Gestrinone was introduced for medical use in 1986.[14] It has been used extensively in
Europe but appears to remains marketed only in a few countries throughout the world.[10][15][7] The medication is not available in the
United States.[16] Due to its
anabolic effects, the use of gestrinone in competition has been banned by the
International Olympic Committee.[17]
Medical uses
Gestrinone is approved for and used in the treatment of
endometriosis. It is described as similar in action and effect to
danazol, which is also used in the treatment of endometriosis, but is reported to have fewer androgenic
side effects in comparison.[18][19] Gestrinone has also been used to shrink
uterine fibroids and to reduce
menorrhagia.[5][6]
Due to its
antigonadotropic effects and ability to inhibit
ovulation, gestrinone has been studied as a method of
hormonal birth control in women.[1] Large studies across thousands of
menstrual cycles have found it to be effective in preventing
pregnancy.[1] However, although effective, the pregnancy rate in the largest study conducted was 4.6 per 100 woman-years, which is too high of a failure rate for the medication to be recommended as a safe method of birth control.[1] The medication has also been investigated as an
emergency post-coital contraceptive.[20]
Contraindications
The medication is
contraindicated in
pregnancy, during
lactation, and in patients with severe cardiac,
chronic kidney disease or liver disease. It is also contraindicated in patients who experienced metabolic and/or vascular disorders during previous estrogen or progestogen therapy, or who are allergic to the medication. The medication is contraindicated in children.
Gestrinone also inhibits
gonadotropinsecretion and causes
amenorrhea or
oligomenorrhea in a high percentage of women.[1] Similarly, circulating
estradiol levels have been found to be reduced by 50%, which may result in
estrogen deficiency and associated
symptoms.[10] Studies of 2.5 mg oral gestrinone twice per week have found a rate of amenorrhea of 50 to 58%, while a study of 5 mg oral gestrinone per day found a rate of amenorrhea of 100%.[1]
It has been found that vaginal gestrinone shows fewer androgenic side effects and
weight gain than oral gestrinone with equivalent effectiveness in endometriosis.[1] Gestrinone appears to show similar effectiveness to
danazol in the treatment of endometriosis but with fewer side effects, in particular androgenic side effects.[1][18][19]
Notes: Values are percentages (%). Reference
ligands (100%) were
progesterone for the
PRTooltip progesterone receptor,
testosterone for the
ARTooltip androgen receptor,
E2 for the
ERTooltip estrogen receptor,
DEXATooltip dexamethasone for the
GRTooltip glucocorticoid receptor,
aldosterone for the
MRTooltip mineralocorticoid receptor,
DHTTooltip dihydrotestosterone for
SHBGTooltip sex hormone-binding globulin, and
cortisol for
CBGTooltip Corticosteroid-binding globulin. Sources:[23][24][25][26]
Gestrinone, also known as 17α-ethynyl-18-methyl-19-nor-δ9,11-testosterone, as well as 17α-ethynyl-18-methylestra-4,9,11-trien-17β-ol-3-one or as 13β-ethyl-18,19-dinor-17α-pregna-4,9,11-trien-20-yn-17β-ol-3-one, is a
syntheticestranesteroid and a
derivative of
testosterone.[27][15] It is more specifically a derivative of
norethisterone (17α-ethynyl-19-nortestosterone) and is a member of the
gonane (18-methylestrane) subgroup of the
19-nortestosterone family of progestins.[28][11][29][30] Gestrinone is the C18
methyl derivative of
norgestrienone (17α-ethynyl-19-nor-δ9,11-testosterone) and the δ9,11analogue of
levonorgestrel (17α-ethynyl-18-methyl-19-nortestosterone) and is also known as ethylnorgestrienone due to the fact that it is the C13β
ethyl variant of norgestrienone.[10][31] It is also the C17α
ethynyl and C18 methyl derivative of the AAS
trenbolone.[32][33]
The androgenic properties of gestrinone are more exploited in its derivative
tetrahydrogestrinone (THG; 17α-ethyl-18-methyl-δ9,11-19-nortestosterone), a
designer steroid which is far more potent as both an AAS and progestogen in comparison.[34] THG was banned by the
Food and Drug Administration (FDA) in 2003.[35]
History
Gestrinone was introduced for medical use in 1986.[14]
Society and culture
Generic names
Gestrinone is the
generic name of the drug and its
INNTooltip International Nonproprietary Name,
USANTooltip United States Adopted Name,
BANTooltip British Approved Name, and
JANTooltip Japanese Accepted Name.[27][15][4][7] It is also known by its developmental code names A-46745 and R-2323 (or RU-2323).[27][15][4][7]
Brand names
Gestrinone is or has been marketed under the brand names Dimetriose, Dimetrose, Dinone, Gestrin, and Nemestran.[27][15][7]
^
abcCarp HJ (9 April 2015).
Progestogens in Obstetrics and Gynecology. Springer. pp. 141–.
ISBN978-3-319-14385-9. Side effects [of gestrinone] are due to the androgenic and anti-estrogenic effects including, voice changes, hirsutism, and clittoral enlargement.
^
abDesai P, Patel P (15 May 2012).
Current Practice in Obstetrics and Gynecology Endometriosis. JP Medical Ltd. pp. 111–.
ISBN978-93-5025-808-8. The clinical side effects are dose dependent and similar but less intense than those caused by danazol.12 They include nausea, muscle cramps, and androgenic effects such as weight gain, acne, seborrhea, oily hair/skin, and irreversible voice changes.
^
abcdefBlackwell RE, Olive DL (6 December 2012).
Chronic Pelvic Pain: Evaluation and Management. Springer Science & Business Media. pp. 106–107.
ISBN978-1-4612-1752-7. Side-effects [of gestrinone] include androgenic and antiestrogenic sequelae. Although most side-effects are mild and transient, several, such as voice changes, hirsutism, and clitoral hypertrophy, are potentially irreversible.
^
abcBromham DR, Booker MW, Rose GL, Wardle PG, Newton JR (1995). "A multicentre comparative study of gestrinone and danazol in the treatment of endometriosis". Journal of Obstetrics and Gynaecology. 15 (3): 188–194.
doi:
10.3109/01443619509015498.
ISSN0144-3615.
^
abOng HH, Allen RC (1 November 1988).
"To Market – 1987". In Allen RC (ed.). Annual Reports in Medicinal Chemistry. Academic Press. pp. 387–.
ISBN978-0-08-058367-9.
Coutinho E, Gonçalves MT, Azadian-Boulanger G, Silva AR (1987). "Endometriosis therapy with gestrinone by oral, vaginal or parenteral administration". Contrib Gynecol Obstet. Contributions to Gynecology and Obstetrics. 16: 227–35.
doi:
10.1159/000414891.
ISBN978-3-8055-4627-0.
PMID3691096.
Coutinho EM (1990). "Therapeutic experience with gestrinone". Prog. Clin. Biol. Res. 323: 233–40.
PMID2406749.