Postmenopausal testosterone therapy and breast cancer risk

Background: Testosterone therapy is being increasingly used in the management of postmenopausal women. However, as clinical trials have demonstrated a significantly increased risk of breast cancer with oral combined estrogen–progestin therapy, there is a need to ascertain the risk of including testosterone in such regimens. Objective: Evaluation of experimental and epidemiological studies pertaining to the role of testosterone in breast cancer. Design: Literature review. Setting: The Jean Hailes Foundation, Research Unit. Main Outcome Measures: Mammary epithelial proliferation, apoptosis and breast cancer. Results: In experimental studies, testosterone action is anti-proliferative and pro-apoptotic, and mediated via the AR, despite the potential for testosterone to be aromatized to estrogen. Animal studies suggest that testosterone may serve as a natural, endogenous protector of the breast and limit mitogenic and cancer promoting effects of estrogen on mammary epithelium. In premenopausal women, elevated testosterone is not associated with greater breast cancer risk. The risk of breast cancer is also not increased in women with polycystic ovary syndrome who have chronic estrogen exposure and androgen excess. However, in postmenopausal women, who are oestrogen deplete and have increased adipose aromatase activity, higher testosterone has been associated with greater breast cancer risk. Conclusion: Available data indicate the inclusion of testosterone in estrogen–progestin regimens has the potential to ameliorate the stimulating effects of hormones on the breast. However, testosterone therapy alone cannot be recommended for estrogen deplete women because of the potential risk of enhanced aromatisation to estrogen in this setting.     

Multiple Regression Analysis of Predictors of Bone Scintigraphy Positivity in Patients with Head and Neck Cancers

Purpose

The value of bone scintigraphy (BS) in patients with head and neck cancers (HNCs) has been questioned, with conflicting findings regarding positivity yield with some reports recommending BS be omitted from work-up of HNC patients since it rarely yields positive results. This study aims to determine the positivity yield of BS in HNCs and to determine predictors for BS positivity to help tailor appropriate BS utilization.

Methods

BS studies of HNC patients were reviewed, the positivity yield was determined. Clinical predictors for BS positivity including age, sex, site of cancer, staging, histological grading were analyzed using univariable and multivariable logistic regression.

Results

Among the 259 BS studies included, 35 (13.5%), 194 (74.9%), and 30 (11.6%) were positive, negative, and equivocal for bone metastasis, respectively. After exclusion of equivocal cases, 229 were analyzed in the regression models. Independent predictors of BS positivity include site of tumor at the nasopharynx (OR 4.37, 95% C.I. 1.04–18.41, p = 0.044), age less than 45 years (OR 3.01, 95% C.I. 1.24–7.33, p = 0.015), and presence of distant metastasis to other organs (OR 3.84, 95% C.I. 1.19–12.43, p = 0.025).

Conclusions

In contrast to several studies, bone metastasis as detected by BS was found in a relatively high proportion of patients with HNCs. Independent predictors of BS positivity include the age of less than 45 years, tumor site at the nasopharynx, and the presence of extraskeletal distant metastasis. BS could be useful in patients with these characteristics which enhance the pretest probability of bone metastasis.

     

Value of SPECT/CT in Diagnostic I-131 MIBG Scintigraphy in Patients with Neuroblastoma

Purpose

Diagnostic I-131 MIBG scintigraphy is an important imaging modality for evaluation of patients with neuroblastoma (NB) especially in centers where I-123 MIBG is not available. Single photon emission computed tomography/computed tomography (SPECT/CT) could potentially improve lesion detection over planar scintigraphy, but studies regarding its usefulness as an add-on to diagnostic I-131 MIBG scintigraphy are limited. This study aimed to determine the usefulness and factors related to usefulness of SPECT/CT in diagnostic I-131 MIBG scintigraphy in NB patients.

Methods

Usefulness of SPECT/CT for lesion detection, lesion localization, resolving suspicious findings, and clarifying the nature of lesions on anatomical imaging were retrospectively reviewed in 86 diagnostic planar I-131 MIBG scintigrams with add-on SPECT/CT.

