estrenes

Summary

Summary: Unsaturated derivatives of the ESTRANES with methyl groups at carbon-13, with no carbon at carbon-10, and with no more than one carbon at carbon-17. They must contain one or more double bonds.

Top Publications

  1. Gogny A, Mallem Y, Destrumelle S, Thorin C, Desfontis J, Gogny M, et al. In vitro comparison of myometrial contractility induced by aglepristone-oxytocin and aglepristone-PGF2alpha combinations at different stages of the estrus cycle in the bitch. Theriogenology. 2010;74:1531-8 pubmed publisher
  2. Rollon E, Millan Y, de las Mulas J. Effects of aglepristone, a progesterone receptor antagonist, in a dog with a vaginal fibroma. J Small Anim Pract. 2008;49:41-3 pubmed
    ..This study shows that benign tumours of the vagina of the dog that contain progesterone receptors can be reduced in size in a palliative or neoadjuvant setting using the progesterone receptor antagonist aglepristone. ..
  3. Newman S, Foster P, Ho Y, Day J, Raobaikady B, Kasprzyk P, et al. The therapeutic potential of a series of orally bioavailable anti-angiogenic microtubule disruptors as therapy for hormone-independent prostate and breast cancers. Br J Cancer. 2007;97:1673-82 pubmed
    ..In contrast to the taxanes, STX140 can be dosed orally, with no toxicity being observed even after prolonged daily dosing. ..
  4. Newman S, Foster P, Stengel C, Day J, Ho Y, Judde J, et al. STX140 is efficacious in vitro and in vivo in taxane-resistant breast carcinoma cells. Clin Cancer Res. 2008;14:597-606 pubmed publisher
    ..The clinical potential of STX140 was further highlighted by the efficacy seen in xenografts recently derived from patients who had failed on taxane therapy. ..
  5. Foster P, Newman S, Leese M, Bernetiere S, Diolez C, Camara J, et al. A new micronized formulation of 2-methoxyestradiol-bis-sulfamate (STX140) is therapeutically potent against breast cancer. Anticancer Res. 2008;28:577-81 pubmed
    ..The new micronized formulation of STX140 is orally bioavailable and efficacious at inhibiting MDA-MB-231 breast tumor growth. ..
  6. Foster P, Stengel C, Ali T, Leese M, Potter B, Reed M, et al. A comparison of two orally bioavailable anti-cancer agents, IRC-110160 and STX140. Anticancer Res. 2008;28:1483-91 pubmed
    ..These studies highlight the activity of two orally bioavailable anti-cancer agents one of which, STX140, may offer a significant clinical advantage over existing drugs as a common dose limiting factor, haemotoxicity, may be minimised. ..
  7. Molostvov G, Fletcher S, Bland R, Zehnder D. Extracellular calcium-sensing receptor mediated signalling is involved in human vascular smooth muscle cell proliferation and apoptosis. Cell Physiol Biochem. 2008;22:413-22 pubmed publisher
    ..05). In conclusion, stimulation of CaSR leads to activation of MEK1/ERK1,2 and PLC pathways and up-regulation of cell proliferation. CaSR-mediated PLC activation is important for SMC survival and protection against apoptosis. ..
  8. LaVallee T, Burke P, Swartz G, Hamel E, Agoston G, Shah J, et al. Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198. Mol Cancer Ther. 2008;7:1472-82 pubmed publisher
    ..ENMD-1198 was selected as the lead molecule in this analogue series and is currently in a phase I clinical trial in patients with refractory solid tumors. ..
  9. Naito Y, Okada M, Yagisawa H. Phospholipase C isoforms are localized at the cleavage furrow during cytokinesis. J Biochem. 2006;140:785-91 pubmed

More Information

Publications62

  1. Leese M, Jourdan F, Gaukroger K, Mahon M, Newman S, Foster P, et al. Structure-activity relationships of C-17 cyano-substituted estratrienes as anticancer agents. J Med Chem. 2008;51:1295-308 pubmed publisher
    ..The potential of these multimechanism anticancer agents was confirmed in vivo, with promising activity observed for both 14 and 15 in an athymic nude mouse MDA-MB-231 human breast cancer xenograft model. ..
