text:
The importance of the progestogenic component of hormone replacement therapy in women with a uterus
Funded by Mylan
Information intended for healthcare professionals only.
Guidelines approached Mylan for an educational grant to support the production of this supplement. Mylan has had no influence over the selection of the authos or the content of the supplement and has reviewed it for technical accuracy and to ensure compliance with regulations. Please see the bottom of the page for full disclaimer.
Dr John C Stevenson, Consultant Physician and Endocrinologist, Royal Brompton Hospital; Reader in Metabolic Medicine, Imperial College London
Dr Sophia Tsiligiannis, Specialty Trainee in Obstetrics and Gynaecology, Chelsea and Westminster Hospital; Clinical Research Fellow, Imperial College London
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Rationale behind progestogen prescribing
Progestogens currently available for prescription
Contraindications and side-effects
Risks associated with progestogen prescribing
Choosing the most appropriate progestogen for patients
Switching patients to a more suitable progestogen
The menopause transition is a critical stage in women's health. The oestrogen deficiency that accompanies the menopause is associated with irregular periods, eventual amenorrhoea, and multiple other symptoms—the most common being hot flushes and night sweats, vaginal dryness, mood changes, sexual dysfunction (including loss of libido), memory and concentration changes, headaches, and joint and muscle complaints. Around 80% of women will experience vasomotor symptoms,1 with most rating these as moderate to severe.2 An American observational study indicated that the median vasomotor symptom duration is 7.4 years.3 Furthermore, vasomotor symptoms are independently associated with multiple indicators of elevated cardiovascular risk,4 and reduction in bone mineral density (BMD).5
NICE guidance advises offering hormone replacement therapy (HRT) for vasomotor symptoms after discussing with women the short‑term (up to 5 years) and longer-term benefits and risks.6 However, the management of menopausal symptoms often presents a clinical challenge to prescribers. Concerns about breast cancer risk have contributed to reduced prescribing of HRT in the UK. Initial data from the 2002 Women's Health Initiative (WHI) trial showed an increased risk of breast cancer, albeit not statistically significant, and possible early harm from coronary heart disease (CHD) in women receiving combined oestrogen and progesterone.7 Subsequently, follow-up data from the same study published in 2013 showed no detrimental effect on CHD.8 With careful consideration of the risks and benefits, around 1 million women in the UK currently use HRT to manage their symptoms.6
Oestrogen alone can be offered to women without a uterus, whereas the addition of a progestogen is required for women with a uterus.6 A regimen containing bazedoxifene (BZA; a selective oestrogen receptor modulator) combined with conjugated equine oestrogens (CEE) is available as a progestogen-free alternative for use in women with a uterus.9 Tibolone is a synthetic compound with weak oestrogenic, progestogenic, and androgenic activity, and is also licensed for HRT use in the UK.10 It may be given to women with low libido, but adverse metabolic effects limit its use.
The association between unopposed oestrogen therapy and endometrial hyperplasia/neoplasia is established.11 A 20% incidence of endometrial hyperplasia was shown with 1 year of unopposed oestrogen use.12 Cyclical progestogen given in combination with low‑dose oestrogen for 10 days monthly reduced endometrial hyperplasia to placebo rate,13 and the WHI trial, which used continuous combined HRT, demonstrated a 19% reduction (non‑significant) in endometrial hyperplasia compared with placebo.14
In some cases, progestogens (in a combined HRT regimen) are prescribed to women without a uterus but with a history of severe endometriosis to prevent symptom reactivation (e.g. pelvic pain), recurrence, and malignant transformation of endometriotic foci.15 Despite a lack of high‑quality studies, case reports consistently show a predominance of oestrogen‑only HRT in women with recurrence of endometriosis and malignancy.15 As a result, combined preparations are often favoured.15
Broadly speaking, progestogens have one effect in common: the induction of a characteristic effect on the oestrogen-primed endometrium.16 There are, however, large variations in the myriad other biological effects elicited by different progestogens.16 The progestogenic activity of any substance also depends on its timing and route of administration. A list of progestogens currently licenced for use in the UK as part of combined HRT and their receptor activities is provided in Table 1.
Progestogens also exhibit antigonadotropic effects, which inhibit ovulation when prescribed for contraceptive use.16
Table 1: Progestogens currently licenced for use in the UK as part of combined HRT
Specific side-effects depend on the type of receptor activity exhibited by each progestogen, as demonstrated in Table 1. Common side‑effects for most progestogens include headache, menstrual cycle irregularities, breast pain, skin reactions, and gastrointestinal discomfort.17 General contraindications include breast, ovarian, or uterine cancer, a history of blood clots, and liver disease,17 with specific contraindications for each preparation.
NICE guidance advises explaining to women around the natural age of menopause that the baseline risk of breast cancer varies according to the presence of underlying risk factors.6 HRT with oestrogen alone is associated with little or no change in the risk of breast cancer relative to baseline risk, whereas HRT with oestrogen and progestogen can be associated with a slightly increased risk of breast cancer.6
NICE guidance reports a baseline population risk of breast cancer of 22.48 per 1000 women over 7.5 years.6 Follow-up data from the WHI trial demonstrated that, for current HRT users, there were four fewer cases of breast cancer per 1000 women among women using oestrogen alone relative to baseline, although this was not statistically significant.8 There were five additional cases of breast cancer per 1000 women among women using oestrogen and progestogen relative to baseline.8 In simple terms, use of combined HRT is associated with approximately one extra case of breast cancer for every 1000 users per year compared with use of oestrogen alone.8
In the WHI trial, combined HRT consisted of CEE with medroxyprogesterone acetate (MPA),7,8 and the same risk may not apply to different types of progestogen. Two cohort studies showed that oestrogen combined with either progesterone or dydrogesterone is not associated with a statistically significantly increased risk of breast cancer.18,19 This may be because some progestogens reduce proliferation; however, their effects on breast tissue are complex and poorly understood.18 A case‑control analysis by the UK-based General Practice Research Database also demonstrated that use of oestrogen with dydrogesterone is not associated with an increased risk of breast cancer.20
The risk of venous thromboembolism (VTE) is increased by oral HRT relative to baseline population risk.8 Conversely, epidemiological studies have not identified a risk of VTE above baseline population risk with the use of transdermal HRT.21–23 This is likely because transdermal delivery avoids first‑pass liver metabolism of oestrone (the main metabolite of oral oestradiol) in the liver, which increases thrombin generation.24
When defining VTE risk, observational studies have also outlined the importance of the type of progestogen associated with oestradiol.21 The addition of MPA to oral oestrogen may be associated with an increased risk of VTE, and continuous combined regimes may present a greater risk of VTE than sequential regimes.25
The ESTHER study, however, demonstrated no significant association between VTE and micronized progesterone.21 In addition, a recent case-control study confirmed that transdermal HRT preparations were not associated with VTE risk; conversely, oral HRT increased the risk of VTE, and the highest risk of VTE was evident with CEE combined with MPA.26 Oral oestradiol used in combination with dydrogesterone was not associated with a significantly increased risk of VTE (Figure 1).26
Figure 1: Adjusted odds ratios for VTE risk with different types of HRT and different doses of oestrogen26
Odds ratios are adjusted for current use of conjugated equine oestrogen cream, estradiol pessaries, oral progestogen, progesterone cream or vaginal preparations, past use of HRT, smoking status, alcohol consumption, Townsend deprivation fifth (QResearch only), body mass index, comorbidities, recent events, current and past use of antidepressants, antipsychotics, aspirin, oral contraceptives, tamoxifen, and years of data. Cases are matched to controls by age, general practice, and index date. *p<0.01
Adapted from Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2019; 364: k4810. Reproduced under the terms of the CC BY 4.0 license (creativecommons.org/licenses/by/4.0/)
HRT has the potential to improve cardiovascular risk because of beneficial effects on lipids, vascular function, and glucose metabolism.27 An updated analysis of the WHI trial showed that initiating oestrogen alone closer to the onset of menopause was associated with lower CHD risk and a reduction in total mortality.8,28 Randomised controlled trials, observational studies, and metaanalyses consistently support primary prevention of CHD and reduction in overall mortality in women initiating HRT nearer to the onset of menopause. The data suggest that the 'window of opportunity' for reducing CHD and overall mortality is initiation of HRT prior to 60 years of age and/or within 10 years of the menopause.29
Lipid profiles
All CEE and CEE/MPA regimens have favourable effects on lipid profiles, including reductions in low‑density lipoprotein cholesterol (LDL) and increases in high-density lipoprotein cholesterol (HDL), although triglyceride increases have also been observed with oral therapy.30 Similarly, an analysis of 248 studies showed that all oestrogen-only regimes raised HDL and lowered LDL.31 Oral oestrogens raised triglycerides, but transdermal 17β-oestradiol lowered triglyceride levels.31 This study also showed that progestogens had little effect on oestrogen‑induced reductions in total and LDL cholesterol.31 These positive effects were opposed least by dydrogesterone.31
In the SMART trials (a series of phase-3 trials), CEE 0.45 mg/BZA 20 mg and CEE 0.625 mg/BZA 20 mg were shown to have generally positive effects on most lipid parameters for up to 2 years of treatment,32 although there was some blunting of the oestrogen-induced rise in HDL.
A further study indicated that sequential combinations of either 1 mg or 2 mg 17β-oestradiol with dydrogesterone are associated with long-term favourable changes in serum lipid profile, and there is no evidence that dydrogesterone compromises these 17β-oestradiol-induced improvements.33
