Medroxyprogesterone Acetate

Sex steroid hormone progesterone is known to have profound effects on the growth and differentiation of the normal mammary gland and malignant breast epithelial cells. In vitro progesterone and synthetic progesterone-like compounds (progestins) inhibit breast cancer cell growth. Medroxyprogesterone acetate (MPA) is a synthetic hormone widely used in the adjuvant treatment of advanced breast cancer, hormone replacement therapy and in oral contraceptives. It is a paradoxical hormone, since it inhibits breast cancer cell proliferation, but has also been implicated in increased breast cancer risk. To better understand the molecular mechanism by which cell proliferation and differentiation are regulated by progesterone and MPA in human breast cancer, we utilized cDNA microarray and quantitative real-time RT-PCR methods to identify their target genes. This study describes novel progestin/progesterone target genes in breast cancer cells and, notably, novel target genes that elucidate the underlying molecular mechanism of the dual role progestins play in the breast. A cDNA microarray containing 3000 genes showed notable regulation in 30 and 27 genes by MPA and progesterone, respectively. Only 6 out of the 30 genes regulated by MPA are down-regulated, but no progesterone downregulation was observed. Overlapping in gene regulation by progesterone and MPA occurred, but the majority of genes regulated by these hormones were distinct. Given that progestins both stimulate and inhibit cancer cell growth, we report our findings on novel progestin and progesterone targets, which could explain the paradoxical actions of progestins in the breast.

Do injectable and oral contraceptives increase the risk of human immunodeficiency virus (HIV) acquisition in women? After adjusting for confounders, evidence of a significantly increased risk of HIV remained for women using injectable depo-medroxyprogesterone (DMPA) (hazard ratio = 1.49, 95% confidence interval (1.06-2.08)) but not for injectable norethisterone-enanthate (Net-En) or oral contraceptive pills (OC). An association between the use of some types of hormonal contraception (HC) methods and an increased risk of HIV, possibly through changes in the genital tract environment and alterations in the immune response, has been previously observed, although not consistently. A recent systematic review of these studies has highlighted the need for more definitive evidence. A secondary data analysis of the MDP301 phase 3 microbicide trial was conducted to estimate the effects of use of different methods of HC on the risk of HIV acquisition in women. HIV-negative women (n = 8663) wit...

BACKGROUND: Progestins have actions on the cardiovascular system, which depend on the structure as well as on receptor binding characteristics. Drospirenone (DRSP) is a progestin that uniquely interferes with the signaling of the mineralocorticoid receptor (MR). Hormone therapy containing DRSP results in blood pressure reduction in hypertensive post-menopausal women. METHODS: We describe the effects of DRSP on endothelial nitric oxide (NO) synthesis and compare them with those of progesterone (P) and of medroxyprogesterone acetate (MPA). In addition, we herein tested the relevance of the anti-mineralocorticoid activity of DRSP for NO synthesis. RESULTS: DRSP results in rapid activation of the endothelial NO synthase (eNOS) through mitogen-activated protein kinases and phosphatidylinositol 3-kinase as well as in enhanced eNOS expression. These actions depend on P receptor. When the cells are exposed to aldosterone, a reduction of eNOS expression is found that is antagonized by DRSP. This action is not shared by P or MPA. In addition, DRSP does not interfere with the induction or activation of eNOS induced by estradiol, as opposed to MPA. CONCLUSIONS: DRSP acts on endothelial cells via a combined action through the P and MRs. These results help to interpret the anti-hypertensive effects of hormonal therapies containing DRSP.

OBJECTIVES: To determine whether small decrements in global cognitive function that conjugated equine estrogen (CEE) therapies have been shown to produce in older women persist after cessation and extend to specific cognitive domains.DESIGN: Randomized controlled clinical trial.SETTING: Fourteen clinical centers of the Women's Health Initiative.PARTICIPANTS: Two thousand three hundred four women aged 65 to 80 free of probable dementia at enrollment.INTERVENTION: CEE 0.625 mg/d with or without medroxyprogesterone acetate (MPA, 10 mg/d) and matching placebos.MEASUREMENTS: Annual administrations of a battery of cognitive tests during and after the trial.RESULTS: Assignment to CEE‐based therapies was associated with small mean relative decrements in global cognitive function and several domain‐specific cognitive functions during the trial, which largely persisted through up to 4 years after the trial. The strongest statistical evidence was for global cognitive function (0.07–standar...

Context: Some studies of hormone treatment in postmenopausal women suggest benefits on specific cognitive functions, particularly memory. The objective of this study was to determine whether hormone therapy influences changes in specific cognitive functions and affect in older women. This study was a randomized, double-blind, placebocontrolled clinical trial. Setting: Participants were women from 14 of 40 clinical centers of the Women's Health Initiative (WHI). Participants: Postmenopausal women (1416) aged 65 yr and older, free of probable dementia, and enrolled in WHI and the WHI Memory Study (WHIMS) trial of combination estrogen and progestin for a mean of 3 yr and followed for a mean of 1.35 yr, were studied. Intervention: Intervention was conjugated equine estrogen (CEE; 0.625 mg) with 2.5 mg medroxyprogesterone acetate (MPA) in one daily tablet (CEE ϩ MPA) or placebo. Main Outcome Measures: Annual rates of change in specific cognitive functions and affect, adjusted for time since randomization, were measured. Results: CEE ϩ MPA had a negative impact on verbal memory (P Յ 0.01) and a trend to a positive impact on figural memory (P ϭ 0.012) over time compared with placebo, but other cognitive domains were not affected. Both effects on memory were evident only after long-term therapy. CEE ϩ MPA did not significantly influence positive affect, negative affect, or depressive symptoms. The effect of CEE ϩ MPA on cognitive function varies across cognitive domains in older women, reflecting both possible beneficial and detrimental actions of ovarian steroids on the aging brain. Our results extend prior findings about dementia and global cognitive function to age-related changes in specific cognitive functions and suggest directions for future research.

