DHT: How High is Too High

[Seagal]

I have pumpkin seed oil and quercetin coming. After that may give saw palmetto a try. I really don't want to try fin/dut....to many horror stories with those.

Of course I know about Fina duta possible negative effects. I tried a small dose of topical Fina few times and it always caused mood disturbances. I think your case is different, you seem to have an extreme abundance of 5-a-reductase. I would start with a really small dose. I believe that the herbal stuff is not strong enough in your case because you need to reduce DHT more than a few percentages. If you don't mind the hair redistribution then only titrating up E2 could work too.

 

[SS1LE]

are you still on testosterone cream and if so how much

No, only tried cream a few years ago. Been on 14mg Test E daily for awhile.

 

[SS1LE]

Of course I know about Fina duta possible negative effects. I tried a small dose of topical Fina few times and it always caused mood disturbances. I think your case is different, you seem to have an extreme abundance of 5-a-reductase. I would start with a really small dose. I believe that the herbal stuff is not strong enough in your case because you need to reduce DHT more than a few percentages. If you don't mind the hair redistribution then only titrating up E2 could work too.

I have HCG coming, I had to resort to UGL for the estradiol vial I broke. I know the tablets are easy to get but I heard they are hard on the liver.

 

[Forty2]

I had more hair loss on higher dose test prop (25-30 mg daily), than on 20 mg prop with pure DHT added in top via gel which raised my DHT over 300 ng/dL.

The pure DHT is a great way to experiment with this in a more controlled fashion.

Do you think even a low dose of DHT gel would suppress endogenous testosterone in a man not on TRT?

 

[Cataceous]

Do you think even a low dose of DHT gel would suppress endogenous testosterone in a man not on TRT?

I assume it's highly dependent on both the dose and the individual. Though speculative, it's possible that taking Cistanche extract simultaneously would hedge against suppressive effects. The echinacoside in this extract appears to have SARM-like effects, blocking androgen receptors in the hypothalamus, and thus reducing negative HPTA feedback. [R]

 

[FunkOdyssey]

Do you think even a low dose of DHT gel would suppress endogenous testosterone in a man not on TRT?

This has been tested before, and the answer is yes, at least somewhat. If you can get the full text of this study, you'll have more details on just how suppressive DHT was. I would be most interested in the serum level of DHT produced and how that relates to suppression, because I don't know how to equate the 125-200 mg dosage they studied to the Alpha Gels product.

https://academic.oup.com/jcem/article-abstract/87/4/1467/2374929?redirectedFrom=fulltext

 

[Seagal]

A role for dihydrotestosterone treatment in older men? - PMC

pmc.ncbi.nlm.nih.gov

"
Idan and colleagues report results from a comprehensive trial in 114 healthy, eugonadal men who received 2 years of either DHT treatment with a transdermal, pharmacologic dose of 70 mg DHT gel daily, or matching placebo gel.

As expected, the DHT-treated group had a 10-fold increase in serum DHT levels, well above the normal range of circulating DHT, and a concomitant decrease in serum testosterone and estradiol concentrations which were all unchanged in the placebo group.

The extremely high serum levels of DHT achieved in this study lead to significant gonadotropin suppression, thereby reducing circulating testosterone levels to nearly castrate levels and reducing circulating estradiol levels by 90%. The most concerning outcome of this study is the effect of high dose DHT gel on bone mineral density. Over 2 years, the subjects receiving DHT gel had a significant, progressive decrease in bone mineral density at the lumbar spine compared to placebo, despite expected anabolic effects on lean body mass.
"

Nothing mentioned about hair growth changes. Research focused on prostate.

 

[madman]

Do you think even a low dose of DHT gel would suppress endogenous testosterone in a man not on TRT?

* All subjects administered 5 g DHT (125 mg DHT) or placebo gel daily for the first 30 d, whereafter the dose was adjusted by a outside person (i.e. blind to the principal investigators) on the basis of serum DHT measurement performed 20 d after study entry. If serum DHT was less than 5.8 nmol/liter, the men used a daily dose of 250 mg, if serum DHT was between 5.8–11.6 nmol/liter, the daily dose was 187.5 mg, and if serum DHT was over 11.6 nmol/liter, the daily dose was 125 mg. The purpose was to reach the upper limit of 5.8–11.6 nmol/liter, which has been found to be the range at which a daily dose of 5 g gel is used (12). The dose of placebo was adjusted randomly by an outside person; 30 subjects continued with 5 g, and 30 used either 7.5 or 10 g.


* Serum DHT concentrations were measured by RIA after organic extraction and hydrophobic chromatography. The lower limit of quantification of serum DHT was 0.1 nmol/liter. The normal range for DHT was 1–10 nmol/liter, and the intra- and inter assay coefficients of variation were 9.1% and 6.6%, respectively. In previous studies the basal serum levels of DHT have been found to be 1.5–2.0 nmol/liter in men between 50–70 yr of age (5, 15, 16) and 2.5–3.5 nmol/liter in men between19–29 yr of age (16).


* After 1 month of DHT treatment, 23% of the subjects used a daily dose of 125 mg, 45% used 187.5 mg, and 32% used 250 mg. The serum concentrations of DHT and other hormones are shown in Table 2. For comparison, the FAI and serum DHT concentrations of healthy men are shown in Table 1.


