Biological methods utilizing dihydrotestosterone heptanoate

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SUMMARY OF THE INVENTION

Injection of dihydrotestosterone heptanoate, having the formula: ##STR1## causes suppression of LH, FSH, testosterone and estradiol, and elevation of DHT levels. It is effective in doing so for about three weeks, and has also been shown effective in treatment of adolescent gynecomastia and hypogonadotrophic hypogonadism. The latter effect is due to the property of DHT-hep as a potent androgen. It causes enlargement of the male genitalia, growth of pubic hair, growth of facial hair, and increase in height and weight and acne.

DHT-hep, inasmuch as it suppresses LH and testicular testosterone production, could also be valuable as a hormonal probe. With its administration, LH from the anterior pituitary is suppressed and thus is not acting to cause testicular testosterone production. Demonstration of residual testosterone and estradiol in the blood after suppression of LH could therefore be used to determine the extent to which the adrenal gland produces testosterone and estradiol.

Because it suppresses gonadotropins, another promising use for this compound is as a male contraceptive.

Another potential use is as a test for androgen response, e.g., for detection in the newborn of male pseudohermaphoditism with androgen insensitivity. Early detection of insensitivity indicates that the infant should be assigned the female gender for feminization would necessarily occur at puberty.
DHT hep has an advantage over testosterone enanthate, the commonly used androgen preparation, in that it is not aromatized, and thus, gynecomastia is not a side effect. Since estrogens are considered to have an antagonistic effect on growth hormone action, growth in height with DHT therapy could theoretically be greater with DHT hep than with testosterone therapy.

Accordingly, it is an object of this invention to provide dihydrotestosterone heptanoate.

It is a further object of the invention to provide dihydrotestosterone heptanoate in substantially pure form.

It is further object of the invention to provide dihydrotestosterone heptanoate dissolved in a pharmaceutically acceptable adjuvant, such as sesame seed oil.

It is a further object of the invention to provide dihydrotestosterone heptanoate which, when administered to a patient, is broken down into dihydrotestosterone and heptanoic acid, the unesterified form of dihydrotestosterone binding to the human androgen receptor with high affinity, the heptanoate ester not binding tightly to the human estrogen receptor, and thus, dihydrotestosterone heptanoate acts through its conversion to dihydrotestosterone.

It is a further object of the invention to provide a method of treating hypogonadotrophism by internally administering dihydrotestosterone heptanoate.

A further object of the invention is a method of reducing the male sperm count by internally administering dihydrotestosterone heptanoate.

A further object of the invention is a method of treating for response to androgen by internally administering a dihydrotestosterone heptanoate and determining whether there is a suppression of leutinizing hormone.

A further object of the invention is a method of suppressing in vivo production of luetinizing hormone, follicle stimulating hormone, testosterone or estradiol hormone by internally administering dihydrotestosterone heptanoate.

A further object of the invention is the provision of a reaction product of dihydrotestosterone 5α-androstane-17β of 3-one), 4-dimethylaminopyridine, dichloromethane, and heptanoic anhydride useful in treating gynecomastia, hypoqonatrophism, as an androgen, a hormonal probe, reducing male sperm count, and useful for in vivo production of luetinizing hormone, follicle stimulating hormone, testosterone or estradiol.

A further object of the invention is a method of synthesizing dihydrotestosterone heptanoate.

A still further object of the invention is a method of preparing a pharmaceutical preparation comprising dihydrotestosterone heptanoate in a pharmaceutically acceptable adjuvant for administration to a male patient.

Other and further objects and advantages of the invention appear through the specification and claims.