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SecundumArtem Current & Practical Compounding COMPOUNDING FOR MALE ANDROPAUSE
GOALS AND OBJECTIVES
Goal: The purpose of this article is to provide a discussion of the occurrence, symptoms and drug and nondrug treatment associated with
male andropause and natural hormone replacement therapy. Objectives: After reading and studying this article, the participant should be able to: 1. describe the symptoms associated with the onset of male andropause.
2. explain the value of laboratory tests providing total and free serum testosterone levels.
3. list current drug therapies available for the treatment of the symptoms of male andropause.
4. discuss current non-drug therapies available for the treatment of male andropause.
INTRODUCTION
One method of treating male andropause is similar to that for women, In the United States, it has been stated that there are over 25 million natural hormone replacement therapy. Hormone replacement therapy men (about 408 million worldwide) between the ages of 40 and 55 that may become as routine for men as it is now for women, leading to ben- may be going through what is termed “male menopause”, “or efits of slowing loss of bone mass and increased heart protection. The “andropause”. In twenty years, the number in the US will increase to psychosocial aspects of andropause and how elders are viewed may over 57 million (960 million worldwide).
need to be altered and considered as they are in some cultures; oldermen are looked upon and valued as peacemakers, wise counselors and Male andropause involves the hormonal, physiological, chemical and psychosocial changes that occur in men, generally between the ages of40 and 55 (range of 35-65). It is also called viropause and is a physical We are presenting this issue for the support of quality compounding of condition with psychological, interpersonal, social and spiritual natural hormone replacement preparations for men and preparations dimensions. Male andropause begins with hormonal and physiolog- designed for men to cope with the symptoms associated with ical changes that affect various aspects of a man’s life; the condition is called hypogonadism where the levels of testosterone (testis) drops.
Human growth hormone (pituitary), DHEA and androstenedione DEFINITIONS AND ABBREVIATIONS
(adrenal gland) also begin to diminish. It is interesting to note that Natural (bio-identical) hormones refer to those hormones that are mol- ancient Indians, Greeks and Egyptians were aware that extracts of ecularly identical to those made in the human body and have the same animal testes could be used in this condition ostensibly to promote exact chemical structure specifically, testosterone, DHEA and estradiol.
virility, potency and vigor in men. Also of note, testosterone was the Synthetic (Patented, Conventional, Artificial) hormones are those that first hormone to be discovered, yet its overall role is still not com- are not usually found in humans and are chemically different from the naturally occurring human hormones specifically, danazol, fluoxyme-strone, methyltestosterone, and oxandrolone. They are not identical in Men experience psychosocial symptoms, or “growing pains”, as they structure or activity to the natural hormones they are designed to enter this stage of their lives: parents are dying, job horizons are nar- rowing, retirement looms, friends are having their first heart attacksand the past rushes by in memories with unrealized dreams and QUESTIONS TO PONDER CONCERNING ANDROPAUSE
unfulfilled opportunities. Children are leaving home to establish their Are all older men hypogonadal? Is the definition of hypogonadal the own lives. Friends are getting sick. Andropause is seen by many as a same in older men as compared to younger men? Should all men threat to masculinity, macho self-image, ego, and self-esteem. Men are receive testosterone supplementation? Will testostosterone supplemen- reluctant to discuss this issue whereas women are very open with it.
tation produce meaningful results in all men? How about in men with Women and men may be more alike than different during the low testosterone levels and sexual dysfunction compared to men with low testosterone levels without sexual dysfunction? How should Many, but not all, men probably experience slight versions of testosterone replacement therapy be administered and at what doses? andropause; hormones and neuropeptides diminish and bodies sagand change shape. Common medical conditions like enlarged Quest Educational Services Inc. is approved by the prostate develop, stamina and temperament change and men do not American Council on Pharmaceutical Education as a seem as well equipped to deal with these extremes as women, who provider of continuing pharmaceutical education.
ACPE No. 748-999-99-033-H04 (0.1 CEU)
This lesson is no longer valid for CE credit after 11/30/01.
Is it really known that testosterone replacement therapy will benefit Visceral fat increase has been associated with an increased vascular muscle function, sexual function, well-being and quality of life in older risk. Body fat in men increases from 18% to 36% between 18 and 85 men; and, can it be done safely? What testosterone assay should be used years of age, with the largest increases in intraabdominal fat. Also, by in older vs younger men? How about free testosterone? age 70, an average man has about 26 pounds less lean body mass thanat age 25.
