Risk of sexual dysfunction with progestin-based contraceptives in women of child-bearing age.

PURPOSE: To examine whether there is a positive association between sexual dysfunction (SD) and different types of progestin-based contraceptives. METHODS: Nested case-control study in women of child-bearing age (15-45 years) from the IQVIA® Ambulatory electronic medical record database from 2008 to 2018. Cases defined by diagnosis of sexual dysfunction identified by international classification for disease clinical modification code 9th and 10th. Each case was matched to four controls and rates of prescriptions of the following were compared: levonorgestrel intra-uterine device (IUD), progestin, and ethinyl estradiol (EE) combined oral contraceptive (COC) formulations including levonorgestrel, norgestimate, drospirenone, desogestrel, norethindrone, and norgestrel; etonogestrel vaginal ring; and medroxyprogesterone injection. RESULTS: Overall, 6689 cases of patients with SD were matched to 26,756 matched controls. Compared with matched controls, more subjects with SD used levonorgestrel IUD (OR 1.24, 95% CI 1.08-1.44), EE-levonorgestrel COC (OR 1.18, 95% CI 1.00-1.41), EE-drospirenone (OR 1.28, 95% CI 1.00-1.67), and medroxyprogesterone (OR 1.38, 95% CI 1.12-1.70). The use of norgestrel exhibited a protective effect (OR 0.83, 95% CI 0.73-0.95). When using the EE-levonorgestrel COC as a comparator, norgestrel users exhibited a protective effect (OR 0.70, 95% CI 0.57-0.87) while no other contraceptives showed a statistically significant difference in association with SD. CONCLUSION: Our study found an increase in the use of levonorgestrel (COC and IUD), drospirenone, and medroxyprogesterone in subjects with SD. The risk of contraceptives did not differ when compared with oral levonorgestrel. The small association size and lack of difference between drug formulations suggest a minimal impact of progestin-based contraceptives on sexual dysfunction.

Menopausal Hormone Therapy and Long-term All-Cause and Cause-Specific Mortality: The Women's Health Initiative Randomized Trials.

Importance: Health outcomes from the Women's Health Initiative Estrogen Plus Progestin and Estrogen-Alone Trials have been reported, but previous publications have generally not focused on all-cause and cause-specific mortality. Objective: To examine total and cause-specific cumulative mortality, including during the intervention and extended postintervention follow-up, of the 2 Women's Health Initiative hormone therapy trials. Design, Setting, and Participants: Observational follow-up of US multiethnic postmenopausal women aged 50 to 79 years enrolled in 2 randomized clinical trials between 1993 and 1998 and followed up through December 31, 2014. Interventions: Conjugated equine estrogens (CEE, 0.625 mg/d) plus medroxyprogesterone acetate (MPA, 2.5 mg/d) (n = 8506) vs placebo (n = 8102) for 5.6 years (median) or CEE alone (n = 5310) vs placebo (n = 5429) for 7.2 years (median). Main Outcomes and Measures: All-cause mortality (primary outcome) and cause-specific mortality (cardiovascular disease mortality, cancer mortality, and other major causes of mortality) in the 2 trials pooled and in each trial individually, with prespecified analyses by 10-year age group based on age at time of randomization. Results: Among 27 347 women who were randomized (baseline mean [SD] age, 63.4 [7.2] years; 80.6% white), mortality follow-up was available for more than 98%. During the cumulative 18-year follow-up, 7489 deaths occurred (1088 deaths during the intervention phase and 6401 deaths during postintervention follow-up). All-cause mortality was 27.1% in the hormone therapy group vs 27.6% in the placebo group (hazard ratio [HR], 0.99 [95% CI, 0.94-1.03]) in the overall pooled cohort; with CEE plus MPA, the HR was 1.02 (95% CI, 0.96-1.08); and with CEE alone, the HR was 0.94 (95% CI, 0.88-1.01). In the pooled cohort for cardiovascular mortality, the HR was 1.00 (95% CI, 0.92-1.08 [8.9 % with hormone therapy vs 9.0% with placebo]); for total cancer mortality, the HR was 1.03 (95% CI, 0.95-1.12 [8.2 % with hormone therapy vs 8.0% with placebo]); and for other causes, the HR was 0.95 (95% CI, 0.88-1.02 [10.0% with hormone therapy vs 10.7% with placebo]), and results did not differ significantly between trials. When examined by 10-year age groups comparing younger women (aged 50-59 years) to older women (aged 70-79 years) in the pooled cohort, the ratio of nominal HRs for all-cause mortality was 0.61 (95% CI, 0.43-0.87) during the intervention phase and the ratio was 0.87 (95% CI, 0.76-1.00) during cumulative 18-year follow-up, without significant heterogeneity between trials. Conclusions and Relevance: Among postmenopausal women, hormone therapy with CEE plus MPA for a median of 5.6 years or with CEE alone for a median of 7.2 years was not associated with risk of all-cause, cardiovascular, or cancer mortality during a cumulative follow-up of 18 years. Trial Registration: clinicaltrials.gov Identifier: NCT00000611.