* DHT treatment decreased serum concentrations of E2, T, and SHBG (P < 0.001–0.003; Table 2). Similarly, serum concentrations of LH and FSH decreased in the DHT group compared with the placebo group.


* This first placebo-controlled study carried out with DHT demonstrated a number of changes in both clinical and biochemical parameters in response to percutaneous DHT administration in men with relatively low bioavailable serum T levels and andropause symptoms.

* Treatment with percutaneous DHT gel increased serum total DHT levels 5-fold and led to concentrations that were clearly above the normal young adult male range (16). Although serum T concentrations decreased simultaneously with DHT administration by 50–70%, it is apparent that the total androgen effect increased significantly, especially because serum SHBG levels decreased simultaneously. This is supported by the observation that percutaneous T and DHT have an equal androgen effect in patients with hypogonadism (20),


* As expected and observed previously (15), serum FSH and LH concentrations decreased during DHT treatment as a result of the negative feedback effect. The long-term effect of DHT on testicular function, e.g. on spermatogenesis, is not yet known, but no evidence of irreversible effects exists (20).








Subjects and Methods

Subjects

A total of 120 males, aged 50–70 yr (mean age, 58 yr), participated in this monocenter, double blind, randomized, placebo-controlled, parallel group study (Fig. 1, flow chart). Based on a telephone conversation or a clinic visit, 178 subjects were known to fulfill the symptom criteria, and they were asked to come for screening. Of them, 55 failed to enter th estudy because of abnormal lipid or liver parameters, high serum prostate-specific antigen (PSA; 10 g/liter), or other reasons. The subjects were randomized to the DHT (n 60) or the placebo (n 60) group. The randomization codes identifying the treatment were kept in sealed envelopes and were broken only after all clinical and biochemical analyses were completed. None of the envelopes had to be opened before completing the study. Subjects included should have had rarefaction of nocturnal penile tumescence (once or less per wk; frequency of early morning erections together with libido are known to have correlation with serum androgen levels) and at least one of the following andropause symptoms: decreased libido, erectile dysfunction, urinary disorders, asthenia, or depressive mood. In addition, the subjects had to have a total serum T concentration of 15 nmol/liter or less (normal range, 9–32 nmol/liter) and/or an SHBG level greater than 30 nmol/liter (normal range, 14–62 nmol/liter). Although serum T levels of 15 nmol/liter or less and SHBG levels greater than 30 nmol/liter do not define all subjects as being hypogonadal or having low free T, these limits were used together with clinical symptoms to find men who would benefit from the treatment.The number of subjects in each category is given in Table 1. Five subjects in the DHT group and nine in the placebo group (P 0.175) had been treated earlier for impotence problems. The exclusion criteria with regard to prostate were prostate weight greater than 100 g, serum PSA level greater than 10 g/liter, acute prostatitis, abnormal prostate in clinical or ultrasonographic examination, or prostatectomy/transurethral resection of the prostate. The other main exclusion criteria were significant cardiovascular disease, abnormal lipid profile (total cholesterol 7.5 mmol/liter and/or triglycerides 1.7 mmol/liter), alcohol abuse, and uncured cancer. Furthermore, subjects with neurological impotence, major depression, or other psychiatric diseases, and those taking hormones or drugs affecting sexual function, lipid/hormone metabolism (-blockers, methyldopa, clonidine,guanethine thiazide diuretics, spironolactone, digitalis, barbiturates, clofibrate, cimetidine, metochlopramide, or antidepressive and neuroleptic drugs), or hematological parameters were excluded. Three subjects (1 taking DHT: unstable hypertension; 2 taking placebo: coronary heart disease with metoprolol medication and skin cancer) were wrongly included in the study; therefore, 3 additional men were randomized. Six men in the DHT group dropped out before the end of the trial (Fig. 1). The reasons for drop-out were withdrawal of consent (n 2), lack of efficacy (n 2), contact lost (n 1), and acute pyoelonephritis due to prostatitis (n 1). For comparison, the serum concentrations of DHT in 35 healthy men, aged 50–67 yr, and the free androgen index (FAI) in 146 healthy men, aged 20–65 yr, were analyzed.




Protocol

DHT and placebo gel were prepared and packed in identical tubes by Laboratories Besins Iscovesco (Paris, France). Both the study drug and placebo were opalescent gels with alcoholic odor, and they were applied on upper arms/shoulders and on abdomen if necessary. The DHT gel contained a 2.5% solution of DHT. After application the gel dried rapidly in a few minutes. The subjects were asked to wash their hands after application and to pay attention to any skin irritation observed. All subjects administered 5 g DHT (125 mg DHT) or placebo gel daily for the first 30 d, whereafter the dose was adjusted by a outside person (i.e. blind to the principal investigators) on the basis of serum DHT measurement performed 20 d after study entry. If serum DHT was less than 5.8 nmol/liter, the men used a daily dose of 250 mg, if serum DHT was between 5.8–11.6 nmol/liter, the daily dose was 187.5 mg, and if serum DHT was over 11.6 nmol/liter, the daily dose was 125 mg. The purpose was to reach the upper limit of 5.8–11.6 nmol/liter, which has been found to be the range at which a daily dose of 5 g gel is used (12). The dose of placebo was adjusted randomly by an outside person; 30 subjects continued with 5 g, and 30 used either 7.5 or 10 g. All tubes were returned and weighed to ensure compliance, and no significant failures were observed. The effect of DHT on general well-being was evaluated by questionnaire (13 questions), which was modified from the Psychological General Well-Being scale (13), and 12 questions regarding sexual function were modified from the International Index of Erectile Function(14). For example, the scoring system for the early morning erections was: 1 never, 2 every other month, 3 every month, 4 every other week, 5 every week, 6 two times a week or more. After the screening visit and entry, follow-up visits were made at 1, 3, and 6 months of treatment, and the subjects filled out the questionnaire before entry andat 3 and 6 months.