One must consider that in female HRT, the debate has been carried onfor 30 years and is just now really beginning in men. All men may not Low testosterone can lead to osteoporosis in elderly men. This tends to be hypogonadal; in fact, it may be that andropause may not even occur happen later in men than in women because of the general tendency for in the majority of men, except for the slow decrease in testosterone men’s bones to be thicker and denser than women’s. In hypogonadal men, bone mineral density tends to increase with testosteronetreatment.
It is established that men’s testosterone levels start declining after 20 to30 years of age. Starting at about age 40, the testosterone level declines In men, there may be an increase in circulating estrogen levels; com- at a rate of about 0.4% total testosterone and 1.2% free testosterone per mon causes of estrogen increase during midlife include age-related year. At what age or at what testosterone level should a man be con- increases in aromatase activity, alteration in liver function, zinc defi- ciency, obesity, overuse of alcohol, drug-induced estrogen imbalanceand ingestion of estrogen-enhancing food or environmental sub- In women, reproductive aging is a definite process with overt signs, i.e., stances. Also, fatty tissue contains more aromatase activity as cessation of menses. However, with men, it is a very gradual process compared with lean tissue resulting in more testosterone being con- verted to estradiol. Vitamin C deficiency is associated with high levelsof aromatase activity whereas zinc inhibits aromatase activity.
MEN’S DAILY CYCLE
In young men, the highest testosterone levels occur in the morning
Low testosterone levels may tend towards depression; the decrease in between 6 and 8 AM, decreasing to a low point in the afternoon sexual function may also lead to depression, irritability and mood between 5 and 6 PM. In elderly men, the circadian rhythm is much flat- swings.this depression further leading to decreased sexual function.
ter and is not necessarily consistent between men, as it is whenyounger.
LABORATORY EVALUATION
Laboratory evaluation for andropausal men can include (1) free testos-
THE STAGES OF A MAN’S LIFE
terone, (2) total testosterone, (3) estradiol levels, (4) prostate specific A man’s life can be divided into different stages as it relates to hormone antigens-PSA test, (5) CBC and (6) cholesterol. Sample laboratory val- function, from infancy into mature adulthood. Testosterone tends to thrust us into adolescence and then usher us into adulthood; as it’s lev-els decrease, it tells us we are finished with our first stage of adulthood A diagnosis of hypogonadism has been suggested if at any age the total and ready to begin the next phase of our lives (mature adulthood). testosterone is less than 200 ng/dL. When the total testosterone level isbelow 200 ng/dL, evaluation should proceed with other laboratory It has been stated that during mature adulthood, men can (1) Focus tests, e.g. gonadotropins, prolactin, etc. If the result is borderline, i.e.
more on being and less on doing, (2) Relate to other men as friends and 200-300 ng/dL, then a measurement of the free or bioavailable testos- allies rather than as competitors, (3) Lay foundation for becoming terone is suggested. Hypogonadism is defined as bioavailable healthy, wealthy and wise, (4) Become a mentor to younger men, (5) testosterone levels less than 60 ng/dL. If one only considers the total Become a respected elder in your community, (6) Grow old gracefully testosterone levels, about 5% of men are classified as hypogonadal. If and, if done properly, (7) Add life to years, not just years to life.
the free testosterone (non-SHBG bound testosterone) is used as thedefinitive assay, as many as 50% of men 60 or over could be testos- SIGNS AND SYMPTOMS OF ANDROPAUSE
Men are generally reluctant or unwilling to acknowledge that the syn-drome has crept up on them. The symptoms are not as overwhelming Serum (Total) testosterone measures all the testosterone in the serum, as the dramatic changes women experience and it may not affect all free and bound. Free (dialyzable testosterone) estimates the fraction of men; however, about 40% of men in their 40s, 50s and 60s will experi- testosterone in blood that is not bound to protein (requiring a dialysis ence some of the symptoms, including lethargy, depression, irritability, procedure). Bioavailable testosterone determines the amount of testos- mood swings and erectile dysfunction.
terone not bound to SHBG and includes that which is nonproteinbound and weakly bound to albumin; it is the portion that is bioavail- Testosterone levels begin to decrease for a number of reasons, including able to tissues (usually obtained by using a precipitation method).