Effect of hormonal contraceptives on serum lipids: A prospective study.

To estimate the effects of using hormonal contraceptives on serum lipoprotein levels. Lipid profile was measured at baseline and afterward at 3, 6, 9 and 12 months. 1391 Pakistani females taking COCs, DMPA, or non hormonal (NH) contraceptives. The results were calculated by repeated measure ANOVA subsequent to tukey's post hoc test for the multiple comparisons. Statistical examination revealed that differences in lipid profile were significant (p <0.001) among all treated group in comparison with control. DMPA also caused significant rise in Castelli index-I and Castelli index-II as compared to COCs group and control group. This study demonstrated raise in total cholesterol (TC) and triglycerides (TG) as well as very low density lipoprotein (VLDL-C) and low density lipoprotein cholesterol (LDL-C). Whereas, an obvious decrease was observed in high density-lipoprotein cholesterol (HDL-C) in the DMPA-treated group. We concluded that, this inductive study specifies atherogenic cardiovascular risk in women using DMPA on long term basis.

Add-back therapy with GnRH analogues for uterine fibroids.

BACKGROUND: Uterine fibroids (also known as leiomyomas) are the most common benign pelvic tumours among women. They may be asymptomatic, or may be associated with pelvic symptoms such as bleeding and pain. Medical treatment of this condition is limited and gonadotropin-releasing hormone (GnRH) analogues are the most effective agents. Long-term treatment with such agents, however, is restricted due to their adverse effects. The addition of other medications during treatment with GnRH analogues, a strategy known as add-back therapy, may limit these side effects. There is concern, however, that add-back therapy may also limit the efficacy of the GnRH analogues and that it may not be able to completely prevent their adverse effects. OBJECTIVES: To assess the short-term (within 12 months) effectiveness and safety of add-back therapy for women using GnRH analogues for uterine fibroids associated with excessive uterine bleeding, pelvic pain, or urinary symptoms. SEARCH METHODS: We searched electronic databases including the Cochrane Menstrual Disorders and Subfertility Group (MDSG) Specialised Register, CENTRAL, MEDLINE, PubMed, EMBASE, LILACS, CINAHL, PsycINFO; and electronic registries of ongoing trials including ClinicalTrials.gov, Current Controlled Trials, World Health Organization (WHO) International Clinical Trials Registry Platform. All searches were from database inception to 16 June 2014. SELECTION CRITERIA: Randomized controlled trials (RCTs) that included women with uterine fibroids experiencing irregular or intense uterine bleeding, cyclic or non-cyclic pelvic pain, or urinary symptoms, and that compared treatment with a GnRH analogue plus add-back therapy versus a GnRH analogue alone or combined with placebo were eligible for inclusion. DATA COLLECTION AND ANALYSIS: Two authors independently reviewed the identified titles and abstracts for potentially eligible records. Two review authors reviewed eligible studies and independently extracted data. Two authors independently assessed the studies' risk of bias. They assessed the quality of the evidence using GRADE criteria. MAIN RESULTS: Fourteen RCTs were included in the review. Data were extracted from 12 studies (622 women). The primary outcome was quality of life (QoL).Add-back therapy with medroxyprogesterone (MPA): no studies reported QoL or uterine bleeding. There was no evidence of effect in relation to bone mass (standardized mean difference (SMD) 0.38, 95% confidence interval (CI) -0.62 to 1.38, 1 study, 16 women, P = 0.45, low quality evidence) and MPA was associated with a larger uterine volume (mean difference (MD) 342.19 cm(3), 95% CI 77.58 to 606.80, 2 studies, 32 women, I(2) = 0%, low quality evidence).Tibolone: this was associated with a higher QoL but the estimate was imprecise and the effect could be clinically insignificant, small or large (SMD 0.47, 95% CI 0.09 to 0.85, 1 study, 110 women, P = 0.02, low quality evidence). It was also associated with a decreased loss of bone mass, which could be insignificant, small or moderate (SMD 0.36, 95% CI 0.03 to 0.7, 3 studies, 160 women, I(2) = 7%, moderate quality evidence). Tibolone may, however, have been associated with larger uterine volumes (MD 23.89 cm(3), 95% CI= 8.13 to 39.66, 6 studies, 365 women, I(2) = 0%, moderate quality