Laboratory techniques

Serum DHT concentrations were measured by RIA after organic extraction and hydrophobic chromatography. The lower limit of quantification of serum DHT was 0.1 nmol/liter. The normal range for DHT was 1–10 nmol/liter, and the intra- and inter assay coefficients of variation were 9.1% and 6.6%, respectively. In previous studies the basal serum levels of DHT have been found to be 1.5–2.0 nmol/liter in men between 50–70 yr of age (5, 15, 16) and 2.5–3.5 nmol/liter in men between19–29 yr of age (16). Serum T concentrations were measured using a ACS:180 chemiluminescence system with an ACS:180 analyzer (ChironCorp., Emeryville, CA). Serum E2 concentrations were measured by RIA(Orion Diagnostica, Turku, Finland). Serum SHBG, LH, FSH and PSA concentrations were quantified by two-site fluoroimmunometric methods with kits obtained from Wallac, Inc. (Turku, Finland), using a 1235 AutoDELFIA automatic immunoassay system. The intra- and inter-assay coefficients of variation were 4.0% and 5.6% for T, 5.7% and 6.4% for E2,1.3% and 5.1% for SHBG, 4.9% and 6.5% for LH, 3.8% and 4.3% for FSH,and 1.2% and 3.8% for PSA, respectively. The FAI was calculated according to the equation: (T 100)/SHBG. Hematological analyses and biochemical measurements were performed using approved routine clinical chemistry methods (Oulu University Hospital).




Results

After 1 month of DHT treatment, 23% of the subjects used a daily dose of 125 mg, 45% used 187.5 mg, and 32% used 250 mg. The serum concentrations of DHT and other hormones are shown in Table 2. For comparison, the FAI and serum DHT concentrations of healthy men are shown in Table 1. The score of early morning erection improved significantly in the DHT group during the first 3 months of treatment (from 3.0 to 3.9; P 0.003). The ability to maintain erections in subjects taking DHT improved significantly compared with that in subjects using placebo (Table 3). There were no statistically significant differences in general well-being, libido, mood, or vitality between the groups. However, the placebo effect was statistically significant in several questions: mood, briskness, self confidence, depression, activity, cheerfulness, and relaxation improved in both groups; libido, general interest in everyday life, and energy in the placebo group; and satisfaction with sexual life in the DHT group. Serum PSA concentrations did not change during the treatment. Similarly, prostate size and International Prostate Symptoms Score (I-PPS) remained unchanged (Table 4).

DHT treatment decreased serum concentrations of E2, T, and SHBG (P < 0.001–0.003; Table 2). Similarly, serum concentrations of LH and FSH decreased in the DHT group compared with the placebo group. DHT treatment did not affect serum lipid parameters (Table 4). No changes were observed in liver enzymes. Hemoglobin (Hb) and hematocrit(Hcr) values increased significantly in the DHT group compared with the placebo group (Table 4). In the DHT group, six men had Hb between 170 and 180 g/liter at least once during the treatment (normal range, 135–170), and one subject had Hb of 184 g/liter and Hcr of 55% (normal range 40–54%) at 3 months, but the values decreased to 176 g/liter and 53% at 6 months. There were no major clinical adverse events during DHT treatment. Three subjects experienced mild headache during DHT treatment compared with two subjects in the placebo group. None of the subjects describeds kin irritation during the treatment, but one subject in the DHT group had hair growth on the left shoulder and upper arm. Two subjects in both groups suffered from mild depression during the study. Other reported adverse events were not considered to be related to the treatment.




Discussion

This first placebo-controlled study carried out with DHT demonstrated a number of changes in both clinical and biochemical parameters in response to percutaneous DHT administration in men with relatively low bioavailable serum T levels and andropause symptoms. Treatment with DHT improved the ability to maintain erections and transiently improved early morning erections. However, these changes were small, though significant; therefore, their clinical importance remains uncertain. Six subjects in the DHT group and none in the placebo group dropped out before the end of the trial. We do not have a good explanation why only subjects in the DHT group stopped the study, but the difference in the dropout frequency between the groups was not statistically significant, and none of the reasons for dropping out were related to side-effects of the drug.

