Frequent and painful urination recurring after antibiotic treatment, why not combine estrogen therapy?

This article involves professional knowledge and is only for reference by medical professionals to see how pharmacists use medication.
Urinary tract infection is a common infectious disease in women.
According to statistics, the incidence of urinary tract infection in women is nearly 10% every year
.

Female urinary tract infection is also a common cause of medical consultation in nephrology specialists and urology clinics
.

Case female, 57 years old, was admitted to the hospital due to "dry mouth, dry eyes, and decreased granulocytes" and was admitted to the hospital to diagnose Sjogren's syndrome
.

Urine routine test after admission showed urine protein 2+, nitrite 1+, white blood cell esterase 4+, and white blood cell 4+
.

The patient complained of a history of repeated urinary tract infections for 5+ years, during which the patient had recurred after several oral antimicrobial treatments improved
.

Klebsiella pneumoniae was detected in urine culture on the 6th day of admission.
The ESBLs of the drug sensitivity test were negative, and he was sensitive to antibacterial drugs such as ceftizolin, ceftriaxone, and ceftazidime
.

Clinical pharmacist consultation opinion: The patient is a menopausal woman with repeated urinary tract infections.
It is recommended to choose ceftazidime 1g q8h for anti-infection based on the drug sensitivity report of Klebsiella pneumonia, and combined with intravaginal administration of estrogen cream 0.
5g/time qd as a supplement Treatment and improvement of urinary tract infections
.

Why are women prone to repeated urinary tract infections after menopause? Abundant estrogen receptors are expressed in female vagina, urethral cells and mucosa of bladder triangle.
Postmenopausal estrogen deficiency, vaginal mucosa atrophy, urethral orifice is stretched to expose urethral mucosa, urethral closure is reduced; at the same time, vaginal mucosa becomes thinner , The glycogen in the vagina disappears, the pH value rises, the growth of Lactobacillus is restricted, the flora changes, the local resistance is reduced, and the postmenopausal urinary tract infection is induced
.

The main pathogens of female urinary tract infections in China are gram-negative bacilli.
Escherichia coli is the first pathogen, followed by gram-positive cocci, Klebsiella and Pseudomonas, the latter in pregnancy and postmenopausal Urinary tract infections are particularly common in women [1]
.

Estrogen preparations 1 Estriol Estriol is a natural estrogen, similar in structure and function to endogenous estrogen, and mainly exists in urine
.

It only exerts estrogenic properties in the urinary tract and vagina and does not stimulate the endometrium.
Compared with subestradiol, it has a stronger effect
.

It selectively acts on the vagina and cervical canal to soften the atrophied vaginal tissue, increase the elasticity of the vaginal wall tissue, thereby increase the glycogen content in the vaginal epithelial cells, maintain the glycogen reserve in the vagina, and make the vagina PH value significantly decrease, and promote The vaginal flora is transformed into lactic acid bacteria, which enhances the self-purification and defense capabilities of the vagina, and fundamentally destroys the micro-ecological environment in which the bacteria grow and multiply in the vagina [2]
.

Estriol ointment is not taken orally, which can reduce the impact on the liver and help maintain the integrity of the urethra and bladder mucosa.
The thickness of the vaginal mucosa increases and the urinary tract infection is improved
.

In the study [3], in the treatment of genitourinary tract infections in postmenopausal women, oral fluoroquinolone drugs combined with estriol cream were used: estrogen cream 0.
5g/time, 1 time/d, after cleaning the vulva every night, local The medicine was administered for 2 weeks, then twice a week, and then administered for 2 weeks.
The results showed that the effective rate of treatment was 95.
45%, which was significantly higher than the effective rate of 88.
64% in the control group
.

In the study [4-5], estriol cream was used continuously for 3 months, and then followed up for 6 months and 3 months respectively.
The recurrence rate of the study [4] was 7.
5%, and the recurrence rate of the untreated group was 28.
57%.
And the study [5] did not see obvious recurrence
.

Among them, the estrogen dosage regimen in the study [5] is 0.
5g/time, 1 time/day in the first 1-2 weeks, once every 2 days in the 3rd week, and once a week starting in the 4th week.
Use for 3 months
.

2Conjugated estrogen, proestrene In addition to the use of estriol, other estrogen supplements include conjugated estrogen cream (0.
625mg/piece) or conjugated estrogen tablets (0.
625mg/tablet), proestrene cream ( 1%)/Proestrene vaginal capsule (10mg/capsule) or Chloroquinado-Proestrene vaginal tablet (200mg: 10mg/tablet)
.

(1) Conjugated estrogen is a natural mixed estrogen extracted from pregnant horse urine.
It is clinically mainly used for hormone replacement therapy to relieve clinical symptoms caused by insufficient estrogen
.