evidence) and more uterine bleeding (results were not combined but three studies demonstrated greater bleeding with tibolone while two other studies demonstrated no bleeding in either group). Four studies (268 women; not pooled owing to extreme heterogeneity) reported a large benefit on vasomotor symptoms in the tibolone group.Raloxifene: there was no evidence of an effect on QoL (SMD 0.11, 95% CI -0.57 to 0.34, 1 study, 74 women, P = 0.62, low quality evidence), while there was a beneficial impact on bone mass (SMD 1.01, 95% CI 0.57 to 1.45, 1 study, 91 women, P < 0.00001, low quality evidence). There was no clear evidence of effect on uterine volume (MD 27.1 cm(3), 95% CI -17.94 to 72.14, 1 study, 91 women, P = 0.24, low quality evidence), uterine bleeding or severity of vasomotor symptoms (MD 0.2 hot flushes/day, 95% CI -0.34 to 0.74, 1 study, 91 women, P = 0.46, low quality evidence).Estriol: no studies reported QoL, uterine size, uterine bleeding or vasomotor symptoms. Add-back with estriol may have led to decreased loss of bone mass, from results of a single study (SMD 3.93, 95% CI 1.7 to 6.16, 1 study, 12 women, P = 0.0005, low quality evidence).Ipriflavone: no studies reported QoL, uterine size or uterine bleeding. Iproflavone was associated with decreased loss of bone mass in a single study (SMD 2.71, 95% CI 2.14 to 3.27, 1 study, 95 women, P < 0.00001, low quality evidence); there was no evidence of an effect on the rate of vasomotor symptoms (RR 0.67, 95% Cl 0.44 to 1.02, 1 study, 95 women, P = 0.06, low quality evidence).Conjugated estrogens: no studies reported QoL, uterine size, uterine bleeding or vasomotor symptoms. One study suggested that adding conjugated estrogens to GnRH analogues resulted in a larger decrease in uterine volume in the placebo group (MD 105.2 cm(3), 95% CI 27.65 to 182.75, 1 study, 27 women, P = 0.008, very low quality evidence).Nine of 12 studies were at high risk of bias in at least one domain, most commonly lack of blinding. All studies followed participants for a maximum of six months. This short-term follow-up is usually insufficient to observe any significant effect of the treatment on bone health (such as the occurrence of fractures), limiting the findings. AUTHORS' CONCLUSIONS: There was low or moderate quality evidence that tibolone, raloxifene, estriol and ipriflavone help to preserve bone density and that MPA and tibolone may reduce vasomotor symptoms. Larger uterine volume was an adverse effect associated with some add-back therapies (MPA, tibolone and conjugated estrogens). For other comparisons, outcomes of interest were not reported or study findings were inconclusive.

Risk of HIV Infection in Depot-Medroxyprogesterone Acetate (DMPA) Users: A Systematic Review and Meta-analysis.

OBJECTIVE: As the HIV/AIDS epidemic continues to spread in Africa and Asia, use of the injectable contraceptive steroid DMPA is widespread and has been increasing. Since studies dating back to 1992 have suggested that DMPA may increase the transmission of HIV to women, we endeavored to determine if the extant epidemiological and biological evidence is sufficient to conclude that DMPA use constitutes a definite hazard to women's health. METHODS: We searched Medline using the search terms: contraceptives or contraception AND HIV and searched bibliographies of articles thus identified. We included in the meta-analysis all studies examining the association between use of DMPA (or injectable contraceptives comprising mostly DMPA) and the presence (cross-sectional studies, n = 8) or acquisition (longitudinal studies, n = 16) of HIV+ status in women, using a random effects models to estimate odds ratios (ORs; cross-sectional studies) and hazard ratios (HRs; longitudinal studies). Studies were excluded if the comparison group included women using any form of steroidal contraception. RESULTS: Statistically significant positive associations between DMPA use and HIV positivity were observed both in cross-sectional (OR = 1.41, 95% CI 1.15 - 1.73) and longitudinal studies (HR = 1.49, 95% CI 1.28 - 1.73). The biological plausibility of increased vulnerability to HIV infection due to progestational action (via thinning of the vaginal epithelial barrier and immunosuppression) as well as glucocorticoid agonistic immunosuppression, are discussed. CONCLUSION: The epidemiological and biological evidence now make a compelling case that DMPA adds significantly to the risk of male-to-female HIV transmission.