Androgens have been shown to have favorable consequences in the central nervous system by having a stimulating and maintaining effect on sexual function in men (17,18). A number of androgen preparations have been used to treat hypogonadism (19). Treatment with percutaneous DHT gel increased serum total DHT levels 5-fold and led to concentrations that were clearly above the normal young adult male range (16). Although serum T concentrations decreased simultaneously with DHT administration by 50–70%, it is apparent that the total androgen effect increased significantly, especially because serum SHBG levels decreased simultaneously. This is supported by the observation that percutaneous T and DHT have an equal androgen effect in patients with hypogonadism (20), and DHT may have even greater pharmacological potency than other androgens (11).Androgen replacement in older men has been reported to increase the sense of well-being (21). In our study we did not find significant effects of DHT gel on well-being or vitality. The reason for this is not clear, but it is possible that many subjects had erectile dysfunction before the study and had great expectations for treatment. As impotence is often multifactorial, and androgen supplementation of older men has generally not met with great success (21, 22), at least some subjects may have been disappointed with the treatment and did not pay attention to general well-being. Furthermore, as in previous studies (21), the placebo effect in this study was significant with regard to several aspects of general wellbeing. In addition, based on the inclusion criteria (T 15 nmol/liter and/or SHBG <30 nmol/liter) the subjects may have had only mild or moderate androgen deficiency. Although the FAI of the study subjects was significantly lower than that of healthy men of the same age and was half that seen in younger men, their serum DHT levels at baseline were comparable. This was expected, because serum DHT levels do not change markedly with advancing age (5), and therefore the measurement of DHT levels may not be useful when considering androgen decline or deficiency in aging men. Furthermore, if some of the effects of androgens, for instance on the central nervous system, are due to metabolism to estrogens, DHT as a nonaromatizable androgen may have a weaker effect. Alternatively, the instruments used to assess subjective symptoms may not be sensitive enough to detect small changes, which is always a problem in studies like this.

As expected and observed previously (15), serum FSH and LH concentrations decreased during DHT treatment as a result of the negative feedback effect. The long-term effect of DHT on testicular function, e.g. on spermatogenesis, is not yet known, but no evidence of irreversible effects exists (20).

It is well known that androgens have an anabolic effect. Androgens increase red cell mass and Hb concentrations mainly through a direct effect on erythropoietin synthesis in the kidneys, and inhibition of androgen secretion decreases Hb concentrations (36). We found that Hb increased significantly as early as after 1 month of DHT treatment. Similar effects on Hcr have been found earlier in long-term use of T in older hypogonadal men (19) and in normal aging males(31). This anabolic effect must be considered during the follow-up of subjects using DHT or other androgens; Hb and Hcr should be assessed after 3–6 months of treatment, and the dose should be decreased if necessary. Weight and body mass index did not change during the study. The possible effects of DHT on bone density as well as on body composition were not assessed, which may reduce the informativity of the study. These matters were considered carefully before the study, and because no significant changes, especially in bone density, were expected in 6 months of treatment they were not included.




TABLE 1. Characteristics of the subjects

TABLE 2. Effects of DHT treatment on serum hormone parameters

TABLE 4. Effects of DHT treatment on weight, prostatic weight, I-PPS score, and hematological, biochemical, and lipid parameters

 

[Forty2]

* All subjects administered 5 g DHT (125 mg DHT) or placebo gel daily for the first 30 d, whereafter the dose was adjusted by a outside person (i.e. blind to the principal investigators) on the basis of serum DHT measurement performed 20 d after study entry. If serum DHT was less than 5.8 nmol/liter, the men used a daily dose of 250 mg, if serum DHT was between 5.8–11.6 nmol/liter, the daily dose was 187.5 mg, and if serum DHT was over 11.6 nmol/liter, the daily dose was 125 mg. The purpose was to reach the upper limit of 5.8–11.6 nmol/liter, which has been found to be the range at which a daily dose of 5 g gel is used (12). The dose of placebo was adjusted randomly by an outside person; 30 subjects continued with 5 g, and 30 used either 7.5 or 10 g.


* Serum DHT concentrations were measured by RIA after organic extraction and hydrophobic chromatography. The lower limit of quantification of serum DHT was 0.1 nmol/liter. The normal range for DHT was 1–10 nmol/liter, and the intra- and inter assay coefficients of variation were 9.1% and 6.6%, respectively. In previous studies the basal serum levels of DHT have been found to be 1.5–2.0 nmol/liter in men between 50–70 yr of age (5, 15, 16) and 2.5–3.5 nmol/liter in men between19–29 yr of age (16).


* After 1 month of DHT treatment, 23% of the subjects used a daily dose of 125 mg, 45% used 187.5 mg, and 32% used 250 mg. The serum concentrations of DHT and other hormones are shown in Table 2. For comparison, the FAI and serum DHT concentrations of healthy men are shown in Table 1.


* DHT treatment decreased serum concentrations of E2, T, and SHBG (P < 0.001–0.003; Table 2). Similarly, serum concentrations of LH and FSH decreased in the DHT group compared with the placebo group.


* This first placebo-controlled study carried out with DHT demonstrated a number of changes in both clinical and biochemical parameters in response to percutaneous DHT administration in men with relatively low bioavailable serum T levels and andropause symptoms.

* Treatment with percutaneous DHT gel increased serum total DHT levels 5-fold and led to concentrations that were clearly above the normal young adult male range (16). Although serum T concentrations decreased simultaneously with DHT administration by 50–70%, it is apparent that the total androgen effect increased significantly, especially because serum SHBG levels decreased simultaneously. This is supported by the observation that percutaneous T and DHT have an equal androgen effect in patients with hypogonadism (20),


* As expected and observed previously (15), serum FSH and LH concentrations decreased during DHT treatment as a result of the negative feedback effect. The long-term effect of DHT on testicular function, e.g. on spermatogenesis, is not yet known, but no evidence of irreversible effects exists (20).