This article is the first of a two-part series discussing hormone replacement therapy (HRT). These articles discuss important concepts that shed light on the less-than-optimal results achieved thus far with conventional HRT, consider the possibility that some types of HRT are safer than others and discuss the reasons why they are safer. They suggest ways we can avoid repeating our mistakes. In Part 1, bioidentical HRT is referred to as BHRT, and conventional HRT is referred to as CHRT. Progestins is used to refer to synthetic compounds that exert an antiproliferative effect on uterine endometrium. Note that, by this definition, progesterone is not a progestin, since it is natural (not synthetic). Progesterone replacement will be discussed in Part 2. Testosterone replacement, although relevant, is beyond the scope of our discussion. This is not intended to be a "how-to" manual for HRT but, hopefully, to supply clinicians with additional information upon which to base decisions about bioidentical estrogen and progesterone replacement, now that the standard of care is in question. When we analyze what we have been doing with HRT for the past 50 years in the light of what we have also learned

Most individuals latently infected with Mycobacterium tuberculosis (M.tb) contain the infection by a balance of effector and regulatory immune responses. This balance can be influenced by steroid hormones such as glucocorticoids. The widely used contraceptive medroxyprogesterone acetate (MPA) possesses glucocorticoid activity. We investigated the effect of this hormone on immune responses to BCG in household contacts of active TB patients. Multiplex bead array analysis revealed that MPA demonstrated both glucocorticoid and progestogenic properties at saturating and pharmacological concentrations in peripheral blood mononuclear cells (PBMCs) and suppressed antigen specific cytokine production. Furthermore we showed that PBMCs from women using MPA produced significantly lower levels of IL-1a, IL-12p40, IL-10, IL-13 and G-CSF in response to BCG which corresponded with lower numbers of circulating monocytes observed in these women. Our research study is the first to show that MPA impacts on infections outside the genital tract due to a systemic effect on immune function. Therefore MPA use could alter susceptibility to TB, TB disease severity as well as change the efficacy of new BCG-based vaccines, especially prime-boost vaccine strategies which may be administered to adult or adolescent women in the future.

RESULTS: The mean age of patients in the study and control groups were 45.2±3.5 and 30.6±4.9 years, respectively (p 0.05). CONCLUSION: According to this study, 40 years of age and older women with endometrial polyps were more obese and had higher basal FSH and E2 levels. Obesity and increased estrogen levels may be contributing risk factors for developing endometrial polyps in women over 40 years of age.

Use of long-acting progestin only contraceptives (LAPCs) offers a discrete and highly effective family planning method. Abnormal uterine bleeding (AUB) is the major side effect of, and cause for, discontinuation of LAPCs. The endometria of LAPC-treated women display abnormally enlarged, fragile blood vessels, decreased endometrial blood flow and oxidative stress. To understanding to mechanisms underlying AUB, we propose to identify LAPC-modulated unique gene cluster(s) in human endometrial stromal cells (HESCs). Protein and RNA isolated from cultured HESCs treated 7 days with estradiol (E 2 ) or E 2 + medroxyprogesterone acetate (MPA) or E 2 + etonogestrel (ETO) or E 2 + progesterone (P4) were analyzed by quantitative Real-time (q)-PCR and immunoblotting. HSCORES were determined for immunostained-paired endometria of pre-and 3 months post-Depot MPA (DMPA) treated women and ovariectomized guinea pigs (GPs) treated with placebo or E 2 or MPA or E 2 +MPA for 21 days. In HESCs, whole genome analysis identified a 67 gene group regulated by all three progestins, whereas a 235 gene group was regulated by E 2 +ETO and E 2 +MPA, but not E 2 +P4. Ingenuity pathway analysis identified glucocorticoid receptor (GR) activation as one of upstream regulators of the 235 MPA and ETO-specific genes. Among these, microarray results demonstrated significant enhancement of FKBP51, a repressor of PR/GR transcriptional activity, by both MPA and ETO. q-PCR and immunoblot analysis confirmed the microarray results. In endometria of post-DMPA versus pre-DMPA administered women, FKBP51 expression was significantly increased in endometrial stromal and glandular cells. In GPs, E 2 +MPA or MPA significantly increased FKBP51 immunoreactivity in endometrial stromal and glandular cells versus placebo-and E 2 -administered groups. MPA or ETO administration activates GR signaling and increases endometrial FKBP51 expression, which could be one of the mechanisms causing AUB by inhibiting PR and GR-mediated transcription.

Molecular mechanisms responsible for abnormal endometrial vasculature in women receiving long-acting progestin-only contraceptives (LAPCs) are unknown. We hypothesize that LAPCs impair vascular smooth muscle cell (VSMC) and pericyte proliferation and migration producing thin-walled hyperdilated fragile microvessels prone to bleeding. Proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (αSMA) double-immunostaining assessed VSMC differentiation and proliferation in endometria from women before and after DepoProvera (Depo) treatment and from oophorectomized guinea pigs (OVX-GPs) treated with vehicle, estradiol (E2), medroxyprogesterone acetate (MPA), or E2+MPA. Whole-genome profiling, proliferation, and migration assays were performed on cultured VSMCs treated with MPA or etonogestrel (ETO). Endometrial vessels of Depo-administered women displayed reduced αSMA immunoreactivity and fewer PCNA (+) nuclei among αSMA (+) cells (P < 0.008). Microarray analysis of VSMCs id...

Objective: Thrombin and hypoxia each target human endometrial stromal cells (HESCs) to mediate long-acting progestin-only contraceptive (LAPC)-induced abnormal uterine bleeding (AUB). Thus, the secretome resulting from treatment of primary cultures of HESCs with thrombin or hypoxia was screened by mass spectrometry (MS) to detect potential protein mediators that lead to AUB. Study design: Cultured HESCs were primed with estradiol±medroxyprogesterone acetate (MPA) or etonogestrel (ETO), the respective progestins in MPA-injected and ETO-implanted LAPCs, and then treated by incubation with thrombin or under hypoxia. Collected conditioned medium supernatants were used for protein identification and quantitation of potential AUB mediators by liquid chromatography combined with tandem mass spectrometry analysis. Microarray analysis of parallel cultures and immunostaining of endometrial biopsies of LAPC users vs. nonusers corroborated MS results. Results: MS identified several proteins displaying changes in expression levels from either thrombin or hypoxia treatments that are integral to angiogenesis or extracellular matrix formation. Several MS-identified proteins were confirmed by mRNA microarray analysis. Overexpressed stanniocalcin-1 (STC-1) was observed in endometrium of LAPC users. Unlike controls, all LAPC users displayed endometrial tubal metaplasia (ETM). Conclusions: MS analysis identified many proteins that can affect angiogenesis or vessel integrity, thereby contributing to AUB. Confirmation of STC-1 overexpression in LAPC users and microarray data supports the validity of the MS data and suggests STC-1 involvement in AUB. The discovery of ETM in LAPC users indicates that LAPC-related side effects extend beyond AUB. The results presented here demonstrate a complex biological response to LAPC use. Implications: MS identified several HESC secreted proteins deregulated by thrombin and hypoxia that may mediate LAPC-induced AUB. The revelation of overexpressed STC-1 by combined in vivo and in vitro observations identifies a potential target for future studies to prevent or minimize LAPC-induced AUB.