(1) the Leydig cells begin to decrease in number and function, (2) a sexhormone binding globulin (SHBG) increases with age, resulting in In men, the total testosterone decreases and the SHBG bound testos- greater binding of testosterone with less free testosterone. There is a terone increases, resulting in a decrease in free testosterone. In higher relative amount of estradiol with less testosterone being pro- summary, free testosterone is decreased with age more rapidly than Symptoms that may be associated with andropause are listed in Table TREATMENT
1. At this time, there are also other changes that are occurring in a man’s The therapeutic goal is not to produce a “Mr. Elderly Strong Man”, but to enable the adult man to maintain or improve strength to functionbetter and more consistently. Many physicians hesitate to use testos- As men pass 50, they tend to develop an enlarged prostate. As the gland terone supplementation as it is new, they have heard stories increases in size, it squeezes the urethra, often causing increased uri- (sometimes related to synthetic androgen supplementation), and they nary frequency, a weaker flow and difficulty beginning urination. The are unsure of the results as it takes quite some time for them to become current treatments include finasteride (Proscar) and Saw Palmetto evident. There is no evidence that exogenous testosterone stimulates (made from the berries of a plant native to the American Southeast) the development of prostate carcinoma; there has been no relationship which reduces the size of the prostate in only four to six weeks and is established between endogenous testosterone and BPH. However, a relatively effective. Zinc is also used to maintain a healthy prostate.
contraindication to androgen replacement therapy is the presence ofprostate cancer.
In addition to enlarged prostate, other prostate problems include pro-statitis, and prostate cancer. It has been stated that men have odds of100% of experiencing one of these three disorders.
The treatment of andropause is, to some degree, seeking an elusive deficiency and in the long term for the prevention of osteoporosis and for answer to a hormone imbalance. The patient and health care provider preventing and treating heart and circulatory problems. Testosterone is are, in many cases, seeking a simple answer to a complex problem, or not, however, effective in erectile dysfunction. Androgen replacement set of symptoms. One simple answer generally does not exist. A few therapy should, ideally, provide physiological serum testosterone levels, general rules can be stated related to hormone replacement therapy.
as well as dihydrotestosterone and estradiol levels while correcting theclinical symptoms of androgen deficiency in hypogonadal men.
1. There is no simple answer or single approach to HRT.
2. Treat each patient as an individual.
Testosterone, the most common agent used in male hormone replacement 3. HRT may be difficult and is time consuming.
therapy, occurs as white or slightly creamy white crystals or crystalline 4. Generally, one cannot successfully treat hormone imbalances powder that is odorless and stable in air. It is practically insoluble in water, soluble 1 g in 5 mL of ethanol, 2 mL of chloroform and 100 mL of ether andis soluble in vegetable oils, melts between 153 and 157˚C., and is subject to The decision to use HRT is an individual one, based on the individu- photodegradation in the presence of light. Testosterone is not very al’s particular risks. The goals of natural HRT are to (1) alleviate the bioavailable when given as an oral-swallow preparation, but is absorbed symptoms caused by the natural decrease in production of hormones when administered buccally and sublingually. The different esters of by the body, (2) replace the hormones to the extent to provide positive testosterone are hydrolyzed to free testosterone and, subsequently, are benefits, (3) bring the body back to normal hormonal balance, and (4) metabolized in the same way as testosterone itself.
imitate the body’s natural processes as much as possible. Naturaltestosterone replacement is central to the treatment of all aspects of MARKETING MALE HRT
Education programs can be provided to doctors and nurses as well as tothe lay public. Promotional materials concerning educational programs Testosterone supplementation has resulted in decreasing body fat can be provided to places where men meet. Formal or informal seminars mass from 6.4% to 1.4% and increases in lean mass from 3.2% to 5%.
have been very successful in presenting the topic. Pharmacists providing Increases in strength (grip strength) also are reported.
these seminars generally begin with a short story of their pharmacy, theimportance and legal aspects of compounding, the male hormones and Total cholesterol and low density lipoproteins tend to significantly their function, symptoms and treatment of andropause, compliance issues decrease with testosterone administration.