Oestrogens promote tumorigenesis in a mouse model for colitis-associated cancer.

BACKGROUND: Hormone replacement therapy increases the risk of developing ulcerative colitis in postmenopausal women. Chronic intestinal inflammation predisposes to colon cancer development, but effects of female hormones on colitis-associated cancer development have not been examined. AIM: To investigate the role of female hormones in the dextran sodium sulfate (DSS)-azoxymethane (AOM) mouse model for colitis-associated cancer. DESIGN: We performed ovariectomies, or sham operations, on mice, and supplemented these animals with indicated hormones. Additionally, we used oestrogen receptor α or ß (Erα or Erß) mutant mice. To study colitis or colitis-associated cancer, we used DSS only, or DSS and AOM, respectively. RESULTS: Ovariectomy protects female mice against colitis-associated tumour development. Hormone replacement in ovariectomised mice with either oestradiol (E2), medroxyprogesterone acetate or a combination of both suggests that oestrogens are the ovary-derived factor that promotes tumour development in the context of inflammatory damage. E2-treated animals showed increased clinical symptoms and Il-6 production upon DSS-induced colitis and enhanced epithelial proliferation. Treatment with E2 markedly increased the numbers of polyps in ovariectomised mice and also strongly promoted tumour progression with all E2-treated animals developing at least one invasive adenocarcinoma, whereas, placebo-treated animals developed adenomas only. Using Er mutant mice, we find that the protumorigenic effect of oestrogen depends on both Erα and Erß. CONCLUSIONS: Our results suggest that oestrogens promote inflammation-associated cancer development by impairing the mucosal response to inflammatory damage.

Breast tenderness and breast cancer risk in the estrogen plus progestin and estrogen-alone women's health initiative clinical trials.

The associations between breast tenderness during use of conjugated equine estrogen (CEE) therapy with or without medroxyprogesterone (MPA) therapy and subsequent breast cancer risk are unknown. We analyzed data from the Women's Health Initiative Estrogen plus Progestin (N = 16,608, 5.6 years intervention) and estrogen-alone (N = 10,739, 6.8 years intervention) clinical trials until trial close-out (Spring 2005). At baseline and annually, participants underwent mammography and clinical breast exam. Self-reported breast tenderness was assessed at baseline and 12 months. Invasive breast cancer was confirmed by medical record review. The risk of new-onset breast tenderness after 12 months was significantly higher among women assigned to active therapy than placebo (CEE-alone vs. placebo risk ratio [RR] 2.15, 95% confidence interval [CI] 1.97-2.35; CEE + MPA vs. placebo RR 3.07, 95% CI 2.85-3.30). CEE + MPA doubled the risk of invasive breast cancer among women with baseline breast tenderness (hazard ratio [HR] 2.16, 95% CI 1.29-3.74), but had a smaller effect among women without baseline breast tenderness (HR 1.17; 95% CI 0.97-1.41). New-onset breast tenderness was associated with a higher risk of breast cancer among women assigned to CEE + MPA (HR 1.33, 95% CI 1.02-1.72, P = 0.03), but not among women assigned to CEE-alone (HR 0.98, 95% CI 0.62-1.53). New-onset breast tenderness during use of CEE + MPA was associated with increased subsequent breast cancer risk. The association of CEE + MPA therapy with increased breast cancer risk was especially pronounced among women with baseline breast tenderness.

Altered arterial stiffness in male-to-female transsexuals undergoing hormonal treatment.

