Abstract
The clinical effectiveness and safety of vaginal micronized progesterone treatment in mastodynia were evaluated in a double-blind placebo controlled study. Eighty regularly menstruating worn-’ en affected by severe cyclical mastodynia were randomly assigned to two groups of 40 patients. One group was treated for 6 cycles from the 19th to the 25th day of the cycle with 4 g of vaginal cream containing 2.5% natural progesterone. The other group was similarly treated with placebo. The treatment was preceded by a control cycle. All patients reported every day their breast pain on a 100 mm visual linear analogue scale (VAS). The response of breast tenderness and nodularity to treatment was assessed by clinical examination. Vaginal progesterone resulted significantly more efficacious than placebo in reducing mean ratings of breast pain on VAS and mean scores of breast tenderness to touch. Success of treatment, defined as reduction greater than 50% of basal mean score of breast pain on VAS, was achieved in the 64.9% of patients treated with progesterone and in the 22.2% of patients receiving placebo (p<0.01). Conversely, at the end of treatment, the improvement in breast nodularity showed a not statistically significant difference between the two groups. No major side-effects were detected.
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Wisbey J.R., Kumar S., Mansel R.E., Preece P.E., Pye J.K., Hughes L.E. Natural history of breast pain. Lancet 2: 672, 1983.
Fentiman I.S., Caleffi M., Bram K., Chandary M.A., Hayward J.L. Double blind controlled trial of tamoxifen therapy for mastalgia. Lancet 1: 287, 1986.
Sitruk-Ware R., Sterkers N., Mowszowicz I., Mauvais-Jarvis P. Inadeguate corpus luteum function in women with benign breast diseases. J. Clin. Endocrinol. Metab. 44:771, 1977.
England P.C., Skinner L.G., Cottrell K.M., Sellwood R.A. Sex hormones in breast disease. Br. J.Surg. 62:806, 1975.
Walsh P.V., Bulbrook R.D., Stell P.M., Wang D.Y., McDicken I.W., George W.D. Serum progesterone concentration during the luteal phase in women with benign breast disease. Eur. J. Cancer. Clin. Oncol. 20:1339, 1984.
Read G.F., Bradley S.A., Wilson D.W., George W.D., Griffiths K. Evaluation of luteal-phase salivary progesterone levels in women with benign breast disease or primary breast cancer. Eur. J. Clin. Oncol. 21: 9, 1985.
Wang D.Y., Fentiman I.S. Epidemiology and endocrinology of benign breast disease. Breast Cancer Res. Treat. 6:5, 1985.
Kumar S., Mansel R.E., Hughes L.E., Woodhead J.S., Edwards C.A., Scanlon M.F., Newcombe R.G. Prolactin response to thyrotropin-releasing hormone stimulation and dopaminergic inhibition in benign breast disease. Cancer 53:1311, 1984.
Kumar S., Mansel R.E., Wilson D.W., Read G.F., Truran P.L., Hughes L.E., Griffiths K. Daily salivary progesterone levels in cyclical mastalgia patients and their controls. Br. J.Surg. 73:260, 1986.
Rannevik G., Doberl A., Gershagen S., Rasmussen T.H., Tobiassen T. Elevated serum concentrations of sex hormone binding globulin in fibrocystic breast disease. In: Angeli A., Bradlow H.L., Dogliotti L. (Eds.), Endocrinology of cystic breast disease. Raven Press, New York, 1983, p. 127.
Carlstrom K., Doberl A., Gershagen S., Rannevik G., Rasmussen T.H., Tobiassen T. Elevated peripheral levels of androgens and of some steroid sensitive plasma proteine in patients with severe fibrocystic breast disease. Acta Obstet. Gynecol. Scand. (Suppl.) 23:157, 1984.
Greenblatt R.B., Nezhat C., Ben Nun I. The treatment of benign breast disease with danazol. Fertil. Steril. 34:242, 1980.
Pye J.K., Mansel R.E., Hughes L.E. Clinical experience of drug treatments for mastalgia Lancet 2: 373, 1985.
Andrews W.C. Hormonal management of fibrocystic disease of the breast. J. Reprod. Med. 35:87, 1990.
Ricciardi I., Ianniruberto A. Tamoxifen-induced regression of benign breast lesion. Obstet. Gynecol. 54:80, 1979.
Shaaban M.M., Morad F., Hassan A-el-R. Treatment of fibrocystic mastopathy by an anti-estrogen, tamoxifen. Int. J. Gynecol. Obstet. 73:348, 1980.
Mansel R.E., Preece P.E., Hughes L.E. A double blind trial of the prolactin inhibitor bromocriptine in painful benign breast disease. Br. J. Surg. 65:724, 1978.