  2. Jurka P, Max A, Hawryńska K, Snochowski M. Age-related pregnancy results and further examination of bitches after aglepristone treatment of pyometra. Reprod Domest Anim. 2010;45:525-9 pubmed publisher
    ..It seems necessary to mate bitches in the first or second oestrus after finishing treatment. The efficacy of treatment can be measured by the after-treatment pregnancy rate. ..
  3. Gulbransen B, Sharkey K. Purinergic neuron-to-glia signaling in the enteric nervous system. Gastroenterology. 2009;136:1349-58 pubmed publisher
  4. Lemini C, Canchola E. Effects of 17beta-aminoestrogens on the sexual behavior of female rats. Physiol Behav. 2009;96:662-6 pubmed publisher
    ..AEs LQDE50 values correlate with previous Uw DE50, LH ID50 and binding studies indicates mediation of the response by estrogen receptors. AEs facilitate sexual behavior of Ovx rats as partial estrogenic agonists...
  5. González G, Alvarado Vásquez N, Fernández G J, Cruz Robles D, Del Valle L, Pinzón E, et al. The antithrombotic effect of the aminoestrogen prolame (N-(3-hydroxy-1,3,5(10)-estratrien-17B-YL)-3-hydroxypropylamine) is linked to an increase in nitric oxide production by platelets and endothelial cells. Atherosclerosis. 2010;208:62-8 pubmed publisher
    ..d) Prolame reduces the formation of thrombi in an in vivo thrombosis model. Prolame could be a preferred alternative to other estrogens because of its reduced thromboembolic risk. ..
  6. Guil Luna S, Sánchez Céspedes R, Millan Y, De Andrés F, Rollon E, Domingo V, et al. Aglepristone decreases proliferation in progesterone receptor-positive canine mammary carcinomas. J Vet Intern Med. 2011;25:518-23 pubmed publisher
    ..5% of RU534-treated tumors with PR expression. Conversely, no effect on AI was observed after RU534 treatment. Neoadjuvant RU534 treatment had PR expression-related inhibiting effects on proliferation of canine mammary carcinoma cells. ..
  7. Islander U, Erlandsson M, Chavoshi T, Jochems C, Moverare S, Nilsson S, et al. Estren-mediated inhibition of T lymphopoiesis is estrogen receptor-independent whereas its suppression of T cell-mediated inflammation is estrogen receptor-dependent. Clin Exp Immunol. 2005;139:210-5 pubmed
    ..Thus, our study is the first to show that estren inhibits T lymphopoiesis via ER-independent pathways, whereas its suppressive effects on inflammation are ER-dependent. ..
  8. Chwalisz K, Elger W, Stickler T, Mattia Goldberg C, Larsen L. The effects of 1-month administration of asoprisnil (J867), a selective progesterone receptor modulator, in healthy premenopausal women. Hum Reprod. 2005;20:1090-9 pubmed
    ..It induces amenorrhea primarily by targeting the endometrium in the absence of estrogen deprivation. ..
  9. DeManno D, Elger W, Garg R, Lee R, Schneider B, Hess Stumpp H, et al. Asoprisnil (J867): a selective progesterone receptor modulator for gynecological therapy. Steroids. 2003;68:1019-32 pubmed
    ..With favorable safety and tolerability profiles thus far, asoprisnil appears promising as a novel treatment of gynecological disorders, such as uterine fibroids and endometriosis. ..
  10. Winks J, Hughes S, Filippov A, Tatulian L, Abogadie F, Brown D, et al. Relationship between membrane phosphatidylinositol-4,5-bisphosphate and receptor-mediated inhibition of native neuronal M channels. J Neurosci. 2005;25:3400-13 pubmed
  11. Kousteni S, Han L, Chen J, Almeida M, Plotkin L, Bellido T, et al. Kinase-mediated regulation of common transcription factors accounts for the bone-protective effects of sex steroids. J Clin Invest. 2003;111:1651-64 pubmed
  12. Kousteni S, Chen J, Bellido T, Han L, Ali A, O Brien C, et al. Reversal of bone loss in mice by nongenotropic signaling of sex steroids. Science. 2002;298:843-6 pubmed
    ..Such ligands merit investigation as potential therapeutic alternatives to hormone replacement for osteoporosis in both women and men [corrected]. ..