AIM: Male-to-female (MTF) transsexuals are treated with estrogen with and without progestin through a variety of routes. The aim of this study is to evaluate the arterial stiffness in MTF transsexuals undergoing hormonal treatment. METHODS: We evaluated the arterial stiffness in 156 MTF transsexuals (22 untreated and 129 treated with estrogen only or plus progestin) using a volume-plethysmographic apparatus equipped with a multi-element applanation tonometry sensor. RESULTS: MTF transsexuals treated with parenteral estrogen were significantly older than untreated MTF transsexuals. Hematocrit, uric acid and activated partial thromboplastin time in treated MTF transsexuals were significantly lower than in untreated MTF transsexuals. The level of high-density lipoprotein cholesterol in MTF transsexuals treated with oral estrogen was significantly higher than in untreated MTF transsexuals or those treated with parenteral estrogen with and without progestin. The systolic blood pressure in MTF transsexuals treated with estrogen only is significantly lower than that in untreated MTF transsexuals. The brachial-ankle pulse wave velocity was significantly decreased in MTF transsexuals treated with estrogen compared to that in untreated MTF transsexuals or in those treated with estrogen plus progestin. The carotid augmentation index in MTF transsexuals treated with oral estrogen was significantly lower than that in MTF transsexuals treated with parenteral estrogen or oral estrogen plus progestin. CONCLUSIONS: Estrogen treatment is likely to have some beneficial effects on lipid metabolism and vascular function in MTF transsexuals; however, progestin administered with estrogen may have adverse effects on arterial stiffness.

Differences in prescription rates and odds ratios of antidepressant drugs in relation to individual hormonal contraceptives: a nationwide population-based study with age-specific analyses.

OBJECTIVES: To examine, among young women, the association of individual hormonal contraceptives, within two broad groupings, with antidepressant therapy. METHODS: In a nationwide register-based study, we examined the prescription rates of antidepressant drugs in relation to individual combined hormonal and progestin-only contraceptives among Swedish women aged 16-31 years (N = 917,993). Drug data were obtained from the Swedish Prescribed Drug Register for the period 1 July 2005-30 June 2008. Data on the total population of women aged 16-31 in 2008 were obtained from the Total Population Register of Statistics Sweden. The proportion of women using both hormonal contraception and antidepressants, and odds ratios (ORs) for antidepressant use for hormonal contraceptive users versus non-users, were calculated, the latter by logistic regression, for each formulation. RESULTS: The highest antidepressant OR in all age groups, particularly in the 16-19 years age group, related to medroxyprogesterone-only, followed by etonogestrel-only, levonorgestrel-only and ethinylestradiol/norelgestromin formulations. Oral contraceptives containing ethinylestradiol combined with lynestrenol or drospirenone had considerably higher ORs than other pills. ORs significantly lower than 1 were observed when ethinylestradiol was combined with norethisterone, levonorgestrel or desogestrel. CONCLUSION: The association between use of hormonal contraceptives and antidepressant drugs varies considerably within both the combined hormonal contraceptive and the progestin-only groups.

Randomized phase III clinical trial of five different arms of treatment in 332 patients with cancer cachexia.

PURPOSE: A phase III, randomized study was carried out to establish the most effective and safest treatment to improve the primary endpoints of cancer cachexia-lean body mass (LBM), resting energy expenditure (REE), and fatigue-and relevant secondary endpoints: appetite, quality of life, grip strength, Glasgow Prognostic Score (GPS) and proinflammatory cytokines. PATIENTS AND METHODS: Three hundred thirty-two assessable patients with cancer-related anorexia/cachexia syndrome were randomly assigned to one of five treatment arms: arm 1, medroxyprogesterone (500 mg/day) or megestrol acetate (320 mg/day); arm 2, oral supplementation with eicosapentaenoic acid; arm 3, L-carnitine (4 g/day); arm 4, thalidomide (200 mg/day); and arm 5, a combination of the above. Treatment duration was 4 months. RESULTS: Analysis of variance showed a significant difference between treatment arms. A post hoc analysis showed the superiority of arm 5 over the others for all primary endpoints. An analysis of changes from baseline showed that LBM (by dual-energy X-ray absorptiometry and by L3 computed tomography) significantly increased in arm 5. REE decreased significantly and fatigue improved significantly in arm 5. Appetite increased significantly in arm 5; interleukin (IL)-6 decreased significantly in arm 5 and arm 4; GPS and Eastern Cooperative Oncology Group performance status (ECOG PS) score decreased significantly in arm 5, arm 4, and arm 3. Toxicity was quite negligible, and was comparable between arms. CONCLUSION: The most effective treatment in terms of all three primary efficacy endpoints and the secondary endpoints appetite, IL-6, GPS, and ECOG PS score was the combination regimen that included all selected agents.

