Friday, July 19, 2013

Positioning for Robotic (DaVinci) Surgery

Article on safe positioning for robotic surgery:
"Robot-assisted laparoscopic surgery is becoming more prevalent and typically is performed in the steepest degree of Trendelenburg possible, yet such positioning can cause several perioperative complications and may, in fact, be unnecessary for benign gynecologic procedures.

Application of the da Vinci Surgical System (Intuitive Surgical Inc, Sunnyvale, California) in gynecologic surgery has been exponentially increasing since it was approved by the United States Food and Drug Administration for that indication in 2005. Robot-assisted laparoscopic surgery, widely referred to as da Vinci surgery, was introduced to overcome many of the shortcomings of conventional laparoscopy and now is in use at many centers across the United States for gynecologic, urogynecologic, and gynecologic oncology procedures. The advantages of robot-assisted laparoscopic surgery over conventional laparoscopy are 3-dimensional camera vision, superior precision and dexterity (EndoWrist instrumentation), elimination of operator tremor, and less fatigue on the part of the surgeon. The drawbacks of the technology include high cost, bulkiness, and lack of tactile feedback.

Proper patient positioning on the operating table is essential to allow optimal surgical exposure and to prevent neuromuscular injuries. Positioning is even more critical in robotic surgery because it must provide access to the surgical field and also accommodate the robotic camera system and working arms. As a result, a steep Trendelenburg position (roughly defined as 30° to 40°) is routine during robotic gynecologic surgery, much more so than during conventional laparoscopy. Part of the reason is that once the robot is docked with arms engaged to the instruments, adjusting the table is not feasible without undocking the robot. That has led to a tendency to use the steepest degree of Trendelenburg possible to maximize surgical exposure and avoid having to readjust the table if more Trendelenburg is required. Performing robotic gynecologic surgery in steep Trendelenburg, however, is associated with rare but serious perioperative complications and the robotic surgical team must have an in-depth understanding of the potential complications that may arise when patients are positioned in this way. 1

This article discusses strategies to simplify patient positioning for robot-assisted gynecologic surgery without compromising patient safety or surgical outcome. It also reviews frequently reported complications of robotic surgery attributed to patient positioning and offers recommendations for preventing such adverse events.

FIGURE 1: The patient’s extremities are well-padded and stabilized using foams and sleds, and her eyes are covered with protective gear.


Positioning of a patient for robot-assisted surgery starts with placement in the dorsal lithotomy position with the legs in Allen Yellofins stirrups (Allen Medical Systems, Acton, Massachusetts), as with conventional laparoscopy (Figure 1). The same principles for adequate padding at all pressure points and avoidance of extreme flexion, extension, and abduction should be followed to help minimize neuromuscular injuries. Padding of the occiput (such as with a gel donut, as shown in Figure 2) cannot be overemphasized to avoid ischemic necrosis resulting in alopecia. A standard motorized operating-room table featuring a maximum 30° tilt is used.

Several steps are recommended to prevent a patient in steep Trendelenburg from shifting while on the operating table. The first is to place a 3’ x 5’ surgical sheet horizontally in the middle of the table, corresponding to the position of the patient’s arms, put a layer of egg-crate foam on top of it, and securely tape the foam to the surgical bed (Figure 2). (The sheet can be used later for tucking.) A tip suggested by other authors is to use 2 layers of egg-crate foam as “anti-skid” material to prevent sliding, which may be particularly helpful for patients who are morbidly obese. 2 Placing surgical gel pads against a patient’s bare skin also may be helpful, but they have to be disinfected after each case and allergic reactions are possible. Some surgeons have success in protecting and stabilizing the arms of obese patients with well-padded arm sleds (Figure 1) made of rigid plastic material, which are designed to cradle the arm and extend under the mattress.

Another device designed to stabilize positioning and provide sufficient padding for robot-assisted surgery in steep Trendelenburg is the Bean Bag Positioner (AliMed Inc, Dedham, Massachusetts). The gel mattress is fastened to the surgical table and conforms to the shape of a patient’s upper body and shoulders when desufflated to stabilize her. Potential drawbacks are a longer setup time, unnoticed deflation during the case, and need for disinfection.

FIGURE 2: The author’s preferred method of padding for robot-assisted surgery, with a layer of egg-crate foam taped to the table mattress and a folded sheet to be used for securing the patient’s arms.