Overall, HRT in the form of CEE, oral esterified oestrogens, or transdermal oestrogen—alone or in combination with progestogens—reduces insulin resistance.34 Although the androgenic progestogen MPA has shown adverse effects on glucose and insulin metabolism,35 dydrogesterone does not appear to oppose the potentially beneficial effects of oestradiol on insulin.36
There is no official UK guidance on choice of progestogen when prescribing combined HRT. The effects of different progestogens on lipids, cardiovascular disease, VTE, glucose metabolism, and risk of breast cancer should therefore be considered by clinicians. Patient preference, side-effect profile, and clinical requirements (e.g. if patient has bothersome bleeding) should also factor in the decision‑making process.
Progestogens can be used in continuous or sequential combined HRT regimens. Sequential regimens are most commonly used for women who are perimenopausal or still menstruating.
'Bio-identical' natural progesterone is synthesised from yams, but it is only licensed for HRT use as an oral micronized progesterone capsule. Cohort studies have shown it may not be associated with increased risk of breast cancer, and it is often favoured for this reason.18,19
Use of a combination patch or combined oral therapy may be convenient, but it is also limited to the available doses, which may not effectively treat symptoms in individual women. Therefore, separate transdermal oestradiol (patch or gel), in combination with progesterone/an alternative progestogen, may offer greater flexibility to individualise treatment.
The HRT-related risk of serious VTE events increases with age, and is positively associated with obesity and thrombophilia.25 NICE guidance advises considering transdermal HRT for menopausal women who are at increased risk of VTE, including those with a body mass index over 30 kg/m2.6 A suitable choice may therefore be the use of transdermal oestradiol in combination with micronized progesterone in women at increased risk of VTE. Progestogen-delivering intrauterine devices are often used if contraception is required in conjunction with HRT. This is often the case in perimenopausal women or women with premature ovarian insufficiency, where a spontaneous pregnancy rate of 5% is assumed.
Use of CEE/BZA may be considered in women with progestogen intolerance.
If transferring from sequential combined HRT, start the new treatment the day after finishing the oestrogen plus progestogen phase. If transferring from continuous combined HRT, start the new treatment at any time.
HRT is used to alleviate menopausal symptoms and maintain BMD,6 and may reduce cardiovascular risk, particularly if started early postmenopause.28 Oestrogen with the addition of a progestogen is required for women with a uterus.6 Although the inclusion of progestogens in HRT regimens is associated with approximately one extra case of breast cancer per 1000 women per year for current HRT users,8 micronized progesterone or dydrogesterone may be associated with a lower risk.18,19 The type of progestogen is also important when considering VTE risk, with micronized progesterone and dydrogesterone appearing to demonstrate the lowest risk.21 CEE and CEE/MPA regimens have favourable effects on lipids,30,31 but progestogens have little effect on oestrogen-induced reductions in total and LDL cholesterol.31 Dydrogesterone does not appear to oppose the potentially beneficial effects of oestradiol on insulin.36 There is no current guidance on choice of progestogen for use in HRT in the UK; therefore, individual risk factors, patient preference, and the clinical scenario should to be taken into consideration.
Dr John Stevenson has received grants/research support from Abbott, Mylan, and Pfizer, consulting fees from Abbott and Pfizer, and speaker's honoraria from Abbott, Bayer, Gedeon Richter, Menarini, Mylan, and Pfizer.
Dr Sophia Tsiligiannis has received funding for events from Novo Nordisk.
Gold E, Colvin A, Avis N et al. Longitudinal analysis of the association between vasomotor symptoms and race/ethnicity across the menopausal transition: study of women's health across the nation. Am J Public Health 2006; 96 (7): 1226–1235.
Freeman E, Sammel M, Sanders R. Risk of long-term hot flashes after natural menopause. Menopause 2014; 21 (9): 924–932.
Avis N, Crawford S, Greendale G et al. Duration of menopausal vasomotor symptoms over the menopause transition. JAMA Intern Med 2015; 175 (4): 531–539.
Thurston R, Sutton-Tyrrell K, Everson-Rose S et al. Hot flashes and carotid intima media thickness among midlife women. Menopause 2011; 18 (4): 352–358.
Crandall C, Tseng C-H, Crawford S et al. Association of menopausal vasomotor symptoms with increased bone turnover during the menopausal transition. J Bone Miner Res 2011; 26 (4): 840–849.
NICE. Menopause: diagnosis and management. NICE Guideline 23. NICE, 2015. Available at: www.nice.org.uk/ng23
Rossouw J, Anderson G, Prentice R et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002; 288 (3): 321–333.
Manson J, Chlebowski R, Stefanick M et al. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women's Health Initiative randomized trials. JAMA 2013; 310 (13): 1353–1368.
British National Formulary. Conjugated oestrogens with bazedoxifene acetate. bnf.nice.org.uk/drug/conjugated-oestrogens-with-bazedoxifene-acetate.html (accessed 17 July 2019).
Manassiev N, Godsland I, Proudler A et al. Effects of tibolone or continuous combined oestradiol/norethisterone acetate on glucose and insulin metabolism. Clin Endocr (Oxf) 2013; 76 (2): 297–302.
Woodruff J, Pickar J. Incidence of endometrial hyperplasia in postmenopausal women taking conjugated estrogens (Premarin) with medroxyprogesterone acetate or conjugated estrogens alone. The Menopause Study Group. Am J Obstet Gynecol 1994; 170 (5 Pt 1): 1213–1223.
Judd H, Mebane-Sims I, Legault C. Effects of hormone replacement therapy on endometrial histology in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial. JAMA 1996; 275 (5): 370–375.
Lethaby A, Suckling J, Barlow D et al. Hormone replacement therapy in postmenopausal women: endometrial hyperplasia and irregular bleeding. Cochrane Database Syst Rev 2004; (3): CD000402.
Anderson G, Judd H, Kaunitz A et al. Effects of estrogen plus progestin on gynecologic cancers and associated diagnostic procedures: the Women's Health Initiative randomized trial. JAMA 2003; 290 (13): 1739–1748.
Gemmell L, Webster K, Kirtley S et al. The management of menopause in women with a history of endometriosis: a systematic review. Hum Reprod Update 2017; 23 (4): 481–500.
Schindler A, Campagnoli C, Druckmann R et al. Classification and pharmacology of progestins. Maturitas 2003; 46 (Suppl 1): S7–S16.
NHS. Hormone replacement therapy (HRT). www.nhs.uk/conditions/hormone-replacement-therapy-hrt/ (accessed 17 July 2019).
Fournier A, Berrino F, Clavel-Chapelon F. Unequal risks for breast cancer associated with different hormone replacement therapies: results from the E3N cohort study. Breast Cancer Res Treat 2008; 107 (1): 103–111.
Lyytinen H, Pukkala E, Ylikorkala O. Breast cancer risk in postmenopausal women using estradiol–progestogen therapy. Obstet Gynecol 2009; 113 (1): 65–73.
Schneider C, Jick S, Meier C. Risk of gynecological cancers in users of estradiol/dydrogesterone or other HRT preparations. Climacteric 2009; 12 (6): 514–524.
Canonico M, Oger E, Plu-Bureau G et al. Hormone therapy and venous thromboembolism among postmenopausal women. Circulation 2007; 115 (7): 840–845.
Renoux C, Dell'Aniello S, Suissa S. Hormone replacement therapy and the risk of venous thromboembolism: a population-based study. J Thromb Haemost 2010; 8 (5): 979–986.
Canonico M, Fournier A, Carcaillon L et al. Postmenopausal hormone therapy and risk of idiopathic venous thromboembolism. Arterioscler Thromb Vasc Biol 2010; 30 (2): 340–345.
Mueck A. Postmenopausal hormone replacement therapy and cardiovascular disease: the value of transdermal estradiol and micronized progesterone. Climacteric 2012; 15 (Suppl 1): 11–17.
Baber R, Panay N, Fenton A; IMS Writing Group. 2016 IMS recommendations on women's midlife health and menopause hormone therapy. Climacteric 2016; 19 (2): 109–150.
Vinogradova Y, Coupland C, Hippisley-Cox J. Use of hormone replacement therapy and risk of venous thromboembolism: nested case-control studies using the QResearch and CPRD databases. BMJ 2019; 364: k4810.
Lobo R, Davis S, De Villiers T et al. Prevention of diseases after menopause. Climacteric 2014; 17 (5): 540–556.
Rossouw J, Prentice R, Manson J et al. Postmenopausal hormone therapy and risk of cardiovascular disease by age and years since menopause. JAMA 2007; 297 (13): 1465–1477.
Hodis H, Collins P, Mack W, Schierbeck L. The timing hypothesis for coronary heart disease prevention with hormone therapy: past, present and future in perspective. Climacteric 2012; 15 (3): 217–228.
Lobo R, Bush T, Carr B et al. Effects of lower doses of conjugated equine estrogens and medroxyprogesterone acetate on plasma lipids and lipoproteins, coagulation factors, and carbohydrate metabolism. Fertil Steril 2001; 76 (1): 13–24.
Godsland I. Effects of postmenopausal hormone replacement therapy on lipid, lipoprotein, and apolipoprotein (a) concentrations: analysis of studies published from 1974-2000. Fertil Steril 2001; 75 (5): 898–915.
Stevenson J, Chines A, Pan K et al. A pooled analysis of the effects of conjugated estrogens/bazedoxifene on lipid parameters in postmenopausal women from the selective estrogens, menopause, and response to therapy (SMART) trials. J Clin Endocrinol Metab 2015; 100 (6): 2329–2338.
Stevenson J, Rioux J, Komer L et al. 1 and 2 mg 17betaestradiol combined with sequential dydrogesterone have similar effects on the serum lipid profile of postmenopausal women. Climacteric 2005; 8 (4): 352–359.
Salpeter S, Walsh J, Ormiston T et al. Meta-analysis: effect of hormone-replacement therapy on components of the metabolic syndrome in postmenopausal women. Diabetes Obes Metab 2006; 8 (5): 538–554.
Lindheim S, Presser S, Ditkoff E et al. A possible bimodal effect of estrogen on insulin sensitivity in postmenopausal women and the attenuating effect of added progestin. Fertil Steril 1993; 60 (4): 664–667.
Crook D, Godsland I, Hull J, Stevenson J. Hormone replacement therapy with dydrogesterone and 17 beta-oestradiol: effects on serum lipoproteins and glucose tolerance during 24 month follow up. Br J Obstet Gynaecol 1997; 104 (3): 298–304.
Guidelines approached Mylan for an educational grant to support the production of a supplement. The grant included honoraria for the authors. Mylan has had no influence over the selection of the authors or the content of the supplement and has reviewed it for technical accuracy and to ensure compliance with regulations.
The views and opinions of the authors are not necessarily those of Mylan, or of Guidelines, its publisher, advisers, or advertisers. No part of this publication may be reproduced in any form without the permission of the publisher.
Date of preparation: July 2019
Menopause and HRT


