Hormonal contraception in Chinese men: variations insuppression of spermatogenesis with injectable testosteroneundecanoate and levonorgestrel implants

Aim: To explore the causes of the difference in spermatogenic suppression between responders and non-responders in Chinese men treated with levonorgestrel (LNG) implants plus testosterone undecanoate (TU) injectable. Methods: The 16 Chinese volunteers treated were divided into two groups in regard to the sperm count during the treatment period, 7 men in the responder group (Group R), including 6 azoospermia and one severe oligozoospermia, and the remaining 9 in the non-responder group (Group N), including 4 oligozoospermia and 5 with sperm counts greater than 20×106/mL. The differences in serum profiles of FSH, LH, T, LNG and T/LH ratio were compared between the two groups and the correlation between the seminal fluid parameters and serum reproductive hormones was analyzed. Results: The serum FSH level was lower in Group R than that in Group N (P<0.05), while the serum LH and LNG levels were higher in Group R than those in Group N (P<0.05). The sperm density (P<0.01, r=0.235), motility (P<0.01, r=0.326) and vitality (P<0.01, r=0.219) showed significantly positive correlation with the serum FSH level. Conclusion: The blood LNG and T levels, the degree of FSH inhibition and/or the sensitivity of the pituitary-testis axis to exogenous steroids, as well as the individual spermatogenetic potential and the functional status of the Leydig cells may be factors bringing about individual differences in spermatogenic suppression in Chinese men treated with LNG and TU.

Giant exophytic cystic adenomyosis with a levonorgestrel containing intrauterine device out of the uterine cavity after uterine myomectomy: A case report

BACKGROUND A cystic lesion arising from the myometrium of the uterus, termed as cystic adenomyosis, has chocolate-like, thick viscous contents and contains various amounts of endometrial stroma below the glandular epithelium. It is an extremely rare type of adenomyosis.CASE SUMMARY Herein, we report an unusual case of a giant cystic mass in the pelvic cavity after uterine myomectomy. The patient complained of abnormal uterine bleeding and severe dysmenorrhea. After a levonorgestrel-containing intrauterine device(LNG-IUD) was inserted, her symptoms were greatly alleviated. However, the LNG-IUD was detected in the cystic cavity during the follow-up. For fear of the intrauterine device migrating into and damaging the surrounding viscera,surgical treatment was proposed. Therefore, laparoscopic resection of the lesion and removal of the LNG-IUD were performed and cystic adenomyosis with an LNG-IUD out of the uterine cavity was diagnosed.CONCLUSION We believe that myomectomy breaking through the endometrial cavity may have been a predisposing factor for the development of cystic adenomyosis in this case.

Comparison of ESI–and APCI–LC–MS/MS methods:A case study of levonorgestrel in human plasma

Electrospray ionization(ESI) and atmospheric pressure chemical ionization(APCI) techniques for liquid chromatography–tandem mass spectrometry(LC–MS/MS) determination of levonorgestrel were evaluated.In consideration of difference in ionization mechanism,the two ionization sources were compared in terms of LC conditions,MS parameters and performance of method.The sensitivity for detection of levonorgestrel with ESI was 0.25 ng/m L which was lower than 1 ng/m L with APCI.Matrix effects were evaluated for levonorgestrel and canrenone(internal standard,IS) in human plasma,and the results showed that APCI source appeared to be slightly less liable to matrix effect than ESI source.With an overall consideration,ESI was chosen as a better ionization technique for rapid and sensitive quantification of levonorgestrel.The optimized LC–ESI–MS/MS method was validated for a linear range of 0.25–50 ng/m L with a correlation coefficient ≥0.99.The intra-and inter-batch precision and accuracy were within 11.72% and 6.58%,respectively.The application of this method was demonstrated by a bioequivalence study following a single oral administration of 1.5 mg levonorgestrel tablets in 21 Chinese healthy female volunteers.

