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Controlled-Release Delivery Systems for Hormones

A Review of their Properties and Current Therapeutic Use

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Summary

Biomedical engineering approaches used to develop controlled-release delivery systems for hormones are here reviewed regarding system design and therapeutic applications.

The biomedical engineering approach uses a system of non-drug components to control the rate and duration of hormone delivery. The non-drug components vary from system to system, but generally include: a reservoir for the hormone; a barrier or regulator to contain the hormone within the reservoir and to control its release; an energy source to remove the hormone from the reservoir; and a pathway for egress of the hormone from the system. Controlled-release delivery systems for hormones discussed in this review include mechanical and osmotic pumps; intraocular, intravaginal and intrauterine platform devices; biodegradable and non-biodegradable subcutaneous implants; and small particulate systems including microcapsules, microspheres and liposomes. Examples of the therapeutic application of the various systems are given along with a discussion of design factors and pharmacological aspects relevant to their clinical use.

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References

  • Alvarez, F., Brache, V., Faundes, A., Johansson, E.D.B., Odlind, V. and Nash, H.: Levonorgestrel plasma levels during continuous administration with different models of subdermal implants. Contraception 27: 123–130 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Baker, R.W. and Lonsdale, H.K.: Controlled release: Mechanisms and rates; in Tanquary and Lacy (Eds) Controlled Release of Biologically Active Materials, pp. 15–72 (Plenum Press, New York 1974).

    Google Scholar 

  • Beck, L.R., Cowsar, D.R., Lewis, D.H., Gibson, J.W. and Flowers, C.E.: New long-acting injectable microcapsule contraceptive system. American Journal of Obstetrics and Gynecology 135: 419–426 (1979).

    PubMed  CAS  Google Scholar 

  • Beck, L.R., Cowsar, D.R. and Pope, V.Z.: Long-acting steroidal contraceptive systems: in Zatuchni and Osborne (Eds) Research Frontiers in Fertility Regulation, pp. 1–16 (Lippincott, Philadelphia 1980).

    Google Scholar 

  • Beck, L.R., Flowers, C.E., Pope, V.Z. and Tice, T.R.: Clinical evaluation of an improved injectable microcapsule contraceptive system. American Journal of Obstetrics and Gynecology 147(7): 815–821 (1983a).

    PubMed  CAS  Google Scholar 

  • Beck, L.R., Pope, V.Z., Flowers, C.E., Cowsar, D.R., Tice, T.R., Lewis, D.H., Dunn, R.L., Moore, A.B. and Gilley, R.M.: Poly (DL-lactideco-glycolide)/norethisterone microcapsules: An injectable biodegradable contraceptive. Biology of Reproduction 28: 186–195 (1983b).

    Article  PubMed  CAS  Google Scholar 

  • Beck, L.R., Ramos, R.A., Flowers, C.E., Lopez, G.Z., Lewis, D.H. and Cowsar, D.R.: Clinical evaluation of injectable biodegradable contraceptive system. American Journal of Obstetrics and Gynecology 140: 799–806 (1981).

    PubMed  CAS  Google Scholar 

  • Beck, L.R. and Tice, T.R.: Polylactic and poly (lactic acid-coglycolide acid) contraceptive delivery systems; in Mishell Jr, D.R. (Ed.) Long-Acting Steroidal Contraception (Raven Press, New York 1983).

    Google Scholar 

  • Bclchctz, P.E., Plant, T.M., Nakai, Y., Keogh, E.J. and Knobil, E.: Hypophyscal responses to continuous and intermittent delivery of hypothalamic gonadotropin releasing hormone (Gn-RH). Science 202: 631 (1978).

    Article  Google Scholar 

  • Blackshear, P.J., Dorman, F.D., Blackshear Jr, P.L., Varco, R.L. and Buchwald, H.: A permanently implantable, self-recycling, low flow, constant rate multipurpose infusion pump of simple design. Surgery Forum 21: 136–138 (1970).

    CAS  Google Scholar 

  • Blackshear, P.J., Dorman, F.D., Blackshear Jr, P.L., Varco, R.L. and Buchwald, H.: The design and initial testing of an implantable infusion pump. Surgery, Gynecology and Obstetrics 134: 51–56 (1972).