Senior figures from the Faculty of Business, Economics and Law (FBEL) have visited China to forge links with a number of universities.
The University of Surrey's existing connections with universities in China have been further strengthened through a visit to the country by FBEL representatives, from 13-25 October.
Professor David Allen, Executive Dean of the Faculty, Professor Graham Miller, Head of the School of Hospitality and Tourism Management (SHTM), and Dr Gang Li, Associate Dean (International), were among those on the trip to five top Chinese universities.
Key areas of discussion included potential research collaborations, creating programme partnerships between Surrey and the respective institutions, and the potential for student exchanges. The visit involved several presentations from Surrey staff on programmes and research at the University.
Zhejiang University:A prestigious higher education institution, Zhejiang University is part of the C9 League, which comprises the most renowned and oldest local universities in China and is often said to be analogous to the Ivy League in the USA.
Zhejiang's excellence is signalled by its inclusion in Project 985, with its School of Management being the first in mainland China to gain AMBA accreditation in 2006. The School was also awarded accreditation by The European Quality Improvement System (EQUIS) in 2012.
The current partnership between Surrey and Zhejiang University focuses on accepting qualified Tourism Management undergraduate students from Zhejiang to Surrey's SHTM Masters programmes.
Harbin Institute of Technology: Founded in 1920, Harbin Institute of Technology (HIT) is a C9 League university. One of the first universities in China to establish economics and management programmes, the School of Management at HIT holds Association of MBAs (AMBA) accreditation.
The current partnership between Surrey and HIT focuses on accepting qualified HIT undergraduate students to FBEL's Masters programmes.
Sun Yat-sen University: Established in 1985, Sun Yat-sen Business School (SYSBS) is one of the oldest and most renowned business schools in China. The Department of Hospitality and Service Management (HSM) was founded in 1988 as one of the oldest institutes in mainland China offering degrees of tourism management majors and has been ranked number one in mainland China for tourism programmes. SYSBS holds triple international accreditation from The Association to Advance Collegiate Schools of Business (AACSB), AMBA and EQUIS.
The visit to SYSUBS comes on the back of Surrey's recent launch of dual degree programmes in International Hospitality and Tourism Management and International Tourism Management and across the two institutions.
Tianjin University: Founded in 1895 as Peiyang University, Tianjin University is the first university in China and one of the top research universities in the country. Part of the 985 Project, Tianjin University is ranked 41st in the QS University Rankings and 93rd in the Asian University rankings 2014.
Nankai University: Ranked 10th in China and 50th in Asia, Nankai University is a key multidisciplinary and research-oriented institution directly under the jurisdiction of the Ministry of Education. Nankai Business School is ranked in the top ten nationally, and also enjoys a top-ten ranking for its MBA and Executive MBA programs.
Please visit our subject pages for more information on business and management, or hospitality and tourism management programmes at Surrey.


