in our cohort of patients, which clearly emphasizes the use of tamoxifen in iOAT.…”

Section: Discussionsupporting

confidence: 90%

“…Furthermore, treatment with tamoxifen showed improved sperm variables and higher pregnancy rates in men with idiopathic oligozoospermia in a prior placebo-controlled trial [10]. Despite this controversy, tamoxifen was proposed as the first line of treatment for iOAT by the World Health Organization (WHO) [8,11].…”

Section: Efficacy Of the Oestrogen Antagonist Tamoxifen On Sperm Paramentioning

confidence: 99%

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Efficacy of the Oestrogen Antagonist Tamoxifen on Sperm Parameters in Patients with Idiopathic Oligoathenoteratozoospermia

Paffenholz

Votteler

Nazari³

et al. 2019

Urol Int

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Background: The oestrogen antagonist tamoxifen has been suggested as an empiric treatment option for treating idiopathic oligoathenoteratozoospermia (iOAT). Objectives: To analyse the use of tamoxifen in iOAT. Method: Fifty-seven men receiving tamoxifen for iOAT were recruited from 2016 to 2017 in a retrospective, single-centre setting. Hormone and semen analysis was performed before and after 3 months of treatment. Results: After a 3-month treatment, serum levels of testosterone (3.4 ng/mL [2.7–4.8] vs. 5.3 [3.1–7.1]; p = 0.026), follicle stimulating hormone (FSH; 7.6 [5.9–11.5] vs. 15.9 mIU/mL [8.4–19.9]; p = 0.003) and luteinizing hormone (4.5 [3.3–6.6] vs. 7.6 mIU/mL [4.8–10.7]; p = 0.007) significantly increased. At a cut-off of >8.8 mIU/mL, serum levels of FSH were predictive for an improved sperm motility (OR 0.229 [95% CI 0.068–0.773]; p = 0.018) and serum levels of inhibin B were predictive for an improved total sperm count at a cut-off of <82 ng/L (OR 18.0 [95% CI 1.267–255.744]; p = 0.033). During an 11 month-follow-up, patients receiving tamoxifen showed a clinical pregnancy rate of 42%, leading to a live birth rate of 56% of all pregnant women. Twenty-three per cent of all patients reported non-serious adverse events. Conclusions: Tamoxifen is effective in improving the total sperm count as well as motility and can thus be safely used as empiric medical therapy in iOAT.

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Section: Discussionsupporting

confidence: 90%

Section: Efficacy Of the Oestrogen Antagonist Tamoxifen On Sperm Paramentioning

confidence: 99%

Efficacy of the Oestrogen Antagonist Tamoxifen on Sperm Parameters in Patients with Idiopathic Oligoathenoteratozoospermia

Paffenholz

Votteler

Nazari³

et al. 2019

Urol Int

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“…Clomiphene citrate has been used in men with eu-gonadotropic hypogonadism, for example, aging men [147,148]. Another estrogen partial antagonist Tamoxifen has been used in elevating serum LH and FSH and serum testosterone levels in infertile and hypogonadal men [149]. Aromatase inhibitors (e.g., letrozole and anastrozole) decrease conversion testosterone to estrogen reducing the negative feedback on pituitary LH production.…”