Levonorgestrel Intrauterine System (LNG IUS) in Menorrahgia: A Follow-Up Study

Objective: To study the acceptability, efficacy, adverse effect and user satisfaction of Levonorgestrel intrauterine system (LNG IUS) for treatment of menorrahgia.?Method: This was an observational descriptive study conducted in ESI PGIMSR over a period from Jan 2008-June 2011. 70 women presented in O.P.D with heavy menstrual bleeding having no contraindication for device, consenting for LNG IUS underwent its insertion. Menstrual pattern, pictorial blood loss assessment chart score, adverse effects, and rate of acceptability and satisfaction were recorded at 3, 6 and 12 months after procedure. Results: The mean age of the sample was 39.92?yrs ± 3.27.?Indication for device insertion was DUB in 81.42% (57), fibroid 8.57% (6), adenomyosis in 10% (7). The expulsion rate was 4.2% (3), removal rate was 7.14% (5) and continuation rate is 88.57% (62). 2.28% (3) patients underwent hysterectomy because of continuous bleeding even after 3?-?4 months of insertion. On follow-up at one year out of 62 patients, 33.87% (21) were amenorrhic and 51.61% (32) have?regular period, while 3.07% (2) patients had irregular period.?Conclusion: LNG IUS is a less invasive, effective treatment modality for menorrahgia with reasonable efficacy.

Quality of Life in Women with Endometriosis Pelvic Pain Treated with the Levonorgestrel-Releasing Intrauterine System

Objective: To evaluate the quality of life in patients with endometriosis pelvic pain before and after the application of the levonorgestrel-releasing intrauterine system (LNG-IUS). Design: Open non-comparative study. Setting: Obstetrics and Gynecology Hospital at Monterrey, Mexico. Sample: 29 women aged 18 to 40 years with pelvic pain associated with endometriosis confirmed by laparoscopy. Methods: After laparoscopy but before LNG-IUS insertion (basal visit) and 6 months afterwards, modified Endometriosis Health Profile (EHP-30) was applied. Main outcomes measures: Size of change of questionnaire scores, need of additional analgesic therapy and adverse effects. Statistical Analysis: Differences in the questionnaire scores before and after intervention were analyzed by Student t-test. Results: Final analysis set included 29 women aged 31.7 ± 4.7 years years. The ASRM surgical staging of endometriosis was mild in 19.3 moderate in 13.7 and severe in 76% of the patients. The general perception of quality of life improved from 52 at baseline to 98% at six months (p < 0.001). Adverse events were mild in nature, 19 patients reported no adverse events during the study (65.5%). Two patients (6.9%) required the use of concomitant therapy with non-steroidal analgesics for relief of pain. Conclusion: The application of LNG-IUS in patients with pelvic pain associated with endometriosis improved significatively all aspects related with quality of life as measured with Endometriosis Health Profile (EHP-30). We concluded that LNGIUS may be an effective and convenient therapeutic alternative for the management of pain associated with endometriosis.

Study on Differences in Spermatogenic Suppression between Azoospermic and Oligozoospermic Responders Treated with Levonorgestrel Implant Plus Testosterone Undecanoate Injectable in Chinese Men

Objective To investigate possible causes resulting in the differences in the spermatogenesis suppression on individual treated with levonorgestrel (LNG) implants and testosterone undecanoate (TU) injectableMethods Totally 21 Chinese male volunteers were given treatment with LNG implants (four rods, 75 mg/rod) and intramuscular injection of TU (500 mg,bimonthly for 3 times). According to the effects of treatment, they were divided into two groups, namely, azoospermia group (group A) and oligozoospermia group (group O). Then seminal FSH, LH, T and estradiol (E2) were determined by immunoenzymetric assay, while seminal and serum dihydrotachysterol (DHT) and serum sex hormone binding globulin (SHBG) were by radioimmunoassay, and seminal transferrin (Tf) by scatter turbidimetry assay.Results Seminal FSH, LH and serum DHT, SHBG, FTI (T/SHBG ×100) levels were significantly lower in group A than in group O, while higher seminal concentrations ofE2 were observed in azoospermia group.Conclusion The differences in the spermatogenic suppression in Chinese men might be attributed to different rate of peripheral androgen metabolism, variations in serum SHBG levels, 5á-reductase activity and individual aromatase activity during LNG plus TU administration. In addition, seminal sex hormones might be more sensitive indexes to assess the extent of feedback inhibition on hypothalamus-pituitary-testis with exogenous testosterone plus progestogen in the efficacy hormone male contraceptive trials.