Tom Brady played a big part in helping the New England Patriots advance past the Houston Texans. So did the Patriots running game, behind 24 carries for 122 rushing yards (5.1 YPA) and two touchdowns.
Rob Gronkowski's role in the win, however, could not have been much smaller. The record-setting tight end left the game roughly seven minutes into the contest, and did not return. It appears he will not return for the remainder of the postseason.
NBC's Pro Football Talk was the first to report the news.
Per source, Rob Gronkowski is done for the rest of the postseason.Re-injured forearm and needs another surgery.
They've been down this road before, having played five games without the All-Pro tight end earlier this season, and they were without tight end Aaron Hernandez in their previous contest with the Ravens.
That being said, it will be a tough loss to overcome.
Brady's number when targeting Gronkowski are otherworldly; he did not throw a single interception while targeting Gronkowski all season long. Gronkowski led all tight ends with 11 touchdown catches this season.
Can the Patriots continue their postseason ride without Gronk? That remains to be seen, but judging by their ability to score at will without him during the regular season, it should be comforting that the Patriots have experience in this situation.
Here's some more news and analysis from around the AFC East.
Mike Reiss of ESPN Boston shares his thoughts on the Patriots adjusting to life without Rob Gronkowski...again.
Bleacher Report featured columnist David Daniels wastes no time in previewing the AFC Championship Game with the most important defensive players in the game.
Rich Cimini of ESPN New York keeps us in the loop on the Jets general manager search, which now includes Jerry Angelo, Scott Cohen and Omar Khan.
Kimberley A. Martin of Newsday points out that the next Jets general manager will inherit myriad problems with the salary cap and other areas.
Mark Gaughan of The Buffalo News says the Bills offense will be much more exciting and explosive with Doug Marrone as the head coach.
According to Kyle Zamiara of BuffaloBills.com, linebacker Bryan Scott hopes his ability to create turnovers will help him stay in Buffalo.
According to Ben Volin of The Palm Beach Post, Dolphins owner Stephen Ross is glad that the Dolphins finally feel like his team.
Andy Kent of MiamiDolphins.com reviews the stellar season of Dolphins defensive end Cameron Wake.
Erik Frenz is the AFC East lead blogger for Bleacher Report. Be sure to follow Erik on Twitter and "like" the AFC East blog on Facebook to keep up with all the updates. Unless otherwise specified, all quotes are obtained firsthand or via team press releases.


