Effects of Atorvastatin on Human Semen and Gonadal Hormones
Condition: Healthy Volunteers; Normocholesterolaemic Men; Normozoospermic Men
Study type: Interventional
Phase: Phase 1

Summary: 
      Recently, concerns about the effect of atorvastatin intake on men fertility have been raised.
      However, this statin has never been investigated regarding its influence on male fertility,
      notably sperm quality.

      The aim of this pilot study is to evaluate the efficacy and the safety of a decrease of
      cholesterol blood levels, induced by taking atorvastatin, on sperm quality of
      normocholesterolaemic and healthy men without confounding factors.
    

Detailed description: 
      The main objective is to estimate the safety of atorvastatin on fertility of
      normocholesterolaemic and healthy men (having normal blood lipid profile and normal sperm
      parameters) by analyzing its effects on sperm parameters: ejaculate volume, sperm count,
      total and progressive motility, percentage of typical forms.

      The secondary objectives are to assess the changes in:

        -  hormonal profile: gonadotropins and testosterone plasma levels

        -  lipid composition of sperm and seminal fluid;

        -  spermatozoa capacitation markers

        -  accessory glands markers.

      The efficacy is estimated by measuring the lipid lowering action of atorvastatin. It is
      expected a decrease by 20 and 40% of total cholesterol blood and LDL-cholesterol levels,
      respectively (total cholesterol <1.5 g / l and LDL-cholesterol <1g / l).

      Considering this protocol as a pilot study to evaluate safety and efficacy, sample size
      estimation was fixed considering a Fleming design at one stage. These designs with one group
      and multi-stages (between 1 and 5) can be seen as filtering steps leading to the decision
      type go/no go. With a type I error a and statistical power (1-β) equals respectively 5% and
      90%, n=17 subjects were necessary to reject the hypotheses of minimal (p=0.85) and maximal
      (p=0.95) acceptable non-toxicity. If 1 subject or more presented a toxicity, the treatment
      was considered no safe. To measure the evolution of total cholesterol and LDL-cholesterol
      levels concerning the efficacy, n=17 subjects were necessary to show a minimal paired
      difference (to be detected) of 0.5 with expected standard-deviation of difference = 0.5,
      correlation coefficient of 0.5, a= 5% (two-sided) for a power greater than 90% (1-β=97%).

      Subjects are included after a screening visit (visit 0), during which routine laboratory
      biochemical tests are performed, an electrocardiogram is taken, blood pressure, weight and
      height are measured; physical examination including testis evaluation and semen parameters
      are analyzed according to WHO standards 1999 .

      The subjects take atorvastatin orally (10mg/day (d), Tahor©, Pfizer Laboratory) during 5
      months allowing to study atorvastatin effects on human spermatogenesis and epididymal
      maturation (one cycle requiring approximately 3 months).

      Blood and semen parameters were measured :

        -  before to take atorvastatin treatment (visit 1)

        -  at the end of the therapy (visit 3)

        -  and 3 months after the end of treatment, (visit 4) to perform measurements during
           different cycles of spermatogenesis on a same subject. After two months of treatment, a
           consultation (visit 2) is realized to ensure good tolerance to treatment and to control
           treatment efficiency.

      Biochemical clinical and semen measurements take before treatment were considered as "control
      baseline measures".
    

Intervention name(s): Atorvastatin
Intervention type(s): Drug
Intervention description(s): The aim of this pilot study is to evaluate the efficacy and the safety of a decrease of cholesterol blood levels, induced by taking atorvastatin, on sperm quality of normocholesterolaemic and healthy men without confounding factors.
Other intervention name(s): cholesterol lowering drug
Intervention MeSH terms: Atorvastatin; Anticholesteremic Agents
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Atorvastatin; Human Spermatozoa; Seminal fluid; Accessory Glands; Cholesterol; Gonadotropins,; Testosterone