  13. Bhatti S, Duchateau L, Okkens A, Van Ham L, Mol J, Kooistra H. Treatment of growth hormone excess in dogs with the progesterone receptor antagonist aglépristone. Theriogenology. 2006;66:797-803 pubmed
    ..5 weeks after the last aglépristone administration the mean plasma IGF-I concentration increased again. In conclusion, aglépristone can be used successfully to treat dogs with progestin-induced hypersomatotropism. ..
  14. Fieni F. Clinical evaluation of the use of aglepristone, with or without cloprostenol, to treat cystic endometrial hyperplasia-pyometra complex in bitches. Theriogenology. 2006;66:1550-6 pubmed
    ..Thirteen of 15 bitches in whom plasma progesterone concentrations were initially low (< 3.18 nmol/L) were cured. The recurrence rate after 12 and 24 months was 13.0% (3/23) and 19.0% (4/21), respectively. ..
  15. Stemkowski P, Tse F, Peuckmann V, Ford C, Colmers W, Smith P. ATP-inhibition of M current in frog sympathetic neurons involves phospholipase C but not Ins P(3), Ca(2+), PKC, or Ras. J Neurophysiol. 2002;88:277-88 pubmed
    ..The possibility remains that "lipid-signaling" mechanisms, perhaps involving PLC-induced depletion of phosphatidylinositol bisphosphate, are involved in PLC-mediated inhibition of g(M) by ATP in amphibian sympathetic neurons. ..
  16. Galac S, Kooistra H, Dieleman S, Cestnik V, Okkens A. Effects of aglépristone, a progesterone receptor antagonist, administered during the early luteal phase in non-pregnant bitches. Theriogenology. 2004;62:494-500 pubmed
    ..The shortening of the interestrous interval suggests that aglépristone administered in the early luteal phase influences the hypothalamic-pituitary-ovarian axis. ..
  17. Knox C, Belous A, Pierce J, Wakata A, Nicoud I, Anderson C, et al. Novel role of phospholipase C-delta1: regulation of liver mitochondrial Ca2+ uptake. Am J Physiol Gastrointest Liver Physiol. 2004;287:G533-40 pubmed
    ..These data indicate that PLC-delta1 exists in liver mitochondria and is involved in regulating mCa2+ uptake through the uniporter. ..
  18. Gordienko D, Bolton T. Crosstalk between ryanodine receptors and IP(3) receptors as a factor shaping spontaneous Ca(2+)-release events in rabbit portal vein myocytes. J Physiol. 2002;542:743-62 pubmed
  19. Chwalisz K, Perez M, DeManno D, Winkel C, Schubert G, Elger W. Selective progesterone receptor modulator development and use in the treatment of leiomyomata and endometriosis. Endocr Rev. 2005;26:423-38 pubmed
    ..Asoprisnil may, therefore, provide a novel, tissue-selective approach to control endometriosis-related pain. SPRMs have the potential to become a novel treatment of uterine fibroids and endometriosis. ..
  20. Chabbert Buffet N, Meduri G, Bouchard P, Spitz I. Selective progesterone receptor modulators and progesterone antagonists: mechanisms of action and clinical applications. Hum Reprod Update. 2005;11:293-307 pubmed
    ..Further developments might also include hormone replacement therapy in post-menopausal women, as well as the treatment of hormone-dependent tumours. ..
  21. Krjukova J, Holmqvist T, Danis A, Akerman K, Kukkonen J. Phospholipase C activator m-3M3FBS affects Ca2+ homeostasis independently of phospholipase C activation. Br J Pharmacol. 2004;143:3-7 pubmed
    ..m-3M3FBS also interfered with store-operated Ca(2+) influx and Ca(2+) extrusion. In conclusion, m-3M3FBS cannot be considered either potent or specific PLC activator. ..
  22. Schubert G, Elger W, Kaufmann G, Schneider B, Reddersen G, Chwalisz K. Discovery, chemistry, and reproductive pharmacology of asoprisnil and related 11beta-benzaldoxime substituted selective progesterone receptor modulators (SPRMs). Semin Reprod Med. 2005;23:58-73 pubmed
    ..Asoprisnil was selected for further clinical development. It shows promising results in the treatment of uterine leiomyomata and endometriosis. ..