A randomized double-blind multicenter study on comparing levonorgestrel and mifepristone for emergency contraception

Objective: To compare the efficacy and side effects of levonorgestrel and low dose mifepristone in emergency contraception. Method: The study is a randomized double--blind multicenter comparative trial. A total of 1, 276 women with unprotected intercourse within 72 hours were allocated to one of the two study groups. In the levonorgestrel (LNG) group, 0. 75 mg LNG was taken twice, 12 hours apart, whereas in the mifepristone (Mife) group, a single dose of 10 mg mifepristone was taken and a placebo 12 hours after. Follow--up visit was paid on the seventh day of the expected next menstruation to evaluate the contraceptive efficacy and side effects. Contraceptive efficacy was calculated by Dixon’s method. Result:In the LNG group 20 pregnancies occurred among 643 women, while in the Mife group 9 pregnancies occurred among 633 women. The pregnancy rates were 3. 10% and 1. 43% respectively. Contraceptive efficacy rate of preventing pregnancy was 59. 16% and 79. 73%, the difference was statistically significant (P<O. 05). The incidence of various side effects, which were mild, was less than 10%. There was no statistical difference between the two groups. The percentage of subjects who had their next menstruation 3 days earlier or later than their expected menstruation in LNG group and Mife group was 77. 7% and 78. 5% respectively. Conclusion: Use of levonorgestrel or low dose mifepristone for emergency contraception is effective and safe.

Study on In Vivo Release of Levonorgestrel-containing Silicon Capsule

The in vivo release rate of levonorgestrel-containing silicon capsule (in vitro releasing rate: 6 μg/d) placed in rabbits was determined.The results showed that the average release per year was 8. 32 μg with r being 0.96000.The release pattern of the levonorgestrel-containing silicon capsule system was proved to be zero-order release. Our study provided some experimental data for clinical use of the system for birth control.

Effect of Domestically-made Levonorgestrel-releasing Intrauterine Device on the Endocrine System and Mensentruation in Monkeys

Effect of domestically-made levonorgestrel-releasing intrauterine device (LNG, release rate: 6 μg/day) on the endocrine system and menstruation in mondeys was investigated. The results showed that the Estradiol (E2) and progesterone (P) levels were significantly decreased 2 ovulatory cycles after iusertion of the devices as compared with those before insertion in 3 monkeys (P>0. 001) ,suggesting an evident ovulation-suppressing effect. In 1 monkey, the E2 and P levels were the same before and after insertion,and expulsion of device was found in the monkey later. The plasma LNG concentration in 3 animals was 493. 69-454. 60 pg/ml and plasma LNG was not detected in 1 monkey. The hormone level returned to normal level after removal of the devices.

Electrical Storms after Levonorgestrel (Synthetic Progestin)-Releasing Intra-Vaginal Device Insertion. A Case Report and a Short Review of Literature

We report a case of arrhythmic storm in a patient with recent vaginal insertion of a device with release of levonorgestrel (synthetic progestin). A woman of 60 years was hospitalized for runs of monomorphic sustained ventricular tachycardia. She received a vaginal device levonorgestrel-releasing 2 days before admission. No history of associated cardiovascular or thyroid disease or risk factors was reported. Laboratory parameters as well as ECG and echocardiogram were normal. After 48 hours from removal of the vaginal device, the patient was asymptomatic and showed only single ectopic beats, sometimes in pairs. The subsequent coronary angiography, electrophysiological study and cardiac magnetic resonance resulted negative.