TROKE IS A MAJOR HEALTH issue for women. Cerebrovascular diseases are the third leading cause of death in the United States 3 and are the leading cause of adult disability. The Women's Health Initiative (WHI), beginning in the early 1990s was designed to examine a number of factors affecting the health of postmenopausal women. Recently 1 arm of the WHI, the clinical trial of estrogen plus progestin, was terminated 3 years before its planned completion date because its harmful effects outweighed its benefits. The overall results in this randomized double-blind clinical trial indicated that women in the estrogen plus progestin group had a 41% increase in locally adjudicated strokes over 5.2 years compared with women in the placebo group. Our report provides results over an additional 4 months (average follow-up 5.6 years) on subtypes of stroke, based on central adjudication of stroke events by neurologists, additional data on the effects of estro-Author Affiliations, Financial Disclosures, and WHI Investigators are listed at the end of this article.

Trained community health workers, including traditional birth attendants (TBAs), safely and effectively administered injectables in northern Mozambique; two-thirds of the women choosing injectables had never used contraception before. Including TBAs in the Ministry of Health's recent task sharing strategy can improve rural women's access to injectables and help meet women's demand for contraception.

Evidence of pituitary-ovarian dysfunction in unexplained and endometriosis-associated infertility has been reported previously. Hormone-suppressive therapy is often used in an attempt to improve fertility, although benefits have not been proven. Our study examines the effect of progestogen (medroxyprogesterone acetate) treatment on women with endometriosis-associated and unexplained infertility, compared with women with tubal damage as functional controls. Pre-ovulatory follicular size and serum and follicular fluid hormone concentrations were measured, and oocyte collection and in-vitro fertilization were attempted, in natural cycles totally unperturbed by exogenous gonadotrophins, for two cycles before and two cycles following treatment with medroxyprogesterone acetate for 2 months. In the endometriosis and unexplained infertility groups, compared with the tubal group, the treatment led to significant reductions in the integrated luteinizing hormone (LH) values (483 versus 664, 559 versus 762 and 864 versus 820 notional IU/1 respectively). There were no changes in serum oestradiol or follicular fluid oestradiol, progesterone, follicle stimulating hormone or LH concentrations after treatment The results suggest that progestogen therapy has no beneficial effect on the pituitary-ovarian dysfunction which contributes to endometriosis-associated and unexplained infertility.

Background: The most studied fertility-sparing therapy for endometrial cancer (EC) is oral progestin therapy. However, complete remission (CR) rate after progestin therapy is not enough ranging from 60 to 80 %, with high recurrence rate. Clinical features that predict treatment efficacy and recurrence after progestin therapy have not yet been revealed in detail. The aim of this study was to investigate prognostic factors in patients with EC who achieved CR after medroxyprogesterone acetate (MPA) therapy. Methods: We retrospectively reviewed 35 EC patients treated with MPA at our institution between 2000 and 2016. Following confirmation of endometrioid adenocarcinoma G1, patients orally took 600 mg MPA daily for 26 weeks. Patients with CR periodically took oral contraceptives. The association of recurrence-free survival (RFS) with several clinical features including age, body mass index (BMI), and polycystic ovarian morphology (PCOM) was analyzed. Results: Of 35 patients, 25 (71%) ac...

The aim of the present study was to evaluate whether measuring endometrial thickness during fertility-sparing treatment with medroxyprogesterone acetate (MPA) can be a predictive marker for effectiveness in women with endometrioid adenocarcinoma, grade 1 (EmCa, G1). A total of 32 patients with stage IA EmCa, G1 underwent treatment with MPA. Patients were <40 years of age and preferred fertility-sparing treatment. MPA (600 mg/day) with low-dose aspirin was administered orally for 26 weeks. Pathological evaluation was performed by total curettage at weeks 8 and 16 and by fractional curettage at week 26. Patients underwent curative surgery in case of disease progression. Endometrial thickness was measured by transvaginal ultrasonography at weeks 8 and 16. Patients who showed non-complete response (non-CR) had thicker endometrium than that of CR patients at weeks 8 and 16. Receiver operating characteristic analysis revealed cut-off values of 8.3 and 4.7 mm endometrial thickness at weeks 8 and 16, respectively, for non-CR. Endometrial thickness >5 mm at week 16 was an independent factor for prediction of non-CR. Measurement of endometrial thickness during MPA treatment may be useful as a predictive marker for pathological response to MPA in patients with EmCa, G1.

Setting: Healthy volunteers in an academic medical referral center in Dallas, Texas. Patient(s): Seventy-five postmenopausal healthy women, ages 40 to 65 years, with follicle-stimulating hormone (FSH) levels greater Ն30 mIU/mL and a serum estradiol level Յ30 pg/mL. Intervention(s): After enrollment, all women were studied at baseline and received vitamin E for 4 weeks. They were then randomized from week 4 to week 12 to receive vitamin E in conjunction with conjugated equine estrogen (CEE) (0.625 mg), CEE (0.625 mg) plus medroxyprogesterone acetate (MPA) (2.5 mg), or placebo. Main Outcome Measure(s): Change from baseline and between groups effects of vitamin E with and without estrogen or hormone therapy on seven circulatory inflammatory markers in postmenopausal women. Result(s): Vitamin E levels increased to a similar extent in all three groups compared with baseline at weeks 4 and 12. Vitamin E increased serum interleukin-6 levels. Combination CEE plus MPA significantly increased C-reactive protein levels. However, there were no consistent statistically significant effects on six other inflammatory markers. Vitamin E attenuated C-reactive protein increases in postmenopausal women treated with estrogen replacement therapy but not with HT. Because there was no other persistent effect on six additional inflammatory markers, it can be concluded that vitamin E and HT do not play a major role in promoting a change in cardiovascular inflammatory markers.

