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The Effects of Testosterone Propionate, Methyl Testosterone, Anhydro-oxy-Progesterone and Progesterone upon Lactation in the Nursing Human Being
THE EFFECTS OF TESTOSTERONE PROPIONATE, }iETHYL TESTOSTERONE, ANHYDRO-OXY-PROGESTERONE AND PROGESTERONE UPON LACTATION IN THE NURSING HUMAN BEING A. R. ABARBA::>
N previous report, it was pointed out that, though afterpains or painful engorgement of the breasts can be adequately relieved by Ismall doses of testosterone propionate ( 10 to 15 mg.), lactation was not A
interfered with, provided the baby continued to nurse. 1 Others/· 4 how. ever, using 40 to 150 mg. of this steroid, have claimed successful in hibition of lactation in the human being. In order to verify our previous observations, the following studies were carried out, using larger dosages of testosterone propionate than any previously reported. In addition, methyl testosterone, anhydro-oxy-progesterone (pregneninolone, ethinyl testosterone), and progesterone were also studied as to their effects upon the initiation of lactation and the maintenance of established milk secretion. PROCEDlJRES AND RESlJLTS
The mothers and babies used in these studies were carefully selected according to the criteria set up in a previous study.s Each gave a history of having adequately nursed a previous child for at least three months. Every one had had a normal spon· taneous delivery of a seemingly normal active infant. Starting on the third day, the baby went to breast for twenty minutes at four-hour intervals five times a day. At 2 A.M., a dilute formula was substituted for tbe breast feeding. By weighing each baby before and after each breast feeding, the daily amount of mother's milk obtained was computed by totaling the results of the five feedings. A minimum of seven and one-half ounces daily was accepted as normal after the third post-partum day. Fifty mothers served as controls, while there were 36 in the test groups. Testoster~.me Propionate.-There were 12 patients in tbis group. To observe the effect of testosterone propionate upon the onset of lactation in the nursing human being, !l of these received from 200 to 300 mg. of testosterone propionate in sesame oil intramuscularly over a period of two to five days, beginning soon after parturition. In not one instance was the onset of normal adequate lactation delayed (Fig. 1). To note the effect of testosterone propionate upon established lactation, the other 6 patients received from 250 to 500 mg. of testosterone propionate intramuscularly over a perioil of two to four iiHys, twenty·fonr to seventy-two hours after adequate milk secretion had been established. No effect whatsoever was noted upon the amount of milk secretion or upon tile baby's gain in weight (Fig. 2). The effect of testosterone propionate upon painfully engorged breasts bas been reported elsewhere.l Clearly, then, provided the baby continues to nurse, testosterone propionate will neither inhibit the normal onset of adequate lactation nor suppress the normal amount of milk secretion after adequate lactation has once been established. Meth-yl Testo~erone.-For the purpose of investigating the effects of this steroid, 10 patients were divided into 2 groups of 5 each. Beginning soon after parturition, 110
ABARRANEL:
EFFECTS 0!<' TESTOSTERONE PROPIONATE UPON LACTATIO'\
111
250 HillS. TES'l'alTE!lOBE PROI'IOIATE TO TEST J.IO'l'HEl!
--lQ_ __ ll_
DAILY ALI>UJI'T OF lilLY. (ounces)
__s_
__ 7_ \EIG!l'l' OF BAE't' (pounds)
!::=:::
f~T~~~~~I 1
1
2
TEST
CO!ITllOL
1 1 Is 1 1 Is I±I 3
4
6
7
Fig. l.~Failure of 250 mg. of testosterone propionate to inhibit the onset of adequate lactation in the nursing human being. Similar tindings were obtained with either 500 mg. of methyl testosterone or 100 mg. of progesterone, as well as with 500 mg. of pregneninolone.
soo ~~!liS.
0!"
