Hormone Therapy News Articles

TABLE 4: BASELINE AND POST-TREATMENT SERUM LEVELS OF SELECT HORMONES

TT: total testosterone; Free T: free testosterone; DHEAS: dehydroepiandrosterone-sulfate; IGF-1: insulin-like growth factor —1; A: androgens (DHEA +_ transdermal T); G: growth hormone

TABLE 5: THE EFFECT OF THE PROGRAM ON HBA1C VARIED BETWEEN GENDERS AND WITH THE APPLICATION OF G.

A: androgens; HRT: estradiol + progesterone; G: growth hormone

Table 7 shows the percent change in weight, LBM, % BF and WHR in four out of the     five groups.    We were unable to obtain follow up data for women on A plus G.

Table 8 shows the change in bone density that occurred over the course of the program in only four groups. No follow up data was available for women on A plus G. The fifth column shows the percent better than predicted of total body bone density for each of the four groups. The purpose is to show how well the patients in each category fared in comparison to the expected change in bone density matched to their age and period of time between scans. Peer reviewed papers were used to obtain a range of expected bone loss per year matched for sex and age to our groups.

TABLE 6: PERCENT CHANGE BY GROUPS

TC: total cholesterol; TG: triglycerides; A: androgens (DHEA ±_testosterone); G: growth hormone; HRT: estradiol progesterone; LDL: low-density lipoprotein; HDL: high-density lipoprotein

TABLE 7: PERCENT CHANGE BY GROUPS

LBM: lean body mass; %BF: % body fat; WHR: waist-to-hip ratio; A: androgens (DHEAitestosterone); G: growth hormone; HRT: estradiol + progesterone

Based on these data, the rates of expected decline in bone density that we used in comparison to those actually experienced in our population were: for men, 1 % per year; for women on A+G+HRT (average age 67), 1.5%

per year; for women on A+HRT (average age 53, perimenopausal), 3% per year.

Table 13 illustrates an effect we noticed on HDL cholesterol by raising testosterone levels above the normal range in women.

TABLE 8: BONE DENSITY- CHANGE T SCORE

Side effects that occurred while on the program are recorded for men on Table 9 and for women on Table 10. This survey was sent to all patients on the program. The response rate was low, partly because we had only a very small window of time to receive the answers back. The survey was sent only to those who were currently on the program. It would therefore, exclude anyone who had dropped out of the program due to side effects.

Perceived benefits of the program based on a subjective survey filled out by patients currently on the program are shown on Table 11 for women, and Table 12 for men. Although statistical analysis was not done, it did appear that a majority of the women who responded positively were on growth hormone.

TABLE 9: MEN ON ALL PROGRAMS ____side effects, (N = 40)____

Positives (n)

Positive responses to a survey sent to all men currently on a hormone program consisting of either androgens (DHEA + testosterone) or growth hormone or both.

TABLE 10: WOMEN ON ALL PROGRAMS: side effucts profile (n = 22)

Positive responses to a survey sent to all women currently on a hormone program consisting of either androgens (A) (DHEA and/or testosterone) androgens + growth hormone or androgens +HRT (estradiol + progesterone) or A+G+HRT.

CONCLUSION

These data support the hypothesis that the many benefits seen in controlled trials of hormone replacement, low glycemic nutrition and exercise in the realm of reduced disease risk and quality of life, can be delivered in the private practice setting with minimal side effects that are easily managed.

DISCUSSION

The first issue of note is that attaining more youthful serum levels of the sex hormones and IGF-1 is achievable and largely predictable. We overshot both our goal and the normal range only for T and only in one group- women on A + G + HRT. This was apparently not without consequence as shown in Table 13, due to the decline in HDL. T has been implicated to lower HDL levels in women^(120121) Reducing the T =dose, fine-tuning the diet, or even using cholesterol-modifying agents are options for dealing with this. Also notable is the relatively high level of HDL in these women both before and after T administration. The rise in T levels in women is partially affected by D. ⁽¹²²-¹²³⁾

The substantial improvement in disease risk outcomes seen in Tables 4-10 and the subjective benefit shown in Tables 11 and 12 cannot be attributed to G or any single or group of hormones, or even to one modality. They can only be attributed to the comprehensive program. For example, studies without calorie restriction unanimously demonstrate a rise in

TABLE 11: HAVE YOU SEEN IMPROVEMENT IN ANY OF THE FOLLOWING SINCE STARTING THE PROGRAM? WOMEN (N = 22)

There was a strong trend of positives toward G. Positive responses to a survey sent to all women currently on a hormone program consisting of either androgens (A) (DHEA and/or testosterone) androgens + growth hormone or androgens +HRT (estradiol + progesterone) or A+G+HRT.