Results

SPECT/CT detected additional lesions in 23.2%(20/86), helped localize lesions in 21.1%(8/38), resolved suspicious findings in 85.7%(6/7), determined functional status of lesions on anatomical imaging in 94.4%(17/18), and changed diagnosis from a negative to a positive study in 19.5%(8/41). Independent predictors of SPECT/CT being useful included presence of suspicious findings on planar imaging (OR 99.08; 95% C.I. 6.99–1404.41; p?=?0.001), positive findings on planar imaging (OR 4.61; 95% C.I. 1.05, 20.28; p?<?0.001), and presence of structural lesions on anatomical imaging (OR 32.54; 95% C.I. 5.37–196.96; p?<?0.001).

Conclusion

SPECT/CT is a useful add-on to diagnostic planar I-131 MIBG scintigraphy. Predictors of usefulness of SPECT/CT include suspicious or positive findings on planar scintigraphy and the presence of structural lesions on anatomical imaging.

     

Preoperative and postoperative agreement of histopathological findings in cases of endometrial hyperplasia.

Objective: To determine agreement of preoperative and postoperative histopathology of endometrial hyperplasia (EH). Materials and Methods: Histopathology of specimens obtained by curettage and hysterectomy within 1 year was retrospectively compared by a skilled gynecological pathologist. Patients who received hormone therapy were excluded. Results: Of 79 women with a preoperative diagnosis of EH, only 32 were diagnosed as EH from hysterectomy specimens. There was no endometrial cancer. The agreement between preoperative and postoperative histology did not achieve statistical significance (Kappa 0.011). Postoperative histopathology was more severe than preoperative diagnosis in 5 (6.3%) patients, including 3 preoperative diagnoses of simple hyperplasia without atypia, 1 simple hyperplasia with atypia, and 1 complex hyperplasia without atypia. Conclusions: For EH diagnosed by curettage, we can be sure of the diagnosis. However, 6.3% had more severe histology from hysterectomy specimens. Thus, repeated curettage or other investigations should be reconsidered in women with recurrent bleeding.     

Androgen and menopause

PURPOSE OF REVIEW: Androgen therapy is being increasingly used in the management of postmenopausal women. The most common indication is to improve sexual function. The aim of this review is to evaluate current knowledge pertaining to testosterone and sexual function in postmenopausal women. RECENT FINDINGS: The change of testosterone levels during the menopause transition remains controversial. A correlation of endogenous testosterone levels and sexual function is still inconclusive. A Cochrane Review and recent randomized control trials have, however, consistently demonstrated that short-term testosterone therapy in combination with traditional hormone therapy regimens improves sexual function in postmenopausal women, particularly surgically menopausal women with hypoactive sexual desire disorder. An adverse effect on the lipid profile has been identified which appears to be mostly associated with oral methyltestosterone. Data for other effects of testosterone and long-terms risks are lacking. Testosterone may act in a variety of ways in different tissues. This is, however, an area that requires further investigation. SUMMARY: Testosterone therapy is a promising option for treating women with hypoactive sexual desire disorder after surgical menopause. Two remaining questions need to be answer: who is most likely to benefit from testosterone therapy and what are the long-term health risks?     

Testosterone therapy for postmenopausal women: efficacy and safety

The treatment of postmenopausal women with a variety of androgen formulations is increasing, despite the lack of clear guidelines regarding the diagnosis of androgen insufficiency. This review summarizes evidence on the efficacy and safety of adding testosterone to hormone therapy in postmenopausal women. Fair to good evidence exists that the use of testosterone in combination with hormone therapy has both benefits and risks. The benefits are an improvement in sexual function with various regimens of testosterone use (good evidence), an improved sense of well-being with transdermal testosterone (fair evidence), and a reduction in triglyceride levels with methyl testosterone (fair evidence). The most consistent risk is a reduction in high-density lipoprotein (HDL) cholesterol, particularly with methyl testosterone (good evidence). There has been insufficient reporting of other side effects; hence, testosterone therapy should be used with caution. The use of testosterone may be justified in specific clinical circumstances and should be limited to short-term use; long-term studies are not available. Close surveillance for HDL cholesterol and other side effects is necessary.     

