Journal of Postgraduate Medicine
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ARTICLE
 
 
Year : 1979  |  Volume : 25  |  Issue : 3  |  Page : 154-157  

Thrombocyte function in relation to the long term application of medroxyprogesterone acetate as a female contraceptive agent

L Mettler, D Shirwani, FJ Brunnberg 
 Department of Obetetrics and Gynaecology, University of kiel

Correspondence Address:
L Mettler
Department of Obetetrics and Gynaecology, University of kiel

Abstract

In two hundred and twenty eight parous women between thirty and forty years o f age, Medroxyprogesterone acetate 150 mg depot injection every three months proved to be a one hundred per cent contraceptive agent. Minimal side effects were noted with some spotting and amenorrhoea. No significant increase in blood coagula­tion and tendency to thrombosis was noted as tested by the platelet aggregation test during medication.



How to cite this article:
Mettler L, Shirwani D, Brunnberg F J. Thrombocyte function in relation to the long term application of medroxyprogesterone acetate as a female contraceptive agent.J Postgrad Med 1979;25:154-157


How to cite this URL:
Mettler L, Shirwani D, Brunnberg F J. Thrombocyte function in relation to the long term application of medroxyprogesterone acetate as a female contraceptive agent. J Postgrad Med [serial online] 1979 [cited 2020 Sep 22 ];25:154-157
Available from: http://www.jpgmonline.com/text.asp?1979/25/3/154/42132


Full Text

 Introduction



Since 1969, medroxyprogesterone acetate has been used clinically as a female contraceptive agent. [13] It is slow­ly absorbed from the injection site and has a prolonged activity which should therefore make it an ideal long acting contraceptive drug. It appears to act as a powerful inhibitor of gonadotro­phins, [5],[6],[11] and the hormone response to it of gonadotrophins and estrogens have been well documented in dogs by Bryan [2] and in man by Laron et al. [6]

Little is, however, known about the blood clotting or thrombogenic effects of medroxyprogesterone acetate and al­though Robinson [10] in 1970, found no ad­verse effects of the drug on clotting factors, Mettler and Meseck-Selchow. [7] in 1972 found an increase in platelet aggregation and therefore a predisposi­tion to thrombosis when the drug was used in monophasic combination with estrogens.

This study was therefore designed to report on the thrombogenic potential of medroxyprogesterone acetate administer­ed intramuscularly at 3 monthly inter­vals.

 Material And Methods



(a) Patients

Two hundred and twenty eight women with an age range of twenty to forty five years volunteered to participate in the study. All had completed their families. Patients were seen and examined clinical­ly every three months and a full men­strual history was taken and twelve ml fresh blood collected directly into a poly­estrol plastic tube containing 1.5 ml of a 3.8% aqueous sodium citrate solution.

(b) Drugs

At each visit the patient was admini­stered 150 mgs (3.0 ml) Medroxy­progesterone acetate* as a single intra­muscular injection. The number of in­jections ranged from one to twelve with the shortest treatment of three months and the longest, of thirty six months, The majority of patients discontinued medroxyprogesterone acetate after three to four treatment cycles.

(c) Laboratory investigations

The blood samples were centrifuged for one to three minutes at 500 to 700 x g. The supernatant thrombocyte rich plasma was then separated and rotated in a 20 ml siliconized glass container at 37°C with a velocity of 20 rotations per minute for 10 minutes. The rotated plasma was then diluted 1: 10 with a citrate sodium physiological saline solu­tion.

Plastic slides were over-layered with 1.5 ml of the diluted plasma and by de­canting and rinsing with the same solu­tion 20 times in 30 minutes the majority of erythrocytes and leucocytes were washed away.

Specimens were then fixed for 5 minutes in 40%% formalin, oxidated for 5 minutes in 0.1 N Potassium permanganate solution and rinsed again in distilled water. The preparations were stained for 60 minutes in a 1/5 diluted and filtered Giemsa solution, and air dried and evaluated with the phase contrast micro­scope.

Following 3 degrees only were dis­tinguished according to the method of Breddin.1 See [Figure 1] below.

Platelet Aggregation Test Degree I de­monstrated solitary platelets and a few reversible aggregations. Platelet Aggre­gation Test Degree II consisted of an in­creasing number of reversible platelet aggregations. Solitary platelets were decreased. Platelet Aggregation Test Degree III showed a growing number of irreversible platelet aggregations and solitary platelets were severely diminish­ed.