    PubMed  CAS  Google Scholar 

  • Blackshear, P.J., Rohde, T.D., Prosl, F. and Buchwald, H.: The implantable infusion pump: A new concept in drug delivery. Medical Progress Technology 6: 149–161 (1979).

    PubMed  CAS  Google Scholar 

  • Breckwoldt, M., Czygan, P.J., Lehmann, F. and Bettendorf, G.: Synthetic LH-RH as a therapeutic agent. Acta Endocrinologica(Kbh) 75: 209–220 (1974).

    CAS  Google Scholar 

  • Burton, F.G., Skiens, W.E. and Duncan, G.W.: Low-level, progestagen-releasing vaginal contraceptive devices. Contraception 19: 507–516 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Burton, F.G., Skiens, W.E., Gordon, N.R., Veal, J.T., Kalkwarf, D.R. and Duncan, G.W.: Fabrication and testing of vaginal contraceptive devices designed for release of prespecified dose levels of steroids. Contraception 17: 221–230 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Chandrasekaran, S.K., Benson, H and Urquhart, J.: Methods to achieve controlled drug delivery; in Robinson (Ed.) Sustained and Controlled Release Drug Delivery Systems, pp. 557–593 (Marcel Dekker, New York 1978).

    Google Scholar 

  • Chien, Y.W.: Novel drug delivery systems (Marcel Dekker, New York 1982).

    Google Scholar 

  • Chien, Y.W., Rozek, L.F. and Lambert, H.J.: Microsealed drug delivery systems, I. In vitro-in vivo correlation on subcutaneous release of desoxycorticosterone acetate and prolonged hypertensive animal model for cardiovascular studies. Journal of Pharmaceutical Sciences 67: 214–217 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Cornette, J.C., Kirton, K.T. and Duncan, G.W.: Measurement of medroxyprogesterone acetate (Provera) by radioimmunoassay. Journal of Clinical Endocrinology 33: 459–466 (1971).

    Article  CAS  Google Scholar 

  • Creque, H.M., Langer, R. and Folkman, J.: One month of sustained release of insulin from a polymer implant. Diabetes 29: 37–39 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Crowley, W.F., Comite, F., Vale, W., Rivier, J., Loriaux, D.L. and Cutler, G.B.: Therapeutic use of pituitary desensitization with a long-acting LHRH agonist: A potential new treatment for idiopathic precocious puberty. Journal of Clinical Endocrinology and Metabolism 52: 370–372 (1981).

    Article  PubMed  Google Scholar 

  • Croxatto, H.B., Diaz, S. and Mirenda, P.: Plasma levels of levonorgestrel in women during longterm use of NORPLANT. Contraception 23: 197–209 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Croxatto, H.B., Diaz, S., Robertson, D.N. and Pavez, M.: Clinical chemistry in women treated with levonorgestrel implants (Norplant™) or a TCu 200 IUD. Contraception 27: 281–288 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Croxatto, H., Diaz, S., Vera, R., Etchart, M. and Atria, P.: Fertility control in women with a progestagen released in microquantities from subcutaneous capsules. American Journal of Obstetrics and Gynecology 105: 1135–1138 (1969).

    PubMed  CAS  Google Scholar 

  • Diaz, S., Croxatto, H.B., Pavez, M., Quinteros, E., Carrillo, D., Simonetti, L., Croxatto, H.D. and Rosati, S.: Ectopic pregnancies associated with low dose progestagen-releasing IUDs. Contraception 22: 259–269 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Diaz, S., Pavez, M., Miranda, P., Robertson, D.N., Sivin, I. and Croxatto, H.B.: A five-year clinical trial of levonorgestrel Silastic implants (NORPLANT™). Contraception 25: 447–456 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Diaz, S., Pavez, M., Quinteros, R., Robertson, D.N. and Croxatto, H.B.: Clinical trial with subdermal implants of the progestin R-2323. Contraception 16: 155–165 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Dohlman, C.H., Pavan-Langston, D. and Rose, J.: A new ocular insert device for continuous constant-rate delivery of medication to the eye. Annals of Ophthalmology 4: 823–832 (1972).

    PubMed  CAS  Google Scholar 

  • Dmowski, W.P., Kapetanakis, E. and Scommegna, A.: Contraceptive effect of intrauterine estriol delivery systems in rabbits and baboons. Contraceptive Delivery Systems 1: 11–19 (1980).

