Hey there, to get right to it I took 20mg before an outing with a girl last weekend as some insurance. Oddly enough before taking the Cialis libido felt strong, and erections were normal, but about an hour after taking it I noticed my libido start to fade. This is resulted in inability to come to orgasm. While I know Cialis can cause delayed ejaculation I always just assumed it was due to reduced sensitivity. Is there any evidence that there is more going on causing this i.e. increased prolactin, significantly lowered estrogen (although even with low estrogen I've never had this issue) etc that could be also effecting libido, and has anyone else experienced this? Thanks.
Systemlord
Member
I encountered the same problem some time after starting Cialis, hot flashes from hell from lowered estrogen.
Cialis is also known to lower penile sensitivity.
Testosterone:estradiol ratio changes associated with long-term tadalafil administration: a pilot study - PubMed
Sustained improvement in sexual function after 12 months of tadalafil administration is associated with increased T:E ratio mainly related to reduction of E levels. We hypothesize that androgen-estrogen cross-talk and possible inhibition of aromatase activity during chronic exposure to tadalafil...
pubmed.ncbi.nlm.nih.gov
Thanks for the response. I wondered about the lowered E2, but it just seemed like too quick of a response, as it was a rather immediate drop in libido, like 2ish hours, but maybe I'm a hyper responder to its inhibition.I encountered the same problem sometime after starting Cialis, hot flashes from hell from lowered estrogen.
Cialis is also known to lower penile sensitivity.
Testosterone:estradiol ratio changes associated with long-term tadalafil administration: a pilot study - PubMed
Sustained improvement in sexual function after 12 months of tadalafil administration is associated with increased T:E ratio mainly related to reduction of E levels. We hypothesize that androgen-estrogen cross-talk and possible inhibition of aromatase activity during chronic exposure to tadalafil...
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madman
Super Moderator
Is there any evidence that there is more going on causing this i.e. increased prolactin, significantly lowered estrogen (although even with low estrogen I've never had this issue) etc that could be also effecting libido,
Highly doubtful one dose of tadalafil is going to drive down let alone significantly lower ones estradiol!
Even then it is far from a given following an on demand or daily dosed tadalafil protocol drive ones estradiol down!
I and many have been taking daily tadalafil for years and estradiol has not budged!
Would not be so quick to place the blame on lower estradiol being responsible for your fading libido!
Tread lightly when it comes to the people preaching that one study performed in a small number of patients almost 2 decades ago.
Many have never even read the full study especially the forums village guru that parrots/posts it every time one brings up lowered libido/estradiol LOL!
Thanks, I would generally tend to agree, just kind of at a loss at what could have been the cause, so grasping at straws here. Maybe it's something I'm not accounting for, but the two seemed pretty correlated and I can't think of any concrete confounding variables that would create such a stark change.
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madman
Super Moderator
I encountered the same problem some time after starting Cialis, hot flashes from hell from lowered estrogen.
Cialis is also known to lower penile sensitivity.
Testosterone:estradiol ratio changes associated with long-term tadalafil administration: a pilot study - PubMed
Sustained improvement in sexual function after 12 months of tadalafil administration is associated with increased T:E ratio mainly related to reduction of E levels. We hypothesize that androgen-estrogen cross-talk and possible inhibition of aromatase activity during chronic exposure to tadalafil...
He popped one dose let alone stated .....is there any evidence that there is more going on causing this i.e. increased prolactin, significantly lowered estrogen (although even with low estrogen I've never had this issue) etc that could be also effecting libido, and has anyone else experienced this? Thanks.
Some critical info here!
* In our study we observed a significant decrease of plasma E levels AFTER A TREATMENT PERIOD OF 12 MONTHS with tadalafil on demand at a flexible dosage (5, 10, and 20 mg), with a significant increase in T:E ratio, although no changes in T and f T serum levels were observed.
* In this study we show for the first time a REDUCTION IN E LEVELS in patients with ED AFTER CHRONIC EXPOSURE TO TADALAFIL and a concomitant increase in the T:E ratio. This hormonal pattern was found MOSTLY IN LEAN SUBJECTS , independent of the etiology of ED, comorbidities, and concomitant drug treatments.