Differential Elevation of Inflammation and CD4+ T Cell Activation in Kenyan Female Sex Workers and Non-Sex Workers Using Depot-Medroxyprogesterone Acetate.

Background: Depot Medroxyprogesterone (DMPA) is one of the most widely used contraceptives in Sub-Saharan Africa where HIV incidence is high. We explored the effect of DMPA on the activation of HIV cellular targets and inflammation as a possible mechanism of increased HIV risk with DMPA use. Since sex work is known to affect the immune system, this study aimed to understand the effect of DMPA on the immune system among sex workers and non-sex worker women. Methods: Twenty-seven DMPA-using HIV seronegative female sex workers (FSW) and 30 DMPA-using HIV seronegative non-sex worker (SW) women were enrolled in the study. Twenty-four FSWs and 30 non-sex workers who were not using any hormonal contraception (no HC) were recruited as controls. Blood and cervico-vaginal samples were collected from all participants and assayed for T cell activation and proinflammatory cytokines. Results: Among no HC users, sex workers had lower expression of CD38 and CD69 on blood-derived CD4+ T cells along with lower CD4+CCR5+ cells frequency in the endocervix. Plasma MCP-1, TNFα and IL-17 also had reduced expression in FSW not using HC. Non-sex workers using DMPA had elevated proportions of blood-derived CD4+CD38+, CD4+CD69+ and CD4+HLA-DR+ T cells relative to non-sex workers who were not taking any HC. DMPA-using non-sex workers also had an increased level of plasma interferon gamma (IFN-γ), monokine induced by interferon-γ (MIG) and sCD40L, alongside higher proportion of CD4+CD38+ and CD4+CD69+ T cells at the cervix compared to non-sex workers no-HC controls., Finally, non-sex workers and FSWs using DMPA had similar levels of genital and peripheral CD4+ T cell activation and inflammation. Conclusion: DMPA increased inflammation and expression of activation markers on potential HIV target cells in non-sex workers. These data show that DMPA is a strong immune modulator and its use counteracts the decreased immune activation associated with sex work. These findings suggest that inflammation and increased HIV target cells in blood and at the genital tract may be mechanisms by which DMPA increases susceptibility to HIV.

Body weight and bleeding pattern changes in women using DMPA-SC.

OBJECTIVE: To determine the 1-year efficacy of contraception, changes in bleeding pattern and weight with the use of Depot medroxyprogesterone acetate-subcutaneous injected subcutaneously once every 3 months. STUDY DESIGN: Descriptive case-series. PLACE AND DURATION OF STUDY: Gynaecology and Obstetrics Unit, Holy Family Hospital, Rawalpindi, from March 2003 to June 2004. METHODOLOGY: Twenty five patients were selected by purposive sampling and followed up in Holy Family Hospital, Gynaecology and Obstetric Unit for a one-year period using DMPA-SC every three months. Hospital Ethical Committee permission was obtained prior to commencement of the study. Informed written consent was taken. Body weight was measured at baseline and every 3 months thereafter. Bleeding analysis in terms of blood flow and severity of bleeding was also done at 3 months interval using a 5-point scale. RESULTS: DMPA-SC showed 100% efficacy in preventing pregnancy in the 25 patients who were followed up. Mean and SD of age was 34.24+/-3.57 years. Mean and SD of weight was 63.44+/-13.81 kg.There was a mean weight gain of 0.1 kg at visit 1-3 (first 3 months) and an average weight gain of 1.036 kg at the end of the year. There was a trend towards amenorrhea with 56% of the patients included in the category of bleeding less than usual at the end of treatment period. CONCLUSION: DMPA-SC can be used in women desiring reversible contraception with unremarkable weight gain and overall bleeding pattern leading towards amenorrhea.

Molecular analysis of human endometrium: short-term tibolone signaling differs significantly from estrogen and estrogen + progestagen signaling.