This is the art galleries section of our Armagh directory.
UK Cities has provided the following Armagh art exhibitions, paintings and art for sale listings in this section. There are art exhibitions directory listings, results from the Web and paid art exhibitions results. This page is one of several similar pages on this site. If you cannot find what you are looking on it, please try searching for art for sale using the search engine above.
To bookmark this page so you can save the paintings listings for later Click Here. If you would like to revisit this art galleries page frequently, you can set it as your browser's homepage. Click Here. The higher level category page displays categories related to art galleries.
If you have a art exhibitions Web site, why not list your site in our directory... Please see the instructions on the front page.


Outsiders premiered on Sky News Australia Sunday morning featuring three well known controversial political commentators including Mark Latham, Rowan Dean and Ross Cameron.
"Trigger warning trigger warning", were the opening words by Mark Latham during the introduction of the show, setting the tone for the politically incorrect commentary that was to follow.
During the show Latham called out the Hypocrisy of the mainstream media's new Fake News narrative, particularly Fairfax media, whilst naming and shaming Australian media pundits who tried to say a Trump victory was impossible on the morning of the election.
Rowan Dean said there is a Jihad that has been declared on the white male when discussing domestic violence in Australia.
The chosen timeslot for Outsiders is quite brilliant. A superb internet trollesque reaction to the biased, tax payer funded political commentary show on the ABC called Insiders, which also airs every Sunday at 10am.
The show appeals to the alternative right or new conservative movement that is sweeping the world, from the Donald Trump Victory and Brexit to One Nation's soaring popularity, all of which promote a shift away from the politically incorrect dogma that is the left wing establishment.
December 5, 2016 in Articles.


text:
Gnégnéri Yaya Touré o Touré Yaya, jugador de fútbol, centrecampista ivorià.
 Kolo Touré, futbolista professional ivorià.
 Mamam Cherif Touré, ex-futbolista Togolès.
 Samory Touré (1830-1900) fou almamy (sobirà) a Guinea i Mali durant l'imperi anomenat Wassoulou.
 Muhammad Touré, rei soninké de l'Imperi Songhai.
 Kwame Touré o Stokely Carmichael, polític negre trinitenc.

redpajama_set_name: RedPajamaWikipedia


Up Until Now with: Biscuits, Murphys, Greys, Mars and More!
Mr. Bugsly, Euphonic Conceptions, New Earth Muziq, and Challenger Presents are bringing you an awesome line up this Thursday night September, 20th, at the Highline Ballroom. All ages can attend so don't be shy and don't miss out!
VERY Limited Advance Tickets are available through the EC Fan Club.
Bluegrass Attack at Penn's Peak; Yonder Mountain Wows!
Next story VibeSquad & Opiuo | Ticket Giveaway!