* In conclusion, in this study we demonstrated that LONG-TERM ADMINISTRATION OF TADALAFIL is ASSOCIATED with increase in T:E ratio mainly due to significant reduction of E levels.
* ANY PRESUMABLE EFFECT OF PDE5i ON AROMATASE ACTIVITY SHOULD BE FURTHER CONFIRMED WITH BOTH IN VITRO AND IN VIVO STUDIES because it may open a new research avenue
Better yet did you even look at the estradiol levels TAD baseline vs TAD-3 month mark?
Figure 1 Hormonal variations after long-term tadalafil (TAD) treatment in men (N = 20) with ED. Values reported have been converted by using standard International Conversion Factors.P = 0.05 vs. baseline. MO = months.
Testosterone:Estradiol Ratio Changes Associated with Long-Term Tadalafil Administration: A Pilot Study (2006)
Emanuela A. Greco, MD,* Marcello Pili, MD,* Roberto Bruzziches, MD,* Giovanni Corona, MD,†Giovanni Spera, MD,* and Antonio Aversa, MD, PhD*
This study has been undertaken to determine whether variations of plasma sex steroids may occur in patients with ED after 12 months of successful exposure to tadalafil administered on demand.
Methods
Subjects and Study Design
This was a flexible, open-label, prospective study on steroid hormone fluctuations over a treatment period of 12 months with tadalafil administered on demand in patients with ED of any etiology. The 20 patients enrolled in this study met all of the following inclusion criteria:
Clinical laboratory measurements including serum chemistry, hematology, urinalysis, and hormones levels (total T, free T [f T], estradiol [E],sex hormone-binding globulin [SHBG], and LH) were performed at visit 2 (baseline), visit 3 (3 months), and visit 6 (12 months), along with an electrocardiogram evaluation just at baseline visit, and were compared with 10 age-matched healthy controls. Safety evaluation was performed by recording clinical adverse events at each visit.
Although in our study each patient served as his own control, to evaluate the hormone profile at baseline, hormonal values were compared with those of an age-matched control group of healthy, sexually active volunteers, with their informed consent.
Diagnostic Evaluation
In addition to sex hormones, serum basal levels of prolactin and thyroid-stimulating hormone were measured to exclude hyperprolactinemia and thyroid disorders.
All hormone assays were performed at the Research Laboratories of the Department of Medical Pathophysiology of the University “La Sapienza” of Rome. Blood samples were collected in the morning after an overnight fast; the period of storage at −80°C varied from 0 to 12 months. All samples obtained from the same subject were measured in the same assay. All determinations were performed in duplicate. Serum concentrations of total T were measured by radioimmunoassay (RIA) using a commercial kit (Diagnostic System Laboratories, Webster, TX, USA). The intra- and inter assay coefficients of the total T assay were 7.5% and 11% at the normal adult male range, which in our laboratory was 300–1000 ng/dL. Serum fT was measured by RIA of the dialysate after an overnight equilibrium dialysis using the same RIA reagents as in the total T assay. The coefficient of variation for fT recovery for increasing doses of total T in the adult male ranged from 10% to 18%.The intra- and inter assay precisions of f T were 14% and 17%, respectively, at the normal adult male range, which in our laboratory was 200–700 pmol/L. Estradiol was measured with chemiluminescence (provided by Architect Systems,Abbotts Diagnostics, Germany), with a normal adult male range of 0–30 ng/dL; SHBG levels were measured by immunoradiometric assay (Radim SpA, Pomezia, Italy) with an intra- and interassay coefficient of variation below 6% at the normal adult range, which in our laboratory was 9–55 nmol/L; LH, prolactin, and thyroid stimulating hormone were measured by direct chemiluminescence (ADVIA Centaur, Bayer Co Germany) with an intra- and inter assay coefficient of variation between 6% and 3% at the normal adult range, which in our laboratory is 1.5–9 IU/L, 2–17 ng/mL, and 0.35–5.5 mIU/L, respectively.