A comparative, randomized study of levonorgestrel Intrauterine System (LNG-IUS) vs Copper T 380 A intrauterine device applied during cesarean section

Objective: To assess levonorgestrel-releasing intrauterine system LNG-IUS (Mirena?) application at caesarean section (CS). Design: Randomized, comparative study. Setting: Department of obstetrics and gynecology in a primary reference hospital at Puebla City, Mexico. Sample: 396 women requiring CS signed informed consent and were randomly allocated to the post-placental application of LNG-IUS (198) or Copper T 380 A (198). Methods: Follow up visits at 6 weeks, and 6 and 12 months were performed. Main Outcomes Measures: IUDs expulsion, maternal and babies’ health conditions, breastfeeding and menstrual patterns, adverse effects and pregnancies. Differences between groups were analyzed by Fisher and X2 tests, Odds ratios, relative risk and 95% confidence limits, as appropriate. Results: After one year of follow up, no pregnancies were reported. The IUD expulsion rate was 4.5% in each group. LNG-IUS users had a higher incidence of amenorrhea (OR 2.5 95% CI 2.2 - 3) and menstrual patterns significantly brief and lighter than Copper T 380 A (p < 0.001) with lower incidence of dysmenorrhea (OR 0.1 95% CI 0.04 - 0.2). No detrimental effects of LNG-IUS on breastfeeding was observed and interestingly babies weights of LNG-IUS users was slightly above the average for age compared with Copper T 380 A users. This was probably related with a major proportion of women with normal ferritin serum levels (94% vs 68%) leading to better mother’s general condition. Conclusions: LNG-IUS inserted during CS provides high efficacy contraception with additional benefits, mainly reducing menstrual bleeding and doing so, faster recovery of ferrous homeostasis after CS.

Levonorgestrel in postcoital contraception

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Antifertility effects of EP-1 (quinestrol and levonorgestrel) on Pacific rats (Rattus exulans)

Pest rodents pose a serious threat to island biodiversity.Fertility control could be an alternative approach to control the impact of rodents on these islands.In this study,we examined the antifertility effects of EP-1 baits containing quinestrol(E)and levonorgestrel(P)using a dose of 50 ppm E and P at three different ratios(E:P ratio=1:2,1:1,and 2:1)on Pacific rats(Rattus exulans)in the Xisha Islands,Hainan,China.Compared to the control group,all animals in EP-1 treatment groups showed significantly decreased food intake and body weight.In treated males,there were obvious abnormalities in testis structure and a significant decrease of relative seminal vesicle weight,but no significant effect on relative uterine and ovarian weights(g kg-1 body weight),or ovarian structure in females.Adding 8%sucrose to the original 50-ppm baits(E:P ratio=1:1)significantly increased bait palatability for males and females.This dose induced uterine edema and abnormalities of ovarian structure in females but had no significant negative effect on the relative testis,epididymis,and seminal vesicle weights(g kg-1 body weight)or sperm density in males.In summary,50-ppm EP-1(1:1)baits have the potential to disrupt the fertility of females,and 8%sucrose addition to the EP-1 baits(E:P ratio=1:1)could improve bait palatability.This dose disrupted the testis structure in males.Future studies are needed to improve bait acceptance and assess the antifertility effects of EP-1(1:1)on Pacific rats in captive breeding trials and underfield conditions.

Anti-fertility effect of levonorgestrel and quinestrol in Brandt’s voles(Lasiopodomys brandtii)

The combination of levonorgestrel and quinestrol(EP-1)has been shown to have anti-fertility effects on several wild rodents,but the mechanism underlying these effects is poorly understood.We investigated the effects of EP-1 and each of its components,levonorgestrel(P)and quinestrol(E),on the fertility of Brandt’s voles(Lasiopodomys brandtii)by using a gastric gavage method.The doses for EP-1,E and P were 1,0.34 and 0.66 mg/kg body weight,respectively.Male voles(n=98)were treated daily for 5 or 14 days,then the testes and epididymides were collected,weighed and examined histologically at 30(D30),60(D60)or 90(D90)days after the end of treatment.Four males were allowed to mate with normal females at D90.Female voles(n=75)were treated for 3 days and a further 3 days after a 7-day interval.The uteri and ovaries were weighed and examined histologically at 15(D15),30(D30)or 75(D75)days after the end of treatment.Each of three females were mated with fertile males at D30 and D75,respectively.Our results indicated that quinestrol(E)significantly decreased the sperm numbers in the testes as well as the weight of the testes and epididymides,with both of these tissues showing obvious structural abnormalities,and significantly reduced the litter size and the pup weight for females mated with males of the E treatment group.For female voles,treatment with E,P or EP-1 resulted in no marked influence on the fertility status.These data indicate that quinestrol(E)alone has a significant anti-fertility effect on male Brandt’s voles,but is ineffective in combination with levonorgestrel(P).

