Kupperman, H. S.: Clinical management of the climacteric syndrome. In: Human endocrinology, vol. II, p. 426 (Davis, Philadelphia 1963).
“ESTROGENS AND ANDROGENS. When androgens, in the form of methyl testosterone, were added to the estrogens, physical vigor and joie de vivre became noticeable. Dull personalities seemed to become a bit less so. Occasionally, patients who had been seen for some time modestly whispered about an increase in libido. There were some, however, who did complain of distinct, bothersome clitoral irritation.
The apparent synergism of combined estrogen - androgen therapy permitted us to use smaller doses of each steroid, yet still maintain an equal or greater effect than was accomplished with larger doses of either preparation alone. Vaginal bleeding did not occur. We were constantly alert for masculinizing effects, but there was no evidence of arrhenomimetic phenomena of significance with the doses of methyltestosterone that were employed.
The general degree of improvement in a patient's well being attributable to androgen therapy had a decided effect in ameliorating her anxieties and nervousness which originally were major complaints. Estrogen therapy alone did not seem to be so all - inclusive in effect. The physiologic explanation of the clinical success attributed to the combined steroid medication is perhaps closely related to the enhanced protein anabolism and the maintenance of nitrogen and phosphorus balance that such therapy induced. Osteoporosis of the menopause may thus be better controlled. Although the site of the specific effect of testosterone is unknown, the modus operandi of the estrogens may be ascribed to improved cell permeability. It is reasoned then that, with the basic anabolic property of testosterone and the resultant protein storage, the enhanced cellular activity produced by estrogen increases the potential of the protein anabolic effect of the androgen. The overall effect of estrogen androgen combination is to prevent the depletion of body protein substances as age increases. While beyond the scope of this chapter, one must also give serious consideration to long - range steroid therapy in geriatrics, as proposed by Masters. 19 In his hands this regimen effectively influenced 75 per cent of the geriatric persons treated, with notable physical and psychological improvement. We are entirely in accord with Masters ' concepts and have confirmed his observations. In addition, it has been noted that such long - continued therapy is not only beneficial from the physical and mental point of view, but also appears to be with out danger as far as neoplastic tendencies are concerned. 30
Advantages of Estrogen - Androgen Medication. It should be mentioned that, in the combined use of estrogens and androgens, we do not mean to imply that estrogens can neutralize the undesirable effects of androgens and vice versa. The advantage of their combined use lies in the fact that smaller doses of each one may be administered, so that undesirable side effects due to either steroid are minimized. On the other hand, the combination of the two steroids results in a synergistic effect, approaching the effectiveness of either one alone when administered in higher doses. In other words, if a patient would bleed when 0.05 mg of ethinyl estradiol per day was administered, we could not prevent that bleeding by the addition of 10.0 mg of methyltestosterone. Similarly, if 10.0 mg of methyltestosterone will produce facial hirsutism in a particularly sensitive patient, we cannot inhibit the iatrogenic hypertrichosis with a dose of 0.05 mg. of ethinyl estradiol. However, one can diminish the dose of ethinyl estradiol to 0.02 mg. and administer 5.0 mg. of methyl testosterone simultaneously and achieve a therapeutic effect comparable to that obtained with either 0.05 mg of ethinyl estradiol or 10.0 mg of methyltestosterone alone. In so doing, one diminishes the bleeding propensity which was observed when the 0.05 mg dose of ethinyl estradiol was employed or the hirsutism noted with the 10.0 mg dose of methyl testosterone. An interesting possible advantage of therapy with combined estrogens and androgens is that the estrogens at times may promote fluid accumulation and induce increased nervousness, anxiety, and irritability in certain menopausal patients. The value of estrogens and androgens in these patients would be that the tendency for estrogens to produce enhanced nervousness and retention of fluid is diminished with a smaller dose of estrogens, but the clinical efficacy is maintained by the addition of androgens without diminishing the desired clinical effect.”