Results
The demographic characteristics of the study groups at baseline (N = 20) are shown in Table 1 .The mean age of patients was 54.8 years (range:35–65), while the mean duration of ED history was 2.6 years. The ED etiology was clinically determined by investigators and reported as organic in 50%, mixed in 30%, and psychogenic in 20% of patients. The comorbidities reported by patients reflect those commonly seen in ED patients in clinical practice; in this study the most common comorbidities were hypertension (N = 6), diabetes mellitus (N = 6), depression(N = 3), and dyslipidemia (N = 6).
Tadalafil assumption was safe and well tolerated and none discontinued medication due to adverse events (Table 2). However, side-effects were greater after the first month of tadalafil assumption (overall adverse events in 30% of patients,mainly dyspepsia, back pain, and headache), were mild in intensity, and tended to resolve over time (10% after 12 months). The preferred dose was 20 mg (N = 11), while the remaining nine patients stayed with the 10 mg dose. Each patient assumed a mean of 10.3 ± 1.7 tablets per month throughout the entire period of study, which resulted in 8.1 ± 1.1 vs. 1.2 ± 0.7 sexual satisfactory attempts for intercourse when compared with baseline (P < 0.0001, data not shown).
The mean hormonal levels as well as T:E ratio of the study group were comparable to controls at baseline.
Figure 1 shows pre- and post treatment hormonal variations and comparison with controls. A significant decrease in E levels in the treated patients at the END OF THE STUDY (from 19.9 ± 9.6 to16.6 ± 8.1 ng/dL, P = 0.042 vs. baseline), with parallel increase in the T:E ratio, was found (26.3 ± 15.3 to 32.6 ± 17.7, P = 0.05; Figure 2), whereas no changes in T and fT serum levels, LH, SHBG, and prolactin (data not shown) levels were observed, respectively.
Interestingly, nonparametric subgroup analysis for related samples revealed that E DECREASE and T:E RATIO INCREASE WERE DETECTABLE ONLY IN LEAN (18.8 ± 9.8 vs. 13.7 ± 6.7, P = 0.019; and 38.5 ±17.8 vs. 29.2 ± 15.9, P = 0.05, respectively, N = 14) BUT NOT OBESE (N = 6, BMI > 27.5 kg/m2) treated subjects, without significant changes from baseline in the BMI. Furthermore, E decrease was maintained even after exclusion of patients with pathological E levels at baseline (15.8 ± 6.4 vs.13.0 ± 6.4, P = 0.039; N = 12). After the overall treatment period of 12 months, a net increase in the IIEF-5 scores was observed (13.7 ± 5.9 vs.25.7 ± 2.9, P < 0.0001).
Discussion
In this study we show for the first time a REDUCTION IN E LEVELS in patients with ED after CHRONIC EXPOSURE TO TADALAFIL and a concomitant increase in the T:E ratio. This hormonal pattern was found MOSTLY IN LEAN SUBJECTS , independent of the etiology of ED, comorbidities, and concomitant drug treatments. We also show that increased T:E ratio was not due to increase in T serum levels, as previously reported in hypogonadal men after resumption of satisfactory sexual activity [6], but rather to POSSIBLE EFFECTS of tadalafil on AROMATASE ACTIVITY.
A key role of androgens in sexual function has been assumed. Testosterone is the main androgen involved in the regulation of the male sexual function. The deficiency of androgens may represen tone of the major causes of ED. On the other hand,the increase of E plasma levels might be important because it also plays a role in determining sexual dysfunction and symptoms of aging [10]. Testicular E synthesis is very low in men. It is predominantly the product of peripheral aromatization of testicular and adrenal androgens. Aromatase activity is found in gonadic tissue and brain, but in humans this enzyme activity can also be detected in placental, adipose tissue, and fetal liver [11–13].Testicular and adrenal steroidogenesis declines with aging; the total plasma levels of E do not decrease owing to increased SHBG and aromatization in fat tissue [14,15]. It is traditionally called a female hormone; E has significant effects in males. Favorable effects on bone and brain have been identified [16], whereas an interference with sexual function and behavior has been described[17]. Recent studies show that increased E levels are associated with venous occlusive disorders inpatients with organic ED [18], and that the aromatase inhibition in elderly men with mild hypogonadism normalizes serum T and fT levels and improves sexual function [19]. Furthermore, i nmen with hypogonadism, a low dose of clomiphene citrate is effective in improving T:E ratio,thus giving more long-term benefit for the management of ED in hypogonadal patients [20].
