The estrogen deficit substantially alters the anabolic-catabolic ratio, and adversely influences metabolic balances. Although the menopause is a physiologic process and represents a period of adjustment to a new milieu interieur, it is a hormonal-deficiency state.

The basic principle of therapy should be not only to assuage symptoms but also to cushion the metabolic insult resulting from the estrogen lack. Homemade psychotherapy, encouragement and sedatives may lessen anxiety, but can never be a substitute for estrogen therapy.

In women with predisposing emotional instability an abrupt decline in ovarian function frequently precipitates violent psychic and somatic reactions. Other women remain completely asymptomatic and may not display inevitable regressive changes for many years.

Corroborative evidence of an estrogen deficit may be found in the regressive changes of the vaginal mucosa. Unfortunately, cytologic changes are not always present because small amounts of estrogens of ovarian, adrenal or extra glandular origin may maintain the vaginal epithelium in a fairly mature state.

The many complaints attributable to the menopausal state may be grouped arbitrarily into three general headings:

Imbalance of the autonomic nervous system, including hot flushes, sexual excesses, sweats, palpitations, spasms and globus hystericus;

Psychogenic disturbances, comprising apprehension, depression, insomnia, nervousness, headaches and frigidity;

Metabolic disorders, manifested by bone demineralization, myalgias and skin and mucous-membrane atrophy.

Of these, vasomotor phenomena are the most common. It appears that the hypothalamus, sensitized by years of endogenous or exogenous estrogens, reacts with heated displeasure when hormonal support is withdrawn.

Far less common, but often disregarded, is senile vaginitis. Genital atrophy, particularly of the vagina, is characterized by marked thinning of the mucosa, loss of glycogen in the epithelial cells and a change in the vaginal flora. Tenderness, pruritus and a leukorrheal discharge that may be blood tinged are usual complaints.

Another frequently overlooked condition is osteoporosis. This disorder, which manifests itself by decrease in stature, kyphosis, pain and crushed vertebras, should not be regarded as solely an agin  g process. A similar degree of demineralization has been observed in much younger women after extirpation of the ovaries. 

Hormonal therapy, increased calcium intake and mobility are presently the treatment of choice.

The many symptoms associated with this period of life may or may not be due to the climacteric. A causal relation should not be assumed because symptoms are alleviated by estrogens. In this category are headaches, atrial tachycardia, depression, frigidity, atrophy of the mucous membranes of the nose and mouth, some of the arthritides, cervical-muscle spasms and various forms of urinary incontinence.

The menopausal woman must be considered physiologic castrate, and replacement therapy should be administered to every one with evidence of an estrogen lack.

First of all, who should be treated? Any woman with signs and symptoms of an estrogen deficiency is a candidate for replacement therapy.

Traditionally, however, estrogen therapy is withheld from women with a history of mammary or uterine cancer. Such restraint is good medical practice but may be motivated by possible legal recourse in the event of recurrence of the malignant process. 

Estrogens and androgens induce salt and water retention, and their use is interdicted in women with cardiac decompensation. Estrogens are contraindicated in women with a recent history of endometriosis. But this objection need not apply if a progestational agent is added to the estrogen therapy.

Secondly, what are the potential hazards? Since ovariectomy often induces temporary remission of breast cancer, some have assumed that estrogens not only exacerbate but also may initiate its growth. However, it has been shown that estrogens are sometimes capable of inducing regressions in breast cancer, particularly in postmenopausal women.

Statistics provided by the United States Public Health Service, and the Commonwealth of Massachusetts, reveal that the death rate from carcinoma of the breast has not materially increased in the past thirty years. Indeed, Shumkin has documented the fact that this type of cancer has maintained a relatively stable incidence rate despite introduction of estrogen into medical practice.

It appears more judicious to use cyclic estrogen therapy since the relevance of uninterrupted estrogen administration to endometrial cancer remains obscure.

No increase in the incidence of cervical carcinoma was observed in a large series of women with metastatic breast carcinoma treated with estrogens. Moreover, Pincus and Garcia believe that the use of estrogen-progesterone therapy as an orally administered contraceptive not only does not contribute in any way to the occurrence of cervical cancer but actually affords a protective action.

One of the frequent sequels of estrogen therapy is uterine bleeding. The patient should be forewarned that with cyclic estrogen administration a withdrawal period may occur. When the flow is normal it can be regarded as a simple estrogen-withdrawal bleeding.

An endometrial biopsy should be obtained, preferably as an office procedure, and then a medical curettage immediately undertaken. To accomplish this, a potent oral progestational agent is given for five to ten days. Bleeding is usually arrested within twenty-four to forty-eight hours; a withdrawal bleeding period of four or five days' duration will occur forty-eight to seventy-two hours after termination of the course of therapy. This is known as "medical curettage."

If the histologic report suggests doubt about underlying disease, or if the response to medical curettage is less than satisfactory, a surgical curettage becomes mandatory.

Pelvic congestion is occasionally an annoying accompaniment of estrogen therapy. To avoid this, dosage can be reduced, with longer intervals between treatments. Edema and weight gain are also frequent complaints. For these patients diet and salt restriction are helpful. On rare occasions increased sexual desire is experienced. Tranquilizers may be used to dampen the sexual urge.

For the discomfort of breast turgidity and mastodynia, progestational agents, androgens or diuretics often prove valuable. 

Thirdly, is estrogen a deterrent in the development of ischemic heart disease and atherosclerosis? Studies in this country and abroad have shown that the relative-incidence of coronary heart disease is fifteen to twenty times greater in men than in women under the age of forty, but after the menopause the gap closes rapidly. Furthermore, the incidence of ischemic heart disease is greatly increased in women whose ovaries have been removed. Such evidence serves to bolster the arguments favouring prophylacticestrogen therapy even though the patient is not troubled by hot flushes and other menopausal complaints.

Lastly, until what age should hormonal therapy be administered? Although several proponents of hormonal therapy believe treatment should be continued indefinitely, others believe that an arbitrary time should be set at fifty to fifty-five years of age. However, the ravages of hormonal depletion such as osteoporosis, skin and mucous-membrane changes and cardiovascular disease may not make their presence known for several years. With increasing longevity this arbitrary figure may have to be set at a higher level, for today the average woman is expected to reach her three-score years and ten.

Treatment is greatly simplified for women who have undergone hysterectomy and the percentage of such women is high. When orally administered medication is ineffective or undependable, or treatment by injections is erratic, implantation of 1 or 2 25-mg. pellets of estradiol and 1 75-mg. pellet of testosterone, at intervals of six to eight months, has proved a method of therapy satisfactory to patient and physician alike.

The difficulties of the menopause - the imbalance of the autonomic nervous system, the psychogenic disorders and the metabolic disturbances - continue, from mild to severe form, until the end of life. It is unrealistic to withhold measures that may make the transition smoother or prevent disabling pathologic processes.