Objective: To investigate the antiadhesion potential of tamoxifen and anastrozole in a rat uterine horn model. Design: Experimental animal study. Setting: University animal laboratory. Animal(s): Forty-five female Wistar albino rats. Intervention(s): We examined the effects of tamoxifen and anastrozole to reduce the extent and severity of postoperative adhesions in a rat uterine horn model: the control group received no therapy while the second and third groups received 500 g/day tamoxifen and 0.2 mg/kg/day anastrazole, respectively, through an enteric tube, starting 5 days before surgery. These protocols were continued for 14 days after the surgery until the rats were killed. Main Outcome Measure(s): Adhesions were scored according to their extent and severity, and specimens were also evaluated and scored histologically according to the following features: inflammation, fibroblastic activities, foreign body reaction, collagen formation, and vascular proliferation. Result(s): Anastrozole had the lowest mean adhesion scores, and these scores were significantly different from those of the controls. However, there were no statistically significant differences between control and tamoxifen groups and between tamoxifen and anastrozole groups. Histologic scores were lowest in the anastrozole group, which were statistically different from those of the tamoxifen and anastrozole groups, whereas scores of the control group were not statistically different from those of the tamoxifen group. Anastrazole decreased postsurgical adhesion scores by both visual scores and histologic analyses in a rat model. Further experimental and clinical trials are required to confirm these results.

Sex hormones play a role in bone density, cardiovascular health, and wellbeing throughout reproductive lifespan. Women with primary ovarian insufficiency (POI) have lower estrogen levels requiring hormone therapy (HT) to manage symptoms and to protect against adverse long-term health outcomes. Yet, the effectiveness of HT in preventing adverse outcomes has not been systematically assessed. We summarize the evidence regarding effects of HT on bone and cardiovascular health in women with POI. A comprehensive search of the electronic databases MEDLINE, EMBASE, and Scopus was conducted by a medical reference librarian from database inception to January 2016. Randomized trials and observational cohort studies with an estrogen-based HT intervention in women with POI under the age of 40 were included. Reviewers worked independently and in duplicate to assess eligibility and risk of bias, and extract data of interest from each study. The search identified 1670 articles; 12 met inclusion cri...

Background: Chemotherapy-induced neuropathy (CIPN) is the most severe consequence, causing both sensory and motor impairment with an incidence of between 19% and over 85%. Leukaemia, lymphoma, and sarcoma are just a few of the cancers that are treated using vincristine (VCR), a typical anticancer treatment used in chemotherapy. Peripheral neuropathy caused by vincristine is the primary impediment to the efficacy of ongoing anti-cancer treatment and continued use. Objectives: The current study's goal was to contemplate the significance of thymoquinone on the development and expression of vincristineinduced neuropathy. Methodology: All groups except normal saline were administered vincristine 0.1mg/kg i.p for 14 days. In selected groups gabapentin (75mg/kg) and thymoquinone were administered at 10, 20, and 30 mg/kg/day for 14 days orally along with vincristine (acquisition) and once at day 14 (expression). Thermal hyperalgesia and mechanical allodynia were quantified on days 1, 6, and 14 after 30, 60, 90, and 120 minutes. The data were processed using the Students' t-test and post hoc Dunnett's test. Results: The acquisition and expression of thermal hyperalgesia as well as mechanical allodynia was significantly improved by thymoquinone at all the tested doses at days 6 and 14 as well as after 30, 60, 90, and 120 minutes, significant improvement was observed. Conclusion: It is manifested that TQ can be an impending candidate for the management of vincristine-induced neuropathy.

In this study, three experiments were conducted to (1) evaluate estrus and ovulation synchronization using the short progesterone-CIDR or the medroxyprogesterone acetate (MAP) sponge protocol; (2) assess fertility after cervical insemination 8 or 4 h before the ovulation time; (3) evaluate the fertility of cervical artificial insemination or laparoscopic artificial insemination of ewes. The progesterone-CIDR protocol anticipated estrus (27.7 ± 5.8 vs. 43.1 ± 14.6) and ovulation (57.9 ± 3.9 vs. 80.0 ± 21.2) and improved estrus synchronization and ovulation compared with the ewes treated with intravaginal medroxyprogesterone acetate (MAP) sponges. Therefore, a progesterone-CIDR protocol was later used to evaluate fertility rates by cervical insemination with frozen semen at 50 or 54 hours after removal of the progesterone device, corresponding to 8 or 4 h, respectively, before the mean ovulation. However, the fertility rate did not differ between the two groups and was close to 20%. I...

Epidemiologic, laboratory, and animal evidence suggests that progestins and vitamin D may be potent ovarian cancer preventives. Our objectives were to evaluate progestins as reproductive tract cancer chemopreventives in the chicken, determine whether restricted ovulation affected the incidence of reproductive tract tumors, and assess whether vitamin D would confer cancer protection either alone or in addition to progestin. A total of 2,400 two-year-old Single Comb White Leghorns were randomized into six groups (400 each) with hormonal and dietary manipulation for 2 years as follows: (i) no intervention, regular feed/caloric intake, (ii) control, (iii) vitamin D, (iv) the progestin levonorgestrel, (v) vitamin D plus levonorgestrel, and (vi) the progestin Provera (medroxyprogesterone acetate). Groups 2 to 6 were caloric restricted to inhibit ovulation. Our results indicated that caloric restriction decreased egg production by more than 60%, and was associated with a greater than 70% decrease in reproductive tract cancers. Ovulatory events did not differ among the caloric-restricted groups (groups 2-6), except for the group receiving levonorgestrel, which had fewer ovulatory events than controls (P ¼ 0.046). After correcting for egg production, birds receiving progestins had significantly fewer reproductive tract cancers [OR, 0.61; confidence interval (CI), 0.39-0.95; P ¼ 0.03], with similar proportionate reductions in tumors arising in either the ovary or oviduct. Vitamin D did not significantly affect cancer incidence overall, or add to the cancer preventive effect of progestins. This study suggests a protective effect of progestins against ovarian and oviductal cancers. These data support the concept that progestins provide a chemopreventive effect unrelated to ovulation. Cancer Prev Res; 6(12); 1283-92. Ó2013 AACR.