  23. Moverare S, Dahllund J, Andersson N, Islander U, Carlsten H, Gustafsson J, et al. Estren is a selective estrogen receptor modulator with transcriptional activity. Mol Pharmacol. 2003;64:1428-33 pubmed
    ..Thus, estren has the capacity to exert genomic effects via both ERalpha and ERbeta. We conclude, in contrast to what was previously reported by others, that estren is a SERM with transcriptional activity. ..
  24. Lemini C, Franco Y, Avila M, Jaimez R. Contrasting effects of estradiol and 17 beta-aminoestrogens on blood clotting time in rats and mice. Eur J Pharmacol. 2005;510:229-33 pubmed
    ..The maximum procoagulant effect of estradiol was obtained after 72 h with 10 microg/animal/day (-45%; P<0.01). 17 Beta-aminoestrogens always produced opposite effects to those of estradiol on blood coagulation...
  25. Saul D, Fabian L, Forer A, Brill J. Continuous phosphatidylinositol metabolism is required for cleavage of crane fly spermatocytes. J Cell Sci. 2004;117:3887-96 pubmed
  26. Centrella M, McCarthy T, Chang W, Labaree D, Hochberg R. Estren (4-estren-3alpha,17beta-diol) is a prohormone that regulates both androgenic and estrogenic transcriptional effects through the androgen receptor. Mol Endocrinol. 2004;18:1120-30 pubmed
    ..Therefore, through local metabolism, estren indirectly activates the androgen receptor to regulate both androgen- and estrogen-like transcriptional responses by bone-forming cells. ..
  27. Trasch K, Wehrend A, Bostedt H. Follow-up examinations of bitches after conservative treatment of pyometra with the antigestagen aglepristone. J Vet Med A Physiol Pathol Clin Med. 2003;50:375-9 pubmed
    ..The presented data show that treatment of pyometra by aglepristone results in a high healing rate. The recurrence rate can be minimized by the selection of bitches without ovarian cysts and cystic endometrial hyperplasia. ..
  28. Svensson E, Markström E, Shao R, Andersson M, Billig H. Progesterone receptor antagonists Org 31710 and RU 486 increase apoptosis in human periovulatory granulosa cells. Fertil Steril. 2001;76:1225-31 pubmed
    ..Nuclear PR-mediated effects are involved in regulating the susceptibility to apoptosis in LH receptor-stimulated human luteinizing granulosa cells. ..
  29. Horowitz L, Hirdes W, Suh B, Hilgemann D, Mackie K, Hille B. Phospholipase C in living cells: activation, inhibition, Ca2+ requirement, and regulation of M current. J Gen Physiol. 2005;126:243-62 pubmed
    ..In each test, the suppression of KCNQ current closely paralleled the expected fall of PIP2. The results are described by a kinetic model...
  30. Azuma M, Tanaka M, Nejigaki Y, Uchiyama M, Takahashi A, Shioda S, et al. Pituitary adenylate cyclase-activating polypeptide induces somatolactin release from cultured goldfish pituitary cells. Peptides. 2009;30:1260-6 pubmed publisher
  31. Tsai M, Chen Y. (+/-)3,4-Methylenedioxyamphetamine elicits action potential bursts in a central snail neuron. Exp Neurol. 2007;203:423-44 pubmed
    ..Instead, the MDA-elicited action potential bursts are closely related to PKC activity and the inhibitory effects on the I(KD). ..
  32. Zhao C, Guan X, Liu X, Zhang H. Synthesis of molecularly imprinted polymer using attapulgite as matrix by ultrasonic irradiation for simultaneous on-line solid phase extraction and high performance liquid chromatography determination of four estrogens. J Chromatogr A. 2012;1229:72-8 pubmed publisher
    ..The limits of detection for these estrogens were in the range of 1-8 ng g(-1) and reproducibility were less than 5.1% as RSDs (n=6) with milk samples spiked at 100 and 1000 ng g(-1) of each analyte...
  33. Vivar R, Soto C, Copaja M, Mateluna F, Aranguiz P, Munoz J, et al. Phospholipase C/protein kinase C pathway mediates angiotensin II-dependent apoptosis in neonatal rat cardiac fibroblasts expressing AT1 receptor. J Cardiovasc Pharmacol. 2008;52:184-90 pubmed publisher
    ..We conclude that Ang II stimulates the intrinsic apoptotic pathway in cultured cardiac fibroblasts by the AT1R/PLC/PKC signaling pathway. ..
