4 Most Common Problems in Women

Polycystic ovary syndrome in younger women

At what stage do the risk factors for cardiovascular disease become apparent in women with PCOS? The majority of studies that have identified the risk factors of obesity and insulin resistance in women with PCOS have investigated adult populations, commonly including women who have presented to specialist endocrine or reproductive clinics. However, PCOS has been identified in much younger populations, in which women with increasing symptoms of PCOS, were found to be more insulin resistant. These data emphasize the need for long-term prospective studies of young women with PCOS in order to clarify the natural history, and to determine which women will be at risk of diabetes and cardiovascular disease later in life. A study of women with PCOS and a mean age of 39 years followed over a period of 6 years, found that 9% of those with normal glucose tolerance developed impaired glucose tolerance (IGT) and 8% developed noninsulin dependent diabetes (NIDDM). Fiftyfour per cent of women with IGT at the start of the study had NIDDM at follow-up. Not surprisingly, the risks of disease progression were greatest in those who were overweight.

Common Cancer in Women

Endometrial cancer

Endometrial adenocarcinoma is the second most common female genital malignancy but only 4% of cases occur in women less than 40 years of age. The risk of developing endometrial cancer has been shown to be adversely influenced by a number of factors including obesity, long-term use of unopposed estrogens, nulliparity and infertility. Women with endometrial carcinoma have had fewer births compared with controls and it has also been demonstrated that infertility per se gives a relative risk of 2. Hypertension and type 2 diabetes mellitus have long been linked to endometrial cancer, with relative risks of 2.1 and 2.8, respectively—conditions that are now known also to be associated with PCOS. The true risk of endometrial carcinoma in women with PCOS, however, is difficult to ascertain. Endometrial hyperplasia may be a precursor to adenocarcinoma, with cystic glandular hyperplasia progressing in perhaps 0.4% of cases and adenomatous hyperplasia in up to 18% of cases over 2–10 years. Precise estimation of rate of progression is impossible to determine. Some authors have reported conservative management of endometrial adenocarcinoma in women with PCOS with a combination of curettage and high-dose progestogens. The rationale is that cancer of the endometrium often presents at an early stage, is well differentiated, with low risk of metastasis and, therefore, is not perceived as being lifethreatening, whilst poorly differentiated adenocarcinoma in a young woman has a worse prognosis and warrants hysterectomy. In general, however, the literature on women with PCOS and endometrial hyperplasia or adenocarcinoma suggests that this group of patients has a poor prognosis for fertility. This may be because of the factors that predisposed to the endometrial pathology—chronic anovulation combined often with severe obesity—or secondary to the endometrium metrial pathology disrupting potential embryonic implantation. Thus, a more traditional and radical surgical approach (i.e. hysterectomy) is suggested as the safest way to prevent progression of the cancer. Early-stage disease may permit ovarian conservation and the possibility of pregnancy by surrogacy.

Although the degree of risk has not been clearly defined, it is generally accepted that for women with PCOS who experience amenorrhea, or oligomenorrhea, the induction of artificial withdrawal bleeds to prevent endometrial hyperplasia is prudent management. There are no data on the frequency with which women with PCOS should shed their endometrium. It seems prudent to induce a withdrawal bleed either monthly or at least every 3 months, not only to prevent endometrial hyperplasia but also to enable the bleed to be acceptable when it occurs—as progressive endometrial development may lead to a prolonged and heavy bleed when it does occur. For those with oligo-/amenorrhea who do not wish to use cyclical hormone therapy we recommend an ultrasound scan to measure endometrial thickness and morphology every 6–12 months (depending upon menstrual history). An endometrial thickness greater than 10mm in an amenorrheic woman warrants an artificially induced bleed, that should be followed by a repeat ultrasound scan and endometrial biopsy if the endometrium has not been shed.

Another option is to consider a progestogen-releasing intrauterine system, such as the Mirena.

Breast cancer

Obesity, hyperandrogenism, and infertility occur frequently in PCOS, and are features known to be associated with the development of breast cancer. However, studies examining the relationship between PCOS and breast carcinoma have not always identified a significantly increased risk. The study by Coulam and colleagues  calculated a relative risk of 1.5 (95% CI 0.75–2.55) for breast cancer in their group of women with chronic anovulation which was not statistically significant. After stratification by age, however, the relative risk was found to be 3.6 (95% CI 1.2–8.3) in the postmenopausal age group. More recently, Pierpoint and associates  reported a series of 786 women with PCOS in the UK who were traced from hospital records after histological diagnosis of polycystic ovaries between 1930 and 1979. Mortality was assessed from the national registry of deaths and standardized mortality rates (SMR) calculated for patients with PCOS compared with the normal population. The average follow-up period was 30 years. The SMR for all neoplasms was 0.91 (95% CI 0.60–1.32) and for breast cancer 1.48 (95% CI 0.79–2.54). In fact, breast cancer was the leading cause of death in this cohort.

Ovarian cancer

In recent years there has been much debate about the risk of ovarian cancer in women with infertility, particularly in relation to the use of drugs to induce superovulation for assisted conception procedures. Inherently, the risk of ovarian cancer appears to be increased in women who have multiple ovulations—that is those who are nulliparous (possibly because of infertility) with an early menarche and late menopause. Thus, it may be that inducing multiple ovulations in women with infertility will increase their risk—a notion that is by no means proven. Women with PCOS who are oligo-/anovulatory might therefore be expected to be at low risk of developing ovarian cancer if it is lifetime number of ovulations rather than pregnancies that is critical. Ovulation induction to correct anovulatory infertility aims to induce unifollicular ovulation and so, in theory, should raise the risk of a woman with PCOS to that of a normal ovulating woman. The polycystic ovary, however, is notoriously sensitive to stimulation and it is only in recent years, with the development of high-resolution transvaginal ultrasonography, that the rate of unifollicular ovulation has attained acceptable levels.The use of clomiphene citrate and gonadotropin therapy for ovulation induction in the 1960s—1980s resulted in many more multiple ovulations (and indeed multiple pregnancies) than in recent times and might therefore present with an increased rate of ovarian cancer when these women reach their sixties—the age of greatest incidence.

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