and compensation and insurance billing. These are often followed up byone-on-one personal consultations. After a personal consultation, many Three steroids of importance in male reproductive function are testos- pharmacists follow up with a communication to the physician/nurse by terone, dihydrotestosterone and estradiol. By far the greatest percentage of testosterone (over 95%) is secreted by the testicular Ley-dig cells. The dihydrotestosterone and estradiol are derived from PATIENT FILES
both the direct secretion from the testes (20%) and also from conver- A consultation is an excellent way to start the process of patient history sion in peripheral tissues on androgen and estrogen precursors review and the use of a symptoms chart. In addition, laboratory test val- secreted by both the testes and adrenal glands (80%).
ues can be maintained in this chart. While laboratory tests such as serumlevels, saliva levels and urine monitoring have their place in patient eval- Hormone preparations that have been used include testosterone, uation, they do have limitations. Using laboratory analysis in combination testosterone propionate, testosterone enanthate, testosterone cypi- with clinical observation pharmacists can better recommend starting doses onate, fluoxymestrone, methyltestosterone (methyltestosterone is and dosage adjustments of hormone replacement for patients.
toxic to the liver and heart and may have clouded the benefits oftestosterone replacement therapy), oxandrolone, progesterone and COMPOUNDED FORMULATIONS FOR MALE HORMONE
estradiol. Commercial testosterone products have been administered REPLACEMENT THERAPY
either by injection, implants/pellets, orally or as transdermalpatches. Rx Testosterone 2% and Menthol Eutectic Ointment
Testosterone-menthol eutectic mixture* 6.33 g Injections: One disadvantage to testosterone enanthate and testos- terone cypionate injections is that they are injected at 2 to 3 weekintervals. The blood profiles are high after the injection, followed by a *The testosterone:menthol eutectic mixture can be prepared using 31.6 g of slow decline over the time interval until the next injection. This clear- testosterone with 68.4 g of menthol. Sufficient methyl alcohol is used to ly does not follow the normal adult physiological pattern. dissolve both ingredients. The solution is set aside and the alcohol allowedto evaporate, with periodic stirring. This step may take one or two days.
Implants/Pellets: Subdermal testosterone implants produce a similar After it is dry, it should be thoroughly pulverized and packaged in a tight, pattern to the injections. Testosterone undecanoate administered oral- light-resistant container until ready for use in the above prescription.
ly gives a rapid onset of action but a short duration of action,consequently it may be administered several times daily. 1. Accurately weigh each ingredient.
2. Mix the testosterone:menthol eutectic mixture with a small quantity of Transdermal: In transdermal testosterone, the hormone is released slowly through the skin to deliver a constant level in the blood, again 3. Geometrically, incorporate the remaining drug into the base and not a routine pattern, but convenient. Transdermal testosterone can be applied either to the scrotal area or to other areas. Rx Testosterone 20 mg/mL in Pluronic Lecithin Organogel
Compounding pharmacists can offer many options to provide for dif- ferent blood level profiles and convenience of administration, including some of the novel dosage forms provided at the end of this article. Topical testosterone can be applied using different vehicles to more closely mimic the normal adult physiological pattern, i.e., applyearly in the morning where it should be absorbed over a period of a 1. Prepare a paste of the testosterone and the propylene glycol.
2. Add the Lecithin:Isopropyl Palmitate Solution and mix well.
Many benefits can be derived by testosterone replacement therapy, 3. Add sufficient pluronic F127 20% gel to volume and mix well.
both in the short term for the eradication of symptoms of androgen *The Lecithin:Isopropyl Palmitate Solution can be prepared by 1. Accurately weigh each ingredient.
mixing 10 g of soy lecithin and 10 g of Isopropyl palmitate; allow 2. Mix the testosterone propionate with a few drops of mineral oil.
to stand overnight for complete dissolution to occur.
3. Add the Aquabase or White petrolatum geometrically and **The Pluronic F127 20% Solution can be prepared by adding 20 g of pluronic F127 to sufficient cold (ice) water to make 100 mL. For complete dissolution, place in a refrigerator and allow to standwith periodic agitation.
Rx Dehydroepiandrosterone 50 mg Capsules (100 capsules)
Rx Testosterone 10 mg Troches (#24)
1. Accurately weigh each ingredient.
2. Comminute each powder to a uniform particle size.
3. Geometrically, incorporate the lactose into the dehy- 4. Encapsulate the powder into 100 No. 1 capsules, each NOTE: The quantity of polyethylene glycol 1450 will depend upon the mold size.
