Elevated Serum Estradiol Is Associated with Higher Libido

Discussion in 'Men's Health Forum' started by Michael Scally MD, Feb 3, 2014.

  1. #1
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Male 50 pg/mL; 200 pm/L

    testosterone has always been considered to be a male hormone, whereas oestrogen has typically been discussed in the context of being a female hormone. Conventionally, the goal of testosterone supplementation therapy (TST) in men was to raise serum testosterone levels and lower oestrogen levels.

    A recent study by Finkelstein et al. highlighted an important role for oestrogen in regulation of sexual function in men on TST. In that study, dramatic declines in libido were observed in conjunction with decreased levels of serum oestrogen.

    Although oestrogen is associated with male sexual behaviour, the distinct roles of testosterone and oestrogen on sexual function in men on TST are controversial. We thus sought to elucidate the associations between serum testosterone, estradiol, and libido in men undergoing TST for symptomatic hypogonadism (total testosterone <300 ng/dl and three or more symptoms on the Androgen Decline in Aging Male [ADAM] questionnaire).

    Men on TST (injections or gels; n = 423) presenting to a large-volume, tertiary referral andrology clinic were asked to rate the quality of their libido using 5-point Likert scales (1 = terrible, 5 = excellent) as part of the validated, quantitative ADAM questionnaire.

    Men were categorised as having low (0.5–5.0 ng/dl) or high (>5.0 ng/dl) estradiol and low (<300 ng/dl) or high (>300 ng/dl) testosterone. Serum levels of follicle-stimulating hormone (FSH), luteinising hormone (LH), serum testosterone, and sex hormone- binding globulin (SHBG) were collected on the same day that men completed their ADAM questionnaires. We subsequently performed univariate (t test, chi-square) and multivariate analyses (ordinal logistic regression) to evaluate factors that predicted libido.

    • Men with serum testosterone levels >300 ng/dl reported greater libido than men whose levels were <300 ng/dl (3.46 vs 2.92; p < 0.01).
    • Men with serum estradiol levels >5 ng/dl reported greater libido than men with estradiol levels <5 ng/dl (3.70 vs 3.23; p < 0.01).

    In total, 60.4% of men with a serum testosterone level >300 ng/dl and estradiol level >5 ng/dl reported very good or excellent levels of libido (scored as 4 or 5) compared with 31.3% of men with testosterone levels <300 ng/dl and estradiol levels <5 ng/dl ( p < 0.01).

    Univariate analysis noted associations between libido and age, and FSH, LH (analysed as continuous variables), estradiol, and testosterone levels (analysed as categorical variables, and which remained significant even when analysed as continuous variables) (Table 1). Interestingly, on multivariate analysis, only estradiol at serum levels >5 ng/dl (2.13; p = 0.04) was associated with greater libido (Table 2).

    While this study highlights the importance of oestrogen in men on TST, the limitations include a lack of control group and no score comparisons before and after commencement of TST. Furthermore, a larger sample size may have unmasked a confounding relationship between testosterone and libido.

    In summary, we have found that elevated serum levels of estradiol are associated with increased libido in men on TST. We recommend judicious use of aromatase inhibitors for indications such as gynaecomastia. Indiscriminate prescription for the sole purpose of reducing serum oestrogen may be met with poor libido-decreasing satisfaction and quality of life.

    Carefully designed placebo-controlled trials to assess the risks and benefits of both testosterone and oestrogen are required.

    Ramasamy R, Scovell JM, Kovac JR, Lipshultz LI. Elevated Serum Estradiol Is Associated with Higher Libido in Men on Testosterone Supplementation Therapy. Eur Urol. Elevated Serum Estradiol Is Associated with Higher Libido in Men on Testosterone Supplementation Therapy - European Urology


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    Last edited: Aug 22, 2014
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  2. #2

    JOWS6 Member

    "Men were categorised as having low (0.5–5.0 ng/dl) or high (>5.0 ng/dl) estradiol and low (<300 ng/dl) or high (>300 ng/dl) testosterone."

    Isn't their categorization of high and low estradiol relative? We are used to seeing estradiol in units of pg/mL with a reference range around 7.0 - 42.0. Wouldn't 5.0 ng/dL translate to < or > 0.05 pg/mL where "high" estradiol would more likely land within the supplied reference range?
  3. #3

    idmd Member

    The following has been my experience and an observation I've made many times here. E2 too low and dick works but desire to have sex is low. E2 too high and desire to have sex is there but dick doesn't work. E2 in middle of range equals firing on a cylinders.
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  4. #4
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    5 ng/dL = 5,000 pg/dL = 50 pg/mL
    Last edited: Feb 4, 2014
    Millard Baker likes this.
  5. #5
    Michael Scally MD

    Michael Scally MD Doctor of Medicine

    Words of Wisdom. Re: Gonadal Steroids and Body Composition, Strength, and Sexual Function in Men.

