Management of sexual dysfunction in postmenopausal breast cancer patients taking adjuvant aromatase inhibitor therapy.

Treatment with aromatase inhibitors for postmenopausal women with breast cancer has been shown to reduce or obviate invasive procedures such as hysteroscopy or curettage associated with tamoxifen-induced endometrial abnormalities. The side effect of upfront aromatase inhibitors, diminished estrogen synthesis, is similar to that seen with the natural events of aging. The consequences often include vasomotor symptoms (hot flushes) and vaginal dryness and atrophy, which in turn may result in cystitis and vaginitis. Not surprisingly, painful intercourse (dyspareunia) and loss of sexual interest (decreased libido) frequently occur as well. Various interventions, both non-hormonal and hormonal, are currently available to manage these problems. The purpose of the present review is to provide the practitioner with a wide array of management options to assist in treating the sexual consequences of aromatase inhibitors. The suggestions in this review are based on recent literature and on the recommendations set forth both by the North American Menopause Association and in the clinical practice guidelines of the Society of Gynaecologists and Obstetricians of Canada. The complexity of female sexual dysfunction necessitates a biopsychosocial approach to assessment and management alike, with interventions ranging from education and lifestyle changes to sexual counselling, pelvic floor therapies, sexual aids, medications, and dietary supplements-all of which have been reported to have a variable, but often successful, effect on symptom amelioration. Although the use of specific hormone replacement-most commonly local estrogen, and less commonly, systemic estrogen with or without an androgen, progesterone, or the additional of an androgen in an estrogenized woman (or a combination)-may be highly effective, the concern remains that in patients with estrogen-dependent breast cancer, including those receiving anti-estrogenic adjuvant therapies, the use of these hormones may be attended with potential risk. Therefore, non-hormonal alternatives should in all cases be initially tried with the expectation that symptomatic relief can often be achieved.First-line therapy for urogenital symptoms, notably vaginal dryness and dyspareunia, should be the non-hormonal group of preparations such as moisturizers and precoital vaginal lubricants. In patients with estrogen-dependent breast cancer (notably those receiving anti-estrogenic adjuvant therapies) and severely symptomatic vaginal atrophy that fails to respond to non-hormonal options, menopausal hormone replacement or prescription vaginal estrogen therapy may considered. Systemic estrogen may be associated with risk and thus is best avoided. Judicious use of hormones may be appropriate in the well-informed patient who gives informed consent, but given the potential risk, these agents should be prescribed only after mutual agreement of the patient and her oncologist.

Ovarian function after autologous bone marrow transplantation.

PURPOSE: To determine the frequency of return of ovarian function after autologous bone marrow transplantation (ABMT), and the major factors that predict recovery. PATIENTS AND METHODS: Records of 200 consecutive women who underwent ABMT at the University of Toronto Autologous Blood and Marrow Program (Toronto, Canada) were reviewed. Seventeen patients met the inclusion criteria, which were (1) alive at the time of evaluation, (2) disease-free at least 18 months after transplantation, (3) age younger than 50 years at transplantation, and (4) premenopausal before transplantation. Recovery of ovarian function was determined by pregnancy or regular menses, with no menopausal symptoms and an estradiol level greater than 20 pmol/L off hormonal therapy. RESULTS: All 17 patients became menopausal immediately after ABMT. Five patients (29%) recovered ovarian function a median of 24 months post-ABMT (range, 6 to 48 months). The median age at transplantation of women with restored ovarian function was 19 years (range, 19 to 28 years) versus 30 years (range, 22 to 48 years) for those who did not regain function. Younger age at transplantation predicted ovarian recovery (P = .03) by means of a log-rank test. Only one of five women who regained ovarian function received total-body irradiation (TBI) compared with five of 12 women who did not. Univariate analysis suggested a trend for TBI to predict a sustained loss of ovarian function (P = .067). The number of regimens of induction or salvage chemotherapy that contained an alkylating agent ranged from none to five and was not predictive (P = .45). CONCLUSION: All women became menopausal after ABMT but 29% recovered ovarian function. Younger age at transplantation predicted return of ovarian function, whereas TBI may have had a negative effect.

Alpha-interferon and pregnancy in a patient with CML.

A 34-year-old woman on interferon for CML for 7 years, experienced problems with conception. Full work-up revealed a short luteal phase and therapy with clomiphene was initiated. Pregnancy occurred and a normal infant was delivered by C-section. The detailed infertility evaluation is described and the impact of interferon therapy on pregnancy is reviewed. Successful pregnancy appears possible in woman taking interferon on a chronic basis.