Talk Sparkers about Social Justice | Resourced!
Describe a time when you felt like a victim of racial, social, or religious prejudice. What's a Christian's responsibility in these situations?
Agree or disagree: "Christianity and politics don't mix." Defend your answer.
If you knew your favourite product (e.g. Nike Shoes) was made through child labour or sweatshops would it stop you using it? Why/why not?
Should Christian faith and social justice go hand in hand? How might the two greatest commandments (Mark 12:28-30) help answer this question?
If you were president of the United States, what's one thing you'd try to change in the world? How can you help bring about these changes without being president?
Agree or disagree: "Minorities in N.Z. deserve preferred treatment today because of the mistreatment they received in the past." Defend your answer.
Which area of injustice upsets you the most: racism; corruption, child slavery/prostitution; poverty; abuse; war; bullying; prejudice; other? What would you like to see done about it?
Use these scriptures to enrich your discussions about social issues: Matthew 25:31-46; Luke 4:16-21; Micah 6:8; 1 John 3:17-18, James 2:14-17.


text:
Physical setting
Sandringham High School
The events described in Trevor Noah's autobiography Born a Crime take place roughly between 1984 and 2009. However, the book also presents some events that took place before that.
Trevor Noah was born in 1984 in South Africa during apartheid, a political system of segregation and discrimination against the non-white population. The influence of apartheid is felt throughout the story. First, the book begins with an extract from the Immorality Act of 1927, which forbids and punishes intimate relationships between whites and people of color. Trevor often talks about the "insane lengths" (Chapter 2, p. 28) that authorities went to enforce laws of segregation: "There were whole police squads whose only job was to go around peeking through windows—clearly an assignment for only the finest law enforcement officers. And if an interracial couple got caught, God help them" (Chapter 2, p. 28).
Trevor also talks about the time before his birth, when black South Africans were forbidden to live in bigger cities like Johannesburg. When he talks about his mother's hiding in the city, Trevor accentuates people's lack of trust in one another: "That's how a police state works—everyone thinks everyone else is the police" (Chapter 2, p. 31).
After Trevor's birth, apartheid laws targeted him as well because he had a black mother and a white father and was thus "born a crime" (Chapter 2, p. 32). For example, Trevor recalls the fear that the police would see a mixed-race child with a black mother and arrest her: "Children could be taken. Children were taken. The wrong color kid in the wrong color area, and the government could come in, strip your parents of custody, haul you off to an orphanage" (Chapter 2, p. 35). Trevor explains that this is the consequence of a racial classification system, which labeled and categorized people to keep them separated.
Trevor also recalls the fall of apartheid, which he associates with extreme violence:
What I do remember, what I will never forget, is the violence that followed. The triumph of democracy over apartheid is sometimes called the Bloodless Revolution. It is called that because very little white blood was spilled. Black blood ran in the streets. (Chapter 1, p. 18)
Trevor mainly talks about the conflict between the Inkatha Freedom Party and the African National Congress, which was, in fact, "a proxy war between Zulu and Xhosa" (Chapter 1, p. 19). Trevor remembers seeing riots and "blockades made of flaming tires" (Chapter 1, p. 19) in the streets, as well as "charred bodies on the side of the road" (Chapter 1, p. 19), visible in plain daylight.
The book's physical setting alternates between the different neighborhoods in which Trevor lives. First, he and Patricia live in a "tiny flat" (Chapter 5, p. 75) in Johannesburg, after which they move to Eden Park, a colored neighborhood. After Patricia sells the house in Eden Park to invest in Abel's workshop, the family moves into the workshop's garage. Then, Abel's business fails, and the family moves to Highlands North, a subu...
Character relationshipsNarrator and point of view

redpajama_set_name: RedPajamaCommonCrawl


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Man accused of murder "went on a date while her body was in a suitcase in his room"
Wednesday 6th November 2019 New Zealand - United Kingdom
The suspect in the death of British backpacker Grace Millane went on a Tinder date while her body was in a suitcase in his room, a court heard on Wednesday 6th November.
The revelation came as the first evidence was presented in the trial of the 27-year-old suspect, who cannot be named for legal reasons.
Ms Millane, 22, who was from Wickford, Essex, was last seen in Auckland, New Zealand, on 1 December 2018, before her body was found a week later.
The suspect denies murder.
Prosecutors allege the British woman was strangled to death in the man's apartment after the two met on the dating app Tinder. Court documents showed he had been living at the Citylife Hotel on Queen Street in central Auckland, which is where Miss Millane was last seen.
Plymouth, Montserrat
Plymouth is still the capital city of Montserrat, making it the only ghost town that is the capital of a political territory.
The Hinterkaifeck Murders
All 6 people living on a farm in Germany were bludgeoned to death in 1922. The murders are still unsolved.