Discrimination of the Thai rejuvenating herbs Pueraria candollei (White Kwao Khruea), Butea superba (Red Kwao Khruea), and Mucuna collettii (Black Kwao Khruea) using PCR-RFLP

The tuberous roots of Pueraria candollei (White Kwao Khruea), Butea superba (Red Kwao Khruea) and Mucuna collettii (Black Kwao Khruea), which belong to the family Leguminosae, are used as rejuvenating herbs in traditional Thai medicine. Although all of these species have an indication for rejuvenation, each differs in its medicinal properties. Two varieties of P. candollei, var. mirifica and var. candollei, affect females, whereas B. superba and M. collettii exhibit effects on males. However, the identification of these roots according to the name “Kwao Khruea” is confusing due to the similarity in their features. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was utilised to identify plant origin. The partial matK gene was amplified and subjected to restriction enzyme digestion with DdeI and TaqI. The restriction fragments generated differed in number and size. To test the reliability of the method, an admixture of the different Kwao Khruea species containing equal amounts of DNA was tested. The results showed combined restriction patterns, and each species could be detected in the background of the others. The method was also used to authenticate eight different crude drugs sold as various types of Kwao Khruea in Thai markets. The results showed that the misidentification of commercial drugs remains a problem in crude drug markets. The PCR-RFLP analysis developed here provides a simple and accurate discrimination of these rejuvenating “Kwao Khruea” species.     

Recurrent ovarian endometrioma after conservative surgery:A retrospective study

Objective:To study the prevalence and associated factors of recurrent ovarian endometrioma after ovarian cystectomy.Methods:This retrospective study analyzed 303 patients who underwent cystectomy for ovarian endometrioma and had at least a 2-year follow-up at Srinagarind Hospital from January 2013 to December 2018.The patients were divided into the recurrent and nonrecurrent groups according to the findings from postoperative transvaginal ultrasonography 6 months after undergoing surgery.Nineteen factors were collected for risk evaluation.The prevalence of recurrent ovarian endometrioma and its 95%confident interval(CI)were calculated.Univariate and multivariable logistic regression analyses were performed to determine the association between factors and recurrence.Results:Recurrent ovarian endometrioma occurred in 33%(95%CI 27.7%-38.3%)patients.The median duration of followup was 36 months.during the median follow-up period of 36 months.Preoperative history of parity,preoperative infertility history,endometriosis surgery,moderate to severe dysmenorrhea,dyspareunia,intraoperative stage 4 according to revised American Society for Reproductive Medicine classification,presence of adenomyosis,and postoperative pain relief were associated factors based on univariate analysis.In contrast,infertility[odds ratio(OR)2.22,95%CI 1.14-4.33],moderate to severe dysmenorrhea(OR 2.13,95%CI 1.09-4.15),and postoperative pelvic pain relief(OR 0.22,95%CI 0.12-0.42)were independently associated factors based on multivariable logistic regression analysis.Conclusions:In our setting,preoperative infertility history and moderate to severe dysmenorrhea were associated with a higher recurrent ovarian endometrioma risk.In contrast,postoperative pain relief was significantly associated with lower recurrence risk.     

Testosterone effects on the breast: implications for testosterone therapy for women

Androgens have important physiological effects in women. Postmenopausal androgen replacement, most commonly as testosterone therapy, is becoming increasingly widespread. This is despite the lack of clear guidelines regarding the diagnosis of androgen insufficiency, optimal therapeutic doses, and long-term safety data. With respect to the breast specifically, there is the potential for exogenous testosterone to exert either androgenic or indirect estrogenic actions, with the latter potentially increasing breast cancer risk. In experimental studies, androgens exhibit growth-inhibitory and apoptotic effects in some, but not all, breast cancer cell lines. Differing effects between cell lines appear to be due primarily to variations in concentrations of specific coregulatory proteins at the receptor level. In rodent breast cancer models, androgen action is antiproliferative and proapoptotic, and is mediated via the androgen receptor, despite the potential for testosterone and dehydroepiandrosterone to be aromatized to estrogen. The results from studies in rhesus monkeys suggest that testosterone may serve as a natural endogenous protector of the breast and limit mitogenic and cancer-promoting effects of estrogen on mammary epithelium. Epidemiological studies have significant methodological limitations and provide inconclusive results. The strongest data for exogenous testosterone therapy comes from primate studies. Based on such simulations, inclusion of testosterone in postmenopausal estrogen-progestin regimens has the potential to ameliorate the stimulating effects of combined estrogen-progestin on the breast. Research addressing this is warranted; however, the number of women that would be required for an adequately powered randomized controlled trial renders such a study unlikely.