Interaction of medical diseases and female physiology

Pulmonary disease

Asthma is more common in boys up until puberty. After puberty, the ratio reverses with women more at risk for asthma until menopause. Asthma is one of several major diseases in which the severity of symptoms is increased around the time of menses ( Box 8.1 ). Premenstrual asthma is well described, affecting up to 40% of reproductive-age women who have asthma, with symptoms including increasing cough, wheezing, and shortness of breath. Up to 50% of hospitalizations for women with asthma in their 20s occur around the time of menses. Women with premenstrual asthma have been shown to have a measurable decline in respiratory function with the end of the menstrual cycle ( ). Data suggest that combination oral contraceptive pills (cOCPs) may blunt this effect and mildly decrease the severity of the asthma ( ). The variability of symptoms between cycles may be caused by the hormonal fluctuations from one cycle to the next.

Hormones can affect asthmatic symptoms through several mechanisms. One theory is that the increased symptomology is related to the estrogen- and progesterone-mediated increase in both serotonin and histamine release from granulocytes and mast cells ( ). Estrogen also increases eosinophilic adhesion to the bronchial lining. In addition, progesterone induces degranulation of eosinophils. Interestingly, both estrogen and progesterone also have antiinflammatory properties, and it may be that the withdrawal of estrogen and progesterone at the end of the cycle contributes to a fluctuation in prostaglandin levels that leads to increased bronchial reactivity and premenstrual asthma.

Regarding the effects of asthma on female physiology, a few small series have noted an increased incidence of abnormal menstrual cycles in women with severe asthma ( ). Whether this is due to glucocorticoid medications or whether this is a direct effect from severe pulmonary disease on the hypothalamus is unclear. It should be noted that multiple studies have found that women with early menarche have twice the risk of asthma in early adulthood ( ). Women who are taking inhaled glucocorticoids may be at increased risk for osteopenia and osteoporosis ( ). Clinicians who care for women with asthma beyond their third decade should obtain vitamin D levels and council the women about adequate calcium intake. There are conflicting reports about the effect of menopause and hormone replacement therapy on asthma symptoms and severity; some have noted an improvement in symptoms, whereas others have noted a worsening ( ; ). Increasing evidence exists to suggest that there may be a perimenopausal/menopausal phenotype of new-onset asthma characterized by neutrophilic airway inflammation and high frequency of severe exacerbations ( ). Other data suggest that independent of asthma onset, asthma exacerbation after menopause tends to be more severe ( ). Given these data, clinicians must be wary of any asthma in a perimenopausal or menopausal patient.

It is now common for women with cystic fibrosis (CF) to reach reproductive age. Tsang and colleagues, in a review of reproductive problems, noted that women with cystic fibrosis tend to have shorter stature, delayed puberty with delayed growth spurts, and delayed menarche ( ). The degree of delay is related to the severity of the disease. Additionally, because of the effects of estradiol on mucin production, periods of the menstrual cycle with high estradiol levels are associated with worse lung function ( ). Girls with cystic fibrosis tend to be as sexually active as their peers; however, they tend to have less counseling regarding contraception than their peers. Estrogen-based contraceptives are acceptable for women with cystic fibrosis as long as they do not have pulmonary hypertension, active liver disease, or a history of thromboembolism ( ). Long-acting reversible contraception (LARC), including the progesterone intrauterine devices (IUDs) and progesterone implants, are also a safe, effective, and practical option for these young women. Issues of sexuality may be problematic for young women with severe cystic fibrosis because of poor body image secondary to chronic disease, infections, and gastrointestinal disturbances from pancreatic problems, as well as enlarged rib cages from chronic hyperventilation in some patients. Thus counseling on sexuality should occur in conjunction with contraceptive counseling.

There is an emerging body of evidence suggesting that fertility is affected in women with cystic fibrosis. Cervical mucus is thicker in women with cystic fibrosis, which may lead to altered fertility. Oligomenorrhea, amenorrhea, and ovulatory dysfunction are increased in women with cystic fibrosis proportionally to the severity of disease. Finally, alterations in uterine levels of bicarbonate, which affects sperm capacitation, also affect fertility in women with cystic fibrosis ( ). Though a full discussion of the management of subfertility and infertility treatment options is beyond the scope of this chapter, intrauterine insemination, intracytoplasmic sperm injection, and in vitro fertilization have all been successfully performed in women with CF.