It mainly exists in the form of conjugated sodium sulfate, among which estrone sodium sulfate, equilin sodium sulfate and 17a-dihydro equilin sodium sulfate are the main ones.
The sum of the three content accounts for the total amount of estrogen.
For more than 90%, oral administration of 0.
625mg conjugated estrogen tablets will produce E2 levels in the body of 109.
8-183.
0pmol/L, reaching the level of the early follicular phase of the normal menstrual cycle[6-7]
.

In addition to adjuvant treatment of urinary tract infections in postmenopausal women, it is also used for atrophic vaginitis
.

(2) Chloroquinaldol-Proestrene, in which Chloroquinaldol is a broad-spectrum antibacterial agent, which has an inhibitory effect on a variety of pathogenic bacteria
.

Prostilbene is a topical estrogen preparation.
It is a synthetic asymmetric estradiol diether.
Compared with the traditional topical estrogen preparations, prostilbene has a poorer ability to penetrate vaginal or epidermal epithelial cells, and is absorbed by the system as well as systemic sex hormones.
The response is small
.

In topical application, prostilbene has the effect of resisting vaginal or cervical mucosal atrophy.
Therefore, it is mostly used for atrophic vaginitis [8-9]
.

3 Precautions During the treatment with estrogen drugs, if there are the following types, it is not advisable to blindly use estrogen therapy: (1) Irregular vaginal bleeding with unclear diagnosis; (2) Known or suspected breast cancer; (3) Known or suspected estrogen-dependent diseases such as endometrial cancer and other malignant tumors, endometrial proliferative diseases (endometrial thickness equal to or greater than 5mm); (4) Active venous or arterial thrombosis Embolic disease (within the last 6 months); (5) Severe liver and kidney dysfunction; (6) Hematoporphyria, otosclerosis; (7) Known meningiomas (progesterone is prohibited); ( 8) Those who are allergic to estrogen components
.

And suffering from uterine fibroids, endometriosis, a history of endometrial hyperplasia, uncontrolled diabetes and severe hypertension, a tendency to thrombosis, gallbladder disease, epilepsy, migraine, asthma, hyperprolactinemia, systemic Women with a family history of lupus erythematosus, benign breast diseases, and breast cancer need to weigh the pros and cons when using it
.

Summary: The efficacy of antibiotics combined with low-dose estrogen in the treatment of postmenopausal women with urinary tract infections is better than that of antibiotics alone.
Therefore, it is recommended to add small doses to the treatment of sensitive antibiotics in postmenopausal women with urinary tract infections.
For estrogen, there is no clear recommendation for the course of treatment
.

After long-term cessation of continued use, there is also a certain risk of recurrence of urinary tract infection, but it is much lower than that of no medicine
.

At the same time, since estrogen is related to the incidence of endometrial cancer and breast cancer, it is necessary to pay attention to the way and time of its use
.

Reference materials: [1] Expert consensus on diagnosis and treatment of female urinary tract infections in China [J], Nephrology and Blood Purification Committee of Chinese Women Physicians Association.
Chinese Medical Journal,2017,97(36):2827-2832.
[2]Perrota C,Aznar M,Mejia R.
Oestrogen for preventing recurrent urinary tract infection[J].
Cochrane database of systematic reviews(Online),2008,16(11):CD005131.
[3]Zhao Ruiyan,Wang Dongsheng,Li Tao.
Norfloxacin combined Efficacy of estriol in the treatment of urinary and reproductive tract infections in postmenopausal women[J].
Chinese Journal of Hospital Infection,2017,27(022):5226-5229.
[4]Sun Rui.
Discussion on low-dose estrogen in postmenopausal women urinary Efficacy in the treatment of recurrent infections[J].
The Journal of Practical Gynecology and Endocrinology (Electronic Edition),2015.
[5]Hu Ping,Deng Min,Liu Shoufu.
Clinical study of low-dose estrogen in the treatment of postmenopausal women with recurrent urinary tract infections[J ].
Chinese Journal of Hospital Infection, 2014, 24(10): 2533-2535.
[6]WANGJ, HUJG, LIJH.
Assay for conjugated estrogens in prematin for injection and in premar incream using GC—FID by trimethylsnylating[J]．ChinJPharmAnal, 2001, 21(1): 18-20.
[7] RogerioA.
Treatment of the postmenopausal woman(thirdedition)lMJ．NewYork: RavenPress, 2007:767-777.
[8]Sun Aijun, Lin Shouqing, Jing Lianhong, et al.
The safety of proestene in the treatment of postmenopausal atrophic vaginitis[J].
Chinese Journal of Obstetrics and Gynecology, 2012, 44(8): 593-596.
[9] Wang Xiang.
Study on the efficacy of chloroquinadoprostilbene vaginal tablets in the treatment of atrophic vaginitis[J].
Contemporary Medicine Review (Phase 2):402-402.