Tibolone, a tissue-selective compound with a combination of estrogenic, progestagenic, and androgenic properties, is used as an alternative for estrogen or estrogen plus progesterone hormone therapy for the treatment of symptoms associated with menopause and osteoporosis. The current study compares the endometrial gene expression profiles after short-term (21 days) treatment with tibolone to the profiles after treatment with estradiol-only (E(2)) and E(2) + medroxyprogesterone acetate (E(2) + MPA) in healthy postmenopausal women undergoing hysterectomy for endometrial prolapse. The impact of E(2) treatment on endometrial gene expression (799 genes) was much higher than the effect of tibolone (173 genes) or E(2) + MPA treatment (174 genes). Furthermore, endometrial gene expression profiles after tibolone treatment show a weak similarity to the profiles after E(2) treatment (overlap 72 genes) and even less profile similarity to E(2) + MPA treatment (overlap 17 genes). Interestingly, 95 tibolone-specific genes were identified. Translation of profile similarity into biological processes and pathways showed that ER-mediated downstream processes, such as cell cycle and cell proliferation, are not affected by E2 + MPA, slightly by tibolone, but are significantly affected by E(2). In conclusion, tibolone treatment results in a tibolone-specific gene expression profile in the human endometrium, which shares only limited resemblance to E(2) and even less resemblance to E2 + MPA induced profiles.

Hormonal contraception and the risks of STI acquisition: results of a feasibility study to plan a future randomized trial.

BACKGROUND: Because of limitations in observational studies, a randomized controlled trial (RCT) would help clarify whether hormonal contraception increases the risks of acquiring a sexually transmitted infection (STI). However, the feasibility of such a trial is uncertain. STUDY DESIGN: We conducted a study to assess the feasibility of conducting a RCT that would compare the acquisition risk for Chlamydia trachomatis and Neisseria gonorrhoeae in women randomized to an intrauterine device (IUD) or depot medroxyprogesterone acetate (DMPA). In our cross-sectional survey conducted at three clinics, we gave information on a potential RCT to clients, asked them questions to assess comprehensibility and finally asked respondents whether they would consider enrolling in such a trial. In addition, the 190 participants provided urine or endocervical swab specimens so we could estimate the prevalence of STIs. RESULTS: Overall, 70% of participants stated that they would take part in a future trial and accept randomization to either the IUD or DMPA. Participant understanding of the trial requirements was high. Twenty-nine percent of the participants were infected with either N. gonorrhoeae or C. trachomatis. CONCLUSION: With a high prevalence of STI in this population and the apparent willingness of appropriate candidates to participate, an RCT to measure risks of incident STI infection from hormonal contraception appears feasible.

Conjugated equine estrogen and medroxyprogesterone acetate are associated with decreased risk of breast cancer relative to bioidentical hormone therapy and controls.

OBJECTIVE: By the 1990s it became popular for women to use hormone therapy (HT) to ease menopause symptoms. Bioidentical estrogen and progesterone are supplements whose molecular structures are identical to what is made in the human body, while synthetic supplements are ones whose structures are not. After the Women's Health Initiative found that the combined use of the synthetics conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increased breast cancer risk, prescriptions for synthetic HT declined considerably. Since then there has been an increased interest in bioidentical HT; today there are a plethora of websites touting their benefits. However, no peer-reviewed articles support these claims. We performed a retrospective study with the objective of verifying the hypothesis that bioidentical HT is associated with decreased breast cancer risk than CEE & MPA. METHODS: We searched The Northwestern Medicine Enterprise Data Warehouse for women who initiated HT use after age 50. Women who did not take any HT drug after age 50 served as controls. Nine HT protocols were investigated for breast cancer risk. RESULTS: Significant results include CEE Alone is associated with decreased breast cancer risk (HR = 0.31), Other Synthetic Estrogen Alone is associated with increased breast cancer risk (HR = 1.49), Bioidentical Estrogen Alone is associated with decreased breast cancer risk(HR = 0.65), CEE & MPA is associated with reduced breast cancer risk (HR = 0.43), and CEE & MPA is associated with reduced breast cancer risk relative to Bioidentical Estrogen & Progesterone (HR = 0.25). DISCUSSION: Our results indicate CEE & MPA is superior to bioidentical HT as far as breast cancer risk. Furthermore, this combination is associated with decrease of breast cancer risk, contrary to previous findings. Additional retrospective studies are needed to confirm our results.

Pure red-cell aplasia secondary to pregnancy, characterization of a syndrome.