Section: Treatment Options For Patients With Secondary Hypogonadismentioning

confidence: 99%

An update on male hypogonadism therapy

Surampudi

Swerdloff

Wang

2014

Expert Opinion on Pharmacotherapy

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Introduction Men who have symptoms associated with persistently low serum total testosterone level should be assessed for testosterone replacement therapy. Areas covered Acute and chronic illnesses are associated with low serum testosterone and these should be recognized and treated. Once the diagnosis of male hypogonadism is made, the benefits of testosterone treatment usually outweigh the risks. Without contraindications, the patient should be offered testosterone replacement therapy. The options of testosterone delivery systems (injections, transdermal patches/gels, buccal tablets, capsules and implants) have increased in the last decade. Testosterone improves symptoms and signs of hypogonadism such as sexual function and energy, increases bone density and lean mass and decreases visceral adiposity. In men who desire fertility and who have secondary hypogonadism, testosterone can be withdrawn and the patients can be placed on gonadotropins. New modified designer androgens and selective androgen receptor modulators have been in preclinical and clinical trials for some time. None of these have been assessed for the treatment of male hypogonadism. Expert opinion Despite the lack of prospective long-term data from randomized, controlled clinical trials of testosterone treatment on prostate health and cardiovascular disease risk, the available evidence suggests that testosterone therapy should be offered to symptomatic hypogonadal men.

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“…Previous research has shown that raloxifene, a SERM, plays an important role in male and female reproduction. The anti-estrogenic effects of raloxifene at the hypothalamic level result in a significant increase of gonadotropin levels [1] . In addition, the administration of raloxifene can cause significant dose-dependent regression of the ventral prostate and seminal vesicles in the intact rat, but testicular weight and testicular androgen biosynthesis were not adversely affected [21] .…”

Section: Discussionmentioning

confidence: 99%

“…Selective estrogen receptor modulators (SERMs) are a group of compounds that can act as an estrogen agonists or antagonists, depending on the specific target tissue [1] . Raloxifene HCl, a nonsteroidal second-generation SERM, manifests estrogenic activity in bone, and the cardiovascular and central nervous systems, whereas in the reproductive system it acts as an estrogen receptor antagonist [2][3][4] .…”

Section: Introductionmentioning

confidence: 99%

Effects of Raloxifene on Voltage- Dependent T-Type Ca<sup>2+</sup> Channels in Mouse Spermatogenic Cells

Wang

Lü²,

Gao

et al. 2011

Pharmacology

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Voltage-dependent T-type Ca²⁺ channels have eminent roles in sperm function. In the present study, we investigated the effects of raloxifene, a selective estrogen receptor modulator, on T-type Ca²⁺ channels in mouse spermatogenic cells by using both electrophysiological and molecular techniques. We found that T-type calcium currents (I_T-Ca) were inhibited by raloxifene in a concentration-dependent manner with an IC₅₀ of 2.97 µM, as assessed with the patch clamp technique. Application of raloxifene at 2 µM inhibited I_T-Ca by 54.9 ± 2.1% at –20 mV (n = 10, p < 0.05). Furthermore, raloxifene-induced inhibition of I_T-Ca was associated with a negative shift of both the activation and the steady-state inactivation properties. The time constants of activation and inactivation were decreased, the time constant of deactivation was increased, but the time constant of recovery was not affected. In addition, the inhibitory effects of raloxifene and 17β-estradiol on I_T-Ca were unaffected by the estrogen receptor antagonist ICI 182,780. We also found that raloxifene treatment decreased the mRNA expression of Ca_V3.2 and Ca_V3.3, but not Ca_V3.1 in GC-2spd (ts) cells (mouse spermatocyte cell line), as assessed by real-time RT-PCR. Taken together, these data indicate that in mouse spermatogenic cells, raloxifene decreases I_T-Ca independent of classical estrogen, and the mRNA expression of T-type calcium channels and therefore may affect male reproductive function.

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The effect of selective estrogen receptor modulator administration on the hypothalamic-pituitary-testicular axis in men with idiopathic oligozoospermia

Cited by 20 publications

References 14 publications

Efficacy of the Oestrogen Antagonist Tamoxifen on Sperm Parameters in Patients with Idiopathic Oligoathenoteratozoospermia

Efficacy of the Oestrogen Antagonist Tamoxifen on Sperm Parameters in Patients with Idiopathic Oligoathenoteratozoospermia

An update on male hypogonadism therapy

Effects of Raloxifene on Voltage- Dependent T-Type Ca<sup>2+</sup> Channels in Mouse Spermatogenic Cells

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