Pregnancy after BMT: three case reports.

A case of successful pregnancy after BMT in a 24-year-old woman with ALL, conditioned with CY, L-asparaginase, methylprednisolone and total body irradiation (TBI) is reported. A second case of two spontaneously aborted pregnancies in a woman transplanted for ALL at the age of 29 years using CY and TBI conditioning and a third case, this time a successful pregnancy in a woman transplanted for AML at age 27 years using CY and TBI conditioning are also described. There are now 6 successful live births after TBI reports of, versus 16 following regimens in which no TBI is used. This is the first report of a successful pregnancy reported in a female transplanted when older than 25 years using any TBI-containing regimen.

Psychologic distress during the menopausal years in women attending a menopause clinic.

OBJECTIVE: This study measures psychologic distress in women attending a menopause clinic to determine if significant differences exist between peri-menopausal and menopausal women. METHOD: Consecutive women attending a university hospital menopause clinic were administered the Brief Symptom Inventory (BSI) and a study questionnaire to determine menopausal symptoms, menstrual cycle status, and use of hormone replacement therapy (HRT). The BSI results were compared between menopausal and perimenopausal women, and to a normative sample of middle-aged women who were nonpatients. RESULTS: Two hundred and fifty-nine menopause clinic women completed the questionnaire: 113 perimenopausal and 146 menopausal women. There was significantly greater psychologic distress on the BSI among perimenopausal as compared to menopausal women on the global severity index, and each of the anxiety, hostility, somatization, depression, paranoid, and psychoticism subscales. Perimenopausal women met BSI caseness severity criteria significantly more often than did menopausal women on the global severity index, and on the subscales for depression, anxiety, and psychoticism. On the BSI, menopausal women showed results similar to those of a normative sample of nonpatient middle-aged women. CONCLUSIONS: Perimenopausal women attending menopause clinics have significantly higher levels of psychologic distress meeting case severity criteria on the BSI. Further research is warranted to define the subgroups of perimenopausal women who are at increased risk, in the hopes of developing effective interventions.

Role of danazol in relieving the premenstrual syndrome.

Approximately 90% of women experience some symptoms of the premenstrual syndrome (PMS); in up to 40% of cases the symptoms are moderate to severe. The signs and symptoms of PMS usually wax and wane according to a four-phase temporal pattern. Within this overall schema there are a number of PMS subtypes. PMS typically manifests before the age of 30 and rarely resolves spontaneously. While genetic factors may play a role in the development of PMS, other epidemiologic factors do not seem to be involved. Various pathophysiologic mechanisms have been proposed as causing PMS. They are an estrogen/progesterone imbalance, prolactin abnormalities, fluid retention, abnormal production of certain prostaglandins, hypoglycemia, pyridoxine deficiency and shifting levels of endorphins. However, the role of these factors in the etiology of PMS has not been established definitively; thus, treatment remains largely empiric. The author's experience with the use of Danocrine (danazol) on 21 patients with PMS suggests that this synthetic steroid, when used in conjunction with nonpharmacologic treatment options, relieves the symptoms of PMS in up to 85% of patients. Women whose PMS is characterized primarily by mastalgia appear to respond most favorably to treatment; danazol is not recommended for women with primary depression or anxiety symptomatology.

Prevalence of antibody to Chlamydia trachomatis in spontaneous abortion and infertility.

A higher prevalence of Chlamydia trachomatis antibody occurred in 57.6% of women with recurrent abortion, but not in their male partners, compared to 33.7% of normal pregnant women (p less than 0.01) and 44.2% of infertile women (NS). The mean titer for the recurrent abortion group was not significantly elevated, compared to controls. Women with blocked fallopian tubes had the highest prevalence of elevated titers (p less than 0.01) and the highest mean titer (p less than 0.001). Despite multiple testing, no women or men were chlamydia culture-positive. The lack of isolation among patients with antibody could be due to cryptic infection at a site not amenable to culture or to inhibition by secretory IgA. There could also be nonspecific stimulation of chlamydial antibody caused by other infections such as mycoplasma. The presence, though at a low level, of antibody in culture-negative patients suggests chlamydia may not be directly associated with recurrent abortion but reflect previous exposure to chlamydia or an altered immune system.

Natural family planning: an update.