    CAS  Google Scholar 

  • Dmowski, W.P., Shih, A., Wilhelm, J., Auletta, F. and Scommegna, A.: Effect of intrauterine estriol on reproductive function in the rabbit. Fertility and Sterility 28: 262–268 (1977).

    PubMed  CAS  Google Scholar 

  • Dunn, R.L. and Lewis, D.H.: Fibrous polymers for the delivery of contraceptive steroids to the female reproductive tract; in Lewis (Ed.) Controlled Release of Pesticides and Pharmaceuticals, pp. 125–146 (Plenum Publishing Corporation, New York 1981).

    Google Scholar 

  • El-Mahgoub, S.: The norgcstrcl-T IUD. Contraception 22: 271–286 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Gallegos, A., Aznar, R., Merino, G. and Guizer, E.: Intrauterine devices and menstrual blood loss. A comparative study of eight devices during the first six months of use. Contraception 17: 153–161 (1978).

    Article  Google Scholar 

  • Gonzalez, A., Aznar, R. and Revilla, M.C.: Ultrastructural changes in endometrium of women exposed to progesterone-releasing intrauterine contraceptive devices for more than 5 years (abstract): in Hafez and van Os (Eds) Medicated IUDs and Polymeric Delivery Systems, International Symposium, Amsterdam, Holland, June 27–30 (1979).

    Google Scholar 

  • Gresser, J.D., Wise, D.L., Beck, L.R. and Howes, J.F.: Larger animal testing of an injectable sustained release fertility control system. Contraception 17: 253–266 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Gupta, G.N.: Sustained release studies of NET and levonorgestrel from bioabsorbable compressed pellets in rats and monkeys. Progress Report to ICCR (Population Council, New York 1977).

    Google Scholar 

  • Hagenfcldt, K. and Landgren, B.-M.: Contraception by intrauterine release of progesterone — effects on endometrial trace elements, enzymes and steroids. Journal of Steroid Biochemistry 6: 895 (1975).

    Article  Google Scholar 

  • Hammond, C.B., Wiebe, R.H., Haney, A.F. and Yancy, S.G.: Ovulation induction with luteinizing hormone-releasing hormone in amenorrheic, infertile women. American Journal of Obstetrics and Gynecology 135: 924–939 (1979).

    PubMed  CAS  Google Scholar 

  • Hsieh, S.T. and Langer, R.: Magnetic modulation of insulin release in diabetic rats. 9th International Symposium on Controlled Release of Bioactive Materials, pp.90–94, Ft. Lauderdale, Florida, July 25–28 (1982).

  • Jeong, S.Y., Sato, S., McRea, J.C. and Kim, S.W.: Controlled release of bioactive glycosylated insulins. 10th International Symposium on Controlled Release of Bioactive Materials, San Francisco. July 24–27, pp. 29–35 (1983).

  • Juliano, R.L.: Controlled delivery of drugs: An overview and prospectus; in Juliano (Ed.) Drug Delivery Systems. Characteristics and Biomedical Applications (Oxford University Press, New York 1980).

    Google Scholar 

  • Katzorke, T., Popping, D., von der Ohe, M. and Tauber, P.F.: Clinical evaluation of the effects of a new long-acting superactive luteinizing-releasing hormone (LH-RH) analog, D-Ser (TBU)6-des-ly-lo-cthylamidc-LH-RH, in women with secondary amenorrhca. Fertility and Sterility 33: 35–42 (1980).

    PubMed  CAS  Google Scholar 

  • Keller, N., Longwell, A.M. and Birss, S.A.: Intermittent vs continuous steroid administration. Archives of Ophthalmology 94: 644–652 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Kitrenos, J.G., Jones, M. and McLeod, D.C.: Comparison of selected intravenous infusion pumps and rate regulators. American Journal of Hospital Pharmacy 35: 304–310 (1978).