To evaluate the effect of l-or 3-monthly sequential combinations of estradiol valerate (E2V) and medroxyprogesterone acetate (MPA) on menopausal symptoms, bone density, muscle strength and lipid metabolism in postmenopausal women. Methods: Changes in bone mineral density (BMD), isometric muscle strength, serum lipids and climacteric symptoms were evaluated in 78 women, 49-55 years of age, with a spontaneous menopause 0.5-3 years earlier. Treatment group I received 2 mg E,V tablets for 11 days, followed by 2 mg E,V + 10 mg MPA for 10 days and placebo for an additional 7 days; treatment group II received 2 mg E,V for 70 days, 2 mg E,V + 20 mg MPA for 14 days, and placebo for 7 days. The placebo group received placebo continuously for 24 months. Each group was further randomised to exercise and non-exercise subgroups, Results: Both hormone regimens significantly reduced menopausal symptoms, and prevented equally well the decrease of BMD both in the lumbar spine and proximal femur. A positive effect of exercise on BMD was observed in the placebo group. No synergistic effect of exercise and estrogen on BMD could be shown. Both hormone regimens increased the isometric strength of back extensor muscles. Serum total and LDL cholesterol decreased during the first year with both estrogen regimens. Conclusions: Estrogen-progestin regimens were equally effective in the control of menopausal symptoms and preventing bone loss, increasing muscle strength and lowering serum cholesterol. 0 1997 Elsevier Science Ireland Ltd.

Upon progesterone stimulation, Endometrial Stromal Cells (EnSCs) undergo a differentiation program into secretory cells (decidualization) to release in abundance factors crucial for embryo implantation. We previously demonstrated that decidualization requires massive reshaping of the secretory pathway and, in particular, of the Golgi complex. To decipher the underlying mechanisms, we performed a time-course transcriptomic analysis of in vitro decidualizing EnSC. Pathway analysis shows that Gene Ontology terms associated with vesicular trafficking and early secretory pathway compartments are the most represented among those enriched for upregulated genes. Among these, we identified a cluster of co-regulated genes that share CREB3L1 and CREB3L2 binding elements in their promoter regions. Indeed, both CREB3L1 and CREB3L2 transcription factors are up-regulated during decidualization. Simultaneous downregulation of CREB3L1 and CREB3L2 impairs Golgi enlargement, and causes dramatic change...

To examine associations between method of contraception, sexually transmitted diseases (STDs), and incident human immunodeficiency virus type 1 (HIV-1) infection, a prospective observational cohort study was done among female sex workers attending a municipal STD clinic in Mombasa, Kenya. Demographic and behavioral factors significantly associated with HIV-1 infection included type of workplace, condom use, and parity. In multivariate models, vulvitis, genital ulcer disease, vaginal discharge, and Candida vaginitis were significantly associated with HIV-1 seroconversion. Women who used depo medroxyprogesterone acetate (DMPA) had an increased incidence of HIV-1 infection (hazard ratio [HR], 2.2; 95% confidence interval [CI], 1.4 -3.4). In a multivariate model controlling for demographic and exposure variables and biologic covariates, the adjusted HR for HIV-1 infection among DMPA users was 2.0 (CI, 1.3 -3.1). There was a trend for an association between use of high-dose oral contraceptive pills and HIV-1 acquisition (HR, 2.6; CI, 0.8 -8.5).

Objective-To identify possible predictive factors of higher bone loss, defined as at least 5%, at the spine or femoral neck, over time in depot medroxyprogesterone (DMPA) users. Methods-Bone mineral density (BMD) was measured at the lumbar spine and femoral neck every 6 months in 240 white, black, and Hispanic women using DMPA. For purpose of analysis, an arbitrary value of at least 5% BMD loss from the baseline value after 24 months of DMPA use at either the lumbar spine or femoral neck was considered as higher BMD loss. Logistic regression analysis was then used to examine factors predictive of at least 5% BMD loss at either site. Results-Of the initial 240 DMPA users, 95 completed 24 months of follow-up. Forty-five of the 95 DMPA users (47.4%) had at least 5% BMD loss at the lumbar spine or femoral neck by 24 months. Multivariable logistic regression model showed that at least 5% BMD loss was associated with current smoking (adjusted odds ratio [OR] 3.88, 95% confidence interval [CI], 1.26-11.96), calcium intake (in 100 mg) (OR 0.81, 95% CI, 0.65-0.99), and parity (OR 0.49, 95% CI, 0.29-0.82). Age, race or ethnicity, previous contraceptive use and body mass index were not associated with higher BMD loss. Conclusions-The risk of higher BMD loss associated with DMPA use may be reduced by quitting smoking and increasing calcium intake. Having had a child is also protective.

Teenager girls represent a particular risk group for unwanted pregnancy and abortion with important consequences on their health, school and professional education and social life. In order to avoid this problem appropriate counseling during contraceptive process is of paramount importance. Apart confi dentiality the contraceptive counselor must also demonstrate other important qualities like expertise, trustworthiness and availability. In hormonal contraception adolescents may be particularly bothered by side eff ects and it is important that they are counseled about these side eff ects prior to method initiation. Combined hormonal contraceptive methods with estrogens and progesterone are commonly used among adolescents, but the failure rate is higher compared to adult women, a possible

Original Article Context: Depot medroxyprogesterone acetate (DMPA), marketed as ANTARA, is a long-acting contraceptive with minimal daily interference. Despite its availability, its uptake remains low in India, with only 0.4% of women using injectables (NFHS-5). This study explores the acceptability of DMPA among women in rural and urban Nagpur. Objective: The objective of the study was to examine the acceptability of DMPA among women of reproductive age in Nagpur. Methods: A constructivist paradigm and descriptive design were employed at the Urban Health Centre (PHC), Nandanvan and Rural Health Training Center, Bela Nagpur, India. Data were collected from 21 Accredited Social Health Activists (ASHAs) using free listing, pile sorting, and focus group discussions. Analysis included Smith's salience score, cognitive mapping, and thematic categorization. Results: Pile sorting identified three major clusters: Menstrual-related concerns, general perceptions, and service delivery barriers. ASHA interviews revealed five key barriers: menstrual and physical side effects, social and cultural factors, health concerns, misunderstandings, and preference for alternative methods. Conclusion: Findings indicate the need for pre-administration counseling, enhanced ASHA training for community education, and sharing positive user experiences to improve DMPA uptake.