T"'-STOSTEOOJIE PROPIO:IATE TO TEST
I.IOTHER
DAILf AIIOtDIT OF
JIILI: (oUIICesl
. Fig. 2.-Failure of 500 mg. of testosterone propionate to suppress established Jactatlon in the nursing human being, The result illustrated here is similar to that obtained with either 500 mg. of methyl testosterone or 1(}0 mg. of progesterone, a.s well as with 500 mg. of pregneninolone. Essentially similar results were noted with 500 mg. of oral stilbestrol.~ Normal variation ranges from one to seven ounces dally. ·
112
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
the first group received from 100 to 500 mg. of methyl testosterone in divided oral doses over a perio.d of one to four days. The babies continued to nurse as usual. The onset of adequate lactation was not inhibited (Fig. 1). In order to observe the effect upon established lactation, the other 5 moth· ers received from 250 to 500 mg. in divided oral doses twenty-four to seventytwo hours after milk secretion had become adequately established. Lactation was not suppressed (Fig. 2). Anhydro-Oxy-Progesterone (Pregneninolcme, Ethinyl Testostercme).-The effect of this steroid upon the initiation of milk secretion was studied in 5 patients. From 100 to 500 mg. were administered orally in divided doses over a period of one to four days, beginning soon after delivery. The onset of lactation was not affected (Fig. 1). The effect upon established milk secretion was then studied. From 250 to 500 mg. were administered orally over a peri.od of one to four days, starting twenty-four to seventy-two hours after adequate lactation had been established. Milk secretion was not interfered with in any way (Fig. 2). Progesterone.-Because of the difficulty in securing large amounts of this steroid, only 4 patients were studied. Two received 100 mg. in sesame oil intramuscularly over a period of three to four days, respectively, beginning soon after delivery. The onset of adequate milk secretion was not delayed (Fig. 1). The other two patients received 100 mg. of progesterone intramuscularly in divided doses twenty-four and seventy-two hours, respectively, after lactation had been adequately established. Milk secretion was not suppressed (Fig. 2). Careful pediatric cheek-up and follow-up of the babies in the test groups failed to reveal any adverse effects. DISCUSSION
The process of lactation resolves itself into two fundamental mechanisms: the initiation of milk secretion which is under hormonal control6 and the maintenance of established lactation which is governed by both hormonal and neurogenic factors. 7 These phenomena must be clearly differentiated from the clinical syndrome of painful engorgement of the breasts. The latter is brought about by lymphatic and vascular stasis, not by distention of the ducts by milk. 8 Failure to differentiate clearly the mechanism by which painful engorgement is brought about from the physiological processes leading to the initiation of milk secretion has led to the confusion apparent in the clinical literature. Although painful engorgement may be associated with the onset of lactation, each is a distinct physiologic entity. Clearly then, the one is not synonymous with the other. In a previous report, it was pointed out that a sufficient daily dose of es~rogen {stilbestrol) would delay the onset of adequate milk secretion in the nursing human being only as long as it was administered. 5 The mechanism of action of stilbestrol was felt to be directly upon the glandular epithelium of the mammary gland, for a cell that is actively proliferating (under the influence of estrogen) cannot secrete at the same time. 9 In other words, the ability of a substance to affect the onset of adequate lactation in the nursing mother seemed to parallel its proliferating influence upon the mammary epithelium. The same conclusion was reached by Folley and Kon 10 in their work on rats. The reason for the failure of the four steroids studied in these experiments (Fig. 1) to affect the onset of adequate milk secretion in the nursing human being becomes apparent from their relatively slight, if any, proliferative effect upon the mammary epithelium. 11 In fact,
ABARBANEL:
EFFECTS OF TESTOSTERONE PROPIONATE UPON LACTATION
113
testosterone greatly stimulates the production by the anterior pituitary of lactogenic principle(s)/ 2 whose release is actively stimulated by the act of suckling. 13 Consequently, the stimulus of a nursing child was more than sufficient to initiate and then maintain adequate lactation. Milk secretion, once established, is controlled by both hormonal and neurogenic factors. 7 The manner in which the nervous stimulus of suckling is essential for the continued secretion of milk is still not clear. 14 Upon the clarification of this point must await the explanation for the reason why not only massive doses of these four steroids, but also of stilbestrol,5 have no effect upon established lactation in the nursing human being (Fig. 2). The mechanism by which painful engorgement of the breasts is relieved by testosterone propionate and methyl testosterone is not as yet known. That it is not by inhibition of lactation is obvious from the results obtained in these studies (Fig. 1). Its fundamental physiology, however, probably involves the ebb and flow of extracellular fluid in some manner. Markee,l 5 for instance, has shown that testosterone will bring about a regression in ocular endometrial transplants as evidenced by a decreased amount of fluid in the stroma and by a lessened vascularity. SUMMARY AND CONCL"CSIONS
1. The effects of relatively large doses of testosterone propionate, methyl testosterone, anhydro-oxy-progesterone and progesterone were studied upon the onset of milk secretion and the maintenance of established lactation in the nursing human being. 2. The onset of adequate milk secretion in the nursing human subject was not affected by: (a) (b) (c) (d)
200 100 100 100
to ilOO to 500 to 500 mg. of
mg. of testosterone propionate in oil given intramuscularly mg. of methyl testosterone orally mg. of anhydro-oxy-progesterone orally progesterone given intramuscularly
3. Established lactation was adequately maintained in the nursing woman, being unaffected by: (a) (b) (c) (d)
250 250 250 100
to 500 to 500 to 500 mg. of
mg. of testostero:tl4l propionate given intramuscularly mg. of methyl testosterone orally mg. of anhydro-oxy-progesterone orally progesterone given intramuscularly
4. The ability of a substance to affect the onset of adequate lactation in the nursing woman seems to parallel its proliferating effect upon the glandular epithelium of the breast. 5. Once lactat,ion is adequately established, however, the stimulus for further milk secretion by the glandular epithelium of the brea..'lt, produced by an actively suckling baby, proved to be far stronger than the stimulus to proliferation of this same mammary epithelium, provided by massive doses of not only the four steroids used in this study, but also of the estrogen, stilbestrol. 6. The mechanism by which relief of painful engorgement of the breasts is brought about by testosterone propionate, as well as by methyl
114
,UmRICAN ,JOURNAI, OF OBS'l'E:'I'RICS ANn GYKI
testosterone, does not depend upon inhibition of lactation but probably involves the shifting tides of extracellular fluid. The author gratefully acknowledges the sincere interest of Drs. Harry Aranow and Milton J. Goodfriend, during the course of these studies. ln addition, the splendid cooneration of the Misses Morgan and Newton, of the Nursing Staff of the Obstetrical Division, is deeply appreciated. Ciba Pharmaceutical Products, Inc., supplied the following steroids: (1) Testosterone propionate under the trade name of Perandren. ( 2) Methyl testosterone under the trade name of Metandren. ( 3) Progesterone under the trade name of Luto-cylin. ( 4) Anhydro-oxy-progesterone. REFERENCES
(1) Abarbanel, A. R,: AM. J, OBST. & GYNEI\ 38: 2-i:l, 1089. (2) K·urzrok, R., and O'Connel, C. P.: Endocrinology 23: 476, 1938. (:-!) Birnberg, C. H., Kwrzrok, L., a~~d Klor, B. J.: AM. J. 0BST. & GYNEe. 39: 109, 1940. ( 4) Si-egler, 8., and Silverstein, L. M.: Ibid. 39: 109, 1940. (5) Abarbanel, A. R., and Goodfriend, Jf. J.: Ibid. 40: 1037, 1940. (6) Nels
THB USE OF TESTOSTERONE PROPIONATE IN THE MANAGEMENT OF PELVIC INFLAMMATORY DISEASE EuGENE T. RusH
SToNE, M.D., NEw YoRK, N.Y.