Subjects and Methods

Subjects

A total of 120 males, aged 50–70 yr (mean age, 58 yr), participated in this monocenter, double blind, randomized, placebo-controlled, parallel group study (Fig. 1, flow chart). Based on a telephone conversation or a clinic visit, 178 subjects were known to fulfill the symptom criteria, and they were asked to come for screening. Of them, 55 failed to enter th estudy because of abnormal lipid or liver parameters, high serum prostate-specific antigen (PSA; 10 g/liter), or other reasons. The subjects were randomized to the DHT (n 60) or the placebo (n 60) group. The randomization codes identifying the treatment were kept in sealed envelopes and were broken only after all clinical and biochemical analyses were completed. None of the envelopes had to be opened before completing the study. Subjects included should have had rarefaction of nocturnal penile tumescence (once or less per wk; frequency of early morning erections together with libido are known to have correlation with serum androgen levels) and at least one of the following andropause symptoms: decreased libido, erectile dysfunction, urinary disorders, asthenia, or depressive mood. In addition, the subjects had to have a total serum T concentration of 15 nmol/liter or less (normal range, 9–32 nmol/liter) and/or an SHBG level greater than 30 nmol/liter (normal range, 14–62 nmol/liter). Although serum T levels of 15 nmol/liter or less and SHBG levels greater than 30 nmol/liter do not define all subjects as being hypogonadal or having low free T, these limits were used together with clinical symptoms to find men who would benefit from the treatment.The number of subjects in each category is given in Table 1. Five subjects in the DHT group and nine in the placebo group (P 0.175) had been treated earlier for impotence problems. The exclusion criteria with regard to prostate were prostate weight greater than 100 g, serum PSA level greater than 10 g/liter, acute prostatitis, abnormal prostate in clinical or ultrasonographic examination, or prostatectomy/transurethral resection of the prostate. The other main exclusion criteria were significant cardiovascular disease, abnormal lipid profile (total cholesterol 7.5 mmol/liter and/or triglycerides 1.7 mmol/liter), alcohol abuse, and uncured cancer. Furthermore, subjects with neurological impotence, major depression, or other psychiatric diseases, and those taking hormones or drugs affecting sexual function, lipid/hormone metabolism (-blockers, methyldopa, clonidine,guanethine thiazide diuretics, spironolactone, digitalis, barbiturates, clofibrate, cimetidine, metochlopramide, or antidepressive and neuroleptic drugs), or hematological parameters were excluded. Three subjects (1 taking DHT: unstable hypertension; 2 taking placebo: coronary heart disease with metoprolol medication and skin cancer) were wrongly included in the study; therefore, 3 additional men were randomized. Six men in the DHT group dropped out before the end of the trial (Fig. 1). The reasons for drop-out were withdrawal of consent (n 2), lack of efficacy (n 2), contact lost (n 1), and acute pyoelonephritis due to prostatitis (n 1). For comparison, the serum concentrations of DHT in 35 healthy men, aged 50–67 yr, and the free androgen index (FAI) in 146 healthy men, aged 20–65 yr, were analyzed.




Protocol

DHT and placebo gel were prepared and packed in identical tubes by Laboratories Besins Iscovesco (Paris, France). Both the study drug and placebo were opalescent gels with alcoholic odor, and they were applied on upper arms/shoulders and on abdomen if necessary. The DHT gel contained a 2.5% solution of DHT. After application the gel dried rapidly in a few minutes. The subjects were asked to wash their hands after application and to pay attention to any skin irritation observed. All subjects administered 5 g DHT (125 mg DHT) or placebo gel daily for the first 30 d, whereafter the dose was adjusted by a outside person (i.e. blind to the principal investigators) on the basis of serum DHT measurement performed 20 d after study entry. If serum DHT was less than 5.8 nmol/liter, the men used a daily dose of 250 mg, if serum DHT was between 5.8–11.6 nmol/liter, the daily dose was 187.5 mg, and if serum DHT was over 11.6 nmol/liter, the daily dose was 125 mg. The purpose was to reach the upper limit of 5.8–11.6 nmol/liter, which has been found to be the range at which a daily dose of 5 g gel is used (12). The dose of placebo was adjusted randomly by an outside person; 30 subjects continued with 5 g, and 30 used either 7.5 or 10 g. All tubes were returned and weighed to ensure compliance, and no significant failures were observed. The effect of DHT on general well-being was evaluated by questionnaire (13 questions), which was modified from the Psychological General Well-Being scale (13), and 12 questions regarding sexual function were modified from the International Index of Erectile Function(14). For example, the scoring system for the early morning erections was: 1 never, 2 every other month, 3 every month, 4 every other week, 5 every week, 6 two times a week or more. After the screening visit and entry, follow-up visits were made at 1, 3, and 6 months of treatment, and the subjects filled out the questionnaire before entry andat 3 and 6 months.