Our preferred method for patient positioning in robot-assisted gynecologic surgery is to use 1 layer of egg-crate foam and tuck the patient’s arms using sheets or arm sleds. In our experience, this is the most straightforward, consistent, and quick way of setting up the operating room table for patient stabilization. As described later in this article, we rarely, if ever, feel the need for steep Trendelenburg, even for morbidly obese patients. If prolonged steep Trendelenburg (30° to 40° of table tilt) is anticipated, however, a surgeon can consider using one of the strategies previously described to prevent the patient’s position from shifting.


The robotic surgeon and anesthesia team must understand the physiologic effects to the patient of pneumoperitoneum in the steep Trendelenburg position. Pulmonary functional residual capacity is impaired during robotic surgery because of insufflation and the Trendelenburg position.3 Hypercapnia and acidosis can ensue secondary to a ventilation-perfusion mismatch. Increasing minute volume may correct this abnormality, but patients with pulmonary compromise may not tolerate such physiologic strains during robotic surgery in steep Trendelenburg.

Cardiovascular effects of robotic surgery in steep Trendelenburg also can be problematic. Venous return and cardiac preload are reduced secondary to pneumoperitoneum. Patients also have an increase in cardiac afterload secondary to compression of the aorta and increased vascular sympathetic tone. The result can be a reduction of cardiac index by as much as 50% and elevation of pulmonary arterial, central venous, and intracranial pressures. Cardiac arrhythmias may occur in as many as 27% of patients, mostly secondary to increased vagal tone and hypercapnia.4

To reduce and successfully manage challenges related to anesthesia and patient positioning during robotic surgery, the robotic surgeon should collaborate closely with a dedicated anesthesia team that is knowledgeable about specific physiologic issues related to performing robotic surgery in steep Trendelenburg.


Steep Trendelenburg traditionally is recommended for robotic gynecologic surgery to maximize surgical exposure of the pelvis. Although there is no clear definition of steep Trendelenburg, 30° to 45° of table tilt is considered a steep angle. Several perioperative complications can arise from performing robotic surgery in such a position, especially if surgery is prolonged.1

Patient slippage

The most obvious concern is cephalad sliding or slippage of the patient on the operating table. That is a particular concern in obese patients, who are more susceptible to downward shifting, with resulting skin breakdown and neuropathic injuries. Nerve injuries can result from overstretching or compression of the nerve bundles, leading to impairment of the microcirculation and nerve conduction.2 These injuries are an important source of perioperative morbidity and can be either transient or permanent. Some previously proposed methods to prevent patient slippage in steep Trendelenburg are now known to contribute to nerve injury. As a result, we do not recommend the use of shoulder straps, shoulder braces, restraints, body straps, or head rests during robotic surgery because of associated neuromuscular injuries, particularly brachial plexus injury.

Patient slippage during the use of fixed robotic trocars also can cause incisional tear, postoperative hernia formation, and increased postoperative pain secondary to overstretching of the anterior abdominal wall. Accurate patient positioning, careful padding of all pressure points, and appropriate application of antiskid materials therefore are paramount for preventing such injuries.


Another devastating complication after robotic surgery related to patient positioning is the development of postoperative rhabdomyolysis.5 Rhabdomyolysis after bariatric surgery is well documented. Morbid obesity, prolonged surgery, extreme patient positions (such as steep Trendelenburg), hypertension, diabetes, and peripheral vascular disease all are risk factors for this complication. Rhabdomyolysis results from compression injury of the skeletal muscle, causing intracellular components (myoglobin, electrolytes, and proteins) to be expelled into the circulation. That, in turn, can result in serious complications, including acute renal failure, hyperkalemia, arrhythmia, compartment syndrome, metabolic acidosis, and significant pain. A patient’s gluteal, back, and shoulder muscle groups are at particular risk in steep Trendelenburg during robotic surgery. Intractable postoperative pain in these areas should serve as a warning sign. The diagnosis is confirmed if the total serum creatinine kinase level is higher than 1000 IU/L or if myoglobinuria is present.5,6 Management includes aggressive fluid resuscitation and correction of metabolic acidosis. If precautions are taken, the risk of rhabdomyolysis after robotic surgery should be similar to that after laparoscopic and open surgery. Gynecologists adopting robotic technologies should be familiar with the pathophysiology, diagnosis, and management of this complication.