In our study we observed a significant decrease of plasma E levels AFTER A TREATMENT PERIOD OF 12 MONTHS with tadalafil on demand at a flexible dosage (5, 10, and 20 mg), with a significant increase in T:E ratio, although no changes in T and f T serum levels were observed. In agreement with previous studies [6,7], the improvement of sexual function (significant increase in the IIEF-5scores) in our small series of patients was associated with a tendency to increase of T and f T serum levels after 3 months of treatment with PDE5i whereas after 12 months of treatment this trend was not maintained and we observed no changes in T and f T levels compared with baseline, although IIEF-5 scores were maintained with excellent overall efficacy scores. Finally we observed no changes in SHBG and LH levels. It should be recognized that our results obtained on a small cohort of patients (20 patients with normal baseline T levels compared with other published cohorts of patients with baseline T levels in the lower range) CANNOT BE COMPARED AT ALL WITH HUNDREDS OF PUBLISHED CASES; but, it is reasonable that the REDUCTION IN E LEVELS SHOULD BE CONFIRMED ALSO IN THE LONG TERM AAND FROM LARGER STUDIES.
Interestingly, nonparametric subgroup analysis for related samples revealed that E DECREASE AND T:E RATIO MODIFICATION WERE DETECTABLE ONLY IN LEAN BUT NOT IN OBESE (BMI > 27.5 kg/m2) TREATED SUBJECTS (see Figure 2), with no differences in T:E ratios among the different subgroups at baseline, due to the small number of subjects examined, and without any variation in the BMI at endpoint. Several studies showed that the expression of aromatase is tissue-specific and may be different between visceral and subcutaneous fat deposits, being highly expressed in the former. The observation that after 12 months of treatment with tadalafil on demand at flexible dosage determines a significant decrease of E levels and a significant increase of T:E ratio might be more importan tthan total serum T increase and may be due to a possible interference of tadalafil action with phosphodiesterase isozymes that may interfere with aromatase pathway. The evidence that E decrease was detectable only in lean but not in obese subjects may be due to the larger amount of aromatase in visceral and subcutaneous adipose tissue in the latter, with consequently increased aromatase activity that characterizes obese subjects, and may be accounted for by the number of overall pills consumed (1 every 3 days). Also, the hypothesis that 1 year of tadalafil treatment depresses aromatase activity in lean but not obese subjects leading to the altered T:E ratio and that the suppression of E may be responsible for the improvement in IIEF scores may be accounted for by the fact that in our series there were six obese diabetic subjects who reported partial responses to tadalafil treatment in terms of sexual satisfaction. Further studies are ongoing to confirm the possible relationship between chronic type 5 phosphodiesterase inhibition and aromatase activity in human adypocites in vitro BECAUSE AS IT STANDS HERE THERE HAS BEEN NO CLEAR-CUT DEMONSTRATION ON SUCH INTERPLAY.
In conclusion, in this study we demonstrated that LONG-TERM ADMINISTRATION OF TADALAFIL long-term is ASSOCIATED with increase in T:E ratio mainly due to significant reduction of E levels. Also, lack of tachyphylaxys in efficacy due to prolonged tadalafil use suggests that this is an effective and well-tolerated therapy in men of different age and broad ED etiologies and has a favorable cardiovascular safety profile [21]. Whether higher E levels are involved in the pathogenesis of ED in our series of patients has not been investigated. ANY PRESUMABLE EFFECT OF PDE5i ON AROMATASE ACTIVITY SHOULD BE FURTHER CONFIRMED WITH BOTH IN VITRO AND IN VIVO STUDIES because it may open a new research avenue, for example, atherosclerosis, prostate disease, breast cancer, and osteoporosis. This is specially true in view of chronic use of these medications for treating organic ED refractory to on-demand therapy [22].
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