 Results



(a) General

In the 228 patients no pregnancies re­sulted. From [Table 1] it can be seen that as the course continued intra-menstrual bleeding and spotting decreased but amenorrhoea developed in 68. cases, Many patients had symptoms of anxiety associated with taking the drug and twenty seven patients experienced some degree of diminished libido.

(b) Laboratory

As can be seen from [Figure 2] (see on page ) no statistical alteration in the degree of platelet aggregation was found during the period of maximal twelve in­jections of medroxyprogesterone,

 Discussion



In this series of 228 women, medroxy­progesterone acetate proved one hund­red per cent effective as a contraceptive agent. The patients tolerated the drugs well and apart from minimul spotting and some cases of amenorrhoea no severe clinical side effects were observed. A number of women, however, discontinu­ed the treatment early although they did not desire to have any more children. This may be in part due to the psycho­logical symptoms of anxiety and diminish­ed libido they experienced which may also have had a degree of effect on men­strual cycle regularity.

The drug appears to be free from thrombotic potential for, unlike ingested estrogen - gestagen - compounds, [3],[4],[7],[8],[9] the platelet aggregation was not altered under medroxyprogesterone acetate con­traceptive intake during the three to thirty six months of treatment.

Therefore, medroxyprogesterone acetate would appear to be a safe useful alternative to the application of intra­uterine devices and laparoscopic sterilisa­tion [12] for the group of women between thirty and forty five years of age who do not desire to have any more children.

 Acknowledgements



Mr. R. F. Harrison for his help with the text.

References

1Breddin, K.: Uber gesteigerte Thrombo­zytenagglutination bei Gefasskrankheiten. Schweiz. med. Wschr., 95: 655-660, 1965.
2Bryan, H. S.: The parenteral use of med­roxyprogesterone acetate as an antiferti­lity agent in dogs. Presented as a Paper at the 99th Annual Meeting of The American Veterinary Medical Association in August, 12-16, 1962 in Miami Beach.
3Caspery, E. A. and Peberdy, M.: Oral contraception and blood platelet adhesive­ness. Lancet, I: 1142-1143, 1965.
4Halberstadt, E., Romer, E. and Stein, W.: Plattchenaggregation unter hormonalen Kontrazeptiva. In, "Sexualhoromone and Blutgerrinung" (Authors: Marx, R. and Theis, H. A.) Schattauer, Verlag, Stuttgart, 1971, S.-147.
5Kupperman, H. S. and Epstein, J. A.: Medroxyprogesterone acetate in the treat­ment of constitutional sexual precocity. J. Clin. Endocrinol, and Metab., 22: 456-458, 1962.
6Laron, Z., Rumney, G., Rat, L. and Naji, N.: Effects of 17-alpha hydroxy, 6 alpha­methyl progesterone acetate (Depot Pro­vera) on urinary gonadotrophins and estrogens in man. Acta. Endocrinol. (Kobenhaven), 44: 75-80, 1963.
7Mettler, L. and Meseck-Selchow, B.: Oral contraceptives and platelet function. Thrombosis et Diathesis Haemorrhagica. 28: 213-220, 1972.
8Pepper, H. and Lindsay, S.: Levels of platelets and eosinophilic leucocytes dur­ing the normal menstrual cycle and the administration of norethynodrel (Enovid), Internat. J. Fertility, 8: 467-473, 1963.
9Poller, L., Priest, C. M. and Thompson, J. M.: Platelet aggregation during oral contraception. Brit. Med. J., 4: 273-279, 1969.
10Robinson, R. W.: Estrogen, progestin and combination estrogen-progestin effects on clotting factors. Circulation, 42: (Suppl. 1I1): 22, 1970.
11Schultz, M. A. and Mosier, H. D.: Treat­ment of constitutional precocious puberty in children with medroxyprogesterone acetate. J. Paediat., 63: 718, 1963.
12Senim, K.: "Pelviskopie and Hysteros­kopie," F. K. Schattauer Verlag, Stutt­gart, New York, 1976.
13Soichet, S.: Depot Provera as a female contraceptive agent. Internal. J. Fertility, 14: 33-38, 1969

 
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