Introduction

The Natural Pcos Diet

Natural Polycystic Ovary Syndrome Treatment System

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Several strategies may be considered in the treatment of hirsutism. They comprise cosmetic procedures and drugs, administered either topically or systemically. In many hirsute subjects, cosmetic procedures may work well. However, in most cases, especially in more hyperandrogenic subjects, all these procedures may fail to achieve satisfactory control of hirsutism. In these cases, drugs are an indispensable addition to correct the underlying causative factor.

The aim of pharmacological treatment is to lower circulating free androgen levels and/or block peripheral androgen action (Fig. 1). Overall, suppression of androgen secretion alone has limited effect on established hirsutism. The most reliable medical therapy in these women is antiandrogen drugs. Alternatively, these drugs are only partially effective on terminalized hairs. Removal of unwanted hairs is generally required in women with established hirsutism. Thus, treatment of hirsutism is often based on a dual approach, pharmacological therapy of hyperandrogenism, and removal of terminal hairs already present (1).

It is noteworthy that there are few licensed drugs for the treatment of hyperandrogenism. In fact, there is only the topical drug eflornithine—licensed for facial hirsutism—or estrogen-progestogen combinations. Oral contraceptives are widely used for this purpose, but their efficacy appears limited.

Spironolactone and cyproterone acetate are the antiandrogen drugs most commonly used in women with hirsutism. These compounds are not pure antiandrogens, as they interact with other steroid receptors and frequently show troublesome side effects. Other drugs, such as flutamide and finasteride, have been assessed in the treatment of this condition, but experience is still limited. It should be borne in mind that the use of any antiandrogens implies the need to avoid a pregnancy, given the potential risk of feminization of male fetuses. For this reason and for potential synergic effects of combined therapy, antiandrogens are often administered in combination with nonandrogenic oral contraceptives.

Fig 1. Sequence of steps between androgen synthesis in endocrine glands and androgen action in the peripheral tissues. Each of these steps is a potential target for the treatment of hyperandrogenic women. DHEAS, dehydroepiandrosterone sulfate; DHT, dihydrotestosterone; LH, luteinizing hormone; ACTH, adrenocortico-tropic hormone; SHBG, sex hormone-binding globulin.

Fig 1. Sequence of steps between androgen synthesis in endocrine glands and androgen action in the peripheral tissues. Each of these steps is a potential target for the treatment of hyperandrogenic women. DHEAS, dehydroepiandrosterone sulfate; DHT, dihydrotestosterone; LH, luteinizing hormone; ACTH, adrenocortico-tropic hormone; SHBG, sex hormone-binding globulin.

Hirsutism treatment is symptomatic. There is a latency of some months in the appearance of clinical effects of drugs, which can take more than 1 year of therapy before the full benefits are observed. In addition, in general, hair growth resumes after treatment is stopped, especially in more hyperandrogenic subjects. Therefore, therapy should be maintained indefinitely, or at least for long periods.

The risk of teratogenicity in case of pregnancy is the main reason that pharmaceutical companies are not willing to fund trials to evaluate the efficacy of antihirsutism treatments. In turn, this may explain why few large-scale, prolonged clinical trials have assessed the use of antiandrogen drugs in women with hirsutism. Indeed, the large majority of studies concerning hirsutism treatment demonstrate considerable shortcomings, including lack of control group, assessment of results only by subjective methods, or too short a duration of therapy relative to the physiology of hair growth (2). These limitations make it difficult to establish relative efficacy of antiandrogen drugs.

Apart from contraceptive pills, reduction of ovarian androgen secretion may be efficaciously obtained by using gonadotropin-releasing hormone analogs (3). However, these drugs also markedly reduce estrogen secretion, causing estrogen deficiency-related symptoms and, in particular, appreciable loss of bone mass. Concomitant estrogen replacement has been proposed to avoid this inconvenience. However, side effects and the cost of these drugs limit their use to highly selected cases.

Increased secretion of adrenal androgens may be observed in congenital adrenal hyperplasia, Cushing's syndrome, and the rare androgen-secreting adrenal tumors. In addition, adrenal hyperandrogenemia may be seen in many subjects with polycystic ovary syndrome (PCOS), as well as in several women with hirsutism not easily classified into a definite diagnosis. Glucocorticoids may be helpful in reducing adrenal secretion. However, adrenal androgen suppression has very limited effects on hirsutism, and titration of glucocorticoids is not easy. Thus, this treatment should be limited to women with congenital adrenal hyperplasia.

Ketokonazole is an antifungal drug that inhibits steroidogenesis. It may attenuate both ovarian and adrenal hyperandrogenism, and some studies reported significant improvement in hirsutism during treatment (4). However, this drug also impairs cortisol secretion, and dose-dependent liver toxicity is common. Overall, this drug is indicated for hirsutism therapy only in subjects with Cushing's syndrome.

A limited number of centers have been using laparoscopic ovarian drilling—the modern evolution of wedge resection—for reproductive goals in patients with PCOS (see Chapter 37). This method induces transient suppression of ovarian androgens. However, evidence of efficacy on hair growth is very limited. As such, improvement in hair growth should not be considered a primary outcome when using this surgical procedure.

Another novel method to attenuate hyperandrogenism in patients with PCOS is through reduction in plasma insulin levels, because insulin resistance and the associated hyperinsulinemia commonly found in these women may contribute to their androgen excess (5). Lifestyle changes and insulin-sensitizing drugs consistently lower androgen levels in PCOS patients. Limited evidence suggests that these procedures may, to some extent, improve hirsutism. Reduction in insulin levels may also be obtained through drugs that block insulin secretion, such as somatostatin. This treatment may also act through its effects on the growth hormone/insulin-like growth factor system. Preliminary data have demonstrated an improvement in the hirsutism score in patients with PCOS treated with long-acting derivatives of somatostatin (6).

At present, several of these pharmacological options are of experimental interest. Only estrogen-progestogen combinations, eflornithine, antiandrogens, finasteride, and metformin are generally used in clinical practice. Therefore, only these drugs will be discussed here. Table 1 summarizes the main characteristics of peripheral-acting drugs.

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