Objective: To assess endogenous androgen and insulin resistance status in postmenopausal women receiving continuous combined hormone therapy (HT), tibolone, raloxifene or no therapy. Methods: A total of 427 postmenopausal women aged 42-71 years were studied in a cross-sectional design. Among them 84 were taking HT (46 women conjugated equine estrogens 0.625 mg; medroxyprogesterone acetate, 5 mg, CEE/MPA; and 38 women 17␤-estradiol 2 mg; norethisterone acetate 1 mg, E2/NETA); 83 were taking tibolone 2.5 mg; 50 were taking raloxifene HCl 60 mg; and 210 women were not receiving any therapy. Main outcome measures were FSH, LH, estradiol, total testosterone, SHBG, free androgen index (FAI), 4 -Androstendione ( 4 -A), Dehydroepiandrosterone sulphate (DHEAS) and HOMA insulin resistance index (HOMA-IR). Results: In women not on hormone therapy smoking and older age was associated with lower DHEAS levels. FAI values increased linearly with increasing BMI. Age and BMI were positive determinants of HOMA-IR, while no association was identified between endogenous sex steroids and insulin resistance. CEE/MPA therapy was associated with higher SHBG, lower FAI and lower HOMA-IR values compared to women not on therapy (age and BMI-adjusted SHBG: CEE/MPA 148.8 nmol/l, controls 58.7 nmol/l, p < 0.01; age-adjusted FAI: CEE/MPA 0.8, controls 3.2, p < 0.05; age-adjusted HOMA-IR: CEE/MPA 1.3, controls 2.6, p < 0.05). On the contrary, E2/NETA treatment had no effect on these parameters. Women on tibolone had lower SHBG, higher FAI and similar HOMA-IR values compared to controls (age and BMI-adjusted SHBG: 24.1 nmol/l, p < 0.01; FAI: 6.0, p < 0.05; HOMA-IR: 2.3, p = NS). Raloxifene users did not exhibit any difference with respect to sex steroids and HOMA-IR levels.

Endometrial cancer (EC) is currently the most common malignancy of the female genital tract in developed countries. Although it is more common in postmenopausal women, it may affect up to 25% in the premenopausal age and 3–5% under the age of 40 years. Furthermore, in the last decades a significant shift to pregnancy at older maternal ages, particularly in resource-rich countries, has been observed. Therefore, in this scenario fertility-sparing alternatives should be discussed with patients affected by EC. This study summarizes available literature on fertility-sparing management of patients affected by EC, focusing on the oncologic and reproductive outcomes. A systematic computerized search of the literature was performed in two electronic databases (PubMed and MEDLINE) in order to identify relevant articles to be included for the purpose of this systematic review. On the basis of available evidence, fertility-sparing alternatives are oral progestins alone or in combination with ot...

Introduction: Anorexia nervosa (AN) is an eating disorder and also a psychiatric disorder, characterized by a weight well below the standard weight due to a distorted image of the body with obsessive fear of weight gain. Material and method: We present the case of a 10 years old girl weighing 16 kg (body mass index BMI = 8.16 kg/m2), who was hospitalized in the Pediatric Clinic for loss of appetite, inability to walk and maintain orthostatism, with motor deficit on the right side of the body. The onset was affirmative five months ago, after separation from the mother (gone abroad), the child being left in the care of a grandmother. Twenty-four hours after admission, the girl experienced periods of voluntary apnea, requiring endotracheal intubation and mechanical ventilation. Results: Endocrine balance showed in this case: elevated cortisol levels, low levels of follicle stimulating hormone (FSH), estradiol and testosterone; high levels of growth hormone (GH) and low levels of insuli...

Purpose: Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increase breast cancer risk, whereas the effect of transdermal estradiol (E2) and MPA is less known. Fenretinide may decrease second breast malignancies in premenopausal women but not in postmenopausal women, suggesting a hormone-sensitizing effect. We compared the 6 and 12-month changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), IGF-I:IGFBP-3 ratio, sex-hormone binding-globulin, and computerized mammographic percent density during oral CEE or transdermal E2 with sequential MPA and fenretinide or placebo. Experimental Design: A total of 226 recent postmenopausal healthy women were randomly assigned in a two-by-two factorial design to either oral CEE 0.625 mg/day (n = 111) or transdermal E2, 50 μg/day (n = 115) and to fenretinide 100 mg/twice a day (n = 112) or placebo (n = 114) for 12 months. Treatment effects were investigated by the Kruskall-Wallis test and analysis ...

Background: Long-acting reversible contraceptive (LARC) methods are cost-effective and offer very effective contraception for lengthy durations without relying on daily adherence or compliance from clients. Despite these benefits, a huge gap exists between demand for and uptake of modern contraceptive methods such as LARC to prevent pregnancy. While majority of married women of reproductive age in Nigeria acknowledged the desire to delay child birth, only a few of them use modern contraceptive method to prevent pregnancy. Objectives: To assess the uptake of long-acting reversible contraceptive (LARC) use among women who accepted a modern method of contraception at the family planning clinic in DELSUTH. Methods: A retrospective record-based review of 628 women who accepted a modern contraceptive method in DELSUTH, Oghara between January 1, 2019 and December 31, 2021. Results: The uptake of LARC in this study was high (72.4%). The uptake of the progesterone only implant (jadelle-93 and implanon-225) was 50.6% while IUCD (133) was 21.2%. Uptake by adolescents and nulliparous women was low 0.9% and 1.5% respectively. Seventy-one percent had secondary level of education. Majority of acceptors were limiters (56.7%) and uptake of LARC increased with increasing parity, but declined after 45 years (1.3%). Conclusion: The prevalence of LARC was relatively high among our attendees of the family planning clinic. Counseling should target adolescent, and nulliparous women and the fa mily planning should made friendly to these groups to improve access.

Hematometra is a rare condition that is most commonly associated with congenital anomalies and prior surgical procedures. This is an unusual case of spontaneous hematometra occuring in 32 years old healthy woman with no prior medical or surgical history. Only five cases of spontaneous hematometra without any risk factors have been reported. Keywords: abdominal pain; Depot medroxyprogesterone acetate; hematometra.