    PubMed  CAS  Google Scholar 

  • Landgren, B.M., Johannisson, E., Masironi, B. and Diczfalusy, E.: Pharmacokinetic and pharmacodynamic effects of small doses of norethisterone released from vaginal rings continuously during 90 days. Contraception 19: 253–271 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Landgren, B.M., Oriowo, M.A. and Diczfalusy, E.: Pharmacokinetic and pharmacodynamic studies with vaginal devices releasing norethisterone at a constant, near zero order. Contraception 24: 29–44 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Lee, V.H. and Robinson, J.R.: Mechanistic and quantitative evaluation of precorneal pilocarpine disposition in albino rabbits. Journal of Pharmaceutical Science 68: 674 (1979).

    Google Scholar 

  • Leyendecker, G., Ludwig, W. and Hansmann, M.: Pregnancies following chronic intermittent (pulsatile) administration of Gn-RH by means of a portable pump (“Zyklomat”) — a new approach to the treatment of infertility in hypothalamic amenorrhca. Journal of Clinical Endocrinology and Metabolism 51: 1214–1216 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Manautou, J.: Contraception by intrauterine release of progesterone: Clinical results. Journal of Steroid Biochemistry 6: 889–894 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Martinez-Manautou, J., Maqueo, M., Aznar, R., Pharriss, B.B. and Zaffaroni, A.: Endometrial morphology in women exposed to uterine systems releasing progesterone. American Journal of Obstetrics and Gynecology 121: 175–179 (1975).

    PubMed  CAS  Google Scholar 

  • Mehta, S., Joshi, U.M., Sankolli, G.M., Odatia, A., Donde, U.M. and Saxena, B.M.: Clinical performance and endocrine profiles with contraceptive vaginal rings containing a combination of estradiol and d-norgestrel. Contraception 23: 241–250 (1981).

    Article  PubMed  CAS  Google Scholar 

  • Mishell Jr, D.R. and Lumkin, M.: Initial clinical studies of intravaginal rings containing norethindrone and norgestrel. Contraception 12: 253–260 (1975).

    Article  PubMed  Google Scholar 

  • Mishell Jr, D.R., Moore, D.E., Roy, S., Brenner, P.F. and Page, M.A.: Clinical performances and endocrine profiles with contraceptive vaginal rings containing a combination of estradiol and d-norgestrel. American Journal of Obstetrics and Gynecology. 130: 55–62 (1978).

    PubMed  CAS  Google Scholar 

  • Mishcll Jr, D.R., Talas, M., Parlow, A.F. and Moyer, D.L.: Contraception by means of a Silastic vaginal ring impregnated with medroxyprogesterone acetate. American Journal of Obstetrics and Gynecology 107: 100–107 (1970).

    Google Scholar 

  • Moore, D.E., Roy, S., Stanczyk, F.Z. and Mishell, D.R.: Bleeding and serum d-norgestrel, estradiol and progesterone patterns in women using d-norgestrel subdermal polysiloxane capsules for contraception. Contraception 17: 315–328 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Nash, H.A., Robertson, D.N., Moo Young, A.J. and Atkinson, L.E.: Steroid release from Silastic capsules and rods. Contraception 18: 367–394 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Newton, J., Szontagh, F., Lebech, P. and Row, P.: A collaborative study of the progesterone intrauterine device (Progestasert). Contraception 19: 575 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Nillius, S.J., Bcrgquist, C. and Wide, L.: Inhibition of ovulation in women by chronic treatment with a stimulatory LRH analogue — a new approach to birth control. Contraception 17: 537 (1978).

    Article  Google Scholar 

  • Nilsson, C.G. and Holma, P.: Menstrual blood loss with contraceptive subdermal levonorgestrel implants. Fertility and Sterility 35: 304–306 (1981).

    PubMed  CAS  Google Scholar 

  • Nilsson, C.G., Johansson, E.D.B., Jackanicz, T.M. and Tuukkainen, T.: A d-norgestrel-releasing IUD. Contraception 13: 503–514 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Nilsson, C.G., Johansson, E.D.B., Jackanicz, T.M. and Tuukkainen, T.: Biodegradable polylactate as a steroid-releasing polymer: Intrauterine administration of d-norgestrel. American Journal of Obstetrics and Gynecology 122: 90–95 (1975).

    PubMed  CAS  Google Scholar 

  • Nilsson, C.G. and Luukkainen, T.: Improvement of a d-norgestrel-releasing IUD. Contraception 15: 295–306 (1977).