  34. Wang D, Sun Y, Zhang W, Huang P. Apical adenosine regulates basolateral Ca2+-activated potassium channels in human airway Calu-3 epithelial cells. Am J Physiol Cell Physiol. 2008;294:C1443-53 pubmed publisher
    ..Our findings provide novel mechanistic insights into the regulation of anion section by adenosine, a key player in the airway surface liquid homeostasis and mucociliary clearance. ..
  35. Xia W, Shen Y, Xie H, Zheng S. Involvement of endoplasmic reticulum in hepatitis B virus replication. Virus Res. 2006;121:116-21 pubmed
  36. Wilkens J, Chwalisz K, Han C, Walker J, Cameron I, Ingamells S, et al. Effects of the selective progesterone receptor modulator asoprisnil on uterine artery blood flow, ovarian activity, and clinical symptoms in patients with uterine leiomyomata scheduled for hysterectomy. J Clin Endocrinol Metab. 2008;93:4664-71 pubmed publisher
    ..Asoprisnil moderately reduced uterine artery blood flow. This effect may contribute in part to the clinical effects of asoprisnil. ..
  37. Tseng L, Shu S, Kuo C, Chou C, Hsieh Y, Chu S, et al. Effect of methoxychlor on Ca2+ handling and viability in OC2 human oral cancer cells. Basic Clin Pharmacol Toxicol. 2011;108:341-8 pubmed publisher
    ..Methoxychlor induced cell death that may involve apoptosis...
  38. Fu J, Song H, Zhou M, Zhu H, Wang Y, Chen H, et al. Progesterone receptor modulators for endometriosis. Cochrane Database Syst Rev. 2017;7:CD009881 pubmed publisher
    ..5 mg dose of mifepristone may be less effective than higher doses. We found insufficient evidence to permit firm conclusions about the safety and effectiveness of other progesterone receptor modulators. ..
  39. Kaabia Z, Dervilly Pinel G, Hanganu F, Cesbron N, Bichon E, Popot M, et al. Ultra high performance liquid chromatography/tandem mass spectrometry based identification of steroid esters in serum and plasma: an efficient strategy to detect natural steroids abuse in breeding and racing animals. J Chromatogr A. 2013;1284:126-40 pubmed publisher
    ..The last equine experiment resulted in a maximal nandrolone laurate concentration of 440 pg/mL in horse plasma 24h after administration. ..
  40. Hjortø G, Kiilerich Pedersen K, Selmeczi D, Kledal T, Larsen N. Human cytomegalovirus chemokine receptor US28 induces migration of cells on a CX3CL1-presenting surface. J Gen Virol. 2013;94:1111-20 pubmed publisher
    ..Overall, this indicates that infected cells probably move more than uninfected cells in inflamed tissues with high CX3CL1 expression, with soluble chemokines affecting the final migration. ..
  41. Battefeld A, Rocha N, Stadler K, Bräuer A, Strauss U. Distinct perinatal features of the hyperpolarization-activated non-selective cation current I(h) in the rat cortical plate. Neural Dev. 2012;7:21 pubmed publisher
    ..Taken together, these data indicate a HCN subunit shift initiated in the first 24 hours after birth and implicate a prominent perinatal role of the phylogenetically older HCN3 and/or HCN4 subunits in the developing neocortex. ..
  42. Zhao Y, Migita K, Sato C, Usune S, Iwamoto T, Katsuragi T. Endoplasmic reticulum is a key organella in bradykinin-triggered ATP release from cultured smooth muscle cells. J Pharmacol Sci. 2007;105:57-65 pubmed
    ..Furthermore, the bradykinin-induced transient accumulation of ATP in the cells treated with PCA may imply a possible release of ATP from the endoplasmic reticulum. ..
  43. Ouyang Q, Sato H, Murata Y, Nakamura A, Ozaki M, Nakamura T. Contribution of the inositol 1,4,5-trisphosphate transduction cascade to the detection of "bitter" compounds in blowflies. Comp Biochem Physiol A Mol Integr Physiol. 2009;153:309-16 pubmed publisher
    ..These results suggest that G-proteins mediate the IP(3) pathway in the transduction cascade in bitter-sensitive receptor cells. ..