Natural Family Planning (NFP) is defined by the World Health Organization (WHO) as "methods for planning or avoiding pregnancies by observation of the natural signs and symptoms of the fertile and infertile phase of the menstrual cycle. It is implicit in the definition of natural family planning, when used to avoid conception that drugs, devices and surgical procedures are not used, there is abstinence from sexual intercourse during the fertile phase of the menstrual cycle, and the act of intercourse, when it occurs, is complete."(1) The fertile period may be determined by using Rhythm, a calculation based on previous cycles, basal body temperature (BBT) charting alone, mucus secretion alone (Billings or Ovulation method), or symptothermal charting (Serena method), which includes observation of both mucus and BBT. The effectiveness of each method is discussed, and the social and psychological profile of couples who use NFP is reviewed. Nfp methods can be used not only to avoid pregnancy, but also to achieve pregnancy and thus are particularly useful in investigating and treating infertility. The function of the Family Life Clinic at St. Michael's Hospital in Toronto is described.

Gynandroblastoma: its ultrastructure.

Gynandroblastoma is a rare, sex-cord stromal tumor of the ovary that shows morphologic evidence of female and male differentiation. Such a tumor produced masculinization in a 24-year-old woman, whose symptoms disappeared following removal of the tumor. By electron microscopy, the granulosa cell nests displayed Call-Exner (CE) bodies of the hyaline type composed of multiple layers of basal lamina resembling CE bodies of the normal graafian follicle. In contrast, CE bodies of a classic granulosa theca cell tumor were of the spongiform type, consisting of a space limited by a single basal lamina containing altered granulosa cells and cell processes. Both types of CE bodies are believed to arise following secretion by and/or degeneration of granulosa cells, the variation in morphology between the two resulting from differences in amounts of basal lamina deposited. The tubular components of the tumor resembled more closely the rete ovarii than did Sertoli cells, and its proposed that such structures be called by the alternate and less specific term "androblastoma." The identity of Leydig cells was established by demonstrated of intracytoplasmic Reinke crystals. Despite a difference in architectural pattern, there was a close ultrastructural resemblance between the different sex-cord components of the gynandroblastoma.

Comparison of thyroid stimulators and thyroid hormone concentrations in the sera of pregnant women.

To clarify the role of various thyroid stimulators in normal human pregnancy, we measured serum TSH, chorionic TSH (hCT), hCG, bioassayable thyroid-stimulating activity, T4, T3, T3 uptake, free T4 and free T3 indexes, free T4, and free T3 by dialysis in 339 serum samples from pregnant women at various intervals of pregnancy and in 40 normal female controls. Serum T4 and T3 and free T4 and free T3 indexes were significantly elevated throughout pregnancy in comparison with controls. Free T4 concentration was elevated after 10 weeks of pregnancy and free T3 concentration was elevated at 13--20 weeks. Bioassayable thyroid-stimulating activity was elevated from 9--16 weeks when serum hCG concentrations were highest. Serum TSH levels were significantly lower at 9--12 weeks compared with the rest of pregnancy. hCT was detected in only 35% of sera tested; the mean detectable value was 0.60 +/- 0.04 (SE) microU/ml; only 15% of the detectable values exceeded 1 microU/ml. The level of hCG correlated with bioassayable thyroid-stimulating activity (P less than 0.01). The data indicate that hCT is not a significant thyroid stimulator. We propose that hCG, as a weak thyroid stimulator, causes a modest rise in free thyroid hormone levels early in pregnancy which in turn causes a modest reduction in pituitary TSH secretion.

Pituitary gonadotropin response to LHRH in human pregnancy.

The effect of synthetic LHRH on serum levels of FSH, LH, and hCG was determined during early and midgestation. Eight healthy volunteers were studied during the first (8--9 weeks) and second (15--20 weeks) trimesters of pregnancy with 4 patients in each group. Serum samples, obtained before and 15, 30, 45, 90, 120, 150, and 180 minutes after an intravenous bolus of 100 microgram LHRH, were assayed for LH, FSH, and hCG by specific radioimmunoassays. Serum levels of estradiol, progesterone, and 17 alphahydroxyprogesterone were also measured in samples obtained prior to and 3 hours after LHRH injection. The serum levels of LH and FSH were undetectable in all samples, and no increase was observed after administration of LHRH. Levels of chorionic gonadadotropin, estradiol, progesterone, and 17alpha-hydroxyprogesterone did show slight fluctuations, but there was no significant effect from LHRH administration. These results support the concept that pituitary gonadotropic function is markedly suppressed during early human pregnancy.