TABLE 12: HAVE YOU SEEN IMPROVEMENT IN ANY OF THE FOLLOWING SINCE STARTING THE CENEGENICS® PROGRAM? MEN  (N = 40)

HA1C with the use of G well beyond what we experienced ¹¹⁴~    . Yet there were at least three interventions working to lower HA1C: LGID ^(102108), exercise ⁽¹¹³⁾, and T ⁽⁷⁾. It is gratifying that we saw a reduction in HA1C in most groups on G and only a minimal increase in women on G. Certainly our patients were consuming more calories than the subjects in Nams study ⁽¹¹⁹⁾ where patients on a daily restriction of 25 kcal/ kg and G lost more fat and became more insulin sensitive than those on the same diet without G.

Every category of women on G experienced, on average, an increase in HA 1C, even though their percentage increase in IGF-1 was slightly less than that in men. We can speculate that they were less compliant with nutrition and exercise. Another possibility is less effect of T ⁽⁷⁾, since their serum level on the program was roughly 8.5% that of men.

In both groups of men, serum PSA increased between 27 and 30%. These

percentages seem somewhat misleading since the baseline values were so low (1.23 and 1.67) and the normal range is relatively wide (0-4.0). The actual increases in PSA were only 0.37 in men on A and 0.45 in men on A + G. Our data conflict with that of Cooper ⁽¹²⁴⁾ who saw no change in PSA in his study of 31 healthy men age 21 to 39 using intramuscular T at up to 500mg per week for 15 weeks. Although his trial was of much shorter duration than our approximate 33 weeks, his dose was up to 12 times ours. This leads us to believe that the difference in results is attributable to the subjects age differences. His eldest was 39 and our average age was 56. Only 7.5% of men currently on our program experienced new nocturia (Table 12). These are not necessarily the same men for whom PSA values are reported. In our 4-year history we have had only one patient drop out for urinary symptoms, a 68 year old with severe BPH who returned to the program after a trans-urethral resection.

Dihydrotestosterone (DHT) levels in our male subjects increased very modestly and remained normal. We were unable to maintain this control of DHT in our early history of using transdermal T without the aid of finasteride. No finasteride was used in any of the subjects reported herein. All our male subjects are encouraged to use saw palmetto, stinging nettle and pygeum but we are unable to report on compliance.

There was a slight increase in IGF-1 in both groups not on G, one group in each gender (Tables 2 and 3). This is likely a T and D effect. Testosterone administration in eugonadal ⁽¹²⁵⁾ and hypogonadal ⁽¹²⁶⁾ men has been shown to raise IGF-1.

TABLE 13: EFFECT OF ELEVATED TESTOSTERONE ON HDL-C IN WOMEN

(n = 77; Age Range: 32-87; Average: 53)

After TC

Total T HDL

TC: testosterone cream daily for 197-274 days

The improvement seen in serum lipids may be die benefit that is most shared among the various interventions. G has been shown to reduce LDL as well as TC in patients with GHD ^(65>76). Cuneo showed this to be true with 6 months treatment ⁽⁶⁵⁾ In a 12-month trial, also on GHD patients, Borson-Chazot noted only a =transient improvement in LDL and TC at 6 months with return to baseline at 12 months, yet reported a decrease in carotid intima-media thickness in the same group at 12 months ⁽⁷⁷⁾. Our trial ended between 6 and 12 months, consistent with the interval where improvement in TC and LDL was seen in botii studies.