(From the Department of Gynecology, Hospital for the Rupt·ure(l and Cripple1l)
HAS long been recognized that the menstrual period is a time of ITdanger or flare-up in the course of pelvic inflammatory disease. Most patients with chronic pelvic inflammatory disease suffer from dysmenorrhea and/or menorrhagia. Exacerbations of pelvic inflammatory disease at the time of menstruation are so common that often patients are warned to stay in bed before and during their menses to avoid or lessen the chance of a flare-up. Conversely, few patients who manage to retain their infected tubes until the menopause, require surgery thereafter for the relief of the disease, suggesting that cessation of the menstrual function is beneficial in these patients. The use of testosterone propionate in treating acute and chronic pelvic inflammatory disease was suggested by the ease with which menstruation ean be suppressed by relatively safe doses of androgen. 1 It was hoped that not only could the exacerbations be prevented but~hat inasmuch as there is a natural tendency for large inflammatory masses to regress and even disappear in well-controlled patients, testosterone propionate might prove to be a helpful adjuvant in the management of this disease. Beclere2 employed testosterone propionate for uterine hemorrhages with goon results. Mazer (C.) and Mazer (M)3 used androgen in 38 cases of menstrual disorder, bothmenorrhagia and mt:~trorrl~agia. Greenhill and Freed' advocated the use of testosterone propionate in mastopathies, menorrhagia, and dysmenorrhea. Huff-
N previous report, it was pointed out that, though afterpains or painful engorgement of the breasts can be adequately relieved by Ismall doses of testosterone propionate ( 10 to 15 mg.), lactation was not A
interfered with, provided the baby continued to nurse. 1 Others/· 4 how. ever, using 40 to 150 mg. of this steroid, have claimed successful in hibition of lactation in the human being. In order to verify our previous observations, the following studies were carried out, using larger dosages of testosterone propionate than any previously reported. In addition, methyl testosterone, anhydro-oxy-progesterone (pregneninolone, ethinyl testosterone), and progesterone were also studied as to their effects upon the initiation of lactation and the maintenance of established milk secretion. PROCEDlJRES AND RESlJLTS
The mothers and babies used in these studies were carefully selected according to the criteria set up in a previous study.s Each gave a history of having adequately nursed a previous child for at least three months. Every one had had a normal spon· taneous delivery of a seemingly normal active infant. Starting on the third day, the baby went to breast for twenty minutes at four-hour intervals five times a day. At 2 A.M., a dilute formula was substituted for tbe breast feeding. By weighing each baby before and after each breast feeding, the daily amount of mother's milk obtained was computed by totaling the results of the five feedings. A minimum of seven and one-half ounces daily was accepted as normal after the third post-partum day. Fifty mothers served as controls, while there were 36 in the test groups. Testoster~.me Propionate.-There were 12 patients in tbis group. To observe the effect of testosterone propionate upon the onset of lactation in the nursing human being, !l of these received from 200 to 300 mg. of testosterone propionate in sesame oil intramuscularly over a period of two to five days, beginning soon after parturition. In not one instance was the onset of normal adequate lactation delayed (Fig. 1). To note the effect of testosterone propionate upon established lactation, the other 6 patients received from 250 to 500 mg. of testosterone propionate intramuscularly over a perioil of two to four iiHys, twenty·fonr to seventy-two hours after adequate milk secretion had been established. No effect whatsoever was noted upon the amount of milk secretion or upon tile baby's gain in weight (Fig. 2). The effect of testosterone propionate upon painfully engorged breasts bas been reported elsewhere.l Clearly, then, provided the baby continues to nurse, testosterone propionate will neither inhibit the normal onset of adequate lactation nor suppress the normal amount of milk secretion after adequate lactation has once been established. Meth-yl Testo~erone.-For the purpose of investigating the effects of this steroid, 10 patients were divided into 2 groups of 5 each. Beginning soon after parturition, 110
ABARRANEL:
EFFECTS 0!<' TESTOSTERONE PROPIONATE UPON LACTATIO'\
111
250 HillS. TES'l'alTE!lOBE PROI'IOIATE TO TEST J.IO'l'HEl!
--lQ_ __ ll_
DAILY ALI>UJI'T OF lilLY. (ounces)
__s_
__ 7_ \EIG!l'l' OF BAE't' (pounds)
!::=:::
f~T~~~~~I 1
1
2
TEST
CO!ITllOL
1 1 Is 1 1 Is I±I 3
4
6
7
Fig. l.~Failure of 250 mg. of testosterone propionate to inhibit the onset of adequate lactation in the nursing human being. Similar tindings were obtained with either 500 mg. of methyl testosterone or 100 mg. of progesterone, as well as with 500 mg. of pregneninolone.
soo ~~!liS.
0!"