The placental renin-angiotensin system (RAS) is involved in placentation. We have shown that prorenin mRNA (REN) is expressed in a first trimester trophoblast cell line (HTR-8/SVneo) but not in a choriocarcinoma cell line (BeWo). We attempted to stimulate RAS expression in these cells by cAMP, 5'-aza-2'-deoxycytidine (AZA; an inhibitor of methylation), cAMP and AZA combined, and the sex steroids medroxyprogesterone acetate (MPA) and estradiol-17β (E2) with and without cAMP. RAS mRNAs were measured by qPCR and prorenin concentration in supernatants measured by an ELISA. In HTR-8/SVneo cells, all treatments increased REN expression compared to controls and cAMP + AZA combined was more effective than either treatment alone. Prorenin levels in supernatants were similarly upregulated. In HTR-8/SVneo cells, angiotensinogen (AGT) mRNA expression was increased by MPA + E2 either with or without cAMP. AGT expression was also significantly increased by AZA. BeWo cells did not express REN or prorenin and it was not inducible with any treatment. AGT expression was significantly increased with AZA, the combination of cAMP + AZA, and MPA + E2 + cAMP treatments. Since cAMP, AZA, cAMP and AZA combined, or MPA and E2 with and without cAMP in HTR-8/SVneo cells, a cell line most similar in its RAS expression to the in vivo placenta, these factors may affect placental RAS activity. Surprisingly, these treatments also induced AGT expression in BeWo cells. Whether they are involved in regulating AGT in choriocarcinomas in vivo remains to be determined.

Background and Objectives: Hormonal replacement therapy (HRT) is effective in treating many debilitating symptoms of menopause. However, its use in women with uterine fibroids is widely debated, based on the susceptibility of these tumors to sexual steroids. This review aims to ascertain the effects of HRT on leiomyomas development and growth in postmenopausal women. Materials and Methods: Electronic databases (i.e., MEDLINE, Scopus, ClinicalTrials.gov, EMBASE, Sciencedirect, the Cochrane Library at the CENTRAL Register of Controlled Trials, Scielo) were searched from January 1990 until May 2019. All English-written studies evaluating the impact of various HRT regimens on uterine leiomyomas were selected. Results: Seventeen papers, considering a total of 1122 participants, were included. Fifteen of these were prospective trials, of which nine were randomized controlled trials. The remaining two works were a retrospective observational trial and a retrospective case series respectively. Five studies evaluated the effects of tibolone, also comparing it with various estrogen/progestin combinations, while two were about raloxifene. Thirteen studies compared different combinations of estrogens/progestins, the most common being transdermal estrogens (used in nine studies) and medroxyprogesterone acetate at different doses (used in 10 studies). Conclusions: For women with uterine fibroids, the choice of the most appropriate HRT regimen is crucial to avoid leiomyomas growth and the symptoms possibly related to it. Available data are conflicting, but suggest that uterine fibroids might be influenced by HRT, without representing an absolute contraindication to hormonal replacement therapy. Women with uterine fibroids subjected to HRT should be periodically examined and hormonal treatment should be discontinued if leiomyomas appear to increase in size. Moreover, the minimal effective dose of progestin should be employed.

Background: Plasma aldosterone/renin ratio (ARR) is the most popular screening test for primary aldosteronism (PA). Because both estrogen and progesterone (including in oral contraceptive agents) affect aldosterone and renin levels, we studied the effects of combined hormonal replacement therapy (HRT) on ARR; renin was measured as both direct renin concentration (DRC) and plasma renin activity (PRA). Methods: Fifteen normotensive, healthy postmenopausal women underwent measurement (seated, midmorning) of plasma aldosterone, DRC, PRA, electrolytes, and creatinine and urinary aldosterone, cortisol, electrolytes, and creatinine at baseline and after 2 weeks and 6 weeks of treatment with combined HRT (conjugated estrogens 0.625 mg and medroxyprogesterone 2.5 mg daily). Results: Combined HRT was associated with statistically significant increases in aldosterone [median (range): baseline, 150 (85 to 600); 2 weeks, 230 (129 to 790); 6 weeks, 434 (200 to 1200) pmol/L; P , 0.001 (Friedman test)] and PRA [2.3 (1.2 to 4.3), 3.8 (1.4 to 7.0), 5.1 (1.4 to 10.8) ng/mL/h, respectively; P , 0.001] but decreases in DRC [21 (10 to 31), 21 (10 to 39), and 14 (8.0 to 30) mU/L, respectively; P , 0.01], leading to increases in ARR calculated by DRC [7.8 (3.6 to 34.8), 11.4 (5.4 to 48.5), and 30.4 (10.5 to 90.2), respectively; P , 0.001]. The ARR calculated by DRC exceeded the cutoff value (70) in three patients after 6 weeks. There were no significant changes in ARR calculated by PRA [79 (26 to 184), 91 (23 to 166), and 88 (50 to 230), respectively; P = 0.282], plasma electrolytes and creatinine, or any urinary measurements. The combined oral HRT used in this study is capable of significantly increasing ARR with a risk of false-positive results during screening for PA but only if DRC (and not PRA) is used to calculate the ratio.

BACKGROUND: A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain. METHODS: This multicentre, 18 month, evaluator-blinded, comparatorcontrolled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months. RESULTS: DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (PՅ0.05) improved in both groups at 6 and 18 months. CONCLUSIONS: DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.

BACKGROUND: A clinical study compared efficacy and safety of depot medroxyprogesterone acetate (DMPA) with leuprolide for endometriosis-associated pain. METHODS: This multicentre, 18 month, evaluator-blinded, comparatorcontrolled trial randomized 300 women with laparoscopically diagnosed endometriosis to 6 month treatment with subcutaneous injection of 104 mg/0.65 ml DMPA (DMPA-SC 104) every 3 months or leuprolide (3.75 mg monthly or 11.25 mg every 3 months), with 12 months post-treatment follow-up. Endpoints included patient response to treatment in five signs/symptoms (dysmenorrhoea, dyspareunia, pelvic pain, pelvic tenderness, induration) and changes in bone mineral density (BMD) and productivity at 6 and 18 months. RESULTS: DMPA-SC 104 and leuprolide produced equivalent (P < 0.02) reductions in at least four pain categories and significant (P < 0.001) improvements in composite score at months 6 and 18. At month 6, reductions in total hip and lumbar spine BMD were significantly less (P < 0.001) with DMPA-SC 104 versus leuprolide. BMD returned to pre-treatment levels 12 months post-treatment in the DMPA-SC 104 but not the leuprolide group. Total productivity also significantly (PՅ0.05) improved in both groups at 6 and 18 months. CONCLUSIONS: DMPA-SC 104 reduces endometriosis-associated pain as effectively as leuprolide and improves productivity with significantly less BMD decline.

