When a drug changes the metabolism of androgens, the question of its effect on cholesterol and bone strength naturally arises. The editors analyzed what is known about dutasteride from randomized trials and why it should not be equated with anabolic steroids or androgen deprivation.
Why the question arises about lipids and bones
Androgens and estrogens affect lipid metabolism and bone tissue, so any drug that changes the hormonal balance raises a natural question: will it harm the cardiovascular system and bone strength? For anabolic steroids, these risks are well documented: supraphysiological doses of androgens lower high-density lipoprotein cholesterol (HDL) and alter other lipid parameters (Pope et al., 2014).
Dutasteride works differently: it does not add androgens from the outside, but only inhibits the conversion of testosterone to dihydrotestosterone (DHT). However, long-term treatment, often lasting years in older men, is exactly the kind of situation where even small changes in lipids or bone mineral density could be clinically relevant.
The age of patients adds relevance: osteoporosis in men is underestimated, and dyslipidemia and cardiovascular diseases are common in this group. Therefore, the effect of dutasteride on these systems was studied separately.
In this article, the editors review what is known from controlled studies, which mechanisms underlie and which examinations make sense during long-term therapy.
The role of DHT, testosterone and estradiol
For bone tissue in men, not only testosterone plays a key role, but also estradiol, which is formed from testosterone under the action of aromatase. In the classic study by Finkelstein et al. (2013), it was estrogen deficiency in men that was associated with increased fat mass and impaired sexual function, and further work by the same group showed the importance of estradiol for bone metabolism.
DHT, on the contrary, does not aromatize into estrogens and, as far as is known, plays a smaller role for the skeleton than testosterone and estradiol. Androgen receptors in bones are activated by testosterone itself, so a decrease in DHT does not deprive the bone of the androgen signal.
Against the background of dutasteride, testosterone increases moderately, and estradiol remains within the normal range or increases slightly. From the point of view of the mechanism, this means that the main hormonal signals for bones and lipid metabolism are preserved, and mainly the "local" androgen, important for the prostate, skin and hair, is suppressed.
It is this difference that explains why expectations about the "hormonal" risks of dutasteride should not be transferred from the experience of anabolic steroids or androgen deprivation in prostate cancer: the mechanisms are fundamentally different.
Lipid profile: research data
The most direct evidence comes from a randomized trial by Amory et al (2008), in which healthy young men received dutasteride 0.5 mg, finasteride 5 mg, or placebo for a year. The authors evaluated lipoproteins, bone mineral density, hemoglobin, PSA, and sexual function. No significant changes in the levels of total cholesterol, HDL and LDL compared to placebo were found.
These results are consistent with the data of large registration studies in men with prostatic hyperplasia, where clinically significant changes in the lipid profile on the background of dutasteride have not been described. In the official instructions, the effect on lipids is not included among the main side effects.
At the same time, separate observational studies investigated the wider metabolic impact of 5-alpha-reductase inhibitors. For example, a population-based cohort study by Wei et al (2019) reported a slightly higher rate of new cases of type 2 diabetes among men treated with these drugs. Such a design does not prove causality, but indicates the need for further research.
| Index | Dutasteride (controlled studies) | For comparison: supraphysiological doses of androgens |
|---|---|---|
| HDL | No significant changes | Reduction |
| LDL | No significant changes | Often increases |
| Bone mineral density | No significant changes during the year | Depends on dose and aromatization |
| Hemoglobin | No significant changes | Increase, risk of erythrocytosis |
Thus, according to the available randomized data, dutasteride does not worsen the lipid profile, but the metabolic aspects of long-term therapy remain a topic for further study.
Bone tissue: mineral density and risks
In the previously mentioned study by Amory et al (2008), densitometry of the spine and hip did not reveal significant changes in bone mineral density after one year of dutasteride compared to placebo. For finasteride, a similar result was obtained in a four-year placebo-controlled study by Matsumoto et al. (2002) in older men.
These data are reassuring but have limitations. The study in healthy young men lasted only a year, and bone effects can be slow to appear. Direct randomized data on the incidence of fractures on long-term dutasteride therapy are insufficient.
It is important to distinguish between dutasteride and androgen deprivation, which is used in prostate cancer. Drugs that lower testosterone to castration levels cause bone loss, because estradiol disappears along with testosterone. Dutasteride does nothing of the sort.
- Bone mineral density was not reduced in controlled studies.
- The mechanism of action preserves estradiol, a key hormone for a man's bones.
- Data on fractures on long-term therapy are insufficient for definitive conclusions.
For older patients, the risk of osteoporosis is primarily determined by age, physical activity level, diet, vitamin D, smoking, and comorbidities, not dutasteride intake.
What to monitor during long-term therapy
Because dutasteride is prescribed mainly to men after 50 years of age, monitoring of lipids and bone status is appropriate regardless of the drug as part of general prevention of cardiovascular disease and osteoporosis. The frequency is determined by the doctor taking into account risk factors.
Lipid profile (total cholesterol, LDL, HDL, triglycerides) and glucose or glycated hemoglobin help assess cardiometabolic risk. If deterioration is detected on the background of treatment, it is considered in the context of lifestyle, weight and other drugs.
Densitometry is usually recommended for men in the presence of risk factors for osteoporosis: low body weight, fractures in the past, long-term use of glucocorticoids, hypogonadism. By itself, taking dutasteride is not an indication for densitometry.
For people who use dutasteride on the background of anabolic steroids, the situation is fundamentally different: changes in lipids and hematocrit are caused by the steroids themselves, and dutasteride does not protect against them. Such risks require medical supervision, not "compensation" with additional drugs.
Editorial conclusions
According to randomized studies, dutasteride does not significantly change the lipid profile and bone mineral density during at least one year of administration. The mechanism of action explains this: the drug reduces DHT, but preserves testosterone and estradiol.
At the same time, long-term data on fractures and metabolic consequences are insufficient, and some observational studies indicate a possible association of 5-alpha-reductase inhibitors with diabetes, which requires further study.
Monitoring of lipids, glucose, and bone health in older men is appropriate regardless of drug intake and should be done in conjunction with a physician.
We also advise you to read "Side effects of Dutasteride", "Contraindications and interactions of Dutasteride" and our review about the lipid profile in athletes.
List of used literature
- Amory JK, Anawalt BD, Matsumoto AM, et al. The effect of 5α-reductase inhibition with dutasteride and finasteride on bone mineral density, serum lipoproteins, hemoglobin, prostate specific antigen and sexual function in healthy young men. J Urol. 2008;179(6):2333â2338.
- Matsumoto AM, Tenover L, McClung M, et al. The long-term effect of specific type II 5α-reductase inhibition with finasteride on bone mineral density in men: results of a 4-year placebo controlled trial. J Urol. 2002;167(5):2105â2108.
- Finkelstein JS, Lee H, Burnett-Bowie SA, et al. Gonadal steroids and body composition, strength, and sexual function in men. N Engl J Med. 2013;369(11):1011â1022.
- Wei L, Lai EC, Kao-Yang YH, et al. Incidence of type 2 diabetes mellitus in men receiving steroid 5α-reductase inhibitors: population based cohort study. BMJ. 2019;365:l1204.
- Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341â375.
- Avodart (dutasteride) soft gelatin capsules. Prescribing information. GlaxoSmithKline; U.S. Food and Drug Administration.
- Clark RV, Hermann DJ, Cunningham GR, et al. Marked suppression of dihydrotestosterone in men with benign prostatic hyperplasia by dutasteride, a dual 5α-reductase inhibitor. J Clin Endocrinol Metab. 2004;89(5):2179â2184.