“The addition of testosterone pellets to the estrogen was distinctly advantageous in offering the patient a general sense of well being. While the estrogen alone produced a well - controlled and satisfied patient, the combination of androgen and estrogen pellets gave a more effective response; improved spirits were readily apparent, as well as enhanced libido, an important factor in maintaining normal marital relationships. In these cases, we were careful to note any evidence of excessive hair growth.”
The Journal of Clinical Endocrinology & Metabolism, Volume 1, Issue 2, 1 February 1941, Pages 162–179, https://doi.org/10.1210/jcem-1-2-162“the therapeutic effectiveness of testosterone propionate is distinctly inferior to that of the estrogens. And the reason for this is that, in the vast majority of menopausal patients, most of the symptoms are caused by an estrogen deficiency. And, whereas, testosterone propionate may exhibit estromimetic activity, this property becomes manifest only if the hormone is administered in highly concentrated doses for prolonged periods of time. The estrogenic effectiveness of testosterone propionate (as estimated by vaginal smear reactions in estrogen-deficient women) is, per unit of weight, considerably less than 1/1000 that of a-estradiol. Administering testosterone propionate in order to produce the therapeutic effect of estrogens is, therefore, an exceedingly impractical and expensive form of therapy. Obviously the estromimetic action of testosterone propionate is chiefly a matter of academic interest and has little, if any, utility in the practical therapy of the menopause.”
“In the normal, sexually mature woman, gynecogens and androgens are conceived as being in a state of dynamic balance, giving rise to the normal female secondary sex characteristics and normal menstruation. The equilibrium may, however, be upset in one direction or the other. If the gynecogens become dominant, either as a result of a qualitative or quantitative deficiency in androgens, or because of an excessive production of gynecogens, the resulting imbalance would be manifested clinically by menorrhagia, metrorrhagia, pre-menstrual tension, mastopathies and dysmenorrhea, separately or in various combinations. If, on the other hand, the androgen influence were to predominate, the clinical picture would consist of oligomenorrhea or amenorrhea and arrhenomimetic phenomena. It is obvious that in such a dynamic system similar biologic and clinical effects would result from an excess of the one as from a deficiency of the opposing factor. It is tempting to accept this theory of a dynamic gynecogen-androgen balance since it appears, at present, to offer a solution to the riddle of functional gynecologic disorders.”
Endocrine Treatment in General Practice. New York. (1953). Springer Publishing Co., lnc., 1953, pp. 158, 202, 350.“As a general rule, those climacteric women who have a predominance of tiredness and muscular weakness need testosterone, and those with the purely vasomotor symptoms do best on estrogen alone.”
“Administration of estrogens alone does not always accomplish all the desired effects in the true menopausal syndrome, particularly the desired improvement of mood. Depressions respond almost specifically to androgens such as methyl testosterone.”
“In addition, the androgen has a distinct "tonic" effect in that it tends to improve muscular strength, appetite, and mental outlook.”
Endocrine Therapy in Gynecologic Disorders, Postgraduate Medicine, 14:5, 410-424, DOI: 10.1080/00325481.1953.11711488“It has been suggested that the combined therapy of estrogen and androgen is more advantageous in controlling the osteoporosis of the climacteric.19 20 Testosterone will augment the protein anabolic effect of estrogens. Also, the addition of testosterone will many times enhance libido when estrogen may fail to do this by itself. Androgens in the doses employed may have a greater ameliorating effect than estrogens alone on the anxiety state and increased nervousness noted in many climacteric patients.”
Greenblatt, R. B., Teran, A.-Z., Barfield, W. E., & Bohler, C. S. (1987). Premenstrual syndrome: What it is and what it is not. Stress Medicine, 3(3), 193–198. https://doi.org/10.1002/smi.2460030219“in women whose principal complaints were loss of libido, lack of energy and headaches we often implanted one or two pellets of testosterone (75 mg each)”