Laboratory techniques

Serum DHT concentrations were measured by RIA after organic extraction and hydrophobic chromatography. The lower limit of quantification of serum DHT was 0.1 nmol/liter. The normal range for DHT was 1–10 nmol/liter, and the intra- and inter assay coefficients of variation were 9.1% and 6.6%, respectively. In previous studies the basal serum levels of DHT have been found to be 1.5–2.0 nmol/liter in men between 50–70 yr of age (5, 15, 16) and 2.5–3.5 nmol/liter in men between19–29 yr of age (16). Serum T concentrations were measured using a ACS:180 chemiluminescence system with an ACS:180 analyzer (ChironCorp., Emeryville, CA). Serum E2 concentrations were measured by RIA(Orion Diagnostica, Turku, Finland). Serum SHBG, LH, FSH and PSA concentrations were quantified by two-site fluoroimmunometric methods with kits obtained from Wallac, Inc. (Turku, Finland), using a 1235 AutoDELFIA automatic immunoassay system. The intra- and inter-assay coefficients of variation were 4.0% and 5.6% for T, 5.7% and 6.4% for E2,1.3% and 5.1% for SHBG, 4.9% and 6.5% for LH, 3.8% and 4.3% for FSH,and 1.2% and 3.8% for PSA, respectively. The FAI was calculated according to the equation: (T 100)/SHBG. Hematological analyses and biochemical measurements were performed using approved routine clinical chemistry methods (Oulu University Hospital).




Results

After 1 month of DHT treatment, 23% of the subjects used a daily dose of 125 mg, 45% used 187.5 mg, and 32% used 250 mg. The serum concentrations of DHT and other hormones are shown in Table 2. For comparison, the FAI and serum DHT concentrations of healthy men are shown in Table 1. The score of early morning erection improved significantly in the DHT group during the first 3 months of treatment (from 3.0 to 3.9; P 0.003). The ability to maintain erections in subjects taking DHT improved significantly compared with that in subjects using placebo (Table 3). There were no statistically significant differences in general well-being, libido, mood, or vitality between the groups. However, the placebo effect was statistically significant in several questions: mood, briskness, self confidence, depression, activity, cheerfulness, and relaxation improved in both groups; libido, general interest in everyday life, and energy in the placebo group; and satisfaction with sexual life in the DHT group. Serum PSA concentrations did not change during the treatment. Similarly, prostate size and International Prostate Symptoms Score (I-PPS) remained unchanged (Table 4).

DHT treatment decreased serum concentrations of E2, T, and SHBG (P < 0.001–0.003; Table 2). Similarly, serum concentrations of LH and FSH decreased in the DHT group compared with the placebo group. DHT treatment did not affect serum lipid parameters (Table 4). No changes were observed in liver enzymes. Hemoglobin (Hb) and hematocrit(Hcr) values increased significantly in the DHT group compared with the placebo group (Table 4). In the DHT group, six men had Hb between 170 and 180 g/liter at least once during the treatment (normal range, 135–170), and one subject had Hb of 184 g/liter and Hcr of 55% (normal range 40–54%) at 3 months, but the values decreased to 176 g/liter and 53% at 6 months. There were no major clinical adverse events during DHT treatment. Three subjects experienced mild headache during DHT treatment compared with two subjects in the placebo group. None of the subjects describeds kin irritation during the treatment, but one subject in the DHT group had hair growth on the left shoulder and upper arm. Two subjects in both groups suffered from mild depression during the study. Other reported adverse events were not considered to be related to the treatment.




Discussion

This first placebo-controlled study carried out with DHT demonstrated a number of changes in both clinical and biochemical parameters in response to percutaneous DHT administration in men with relatively low bioavailable serum T levels and andropause symptoms. Treatment with DHT improved the ability to maintain erections and transiently improved early morning erections. However, these changes were small, though significant; therefore, their clinical importance remains uncertain. Six subjects in the DHT group and none in the placebo group dropped out before the end of the trial. We do not have a good explanation why only subjects in the DHT group stopped the study, but the difference in the dropout frequency between the groups was not statistically significant, and none of the reasons for dropping out were related to side-effects of the drug.

Androgens have been shown to have favorable consequences in the central nervous system by having a stimulating and maintaining effect on sexual function in men (17,18). A number of androgen preparations have been used to treat hypogonadism (19). Treatment with percutaneous DHT gel increased serum total DHT levels 5-fold and led to concentrations that were clearly above the normal young adult male range (16). Although serum T concentrations decreased simultaneously with DHT administration by 50–70%, it is apparent that the total androgen effect increased significantly, especially because serum SHBG levels decreased simultaneously. This is supported by the observation that percutaneous T and DHT have an equal androgen effect in patients with hypogonadism (20), and DHT may have even greater pharmacological potency than other androgens (11).Androgen replacement in older men has been reported to increase the sense of well-being (21). In our study we did not find significant effects of DHT gel on well-being or vitality. The reason for this is not clear, but it is possible that many subjects had erectile dysfunction before the study and had great expectations for treatment. As impotence is often multifactorial, and androgen supplementation of older men has generally not met with great success (21, 22), at least some subjects may have been disappointed with the treatment and did not pay attention to general well-being. Furthermore, as in previous studies (21), the placebo effect in this study was significant with regard to several aspects of general wellbeing. In addition, based on the inclusion criteria (T 15 nmol/liter and/or SHBG <30 nmol/liter) the subjects may have had only mild or moderate androgen deficiency. Although the FAI of the study subjects was significantly lower than that of healthy men of the same age and was half that seen in younger men, their serum DHT levels at baseline were comparable. This was expected, because serum DHT levels do not change markedly with advancing age (5), and therefore the measurement of DHT levels may not be useful when considering androgen decline or deficiency in aging men. Furthermore, if some of the effects of androgens, for instance on the central nervous system, are due to metabolism to estrogens, DHT as a nonaromatizable androgen may have a weaker effect. Alternatively, the instruments used to assess subjective symptoms may not be sensitive enough to detect small changes, which is always a problem in studies like this.