T"'-STOSTEOOJIE PROPIO:IATE TO TEST
I.IOTHER
DAILf AIIOtDIT OF
JIILI: (oUIICesl
. Fig. 2.-Failure of 500 mg. of testosterone propionate to suppress established Jactatlon in the nursing human being, The result illustrated here is similar to that obtained with either 500 mg. of methyl testosterone or 1(}0 mg. of progesterone, a.s well as with 500 mg. of pregneninolone. Essentially similar results were noted with 500 mg. of oral stilbestrol.~ Normal variation ranges from one to seven ounces dally. ·
112
AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY
the first group received from 100 to 500 mg. of methyl testosterone in divided oral doses over a perio.d of one to four days. The babies continued to nurse as usual. The onset of adequate lactation was not inhibited (Fig. 1). In order to observe the effect upon established lactation, the other 5 moth· ers received from 250 to 500 mg. in divided oral doses twenty-four to seventytwo hours after milk secretion had become adequately established. Lactation was not suppressed (Fig. 2). Anhydro-Oxy-Progesterone (Pregneninolcme, Ethinyl Testostercme).-The effect of this steroid upon the initiation of milk secretion was studied in 5 patients. From 100 to 500 mg. were administered orally in divided doses over a period of one to four days, beginning soon after delivery. The onset of lactation was not affected (Fig. 1). The effect upon established milk secretion was then studied. From 250 to 500 mg. were administered orally over a peri.od of one to four days, starting twenty-four to seventy-two hours after adequate lactation had been established. Milk secretion was not interfered with in any way (Fig. 2). Progesterone.-Because of the difficulty in securing large amounts of this steroid, only 4 patients were studied. Two received 100 mg. in sesame oil intramuscularly over a period of three to four days, respectively, beginning soon after delivery. The onset of adequate milk secretion was not delayed (Fig. 1). The other two patients received 100 mg. of progesterone intramuscularly in divided doses twenty-four and seventy-two hours, respectively, after lactation had been adequately established. Milk secretion was not suppressed (Fig. 2). Careful pediatric cheek-up and follow-up of the babies in the test groups failed to reveal any adverse effects. DISCUSSION
The process of lactation resolves itself into two fundamental mechanisms: the initiation of milk secretion which is under hormonal control6 and the maintenance of established lactation which is governed by both hormonal and neurogenic factors. 7 These phenomena must be clearly differentiated from the clinical syndrome of painful engorgement of the breasts. The latter is brought about by lymphatic and vascular stasis, not by distention of the ducts by milk. 8 Failure to differentiate clearly the mechanism by which painful engorgement is brought about from the physiological processes leading to the initiation of milk secretion has led to the confusion apparent in the clinical literature. Although painful engorgement may be associated with the onset of lactation, each is a distinct physiologic entity. Clearly then, the one is not synonymous with the other. In a previous report, it was pointed out that a sufficient daily dose of es~rogen {stilbestrol) would delay the onset of adequate milk secretion in the nursing human being only as long as it was administered. 5 The mechanism of action of stilbestrol was felt to be directly upon the glandular epithelium of the mammary gland, for a cell that is actively proliferating (under the influence of estrogen) cannot secrete at the same time. 9 In other words, the ability of a substance to affect the onset of adequate lactation in the nursing mother seemed to parallel its proliferating influence upon the mammary epithelium. The same conclusion was reached by Folley and Kon 10 in their work on rats. The reason for the failure of the four steroids studied in these experiments (Fig. 1) to affect the onset of adequate milk secretion in the nursing human being becomes apparent from their relatively slight, if any, proliferative effect upon the mammary epithelium. 11 In fact,
ABARBANEL:
EFFECTS OF TESTOSTERONE PROPIONATE UPON LACTATION
113
testosterone greatly stimulates the production by the anterior pituitary of lactogenic principle(s)/ 2 whose release is actively stimulated by the act of suckling. 13 Consequently, the stimulus of a nursing child was more than sufficient to initiate and then maintain adequate lactation. Milk secretion, once established, is controlled by both hormonal and neurogenic factors. 7 The manner in which the nervous stimulus of suckling is essential for the continued secretion of milk is still not clear. 14 Upon the clarification of this point must await the explanation for the reason why not only massive doses of these four steroids, but also of stilbestrol,5 have no effect upon established lactation in the nursing human being (Fig. 2). The mechanism by which painful engorgement of the breasts is relieved by testosterone propionate and methyl testosterone is not as yet known. That it is not by inhibition of lactation is obvious from the results obtained in these studies (Fig. 1). Its fundamental physiology, however, probably involves the ebb and flow of extracellular fluid in some manner. Markee,l 5 for instance, has shown that testosterone will bring about a regression in ocular endometrial transplants as evidenced by a decreased amount of fluid in the stroma and by a lessened vascularity. SUMMARY AND CONCL"CSIONS