  44. Dong X, Smoll E, Ko K, Lee J, Chow J, Kim H, et al. P2Y receptors mediate Ca2+ signaling in duodenocytes and contribute to duodenal mucosal bicarbonate secretion. Am J Physiol Gastrointest Liver Physiol. 2009;296:G424-32 pubmed publisher
  45. Vetter I, Wyse B, Roberts Thomson S, Monteith G, Cabot P. Mechanisms involved in potentiation of transient receptor potential vanilloid 1 responses by ethanol. Eur J Pain. 2008;12:441-54 pubmed
    ..The results presented here suggest that morphine may be of limited use in inhibiting nociceptive TRPV1 responses that have been sensitised by exposure to ethanol. ..
  46. Winter C, Kampik N, Vedovelli L, Rothenberger F, Paunescu T, Stehberger P, et al. Aldosterone stimulates vacuolar H(+)-ATPase activity in renal acid-secretory intercalated cells mainly via a protein kinase C-dependent pathway. Am J Physiol Cell Physiol. 2011;301:C1251-61 pubmed publisher
    ..PKA and cAMP appear to have a modulatory effect. The rapid nongenomic action of aldosterone may participate in the regulation of H(+)-ATPase activity and contribute to final urinary acidification. ..
  47. Kwaaitaal M, Huisman R, Maintz J, Reinstädler A, Panstruga R. Ionotropic glutamate receptor (iGluR)-like channels mediate MAMP-induced calcium influx in Arabidopsis thaliana. Biochem J. 2011;440:355-65 pubmed publisher
    ..We conclude that the initiation of innate immune responses upon flg22, elf18 and chitin recognition involves apoplastic Ca2+ influx via iGluR-like channels. ..
  48. Avila M, Garcia S, Reyes Salas M, Antuna S, Lemini C. Effect of the 17beta-aminoestrogen pentolame on bone mineral levels in ovariectomized rats. Proc West Pharmacol Soc. 2009;52:43-6 pubmed
    ..The other minerals showed great variability and no significant differences were detected. Our results indicate differential action of AEP related to E2 in the restitution of bone mineral content. ..
  49. Dobrydneva Y, Weatherman R, Trebley J, Morrell M, Fitzgerald M, Fichandler C, et al. Tamoxifen stimulates calcium entry into human platelets. J Cardiovasc Pharmacol. 2007;50:380-90 pubmed
    ..The ability of tamoxifen to increase [Ca2+]i in platelets, leading to platelet activation, and its ability to act synergistically with other platelet agonists may contribute to development of tamoxifen-induced thrombosis...
  50. Liu B, Liang H, Liu L, Zhang H. Phosphatidylinositol 4,5-bisphosphate hydrolysis mediates histamine-induced KCNQ/M current inhibition. Am J Physiol Cell Physiol. 2008;295:C81-91 pubmed publisher
    ..We concluded that the inhibition of KCNQ/M currents by histamine in HEK293 cells and SCG neurons is due to the consumption of membrane PIP(2) by PLC. ..
  51. Ortiz Capisano M, Reddy M, Mendez M, Garvin J, Beierwaltes W. Juxtaglomerular cell CaSR stimulation decreases renin release via activation of the PLC/IP(3) pathway and the ryanodine receptor. Am J Physiol Renal Physiol. 2013;304:F248-56 pubmed publisher
    ..001). We conclude stimulating JG cell CaSR activates G(q), initiating the PLC/IP(3) pathway, activating RyR, increasing intracellular calcium, and resulting in calcium-mediated renin inhibition. ..
  52. Bai G, Yuan K, Park W, Kim S, Kim S. Attenuation of hypoosmotic stress-induced ANP secretion via I(Cl,swell) in renal hypertensive rat atria. Peptides. 2008;29:1566-74 pubmed publisher
    ..The modification of responses of ANP release to hypoosmolarity and DIDS in hypertrophied atria may relate to changes in I(Cl,swell) activity by persistent high blood pressure. ..
  53. Fieni F, Gogny A. Clinical evaluation of the use of aglepristone associated with oxytocin to induce parturition in bitch. Reprod Domest Anim. 2009;44 Suppl 2:167-9 pubmed publisher
    ..05). This study confirms previous results and demonstrates that the combination of aglépristone and oxytocin can be safely and reliably used to induce parturition in beagle bitches, at 60 days post-estimated LH surge. ..