As expected and observed previously (15), serum FSH and LH concentrations decreased during DHT treatment as a result of the negative feedback effect. The long-term effect of DHT on testicular function, e.g. on spermatogenesis, is not yet known, but no evidence of irreversible effects exists (20).

It is well known that androgens have an anabolic effect. Androgens increase red cell mass and Hb concentrations mainly through a direct effect on erythropoietin synthesis in the kidneys, and inhibition of androgen secretion decreases Hb concentrations (36). We found that Hb increased significantly as early as after 1 month of DHT treatment. Similar effects on Hcr have been found earlier in long-term use of T in older hypogonadal men (19) and in normal aging males(31). This anabolic effect must be considered during the follow-up of subjects using DHT or other androgens; Hb and Hcr should be assessed after 3–6 months of treatment, and the dose should be decreased if necessary. Weight and body mass index did not change during the study. The possible effects of DHT on bone density as well as on body composition were not assessed, which may reduce the informativity of the study. These matters were considered carefully before the study, and because no significant changes, especially in bone density, were expected in 6 months of treatment they were not included.




TABLE 1. Characteristics of the subjects
View attachment 51355




TABLE 2. Effects of DHT treatment on serum hormone parameters
View attachment 51356




TABLE 4. Effects of DHT treatment on weight, prostatic weight, I-PPS score, and hematological, biochemical, and lipid parameters
View attachment 51357

Thanks.
Do you think concomitant use of hCG would mitigate against DHT induced testosterone & E2 suppression in those with secondary hypogonadism?

 

[SS1LE]

So I tried some progesterone cream(15mg) for about 4 days it just made me super irritable, I'm talking like if someone said hello it pissed me off.....So progesterone does not give me a calming effect I guess...lol. So I can't use that to try to balance my DHT

 

[zuckerbaer]

Thanks.
Do you think concomitant use of hCG would mitigate against DHT induced testosterone & E2 suppression in those with secondary hypogonadism?

I believe it works very well for this purpose.
I want to tell you my story: First, of how HCG worked for me, and then how I found out why it should also help regulate DHT levels.

A few years ago, I began over a year of HCG monotherapy to increase my libido and improve erection problems. Basically, it was another attempt on my part to overcome severe burnout that I had suffered a year earlier, which had led to a sharp drop in my hormone levels. The HCG significantly improved my situation, and I felt fine again.

I am 62 years now, here are test results at the time of my burnout, couldn´t get DHT tested though. They just do not test for it where I live in Europe. Next time I must go for private testing and pay for everything myself if I want DHT levels.

Then the results one year later after starting the HCG in December 2025 that year, 500-600 i.U. twice weekly:

With these levels I felt fine for the most part, but erections were still not much improved, even though libido was quite high and sensitivity very good. Energy and mood was all good as well, stress tolerance not bad.

Over the next three years, my symptoms such as erectile dysfunction, libido, energy, stress tolerance, and memory problems unfortunately worsened. I tried various combinations to improve this, mainly with testosterone enanthate IM between 100 and 200 mg per week, then also with boron at a dosage of 20 to 40 mg, but my estradiol level rose too high every time after about two months, so I stopped the treatment.
The reason I stopped was primarily, because I was still scared of TRT, since at my age it will be for the rest of my life.

At my second try last year in autumn of starting out with testosterone enanthate, I thought of managing high estrogen symptoms with anastrozole, but failed because I took too much of it from increasing the dosage too quickly, after reading that results would show in a short time. Although I had started very cautiously with a low dose of 0.125 mg twice a week, after a month I was taking 1–1.25 mg weekly, causing my estrogen levels to crash and got me bed-ridden for nearly two weeks with all the symptoms of a flu, only without the fever.

I stopped immediately and vowed never to touch this stuff again. I took a break for about two months and didn't take anything, just about 15 mg of boron, which has been a staple of my supplements for several years, mainly for hormone balance and athlete's foot, where it has worked wonders while everything else has failed.

Now comes the part with my DHT experience.

After my bad experience with aromatase inhibitors I decided to try testosterone cream instead, by buying a HRT cream base and combine it with testosterone enanthate powder to make my own formula.

The cream finally was the beginning of my breakthrough!

The first time in March 2025, I started out with a common dosage of 100mg/daily. I knew that aromatase is reduced with skin absorption, but I did not expect it to make such a huge difference! Believe it or not, even if I had recovered from my first estrogen crash recently, the cream had totally different effects compared to injectable testosterone. As hard as it is to believe, but I ended up getting the SAME symptoms of estrogen crash from anastrozole with the cream too! This is no joke, I now knew quite well what a crash is and it is not fun.

Once again, I stopped using the cream after about six weeks and started to slowly become desperate, as I needed a solution that worked for my problems. I decided to go back to injections for another time, because I could not put up with the low estrogen levels.