    Article  PubMed  CAS  Google Scholar 

  • Nilsson, C.G., Luukkainen, T., Diaz, J. and Allonen, H.: Clinical performance of a new levonorgestrel-releasing intrauterine device. A randomized comparison with a Nova-T-copper device. Contraception 25: 345–356 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Nilsson, C.G., Luukkainen, T. and Lahteenmaki, P.: Contraception with a norethisterone-releasing IUD. Plasma levels of norethisterone and its influence on the ovarian function. Contraception 17: 115–122 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Nursall, J.F.: Systemic effects of the topical use of ophthalmic corticosteroid preparations. American Journal of Ophthalmology 59: 29–30 (1965).

    PubMed  CAS  Google Scholar 

  • Patel, H.M. and Ryman, B.E.: Oral administration of insulin by encapsulation within liposomes. FEBS Letters 62: 60–63 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Perkins, P.R., Dorman, F.D., Rohde, T.D., Blackshear, P.J., Blackshear Jr, P.L., Varco, R.L. and Buchwald, H.: Design and initial testing of a totally implantable transcutaneously controllable insulin delivery device. Transactions of the American Society of Artificial Internal Organs 24: 229–231 (1978).

    CAS  Google Scholar 

  • Pharriss, B.B., Erickson, R., Bashaw, J., Hoff, S., Place, V.A. and Zaffaroni, A.: Progestasert: An uterine therapeutic system for long-term contraception, I. Philosophy and clinical efficacy. Fertility and Sterility 25: 915–921 (1974).

    PubMed  CAS  Google Scholar 

  • Pickup, J.C., Keen, H., Parsons, J.A. and Alberti, K.G.M.: Continuous subcutaneous insulin infusion: An approach to achieving normoglycemia. British Medical Journal 1: 204–207 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Pickup, J.C., Keen, H., Parsons, J.A., Alberti, K.G.M. and Rowe, A.S.: Continuous subcutaneous insulin infusion: Improved blood-glucose and intermediary-metabolite control in diabetics. Lancet 1: 1255–1257 (1979).

    Article  PubMed  CAS  Google Scholar 

  • Pitt, C.G., Christensen, D., Jeffcoal, A.R., Kimmel, G.L., Schindler, A., Wall, M.E. and Sweidinger, R.A.: Biodegradable polymers and sustained delivery of contraceptive drugs; in Gabelnick (Ed.) Proceedings: Drug Delivery Systems. DHEW Publication No. (NIH) 77: 1238, pp. 141–192 (1977).

  • Rhine, W.D., Hsieh, D.S.T. and Langer, R.: Polymers for sustained macromolecule release: Procedures to fabricate reproducible delivery systems and control release kinetics. Journal of Pharmaceutical Sciences 69: 265–270 (1980).

    Article  PubMed  CAS  Google Scholar 

  • Riondel, A., Tait, J.F., Tait, S.A.S., Gut, M. and Little, B.: Estimation of progesterone in human peripheral blood using S-thiosemicarbozide. Journal of Clinical Endocrinology 25: 229–242 (1965).

    Article  CAS  Google Scholar 

  • Robertson, D.N., Sivin, I., Nash, H.A., Braun, J. and Dinh, J.: Release rates of levonorgestrel from Silastic® capsules, homogencous rods and covered rods in humans. Contraception 27: 483–495 (1983).

    Article  PubMed  CAS  Google Scholar 

  • Rupp, W.M., Barbosa, J.J., Blackshear, P.J., McCarthy, H.B., Rohde, T.D., Goldenberg, F.J., Rublein, T.G., Dornam, F.D. and Buchwald, H.: The use of an implantable insulin pump in the treatment of type II diabetes. New England Journal of Medicine 307: 265–270 (1982).

    Article  PubMed  CAS  Google Scholar 

  • Ryman, B.E., Jewkes, R.F., Jeyasingh, K., Osborne, M.P., Patel, H.M., Richardson, V.J., Tattersall, M.H.N. and Tyrrell, D.A.: Potential applications of liposomes to therapy. Annals of the New York Academy of Sciences 308: 281–307 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Santiago, J.V., Clemens, A.H., Clarke, W.L. and Kipnis, D.M.: Closed-loop and open-loop devices for blood glucose control in normal and diabetic subjects. Diabetes 28: 71–84 (1979).