1. Accurately weigh or measure each of the ingredients.
COMPOUNDED FORMULATIONS FOR MALE SEXUAL
2. In a mortar, triturate the testosterone, aspartame, silica gel DYSFUNCTION
3. Melt the polyethylene glycol 1450 to about 55 to 60˚C.
Rx Prostaglandin E1/Papaverine Hydrochloride/
Phentolamine Mesylate Injection
5. Cool slightly, add the flavor(s) and pour into troche molds.
6. Allow to solidify, package and label.
Rx Testosterone 10 mg/0.1 mL Sublingual Drops
NOTE: This preparation should only be prepared in a laminar air- flow hood in a cleanroom. Pharmacists compounding thesepreparations must be validated in aseptic compounding 1. Accurately weigh or measure each ingredient.
technique. Compounding this preparation requires working with 2. Triturate the testosterone, saccharin and silica gel in a mortar.
very small quantities of some ingredients. Calculations and tech- 3. Add a small amount of almond oil and triturate to a smooth 1. Accurately weigh or measure each ingredient.
4. Add sufficient flavor and almond oil to volume and mix well.
2. Add each ingredient to the 0.9% sodium chloride Rx Testosterone Propionate Gel
3. Add sufficient sterile water for injection to volume and 4. Sterile filter into a sterile container/syringe.
Rx Sildenafil Citrate 25 mg Sublingual Troches (#24)
1. Accurately weigh/measure each of the ingredients.
2. Levigate the testosterone propionate with the light mineral oil.
3. Add the polysorbate 80 to the testosterone propionate:mineral 4. Add the methylcellulose 2% gel and thoroughly mix until *Will vary depending upon mold and size of tablet used as the Rx Testosterone Propionate Cream
1. Accurately weigh or measure each ingredient.
2. In a mortar, triturate the required number of sildenafil citrate 1. Accurately weigh/measure each of the ingredients.
3. Add the aspartame, silica gel and acacia and triturate further to 2. Dissolve the testosterone propionate in the peanut oil.
3. Add the Dermabase with gentle heating until softened.
4. Melt the Polyethylene glycol 1450 to about 55 to 60˚C.
4. Add the purified water, mix well, and cool.
6. Cool slightly, add flavor, mix well and pour into troche molds.
7. Allow to solidify, package and label.
Rx Testosterone Propionate Ointments
TABLE 1. SYMPTOMS ASSOCIATED WITH “MALE
acting androgen ester. J Clin Endocrinol Metab. 1992;75:1204-1210.
MENOPAUSAL SYNDROME”
5. Brodsky IG, Balagopal P., Nair KS. Effects of testosterone replacement on muscle mass and muscle protein synthesis in hypogonadal men-A clinical research center study. J Clin Endocrinol Metab. 1996; 81:3469-3475.
6. Burris AS, et al. A long-term, prospective study of the physio- logical and behavioral effects of hormone replacement in untreated hypogonadal men. J Androl. 1992;13:297-304.
✗ Muscle soreness and stiffness ✗ Muscle weakness✗ Osteoporosis ✗ Prostate enlargement/ 7. Cunningham GR, Cordero E, Thornby JI. Testosterone replace- ment with transderm altherapeutic systems. JAMA1989;261: 2525- ✗ Reading difficulty (small print) ✗ Skin thinning 8. Goldberg RB, et al. Suppression of plasma testosterone leads to an increase in serum total and high density lipoprotein cholesterol ✗ Thinning or loss of hair ✗ Weight gain and apoproteins A-1 and B. J Clin Endocrinol Metab. 1992;116:967- ✗ Anxiety and fear about losing ✗ Depression 9. Goldman JA et al. Contrast analysis for the evaluation of the cir- cadian rhythms of plasma cortisol, androstenedione, and testerone in normal men and the possible influence of meals. J Clin 10. Gooren LJG. The age-related decline of androgen levels in men: clinically significant? Br J Urol. 1996;78:763-768.
11. Griggs RC, et al. Effect of testosterone on muscle mass and mus- cle mass synthesis. Am J Appl Physiol. 1989;66:498-503.
12. Guo CY, Jones TH, Eastell R. Treatment of an isolated hypogo- nadotropic hypogonadism. effect on bone mineral density andbone turnover. J Clin Endocrinol Metab. 1997;82:658-665.
TABLE 2. LABORATORY VALUES OF HORMONES.