Hong Kong: Two decades after developed nations agreed to halt the proliferation of strategic missile technology, China and India are leading the most significant modernization of nuclear-capable ballistic missile and cruise missile forces in Asia since the Cold War, according to arms control analysts.
The growth in the sophistication and number of strategic missiles across the region in recent years, the analysts said, underscores the impotence of global missile nonproliferation initiatives and heightening risk of missile and nuclear force competition between major powers.
"We are on the cusp of a new level of strategic rivalry in the region," said Daryl Kimball, executive director of the Arms Control Association, based in Washington, DC. "India and Pakistan are about to move beyond short- and intermediate- missile range capabilities. China too is slowly exploring more advanced intercontinental ballistic missiles."
On April 12, just a week before the Missile Technology Control Regime marked its 20th anniversary, India carried out the first test of a developmental missile, monitored by navy ships in the Bay of Bengal. With the test of the missile, the Agni-III, Indian officials said they had confirmed a capability to deliver a nuclear or conventional warhead as far away as Beijing.
While the Indian missile test generated a brief flurry of news reports around the world, the anniversary of the 1987 missile nonproliferation initiative, established by the Group of Seven, passed days later with barely a mention.
"It has largely failed in its primary objectives," said Waheguru Pal Singh Sidhu, an arms control analyst at the Geneva Center for Security Policy, referring to the nonproliferation initiative. "Everyone thinks their missiles are part of the solution. It's the other guy's missiles that are part of the problem."
Analysts said the ineffectiveness of missile control initiatives is most apparent in East and South Asia, where several countries are rapidly expanding arsenals of new types of ballistic and cruise missiles. Few countries in the region are signers to any of the international nonproliferation agreements aimed at inhibiting missile and missile-technology development and exports.
Leading the way in the development of new missiles are the region's established nuclear powers—China, India and Pakistan—all of which have embarked on significant modernization of nuclear-capable missile forces to improve the range, precision and survivability of weapons. This will bolster the credibility of the nuclear deterrence of these countries in the coming years and underscore their growing strategic power.
But the region also has to contend with the missile ambitions of North Korea and Iran, which have for a number of years invested heavily in trying to acquire long-range ballistic missiles with mixed success. Last year, North Korea carried out an underground nuclear test, although it has yet to show it can mount a warhead on a missile. Iran is suspected of pursuing a nuclear weapons programme.
In addition, several Asian countries that do not have aspirations to join the nuclear club are looking to buy or develop their own conventional strategic missile capabilities, in particular cruise missiles able to strike at targets from distances of several hundred kilometres. The spread of cruise missiles has become an issue of increasing importance and grave concern on the nonproliferation agenda.
In both the indigenous development of ballistic and cruise missiles, India has emerged in recent years as a formidable power. It is also being looked to as a major supplier of state-of-the-art cruise missiles to friendly countries.
The importance of the Agni-III test in April would not have been lost on Beijing. Since they fought a border war in 1962, the two countries have established stable relations, despite the unresolved border issue.
The explicit purpose of the Agni-III, which has a range of 3,500km, or 2,200 miles, is to have the option of targeting Chinese cities and maintaining a policy of minimum nuclear deterrence. Indian defence experts say a second test firing of the Agni-III is expected before the year is out. India has also developed a generation of shorter-range missiles to target Pakistan.
Kapil Kak, director of the Center for Strategic and International Studies in New Delhi, said India's armed forces are likely to add a submarine-launched ballistic missile to strategic nuclear forces in the coming decade.
Kak said India was discussing with Russia the possible loan of one or two nuclear submarines to build up technical and operational skills for the eventual domestic construction of a vessel.
Both the submarine-launched missile and the Agni programmes are "vital for the credibility of minimum nuclear deterrence," said Kak, a retired Indian Air Force vice-marshal.
India has separately developed a supersonic cruise missile, which Kak described as a "quantum jump" in cruise missile technology. Built by BrahMos Aerospace, a joint venture between India and Russia, it is capable of travelling at 2.8 times the speed of sound and has a range of 290km. By contrast, the US Tomahawk travels at subsonic speeds.
This year, Indian newspapers quoted Sivathanu Pillai, the BrahMos chief executive, as saying that 1,000 of the land-and-sea-launched missiles could be exported over a decade, with the first deal signed as early as December.
Malaysia and Indonesia have been cited as among the potential customers in Asia.
Military analysts said the significance of the BrahMos missile is that its supersonic speed makes the air defence systems on surface ships extremely vulnerable.
Aircraft carriers would be forced to operate much further back from potential conflict zones to stay out of missile range.
The Indians are not alone in the region in sharply improving missile technologies.
In the field of cruise missiles, China, Pakistan and Taiwan all have well-advanced indigenous development programmes.
At the end of August, Pakistan tested an air-launched cruise missile known as Ra'ad, or Thunder, with a range of 350km.
A statement issued by the Pakistani military said the missile was capable of carrying "all types" of warheads and had a stealth design to minimize radar detection. India plans an air-launched version of the BrahMos soon.


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Volleyball Ends Season with Sweep of Bulls
By Nick Arthur for WVUsports.com
» BOX SCORE
BUFFALO, N.Y. - The West Virginia University volleyball team defeated Buffalo, 3-0 (25-23, 25-23, 25-21), on Saturday afternoon in its season finale.
"I thought Buffalo played great tonight," says coach Jill Kramer. "They served really tough and played great defense. We were down by at least four at one point or another in each set, but our team stuck together, stayed composed and played disciplined in clutch time."
The sweep was West Virginia's 11th sweep win of the season.
The Mountaineers (20-13, 5-11 Big 12) finished the year with its first 20-win season since 1991, and coach Kramer recorded her 50th career win in the victory over the Bulls.
"(Sophomore setter) Brittany Sample did a great job of spreading the offense out and giving everybody good looks," Kramer says. "There were a couple of times throughout the match that our passing broke down a bit, but she continued to keep us in tempo."
West Virginia freshman outside hitter Jordan Anderson led all players with 17 kills and just two errors for a .429 attack percentage. Sample dished 40 assists while helping the Mountaineers record a .327 hitting percentage for the match.
As a team, West Virginia had 46 kills and just 11 hitting errors.
The Mountaineers fell behind in the first set. The Bulls held a 20-16 advantage late in the set, but WVU claimed nine of the final 12 points in the set to win the first game 25-23. West Virginia posted a .395 team hitting percentage in the set, behind 14 assists from Sample.
Buffalo jumped out to an early 4-0 lead in the second. The Mountaineers settled down, though, and led by as many as five, 15-10. They were able to hold off a late comeback from Buffalo to win the second game 25-23.
Anderson added seven more kills in the third set. The Mountaineers held the Bulls to just a .167 hitting clip. WVU senior outside hitter Elzbieta Klein recorded a kill on the final swing of the season to give West Virginia a 25-21 set win to complete the sweep.
"Our improvement this year is 100 percent on the team. They are committed to pursuing excellence and our staff is committed to giving them all of the tools they need to do so," Kramer says. "The time and effort they put into their spring and summer workouts gave us a tremendous foundation to build on. We are just getting started with this young group. I have so much faith in them and all we can accomplish together."
West Virginia set many firsts in 2013, including the best start in program history (10-0) and the most wins in a single season since 1991.
http://www.wvusports.com/page.cfm?story=24701&cat=exclusives