The aim of this study was to characterize the syndrome of pure red-cell aplasia (PRCA) secondary to pregnancy. All published cases of PRCA induced by pregnancy were reviewed. Additionally, we reported a patient who developed PRCA on three occasions; two were triggered by pregnancy and one after medroxyprogesterone administration. Ten patients with 13 pregnancy-induced PRCA episodes were reported. The PRCA occurred at any gestational age. All patients received blood transfusions, and six of them were treated corticosteroids. The PRCA resolved in all subjects postpartum. Five women had subsequent pregnancies; three were complicated by PRCA, one was normal, and one had spontaneous abortion without PRCA. One subject developed a PRCA after long-term exposure to medroxyprogesterone. Infant blood values were normal in the nine reported cases. Pregnancy-induced PRCA is a self-limited syndrome with a high risk for relapse during subsequent pregnancies. It can be managed by blood transfusions. Progestins might cause PRCA in these women.

The Deterioration of the Glycemic Profile during Hormone Replacement Therapy in a Patient with Fulminant Type 1 Diabetes.

Although most women with type 1 diabetes experience the normal transition to menopause, there is little information about the impact of hormone replacement therapy on their glycemic profiles. A 54-year-old postmenopausal woman with fulminant type 1 diabetes was admitted to our hospital due to diabetic ketoacidosis. She was treated with fluid replacement and a continuous insulin infusion. Thereafter, her glycemic profile was well maintained by daily multiple insulin injections. However, her glycemic profiles immediately deteriorated following the administration of progesterone in hormone replacement therapy. This transient deterioration implies that external progesterone can lead to the deterioration of glycemic profiles in postmenopausal women with type 1 diabetes.

Weight gain in obese and nonobese adolescent girls initiating depot medroxyprogesterone, oral contraceptive pills, or no hormonal contraceptive method.

OBJECTIVE: To examine weight changes in a large cohort of obese and nonobese adolescent girls initiating depot medroxyprogesterone acetate (DMPA), an oral contraceptive (OC), or no hormonal contraceptive method (control). DESIGN, SETTING, AND PARTICIPANTS: Prospective study of 450 adolescent girls, aged 12 to 18 years, who attended 4 urban health clinics and selected DMPA, OC, or control. Data collection occurred at baseline and at 6, 12, and 18 months; consisted of structured interview and measurement of height and weight; and occurred from April 19, 2000, through September 26, 2003. MAIN OUTCOME MEASURE: Weight was examined as mean change over 18 months and actual weight at each study visit. On the basis of preliminary analyses, we stratified the sample according to baseline obesity status (nonobese, body mass index [calculated as weight in kilograms divided by the square of height in meters] < 30; obese, body mass index > or =30). RESULTS: Adolescent girls who were obese at initiation of DMPA gained significantly more weight than did obese girls starting OC or control (P<.001 for both). At 18 months, mean weight gain was 9.4, 0.2, and 3.1 kg for obese girls receiving DMPA, receiving OC, and control, respectively. Weight gain in obese girls receiving DMPA was also greater than weight gain in all nonobese categories (4.0 kg, DMPA; 2.8 kg, OC; 3.5 kg, control; P<.001). A significant interaction (P = .006) between length of time receiving DMPA and weight gain was evident for obese subjects. CONCLUSIONS: Over 18 months, DMPA use was associated with increasing rates of weight gain in obese subjects. The potential contribution to severe obesity in this population is concerning.

Randomized trial comparing aminoglutethimide with high-dose medroxyprogesterone acetate in therapy for advanced breast carcinoma.

A total of 218 postmenopausal patients were entered in a prospective randomized trial comparing aminoglutethimide (AG) and high-dose medroxyprogesterone acetate (MPA) as second-line hormonal therapy for advanced breast carcinoma. All responses were assessed by the criteria of the International Union Against Cancer. The response rates were 27% (29 of 106 patients) for AG and 31% (35 of 112) for MPA, but if stabilization of previously progressive disease is included, then the overall response rates were 51% (54 of 106) and 54% (61 of 112) for patients receiving AG or MPA, respectively. There was no difference in response to the two drugs at any site of disease, and the durations of response and survival were identical for the two drugs. The time to response was significantly shorter for patients treated with MPA (median, 8.7 wk) than for those treated with AG (median, 15.3 wk) (chi 2 = 9.96, 1 df, P = .0016). The percentage of patients experiencing toxic effects was equivalent in both arms, although the patterns and time courses of these effects were different.