This time I started with a low dosage to avoid high estrogen levels, which have a negative effect on me and lead to erectile dysfunction, water retention, loss of energy, joint pain etc. In May I started taking Test-E 60 mg twice a week, and increased it to 75 mg after a couple months, until end of September. During this time, I recovered from the estrogen crash and, even better, the levels did not rise as high as before. About two weeks before the hormone test, I increased the dose to 90 mg twice a week. My energy levels were good, as was the improvement in my memory, concentration, and libido, erections were better as well.

Here are the lab results from September 2025. Unfortunately, estradiol and T3/T4 were not tested due to errors on the part of the lab. Instead, estrone was tested, and the value was quite high. But I know my body quite well by now and know how it reacts to estrogen. This time, there were no symptoms of high estrogen levels at all; I just felt good. Again, DHT could not be tested unfortunately.

Last test results from 16. September 2025:

At this time I felt fine with the 180mg testosterone enanthate split into two injections weekly without any high estrogen symptoms to my own disbelief, contrary to previous trials. Even then as I felt fine, I had problems from the injections, where swelling and itching developed that took weeks to disappear. I use my own homemade formula, but it wasn't the obvious problem with sterility or infections. After extensive research, I found out that steroid powders must be dissolved quickly in an oil-based solution and stored at low temperatures. I didn't do that, and after simply storing the powder at room temperature for a few months, the condition had apparently already changed.

Anyway, that eventually forced me to go back to the cream and I am happy I did.
From the beginning of October, everything has been working really well and consistently!

I finally switched back to cream, using a lower dose of 100 mg of testosterone enanthate cream daily for the transition period. After a month, I increased the dose to about 150 mg, and soon after, I felt my libido improving and my erections getting better. However, as symptoms of low estrogen levels reappeared, I also took 20 mg of DHEA daily, as my levels were rather low after the last test and it is also converted into estrogen. Topical testosterone cream or gel lowers both testosterone and estrogen levels, and DHEA was supposed to fill the gap here.

I was getting better and finally increased the dose to 200 mg daily, which seems like a lot, but it gave me the final push! Now I feel really good, with a consistently high libido, significantly improved erections, and everything else fine so far. There are NO symptoms of high estrogen levels at all, the levels seem to be fine, but I will do another test very soon. Since the response to the cream (or gel) is much faster than to the injection, I can adjust the dosage much better. I even had to add some estradiol to prevent my estrogen levels from dropping too low again.

After trying everything possible for several years, I finally believe I have found the solution to improving my well-being through the controlled use of hormones.

For me, this seems to be possible only through the use of a transdermal testosterone cream, as only this method of application leads to a real improvement in libido and erections, as well as many other positive changes.

I have read so much about DHT and how it supposedly affects the body, but I have not been able to achieve any benefits from using pure DHT alone, either orally or topically.

My final formula now consists of combining 200 mg of testosterone enanthate cream, 3 mg estradiol valerate daily with HCG, again 1000 IU weekly, and I believe that after so long, I am finally on the right track.

Sorry for the long post, but I wanted to explain my journey of how I ultimately ended up here, and hope others find it useful in finding their own solution.

 

[Nelson Vergel]

Thanks @zuckerbaer for the detailed post! I learned a lot by reading it.

Have you ever tried T creams plus twice per week 500 IU hCG? Are you still taking DHEA?

I am glad you are feeling better!

 

[zuckerbaer]

Thanks @zuckerbaer for the detailed post! I learned a lot by reading it.

Have you ever tried T creams plus twice per week 500 IU hCG? Are you still taking DHEA?

I am glad you are feeling better!

Hallo Nelson,

I am very grateful to be here, this thread here has helped me so much in making the right decisions to find the right TRT protocol after so many trials and errors! I am ever so thankful to have found this forum with so many knowledgable people here, including you. I too learned a lot here already!

Particularly where it is mentioned that DHT causes estrogen and even testosterone to drop, plus the link to the study with older men and DHT benefits from @Seagal -->

A role for dihydrotestosterone treatment in older men?​

(cant post links yet since I am new here)

This lit the light bulb in my head in that I should not lower the dosage of the cream to avoid low estrogen levels again but include estradiol into the formula as well.

Actually, I am taking the T-cream (with added estradiol) now with twice weekly 500 IU hCG. I will add 10mg DHEA to the T-cream in the next batch in a week or so as I have to finish the current one first, and then stay on it for a while. So far I took the DHEA 20mg oral for the last two months. Then do another hormone panel including DHT next month to see where I am.

 

[Nelson Vergel]

Have you tried scrotal testosterone cream ?

 

[zuckerbaer]

Have you tried scrotal testosterone cream ?

Yes, tried this as well, but quickly stopped after only two weeks as low estrogen symptoms appeared fast.
Couldn´t believe that this is happening in just a few days.

There is one more thing I wanted to say which I didn´t include in the original post before:
After my first estrogen crash I do not aromatize as much as before!

In fact much less as it appears. At first I was puzzled, but after doing research, I found that you had actually posted a paper talking about Post AI Major Dysfunction (PAMD), the original title is PSSD, PFS, PRSD: Aetiology and Treatment. It talks about men having low estrogen symptoms even when they have high levels in reality, after abruptly stopping high dose aromatase inhibitors.

This is actually true, I apparently experience the same and I do not have a problem with it. It does not seem to cause any issues other than lower aromatase, so I am happy about it. Still, I need to get a test done soon as possible to get a current hormone status to see where my estradiol values are now.