ONeal, however, saw improvement in TC and LDL after 24 months of G in GHD patients⁽⁷⁸⁾ He did, however, note an increase in =lipoprotein (a), which we did not measure. The improvement in serum lipids in men were also likely supported by T. ^^-²^

Table 7 illustrates that weight and %BF dropped and LBM increased in all subjects

except women on A + HRT. Were unable to explain the increase in %BF and decrease in lean body mass in women on A + HRT, other than that follow-up measurements were obtained in only two subjects. No one from die group of women on A + G was available for follow-up measurements. The greatest rise in LBM was seen in men on A + G, as would be expected ⁽¹⁵⁶⁴⁷~⁵¹⁾. WHR decreased in three of four groups, and increased negligibly in women on A + G + HRT. We were pleased with the overall effect on body composition, particularly if we overlook the group with only two subjects. Men on A lost more body fat than men on A + G. This is inconsistent with the data from the NIA data that showed an additive effect of the two hormones on fat loss in elderly men.⁽¹²⁸⁾ One explanation is that in the NIA study there were no components of nutrition or exercise, which clearly can have a profound differential influence among groups, particularly given the small numbers in our groups.

Table 8 shows the improvement in bone density of 1.4 to 2.4% over the predicted for four groups. Again we were unable to collect follow-up data on women on A + G. Although the results appear mixed when reading the change in T score, one must take into account normal bone loss for age and sex over the given time studied. Most studies report a 1% annual loss for men and 1 to 3% for women with the exception of women in the perimenopausal period where bone loss is reported to be 3% or more per year ⁽¹²⁹~¹³²⁾. We therefore, used 1% as the expected bone loss per year for all groups of men and 1.5% for women except women on A + G. Since those women averaged 53 in age, we used the low end of die perimenopausal expected decline, or 3%. We factored the expected bone loss per year over the number of montiis between DEXA scans.

Our side effect survey (Tables 9 and 10) pertains to a different group of subjects than those discussed above, although there was some overlap. It was sent randomly to patients currently on our program and therefore excluded those who had dropped out, making it less objective. The occurrence of testicular

atrophy in 25% of men was the most frequent adverse event. This was surprisingly well tolerated because men were forewarned but also because they were so appreciative of the benefits of T. Human chorionic gonadotropin (HCG) was used to reverse it. The benefit of HCG was incomplete but substantial. Arthralgias were the second most common at 20% with swelling of hands or feet at 10%. These are well known side effects of G related to its antinatruretic effect and are dose dependent ; they were easily reversed in our population by abstaining from G for 1 week and resuming at a dose reduced by 15%. Weight gain occurred in 15% of respondents. This fits with the antinatruretic effect of G but is likely also related to the anabolic effect of T ^(1>5>6). Nipple discomfort is likely related to the rise in estradiol (E2) that often accompanied the rise in T level. It was easily controlled by bringing E2 back down to the upper normal range with a very low dose aromatase inhibitor. 10% of our patients experienced some level of erectile dysfunction while on a program. This is less than or equal to the norm expected for men over 40.^(133134) The National Health and Social Life Survey reported a prevalence rate for erectile dysfunction of 11% for ages 40 to 49 years and 18% for ages 50 to 59 years.⁽¹³⁴⁾ In our practice new erectile dysfunction has never proven to be more than transient and therefore is thought to be either psychological or related to fluctuations in T or estradiol levels. Acne, seen in 7.5%, in our experience is a common side effect of D and is dose dependent. Nocturia and hair loss might both be considered related to a rise in DHT and PSA, although in our study group the rise in both was slight and they remained normal (Table 2).

Table 10 represents symptoms reported by women on our program that could represent side effects. The most common at 27.3% was weight gain. To this we assign the same discussion as for men in the above paragraph. Looking at the data from our other study population shown in Table 10, we see that of the 8 women, there was a net loss in BF% and a net gain in LBM. This would support the

likelihood of weight gain being a result of gains in LBM and water. The next most common symptom was acne, which we discussed in the above paragraph. Hot flashes, abnormal vaginal bleeding and nipple soreness can usually be attributed to physiologic response to non-optimal levels of estradiol or progesterone. They require measurement and adjustment in dosage followed by the appropriate work-up if unsuccessful, the scope of which is beyond this paper. Swollen joints, swelling of hands and feet and arthralgias we would again attribute to fluid retention from G, which is discussed in the above paragraph. Decreased libido was reported by 9.1% of women. Were at a loss to explain this. As you can see from Table 11, libido increased in 62% of these same women and sexual performance improved in 55%. T is credited in a number of studies to enhance libido and sexual performance in postmenopausal women

Tables 11 and 12 represent the positive side of our survey. These data speak for themselves and detailed discussion of their relation to individual aspects of our program would be redundant. Suffice it to say that we were gratified to see the high percentages of patients who felt they had improved in so many outcomes so critical to quality of life.

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