    PubMed  CAS  Google Scholar 

  • Schmitt, E.E.: Pharmaceutical composition of poly(orthoester) coand homopolymers and poly(orthocarbonate) co- and homopolymers having carbonyloxy functionally with drug, U.S. Patent 4, 155,922, May 22 (Alza Corporation) [1979].

  • Scommegna, A., Pandya, G.N., Christ, M., Lee, A.W. and Cohen, M.R.: Intrauterine administration of progesterone by a slow releasing device. Journal of Fertility and Sterility 21: 201–210 (1970).

    CAS  Google Scholar 

  • Sidman, K.R., Schwope, A.D., Steber, W.D., Rudolph, S.E. and Poulin, S.B.: Use of synthetic poiypeptides for biodegradable drug delivery systems. Polymer Preprints 20: 27 (1979).

    CAS  Google Scholar 

  • Sidman, K., Steber, W.D. and Burg, A.W.: A biodegradable drug delivery system: in Gabelnick (Ed) Proceedings: Drug Delivery Sysiems. DHEW Publication No. (NIH) 77-1238. p. 120 (1977).

  • Sivin, I., Sanchez, F.A., Diaz, S., Holma, P., Coutinho, E., McDonald, O., Robertson, D.N. and Stern, J.: Three-year experience with Norplant subdermal contraception. Fertility and Sterility 39: 799–808 (1983).

    PubMed  CAS  Google Scholar 

  • Thecuwes, F. and Yum, S.I.: Principles of the design and operation of generic osmotic pumps for the delivery of semisolid or liquid drug formulations. Annals of Biomedical Engineering 4: 343–353 (1976).

    Article  Google Scholar 

  • Thiery, M., Vandekerckhove, D., Dhont, M., Vermeulen, A. and Decoster, J.M.: The medroxyprogesterone acetate intravaginal silaslic ring. Contraception 13: 605–617 (1976).

    Article  PubMed  CAS  Google Scholar 

  • Tillson, S.A., Hudson, R., Swisher, D. and Leong, P.: Preclinical evaluation of intrauterine progesterone as a contraceptive agent. II. Possible mechanisms of action. Contraception 17: 475–488 (1978).

    Article  PubMed  CAS  Google Scholar 

  • Tillson, S.A., Marian, M., Hudson, R., Wong, P., Pharriss, B., Aznar, R. and Martinez-Manautou, J.: The effect of intrauterine progesterone on the hypothalamic-hypophyseal-ovarian axis in humans. Contraception 11: 179–192 (1975).

    Article  PubMed  CAS  Google Scholar 

  • Toivonen, J., Lahteenmaki, P. and Luukkainen, T.: The use of the contraceptive vaginal ring governed by the pattern of individual uterine bleeding. Contraception 19: 401–409 (1979a).

    Article  PubMed  CAS  Google Scholar 

  • Toivonen, J., Lahteenmaki, P. and Luukkainen, T.: Bleeding and ovulation control with use of a small contraceptive vaginal ring releasing levonorgestrel and estradiol. Contraception 20: 11–18 (1979b).

    Article  PubMed  CAS  Google Scholar 

  • Vickery, B.H., McRae, G.I., Tallentire, D., Foreman, J., Nerenberg, C., Jushinsky, S. and Sanders, L.M.: Sustained administration of a highly potent LH-RH agonist from subcutaneous reinjected polymeric microspheres. 10th International Controlled Release Symposium, San Francisco, California, p. 97. July 24–27 (1983).

  • Viinikka, L., Victor, A., Janne, O. and Raynaud, J.P.: The plasma concentration of a synthetic progestin R-2323 released from poly silastic vaginal rings. Contraception 12: 309 (1975).

    Article  PubMed  CAS  Google Scholar 

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  1. Department of Obstetrics and Gynecology, Division of Reproductive Biology and Endocrinology, University of Alabama in Birmingham, University Station, Birmingham, AL, 35294, USA

    Lee R. Beck & Valerie Z. Pope

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Beck, L.R., Pope, V.Z. Controlled-Release Delivery Systems for Hormones. Drugs 27, 528–547 (1984). https://doi.org/10.2165/00003495-198427060-00002

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