Antifertility effects of levonorgestrel,quinestrol,and their mixture(EP-1)on plateau zokor in the Qinghai–Tibetan Plateau

The plateau zokor(Eospalax baileyi)is a key species in the Qinghai-Tibetan Plateau ecosystem,and fertility control could be an ideal approach to manage populations of this subterranean species.In this laboratory study,we explored the effects of the mixture of levonorgestrel and quinestrol(EP-1,1:2),quinestrol(E),and levonorgestrel(P)on the reproductive status of plateau zokors.Groups of 5 animals of each sex were treated with different concentrations of EP-1(1,5,and 10 mg/kg),E(0.33,3.3,and 6.6 mg/kg),and P(0.67,3.35,and 6.7 mg/kg)by oral gavage over 7 successive days and killed on day 15.Body mass reduction was observed in the EP-1 and E groups.EP-1 and E significantly reduced the weight of testis and epididymis at 10 and 3.3 mg/kg,respectively.Sperm count and motility were significantly reduced by 5 mg/kg EP-1 and 0.33 mg/kg E.The levels of serum testosterone,estradiol,luteinizing hormone,and follicle stimulating hormone were significantly reduced by 5 mg/kg EP-1 and 3.3 mg/kg E.EP-1 and E significantly increased the uterine and ovarian weights at 10 and 3.3 mg/kg,respectively.In the plateau zokors,treatment with P had no influence on the reproductive status.These data demonstrate that EP-1 and E have an inhibitory effect on a range of reproductive parameters in the plateau zokors.Further assessment is required to determine the effects on breeding and recruitment in enclosure orfield experiments.

Anti-fertility effect of levonorgestrel and/or quinestrol on striped field mouse(Apodemus agrarius):evidence from both laboratory and field experiments

The effect of combined levonorgestrel(P)and quinestrol(E)on the fertility of stripedfield mouse(Apodemus agrarius)has not been evaluated.We performed a series of experiments in both the laboratory andfield to assess the effect of P and/or E on the fertility of A.agrarius.In the laboratory,to test the time-dependent anti-fertility ef-fects of P and E,as well as their mixtures,90 male stripedfield mice were randomly assigned to 6 treatment groups(n=60),and a control group(n=30).Mice in 3 treatment groups were administered 1 of the 3 compounds(1 mg�kg–1[body weight]EP-1,0.34 mg�kg–1 E,0.66 mg�kg–1 P)for 3 successive days(another half for 7 suc-cessive days)via oral gavage;mice were then sacrificed 15 and 45 days after initiating the gavage treatment.Ourfindings indicated that E and EP-1 treatment,but not P or control treatment,significantly decreased the sperm count in the caudal epididymis,as well as the weight of the testes,epididymides,and seminal vesicles.Additionally,fer-tile female mice mated with E-and EP-1-treated males produced smaller pups.These data indicate that E and EP-1 can induce infertility in male A.agrarius.In thefield,the population density of A.agrarius was significantly influ-enced by EP-1,and the rodent density in the treatment group was lower than that in the control group.Overall,our results indicate that EP-1 is an effective contraceptive in A.agrarius,a dominant rodent species in the farmland.

The fate of prazosin and levonorgestrel after electrochemical degradation process: Monitoring by-products using LC-TOF/MS