1. The effects of relatively large doses of testosterone propionate, methyl testosterone, anhydro-oxy-progesterone and progesterone were studied upon the onset of milk secretion and the maintenance of established lactation in the nursing human being. 2. The onset of adequate milk secretion in the nursing human subject was not affected by: (a) (b) (c) (d)
200 100 100 100
to ilOO to 500 to 500 mg. of
mg. of testosterone propionate in oil given intramuscularly mg. of methyl testosterone orally mg. of anhydro-oxy-progesterone orally progesterone given intramuscularly
3. Established lactation was adequately maintained in the nursing woman, being unaffected by: (a) (b) (c) (d)
250 250 250 100
to 500 to 500 to 500 mg. of
mg. of testostero:tl4l propionate given intramuscularly mg. of methyl testosterone orally mg. of anhydro-oxy-progesterone orally progesterone given intramuscularly
4. The ability of a substance to affect the onset of adequate lactation in the nursing woman seems to parallel its proliferating effect upon the glandular epithelium of the breast. 5. Once lactat,ion is adequately established, however, the stimulus for further milk secretion by the glandular epithelium of the brea..'lt, produced by an actively suckling baby, proved to be far stronger than the stimulus to proliferation of this same mammary epithelium, provided by massive doses of not only the four steroids used in this study, but also of the estrogen, stilbestrol. 6. The mechanism by which relief of painful engorgement of the breasts is brought about by testosterone propionate, as well as by methyl
114
,UmRICAN ,JOURNAI, OF OBS'l'E:'I'RICS ANn GYKI
testosterone, does not depend upon inhibition of lactation but probably involves the shifting tides of extracellular fluid. The author gratefully acknowledges the sincere interest of Drs. Harry Aranow and Milton J. Goodfriend, during the course of these studies. ln addition, the splendid cooneration of the Misses Morgan and Newton, of the Nursing Staff of the Obstetrical Division, is deeply appreciated. Ciba Pharmaceutical Products, Inc., supplied the following steroids: (1) Testosterone propionate under the trade name of Perandren. ( 2) Methyl testosterone under the trade name of Metandren. ( 3) Progesterone under the trade name of Luto-cylin. ( 4) Anhydro-oxy-progesterone. REFERENCES
(1) Abarbanel, A. R,: AM. J, OBST. & GYNEI\ 38: 2-i:l, 1089. (2) K·urzrok, R., and O'Connel, C. P.: Endocrinology 23: 476, 1938. (:-!) Birnberg, C. H., Kwrzrok, L., a~~d Klor, B. J.: AM. J. 0BST. & GYNEe. 39: 109, 1940. ( 4) Si-egler, 8., and Silverstein, L. M.: Ibid. 39: 109, 1940. (5) Abarbanel, A. R., and Goodfriend, Jf. J.: Ibid. 40: 1037, 1940. (6) Nels
THB USE OF TESTOSTERONE PROPIONATE IN THE MANAGEMENT OF PELVIC INFLAMMATORY DISEASE EuGENE T. RusH
SToNE, M.D., NEw YoRK, N.Y.
(From the Department of Gynecology, Hospital for the Rupt·ure(l and Cripple1l)
HAS long been recognized that the menstrual period is a time of ITdanger or flare-up in the course of pelvic inflammatory disease. Most patients with chronic pelvic inflammatory disease suffer from dysmenorrhea and/or menorrhagia. Exacerbations of pelvic inflammatory disease at the time of menstruation are so common that often patients are warned to stay in bed before and during their menses to avoid or lessen the chance of a flare-up. Conversely, few patients who manage to retain their infected tubes until the menopause, require surgery thereafter for the relief of the disease, suggesting that cessation of the menstrual function is beneficial in these patients. The use of testosterone propionate in treating acute and chronic pelvic inflammatory disease was suggested by the ease with which menstruation ean be suppressed by relatively safe doses of androgen. 1 It was hoped that not only could the exacerbations be prevented but~hat inasmuch as there is a natural tendency for large inflammatory masses to regress and even disappear in well-controlled patients, testosterone propionate might prove to be a helpful adjuvant in the management of this disease. Beclere2 employed testosterone propionate for uterine hemorrhages with goon results. Mazer (C.) and Mazer (M)3 used androgen in 38 cases of menstrual disorder, bothmenorrhagia and mt:~trorrl~agia. Greenhill and Freed' advocated the use of testosterone propionate in mastopathies, menorrhagia, and dysmenorrhea. Huff-