    Experts’ summary:

    The investigators studied and reported on 400 healthy men aged 20–50 yr who were given monthly injections of goserelin acetate for 16 wk to suppress endogenous testosterone. Men were randomly assigned to a placebo gel or one of four doses of transdermal testosterone gel (1.25, 2.5, 5, or 10 g/d). An additional 200 men received anastrazole, an aromatase inhibitor, to block the conversion of testosterone to estradiol, in addition to placebo or testosterone gel. The investigators examined the changes in percentages of body fat and lean mass as primary outcomes. The men were also assessed for subcutaneous and intra-abdominal fat, muscle area and strength, and sexual function. The findings were clear: Muscle size and strength were androgen-dose dependent, body fat was estrogen dependent, and sexual function (libido and erectile strength) was both androgen dependent and estrogen dependent.

    Experts’ comments:

    The Endocrine Society's guidelines define male hypogonadism as a “clinical syndrome” in which the diagnosis is based on symptoms or signs and unequivocally low serum testosterone levels. The symptoms of hypogonadism vary widely and include sexual symptoms (eg, decreased erectile function and decreased libido), decreased mood, decreased muscle mass and increased fat mass, and decreased bone density.

    Although self-reported questionnaires such as the Androgen Deficiency in the Aging Male questionnaire and the Aging Males’ Symptoms scale have attempted to capture the spectrum of this disease, their specificity remains poor. Because of the controversy in diagnosis, practitioners uniformly treat men with a low testosterone level and any one or several symptoms of hypogonadism. Consequently, prescriptions for testosterone products have increased by >170% in the previous 5 yr.

    In this study, one of the striking findings is that different symptoms of hypogonadism can develop at different gonadal steroid levels. For example, visceral fat increases even at testosterone levels between 300 and 400 ng/dl. However, muscle strength and size are unaffected until testosterone levels are <200 ng/dl. Therefore, the target levels of testosterone supplementation in a man who is concerned about weight gain and increase in abdominal girth could be different from the target in a man who is concerned about loss of muscle strength and size.

    Research thus far has focused almost exclusively on how estrogen affects women and how testosterone affects men. This study highlights the important role of estrogen in the regulation of body fat and sexual function in men. Losing estrogen did not affect lean mass, muscle size, or leg strength any more than did testosterone deprivation.

    The most adverse effects of estrogen deficiency were on sexual desire, with men in this group reporting dramatic declines in arousal and erectile function. Additionally, the increase in intra-abdominal fat seen in men with decreased estrogen (due to aromatase inhibition) could increase the risk of cardiovascular disease, diabetes, and metabolic syndrome if long-term estrogen deficiency exists.

    Some of the limitations of the study include a younger participant profile and a short follow-up. In summary, this study provides insight into the different roles of testosterone and estradiol in the body composition, strength, and sexual function of men. The available evidence of long-term risks and outcomes of testosterone replacement therapy is still very limited, and much less has been studied about the effect of estrogen on the same end points. Carefully designed placebo-controlled trials of testosterone administration to assess the risks and benefits of both sex hormones are required.

    Ramasamy R, Lipshultz LI. Words of wisdom. Re: Gonadal steroids and body composition, strength, and sexual function in men. Eur Urol 2014;65(4):843-4. http://www.sciencedirect.com/science/article/pii/S0302283813014280
  6. #6

    foreveryoung Member

    Yup, experience that on hcg often before. Extremely horny but completely unable to keep an erection
  7. #7
    its always been known estradiol plays an important role in libido. although the most significant differences seem to occur with higher histamine levels. I've had low e2 but with high serum histamine and no libido issues at all. but when I took antihistamines it hit the floor. so my guess is histamine helps determine the sensitivity of one's hypothalamus to estrogen changes and that it may help counteract side-effects of low E2. which makes sense because histamine and estrogen take similar pathways in the brain - histamine and estrogen BOTH stimulate nNOS (neuronal nitric oxide synthase) and histamine also primes systemic and central vasodilation.
    both histamine and estrogen also induce Oxytocin release.
  8. #8

    idmd Member

    While I'm certain my observations about E2 and sexual function/libido are accurate and 100% reproducible for me I'm glad someone is finally trying to look at these issues scientifically. TRT and men' sexual health have been and still are the red headed step children of medicine with most research efforts not going much past figuring out what pharmaceuticals can be sold to us.
  9. #9

    LW64 Member

    It would have been truly baffling if their results suggested something different. In my own limited understanding hormones come in opposing pairs and each has an optimal range that can vary from man-to-man. It was not easy to see why testosterone-estradiol would be an exception but until some reliable results come in: who knows? OTOH, absence of evidence is not evidence of absence.
  10. #10

    Herbalist Junior Member

    all I know is I was more horny with an AI during my cycle then a time I didn't. Balance is Key I think.
  11. #11
    its amazing how some people have a different definition and regard for "horny" and "libido"..you'd be amazed. trust me.
  12. #12
    and I'm talking in terms of ratio. some consider that they are losing their sex drive when there isn't 150,000 (exaggerated #) sexual fantasies going through their head a day - instead their is 148,000 ONE DAY, and yet, they are losing their sex drive, go figure. the human brain is an interesting thing. and in doing all this, they inevitably create more anxiety for themselves, now reducing that # (again a greatly exaggerated one) to 132,000.

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