Prazosin（PRZ） and levonorgestrel（LNG） are widely used as an anti-disease drugs due to their biological activity in the human body. The frequent detection of these compounds in water samples requires alternative technologies for the removal of both compounds. After electrochemical degradation of PRZ and LNG, the parent compounds could be completely removed after treatment, but the identification and characterization of by-products are necessary as well. In this study, the effects of NaCl concentration and applied voltage were investigated during the electrochemical degradation process. The results revealed that the increase of NaCl concentration and applied voltage could promote the generation of hypochlorite OCl-and then enhance the degradation of PRZ and LNG. After initial study, 6 V and 0.2 g NaCl were selected for further experiments（96% and 99% removal of PRZ and LNG after 40 min, respectively）. Energy consumption was also evaluated and calculated for PRZ and LNG at 3, 6 and 8 V. Solid phase extraction（SPE） method plays an important role in enhancing the detection limit of by-products. Furthermore, characterization and identification of chlorinated and non-chlorinated by-products were conducted using an accurate liquid chromatography-time of flight/mass spectrometry LC-TOF/MS instrument. The monitoring of products during the electrochemical degradation process was performed at6 V and 0.2 g NaCl in a 50 m L solution. The results indicated that two chlorinated products were formed during the electrochemical process. The toxicity of by-products toward E. coli bacteria was investigated at 37°C and 20 hr incubation time.

Phytoremediation of levonorgestrel in aquatic environment by hydrophytes

Adsorption and degradation of levonorgestrel （LNG） by two hydrophytes, Cyperus alternfolius （CA） and Eichhornia crassipes （EC）, were investigated under light-shielding conditions in the water column. Variations of LNG concentrations in water, plant root epidermis, root, stem and leaf of the plants were analyzed. The results indicated that the removal efficiency of LNG by hydrophytes over the period of 50 days was significantly greater than the blank control （p 〈 0.05）, with the removal rates of 79.80%± 3.10% and 78.86% ± 2.55% for CA and EC, respectively. Compared with bio-adsorption, bio-conversion of LNG was found to be the dominant elimination pathway, evidenced by relatively high conversion rates （77.31% ±2.68% for CA and 77.82% ± 2.95% for EC）, while the adsorption rates were lower （1.77% ± 0.90% for CA and 1.05% ± 0.40% for EC）. The bio-adsorption and conversion of LNG showed no significant differences between the two hydrophytes. Additionally, the mineralization on root epidermis played an important role in the reduction of LNG in water.

Profile of the levonorgestrel-releasing intrauterine system users in China

The widespread usage of modem contraceptive methods has predominantly been driven by government family planning policies in efforts to mandate reduced total fertility rates.1 In particular,the high prevalence of long-acting contraception usage can be attributed to the mandatory requirement in the early 1980s for women with one child to have a copper intrauterine device （IUD） fitted and for sterilization for those with two or more children,2and more recently through financial incentives for married couples to use long-acting contraceptive methods.1 The levonorgestrel-releasing intrauterine system （LNG-IUS） has been available in China since 2000 for contraception and treatment of heavy menstrual bleeding.Little is known about the profile of the Chinese women opting to use the LNG-IUS and the type of information they received before intrauterine system placement.We undertook this survey to profile the Chinese women choosing to use the LNG-IUS in clinical practice.

左炔诺孕酮宫内节育系统放置对宫腔镜下息肉切除术患者子宫内膜厚度、性激素及炎症因子水平的影响

目的:探讨左炔诺孕酮宫内节育系统放置对宫腔镜下息肉切除术患者性激素、子宫内膜厚度以及炎症因子水平的影响。方法:选取2020年1月—2022年12月于酒泉市人民医院接受宫腔镜下息肉切除术治疗的160例患者作为研究对象,按信封随机法分为试验组(n=80)与对照组(n=80)。对照组施行黄体酮胶囊治疗,试验组施行左炔诺孕酮宫内节育系统放置治疗,比较两组月经量、子宫内膜厚度、性激素指标和炎症因子等。结果:两组术后月经量减少,子宫内膜厚度降低,且试验组术后4个月、8个月月经量少于对照组,子宫内膜厚度低于对照组,差异有统计学意义(P<0.05)。术后8个月,两组性激素指标和炎症因子水平降低,且试验组孕酮、促黄体生成素、雌二醇、γ干扰素(IFN-γ)、白细胞介素(IL)-1与基质金属酶-3(MMP-3)水平低于对照组,差异有统计学意义(P<0.05)。结论:左炔诺孕酮宫内节育系统放置用于宫腔镜下息肉切除术后的疗效显著,有助于减少患者经期出血量,降低炎症因子水平,改善性激素指标,并促进子宫内膜厚度降低。