Blichert-Toft M., Anderson A.N., Henriksen O.B., Migind T. Treatment of mastalgia with bromocriptine: a double blind cross-over study. Br. Med. J. 1: 237, 1979.
Vorherr H. Fibrocystic breast disease: Pathophysiology, pathomorphology, clinical picture and management. Am. J. Obstet. Gynecol. 154:161, 1986.
Ruf H., Codaccioni J.L., Serment H. Le norethynodrel dans le syndrome premenstruel et les dysplasies mammaires. Bull. Fed. Gynec. Obstet. Franc. 76:587, 1964.
Mauvais-Jarvis P. Current therapeutic data concerning mastodynia and benign mastopathy. Therapeutique 43:575, 1972.
Meyrick R.L., Smith I. Benign breast swelling. Br. Med. J. 2:585, 1972.
Colin C., Gaspard V., Lambotte R. Relationship of mastodynia with its endocrine envi-roment and treatment in a double blind trial with lyne-strol. Archiv. fur Gynaekologie 225: 7, 1978.
Bradley D.D., Wingerd J., Petitti D.B. Serum high density lipoprotein cholesterol in women using oral contraceptives, estrogens and progestins. N. Engl. J. Med. 299:17, 1978.
Hirnoven E., Malkonen M., Manninem V. Effects of different progestogens on lipoproteins during postmenopausal replacement therapy. N. Engl. J. Med. 304:560, 1981.
Fahraeus L., Larsson-Cohn U., Wallentin L. L-norgestrel and progesterone have different influences on plasma lipoproteins. Eur. J. Clin. Invest. 30:447, 1983.
Ottoson V.B., Johansson B.G., Von Schoultz B. Subtraction of high-density lipoprotein cholesterol during estrogen replacement therapy: comparison between progestogens and natural progesterone. Am. J. Obstet. Gynecol. 151: 746, 1985.
McFadyen I.S., Raab G.M., Maclntyre C.C.A., Forrest A.P.M. Progesterone cream for cyclic breast pain. Br. Med. J. 298:931, 1989.
Maxson W.B., Hargrove J.T. Bioavailability of oral micronized progesterone. Fertil. Steril. 44: 622, 1985.
Villaneuva B., Casper R.F., Yen S.S.C. Intravaginal administration of progesterone: enhanced after estrogen treatment. Fertil. Steril. 35:433, 1981.
Nappi C., Mercorio F., Affinito P., Lepore L., Montemagno U. Vaginal administration of natural progesterone in premenopausal women with endometrial hyperplasia. In: Genazzani A.R., Petraglia F. and Volpe A. (Eds.), Research Reports on Gynecology and Obstetrics. The Parthenon Publishing Group, Carnforth, 1989, p. 543.
Haagensen CD., Bodian C., Haagensen D.E.Jr. Fibrous disease of the breast. In: Breast carcinoma. Risk and detection. W.B. Saunders Company, Philadelphia, 1981, p. 132.
Hsueh A.J.W., Peck E.J., Clark J.H. Progesterone antagonism of the estrogen receptor and estrogen-induced uterine growth. Nature 254: 337, 1975.
Tseng L., Gurpide E. Induction of human endometrial estradiol dehydrogenase by progestins. Endocrinology 97: 825, 1975.
Prudhomme J.F., Malet C., Gompel A., Lalardne J.P., Ochoa C., Boue A., Mauvais-Jarvis P., Kutten F. 17β-hydroxysteroid dehydrogenase (E2DH) activity in human breast epithelial cell and fibroblast cultures. Endocrinology 114:1483, 1984.
Gompel A., Malet C., Spritzer P., Lalardrie J.P., Kutten F., Mauvais-Jarvis P. Progestin effect on cell proliferation and 17β-hydroxysteroid dehydrogenase activity in normal human breast cells in culture. J. Clin. Endocrinol. Metab. 63:1174, 1986.
Morville R., Dray F., Reyner J., Barrat J. Biodisponibilité de la progesterone naturelle admin-istrée par voie orale. Mésure des concentrations du stéroide dans le plasma, l’endomètre et le tissue mammaire. J. Gynecol. Obstet. Biol. Repr. 11:355, 1982.
Krause W., Wichmann U., Horn W. Resorption of progesterone through the intact skin of the breast in comparison with other body regions Geburtshilfe Frauenheilkd 47:562, 1987.
Bucks D.A., McMaster J.R., Maibach H.I., Guy R.H. Biovailability of topically administered steroids: a “mass balance” technique. J. Invest. Dermatol. 91: 29, 1988.
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Nappi, C., Affinito, P., Di Carlo, C. et al. Double-blind controlled trial of progesterone vaginal cream treatment for cyclical mastodynia in women with benign breast disease. J Endocrinol Invest 15, 801–806 (1992). https://doi.org/10.1007/BF03348808
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DOI: https://doi.org/10.1007/BF03348808