Hi there, my name is Kevin Ponce. I am a Web & Graphic Designer in Brooklyn. I graduated from New York City College of Technology in 2016 with a Bachelors of Technology in Computer Systems.
Where Have I Been? Degree + College (When did you / will you graduate; Past Jobs/Internships (Mention the most relevant, recent ones); More... (Volunteering, leadership within community) I graduated from college in February 2016. During my years as a college student I have had numerous internships that I took upon myself to seek out knowing that it will better help me gain experience in the field. I also volunteered for the St. Bernard Project, Friends of Rockaway, Sandy Relief. The St. Bernard Project I volunteered for helped the people that were affect by Hurricane Sandy in restoring the houses affected.
Where Am I Now? Current job (title, company, skills relevant to career in digital marketing); COOP (why did you join, what do you want to gain from the experience?); More... (Volunteering, leadership within community) I am currently working at the NYC Human Resource Administration in the Finance Office, with the Strategic Enterprise Analysis & Development department as an ASP.NET Developer. I am currently working on this project using the C# programming language and developing both the front and back-end for it. I joined COOP to better broaden my knowledge on digital marketing and analytics. I see COOP helping me in enhancing my skills.
Where Am I Going? Near future plans beyond starting a career in digital marketing (think about the skills you want to develop); 10 years from now (where do you see yourself, what are dreams/goals) I want to work in a career that will challenge me to learn new skills, while also enhancing the skills I already know. I have always enjoyed helping people, so I want to volunteer overseas to help the less fortunate.
I can very easily adapt to new challenges that arise.
I can communicate well and have great interpersonal skills, which work well in a group environment.
I can be a good technical go to person, given my educational background.
I can work on how to better explain any technology reference to people in a simpler way.
Why do you like this company? What makes them special? Is there a leader at this organization you really admire? I like Kinvolved because of their mission to increase student performance by increasing student attendance. I admire both the co-founders, Miriam Altman and Alexandra Meis for their mission to help kids in schools to achieve the best performance they can.
In my final year at NYC College of Technology, I began interning at the NYC Human Resource Administration. I was given the assignment to gather the software the was on everyone's computer, to better help my supervisor know what software they have and what version of it.
The company already had part of the database schema setup, so my task was to create both the back-end and front-end design of the web site. I had to make the website work efficiently and make the graphical user interface appealing to the user. Also being that this project would be on my own, I had to find the best approach to completing the project with the most current software practices.
I asked my supervisor the best approach for the layout design. Once i completed the database part of the project, I then proceeded to the back-end, the actual coding part and making the connections to the actual database.
I first started with the database since once i have all the queries and stored procedures set up the right way, then the back-end will be a easier task to tackle.


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Fortnite Summer Block Party announced
Epic Games has announced that it will be holding a two-day Summer Block Party event for Fortnite next month.
The event takes place on June 15th and June 16th at the Forum in Inglewood, California and will feature appearances from Ninja, Brendon Urie of Panic! At The Disco, Dillon Francis, Kitty Plays, Cray, and Jordan Fisher.
The first day of the event will see celebrities and streamers battle it out in the first ever Creative tournament, which pits eight teams of four against each other in a new player-made game mode that has been designed for the event. Following this on Sunday, June 16th, will be the return of the Fortnite Celebrity Pro-Am, which sees 50 teams competing for the Victory Royale.
"Meet more than 20 of your favorite Fortnite characters including Peely, Fishstick, and Brite Bomber. Glide on the island's ziplines, visit the Pirate Ship, or play a round of Fortnite Mini Golf," the developer adds. "Get your fill at the Durr Burger, Pizza Pete's, Sofdeez Ice Cream Shop and other in-game eateries brought to life. You can even complete a real-world Battle Pass to earn collectible swag."
Tickets for the event are due to go on sale soon for $35 via Ticketmaster. Preregistration is available now via Fortnite's Ticketmaster Verified Fan website to "be among the first to be notified" when tickets go on sale.
Fortnite Celebrity Pro-Am
Fortnite Summer Block Party
Fortnite's Celebrity Pro-Am will return during the two-day Summer Block Party event in June.
By Matthew Bennett | 05/13/2019 06:21 AM PT


For a good map of our location, click here to go to the Ordnance Survey map website, and enter SW956785 in the search box.
Click here to save or print a set of the following directions and maps - opens as a pdf.
Just past Exeter take the A30 sign to Launceston.
Some 50 miles past Exeter is the sign to Launceston.
Stay on the A30 for a few miles beyond Launceston and there is a sign to the right at Kennards House which says A395 to Camelford, Wadebridge and North Cornwall (A39). Take this turn to the right and follow it until T junction with the A39 which is approximately 13 miles from the A30.
Take the left hand turn on the A39 towards Wadebridge.
Approximately 2-3 miles along the A39 take the right hand turn that is signposted to Delabole, Tintagel and Port Isaac, the B3314.
After a further 2-3 miles there is another cross roads, go straight across staying on the B3314 still signposted to Wadebridge.
Continue on this road through Delabole for approximately 7 miles.
Take the right hand turn towards Port Quinn and Polzeath, follow the tourist sign to the Bee Centre. After half a mile there is a further junction take the right hand turn towards the Bee Centre. Do not take the very sharp hand turn here to Port Quinn as it is a minor lane only.
Passing the Bee centre on your right, the road then bends to the right, on the bend go left down a small road that is signed at the end 'Mesmear Farm'.
Drive past Mesmear and Moyles is the next farm on the left after about half a mile.
The 'Moyles' slate sign is in the wall. Go down the drive, and keep Cornish 'Hedge' (wall) on your right.
Moyles Mill is straight ahead continue right to the end of the wall (keeping wall on your right) to Mynford cottage.


Washington, D.C. – Today the national pro-life group Susan B. Anthony List (SBA List) announced its endorsement of Katie Arrington in South Carolina's 1st Congressional District.
Katie Arrington has served in the South Carolina House of Representatives since 2017. The wife of a soldier, she began her career by providing daycare services to military families, then worked in international trade before becoming a cybersecurity expert for the Department of Defense and running her own defense contracting company. She and her husband Rob have three children, including a son who was born with special needs and is now thriving.