Hormonal contraception is central in the prevention of unintended pregnancy; however there are concerns that certain methods may increase the risk of HIV acquisition and transmission. Hormonal contraceptives may modify the genital mucosa in several ways, however the mechanisms are incompletely understood. Few studies have examined genital HIV shedding prospectively before and after initiation of hormonal contraception. The effects of hormonal contraception on genital HIV shedding in the setting of antiretroviral therapy (ART) are also unknown. We designed a pilot clinical trial in which HIV-infected and uninfected women were randomized to either depot medroxyprogesterone acetate (DMPA) injectable or levonorgestrel (LNG) implant in Lilongwe, Malawi. The objectives were to: 1) assess the effect and compare the impact of type of progestin contraception (injectable versus implant) on HIV genital shedding among HIV-infected women, 2) assess the effect and compare the impact of type of progestin contraception on inflammatory/immune markers in the genital tract of both HIV-infected and uninfected women, and 3) assess the interaction of progestin contraception and ART by examining contraceptive efficacy and ART efficacy. An additional study aim was to determine the feasibility and need for a larger study of determinants of HIV transmissibility and acquisition.

Background Lighthouse Trust operates two public HIV testing, treatment and care clinics in Lilongwe, Malawi, caring for over 26 000 people living with HIV, 23 000 of whom are on antiretroviral treatment (ART). In August 2010, Lighthouse Trust piloted a step-wise integration of sexual and reproductive health (SRH) services into routine HIV care at its Lighthouse clinic site. The objectives were to increase uptake of family planning (FP), promote long-term reversible contraceptive methods, and increase access, screening and treatment for cervical cancer using visual inspection with acetic acid. Methods and results Patients found integrated SRH/ART services acceptable; service availability appeared to increase uptake. Between August 2010 and May 2014, over 6000 women at Lighthouse received FP education messages. Of 859 women who initiated FP, 55% chose depot medroxyprogesterone acetate, 19% chose an intrauterine contraceptive device, 14% chose oral contraceptive pills, and 12% chose an implant. By May 2014, 21% of eligible female patients received cervical cancer screening: 11% (166 women) had abnormal cervical findings during screening for cervical cancer and underwent further treatment. Conclusions Several lessons were learned in overcoming initial concerns about integration. First, our integrated services required minimal additional resources over those needed for provision of HIV care alone. Second, patient flow improved during implementation, reducing a barrier for clients seeking multiple services. Lastly, analysis of routine data showed that the proportion of women using some form of modern contraception was 45% higher at Lighthouse than at Lighthouse's sister clinic where services were not integrated (42% vs 29%), providing further evidence for promotion of SRH/ART integration.

Background: Gonadal hormones can modify immune function, which may impact susceptibility to infectious diseases, including Human Immunodeficiency Virus (HIV). There is limited knowledge about how hormonal contraceptives (HC) influence the immune response during the course of use. The CHIME study aims to evaluate the effect of long-acting progestin-based hormonal contraceptives (depot medroxyprogesterone acetate, etonogestrel implant, and levonorgestrel intrauterine device) on immunologic changes in the female genital tract (FGT) and systemic compartment. Methods: CHIME is an observational cohort study where participants attend 2 visits prior to initiating the HC method of their choice, and then attend 6 visits over 12 months with biological sampling (vaginal swabs, cervicovaginal lavage, cytobrush and blood) for immunological, bacteriological, and virological analyses at each visit. Immune profiling will be evaluated by multi-color flow cytometry to determine how different T-cell subsets, in particular the CD4 T-cell subsets, change during the course of contraceptive use and whether they have different profiles in the FGT compared to the systemic compartment. The study aims are (1) to characterize the alterations in FGT and systemic immune profiles associated with three long-acting progestin-only HC and (2) to evaluate the vaginal microenvironment, determined by 16 s rRNA sequencing, as an individual-level risk factor and moderator of genital and systemic immune profile changes following exposure to three commonly used HC. Data collection started in March 2019 and is scheduled to be completed in October 2024.

While prior epidemiologic studies have suggested that injectable progestin-based contraceptive depot medroxyprogesterone acetate (DMPA) use may increase a woman's risk of acquiring HIV, recent data have suggested that DMPA users may be at a similar risk for HIV acquisition as users of the copper intrauterine device and levonorgestrel implant. Use of the etonogestrel Implant (Eng-Implant) is increasing but there are currently no studies evaluating its effect on HIV acquisition risk. Evaluate the potential effect of the Eng-Implant use on HIV acquisition risk by analyzing HIV target cells and cytokine profiles in the lower genital tract and blood of adult premenopausal HIV-negative women using the Eng-Implant. We prospectively obtained paired cervicovaginal lavage (CVL) and blood samples at 4 study visits over 16 weeks from women between ages 18-45, with normal menses (22-35 day intervals), HIV uninfected with no recent hormonal contraceptive or copper intrauterine device (IUD) use, no clinical signs of a sexually transmitted infection at enrollment and who were medically eligible to initiate Eng-Implant. Participants attended pre-Eng-Implant study visits (week -2, week 0) with the Eng-Implant inserted at the end of the week 0 study visit and returned for study visits at weeks 12 and 14. Genital tract leukocytes (enriched from CVL) and peripheral blood mononuclear cells (PBMC) from the study visits were evaluated

To assess the effect of the depot medroxyprogesterone acetate injectable (DMPA) and of the levonorgestrel (LNG) implant on genital HIV shedding among women receiving antiretroviral therapy (ART). We randomized HIV-infected Malawian women to either DMPA or LNG implant from May 2014 to April 2015. HIV RNA was measured in cervicovaginal lavage (CVL) fluid and TearFlo Strips (TFS), and HIV DNA was measured in cells collected by CVL. We compared the frequency and magnitude of HIV genital shedding before and for 6 months after initiation of contraception and between arms among women receiving ART. We also compared genital HIV RNA levels obtained by sample type (TFS versus CVL). We analyzed data for 68 HIV-infected women receiving ART: 33 randomized to DMPA and 35 randomized to the LNG implant. Overall, HIV RNA was more often detectable and the quantity was higher on TFS compared with CVL. HIV DNA was detected very rarely in CVL cell samples (4 of 360 samples). The frequency of genital she...