Fluoxymesterone (halotestin) and the musculoskeletal system

Androgens are traditionally considered “friends” of bones, and this is partly true. But fluoxymesterone (halotestin) has features that make the picture more complex: it is not converted into estrogen, it can accelerate the closure of growth plates in adolescents, and the strength it gives may outpace the strength of the tendons. Our editors examined what is known about the drug’s effect on bones, joints and the ligamentous apparatus.

Androgens and bone tissue

Bone is a living tissue that is constantly renewed: osteoclasts break down the old matrix, osteoblasts build a new one. Sex hormones regulate this balance. Androgens stimulate bone formation, especially its outer layer, and contribute to wider, stronger bones in men compared with women.

The indirect effect is also significant. Androgens increase muscle mass and strength, and muscles, by contracting, mechanically load the bones and stimulate their strengthening. This is precisely why men with hypogonadism often have reduced bone mineral density, and replacement therapy improves it.

The Endocrine Society guidelines (2018) acknowledge that testosterone therapy in men with confirmed deficiency increases bone mineral density. However, data on a reduction in fractures are limited, and for synthetic androgens such as fluoxymesterone there are no such studies.

An important detail that is often overlooked: a significant part of testosterone’s protective effect on bones is realized not directly but through its conversion into estradiol. And here fluoxymesterone differs from testosterone fundamentally.

The role of estrogen and why it matters for halotestin

The most convincing data on the role of estrogen in male bones came from rare clinical cases. Smith and colleagues (1994) described a man with a mutation of the estrogen receptor gene: despite normal testosterone, he had unclosed growth plates, tall stature and reduced bone density. A similar picture was observed in men with aromatase deficiency.

These observations showed that estrogen is necessary for the closure of growth plates and the maintenance of bone mass in men. Androgens without estrogen cannot fully ensure skeletal health.

Fluoxymesterone is not aromatized. In addition, like other exogenous androgens, it suppresses the body’s own production of testosterone and hence the formation of estradiol from it. Theoretically this means that on fluoxymesterone alone the level of estradiol may decrease, and with it part of the protective effect on bones.

The clinical significance of this effect for short-term use is unknown, and there are no grounds to claim that halotestin “destroys bones.” But the notion that any androgen automatically strengthens the skeleton is also an oversimplification.

Adolescents: the risk of premature closure of growth plates

In children and adolescents, long bones grow thanks to the epiphyseal plates — zones of cartilage tissue. At the end of puberty, under the influence of sex hormones, primarily estrogen, these zones close and growth stops. Androgens accelerate skeletal maturation both directly and through aromatization.

The Halotestin prescribing information warns that in children androgens can accelerate bone maturation without a corresponding gain in length, which ultimately reduces final height. Therefore, in medical use in adolescents with delayed puberty, radiographic monitoring of bone age is recommended.

Despite the lack of aromatization of fluoxymesterone, this warning remains in force: androgens affect skeletal maturation through other mechanisms as well, and suppression of one’s own hormones makes the consequences less predictable.

For adolescent athletes this is one of the most serious arguments against any androgens. Lost growth potential cannot be recovered, and a decision made at 15–17 years of age affects the whole of later life.

Tendons and ligaments: a gap in the rate of adaptation

Under the influence of androgens, muscles can become stronger relatively quickly, while tendons and ligaments adapt more slowly. An imbalance arises: the muscle generates a force for which the tendon is not yet ready. For drugs with a strong androgenic effect, which are used to increase strength without gaining weight, this argument is especially relevant.

Kanayama and colleagues (2015) compared weightlifters who used anabolic steroids with those who did not, and found a higher rate of tendon ruptures in the first group. Especially often it concerned the tendons of the upper limbs, in particular the biceps and pectoral muscles.

Experimental data in animals also indicate possible changes in collagen structure and the mechanical properties of tendons under the influence of anabolic steroids, although these results should be extrapolated to humans with caution.

The practical conclusion: an increase in working weights while on any androgens does not mean the connective tissue is ready for such loads. A sharp pain with a “snapping” sensation during an exercise, sudden weakness or deformation of the muscle contour require urgent examination by an orthopedist, since some ruptures are successfully operated on only in the first weeks.

Joints, calcium and monitoring

In the sports community there is a widespread notion of “dry joints” — the idea that non-aromatizing androgens worsen joint condition due to a lack of estrogen. There are no direct studies confirming this effect for fluoxymesterone. Joint pain in strength athletes is more often associated with overload, technique and injuries, and should not be automatically attributed to hormones.

The drug’s prescribing information contains another warning related to the skeleton: in women with breast cancer and bone metastases, androgen therapy can cause hypercalcemia. This concerns oncology patients, but it illustrates that the effect of androgens on bone metabolism can be clinically significant.

What people who have used androgens and have problems with the musculoskeletal system should monitor:

• densitometry (DXA) — in case of fractures from minor trauma or osteoporosis risk factors;
• the level of vitamin D and calcium in the blood as directed by a doctor;
• estradiol and testosterone — if a hormonal imbalance is suspected after discontinuation;
• examination by an orthopedist and ultrasound or MRI — for persistent tendon pain.

The basic measures for skeletal health do not change: sufficient intake of calcium and protein, vitamin D as needed, a gradual increase in loads, recovery between workouts and quitting smoking. No drug replaces these conditions.

Editorial conclusions

Androgens generally support bone mass, but a significant part of this effect in men is realized through estrogen, and fluoxymesterone is not aromatized. Therefore data on testosterone cannot be extrapolated to halotestin.

For adolescents the greatest risk is premature closure of growth plates and loss of growth potential. For adult athletes it is tendon injuries due to the mismatch between muscle strength and connective tissue adaptation.

The myth of “dry joints” has no direct scientific confirmation, but pain and injuries require medical examination rather than self-diagnosis.

We also recommend reading our materials on the role of estradiol in the male body, on vitamin D for athletes and on the prevention of tendon injuries in strength sports.

References

1. Smith EP, Boyd J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 1994;331(16):1056–1061.
2. Kanayama G, DeLuca J, Meehan WP 3rd, et al. Ruptured tendons in anabolic-androgenic steroid users: a cross-sectional cohort study. Am J Sports Med. 2015;43(11):2638–2644.
3. Bhasin S, Brito JP, Cunningham GR, et al. Testosterone therapy in men with hypogonadism: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2018;103(5):1715–1744.
4. Halotestin (fluoxymesterone tablets, USP). Prescribing information. Pharmacia & Upjohn.
5. 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):341–375.
6. Hartgens F, Kuipers H. Effects of androgenic-anabolic steroids in athletes. Sports Med. 2004;34(8):513–554.