13. Marin P, Krotkiewski M, Bjomtorp P. Androgen treatment of middle-aged, obese men: effects of metabolism, muscle and adi- Free testosterone Men 700 ng/dL 300-1100 ng/dL pose tissues. Eur J Med. 1992;1:329-336.
Free testosterone Women 40 ng/dL 15-70 ng/dL 14. Matsumoto AM. Hormonal therapy of male hypogonadism.
TABLE 3. NON-DRUG RECOMMENDATIONS FOR
15. Morales A, et al. Testosterone supplementation for hypogo- TREATING ANDROPAUSE.
nadal impotence:Assessment of biochemical measures and therapeutic outcomes. J Urol. 997;157:849-854.
Eat right- Eat lots of fruits, vegetables, grains and healthy meat ✗ Exercise- A minimum of 30 minutes three times a week.
16. Morley JE, Kaiser FE. Sexual function with advancing age. MedClin North Am. 1989;73:1483-1495.
✗ Vitamins and supplements- Take them wisely and consistently.
17. Morley JE, et al. Effects of testosterone replacment therapy in ✗ Physical examinations- Regularly scheduled health checkups.
old hypogonadal males: a preliminary study. J Am Geriatr Soc.
✗ Check hormone levels- As one ages, hormone levels begin 18. O’Carroll R, Shapiro C, Bancroft J. Androgens, behavior and ✗ Reduce stress and worry- Stress and worry are major contribu- nocturnal erection in hypogonadal men; the effects of varying the replacement dose. Clin Endocrinol. 1985;23:527-538.
✗ Healthy social life- A healthy social life with emphasis on 19. Ozata M, et al. Effects of gonadotropin and testosterone treat- ments on lipoprotein, high-density lipoprotein particles, and other ✗ Drink lots of water (urine should be light in color).
lipoprotein levels in male hypogonadism. J Clin Endocrinol Metab.
1996;81:3372-3378.
✗ Eat plenty of soy foods (containing phytoestrogens).
20. Salehian B, et al. Pharmacokinetics, bioefficacy, and safety of ✗ Reduce the amount of saturated fat intake.
sublingual testosterone cyclodextrin in hypogonadal men: com- parison to testosterone enanthate. J Clin Endocrinol Metab.
1995;80:3567-3575.
SUGGESTED READING
1. Bhasin S. Therapeutic Perspective: Issues in Testosterone
21. Tenover JS. Effects of testosterone supplementation in the aging Replacement in Older Men. J of Clin Endocrin and Metab.
male. J Clin Endocrinol Metab. 1992;75:1092-1098.
22. Vermeulen A. Androgen in the aging male. J Clin Endocrinol 2. Velazuez EM, Arata GB. Testosterone Replacement Therapy. 23. Wang C. Sublingual testosterone replacement improves muscle 3. Balds-Pratsch M, Yoon YD, Knuth UA et al. Transdermal testos- mass and strength, decrease bone resorption, and increases bone terone substitution therapy for male hypogonadism. Lancet formation markers in hypogonadal men. J Clin Endocrinol Metab 24. Zgliczynski S et al. Effect of testosterone replacement therapyon lipids and lipoproteins in hypogonadal and elderly men. Ath-erosclerosis. 1996;21:35-43.
1. After age 40, the total testosterone levels of males decrease at a 4. Behre HM, Nieschlag E. Testosterone buciclate in hypogonadal- men: pharmacokinetics and pharmacodyamics of the new long Send this completed form in for CE credit Today!
Please circle the most appropriate answer for each of the following questions. There is only ONE correct answer per question.
2. Approximately ____% of men between the ages of 40 and 60 will 8. A reasonable daily testosterone replacement dose for males would experience some of the symptoms of what is called “andropause”? 3. Free serum testosterone levels decline at a ________ rate than 9. Testosterone alone appears to be effective in treating male sexual 4. A total serum testosterone level of 175 mg/dL would be 10. The highest testosterone levels in males occur between what 5. A known contraindication to testosterone supplementation is: 12. The quality of the information presented in this article was: 6. Which of the following commercial dosage forms of testosterone are given in a way that mimics the body’s circadian testosterone levels? 13. The test questions correspond well with the information presented.
14. Approximatley how long did it take you to read the Secundum Artem article AND respond to the test questions?______________ 7. Which of the following would be used in natural hormone ACPE No. 748-999-99-033-H04
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