Facial trauma and corneal abrasion

A patient’s face and especially her eyes are at risk of direct injury during robotic surgery, in contrast to conventional laparoscopy, and they should be given particular consideration during positioning and throughout the procedure. During robotic surgery, especially when the ports are placed superior to the umbilicus, the robotic camera system may come in contact with a patient’s face, causing facial and ocular trauma such as corneal abrasions. That is particularly problematic when a 30° down scope is used in steep Trendelenburg because the camera system may be only a few centimeters away from the face. There are no standard recommendations for the best way to protect a patient’s face and eyes during robotic surgery. Face masks, Mayo stands, foam wraps, and adhesive eye shields (Figure 1) all have been used, but no one method has proven superior to the others.

We have noticed a few cases of corneal abrasion after robotic surgery at our institution despite taking preventive measures. Corneal abrasion is the most common ocular complication after any surgical procedure.7 Most abrasions are thought to be caused by lagophthalmos (failure of the eyelid to fully close), which results in corneal drying. In addition, general anesthesia reduces tear production and, therefore, increases the incidence of this painful condition. Direct trauma causes up to 20% of perioperative corneal abrasions. The cornea is very sensitive to oxygen deprivation. For example, an ill-fitted mask or tightly applied facial foam wrap that applies pressure to the eye globe will induce corneal hypoxia and dryness. Desquamation of the epithelial layer more readily induces abrasion in a hypoxic and dry environment. Corneal abrasion can also result from increased intraocular pressure and edema, as occurs in steep Trendelenburg.7

To protect against corneal abrasion, we recommend taping the patient’s eyelids shut after induction of general anesthesia. Aqueous solutions, viscous gels, and ointments also are used routinely, but some experts recommend against such measures because of insufficient added protection and possibly increased ocular morbidity, especially with ointments. Our hospital’s policy is application of the disposable IGuard eye protector (Figure 1, SunMed, Largo, Florida) once a patient’s eyes are taped shut and avoidance of lubricating eye ointments.

Intraocular pressure rises significantly in steep Trendelenburg.8 As early as the 1950s, serious ocular complications, such as retinal detachment, were attributed to this positioning.9 Two patients developed ischemic optic neuropathy leading to partial visual loss and complete blindness after prolonged robotic surgery in steep Trendelenburg.10 As more gynecologic procedures are performed with robots, more ocular complications attributed to increased intraocular pressure and ischemic optic neuropathy may be encountered, especially in elderly patients who may have elevated baseline intraocular pressure.

Facial and laryngeal edema

Most patients undergoing prolonged robotic surgery in steep Trendelenburg awake from anesthesia with varying degrees of facial and laryngeal edema.1 Consequently, postextubation respiratory distress can occur, with the need for reintubation.11 Several measures may help prevent this complication, such as selecting patients carefully, avoiding prolonged operative time, reducing the degree of Trendelenburg, and decreasing intraoperative volume replacement.


To reduce the potential complications of robotic surgery attributed to patient positioning, we recently completed a pilot study to investigate the safety and effectiveness of performing robotic gynecologic surgery without routine use of steep Trendelenburg.1 We demonstrated that routine patient positioning in steep Trendelenburg for benign robotic gynecologic surgery seems to be unnecessary. Twenty consecutive robotic gynecologic procedures for benign indications were included in the study (Table 1). Patients were positioned to obtain sufficient surgical exposure, as opposed to being routinely placed in the steepest degree of Trendelenburg possible. The degree of Trendelenburg was measured using a digital level after each case was completed. The surgeons were blinded to the degree of Trendelenburg used until after the study was completed.

Our mean degree of Trendelenburg was 16°, which is far less than the recommended 30° to 40°.1 All cases were completed successfully without a need to modify the table tilt. There were no perioperative complications, and the operating times were similar to those in previous reports. We, therefore, advise that patients undergoing robotic gynecologic surgery for benign indications be placed in as much Trendelenburg as is safely needed to provide sufficient bowel mobilization and exposure, rather than routinely using the steepest degree of Trendelenburg possible. Avoiding routine use of steep Trendelenburg in robotic surgery would potentially reduce, if not eliminate, issues pertaining to position slippage and related perioperative complications. The likelihood of intraoperative and anesthesia-related complications also would be decreased because less physiologic strain is placed on a patient’s body.

Abbreviations: BMI, body mass index; BSO, bilateral salpingo-oophorectomy; CI, confidence interval; EB L, estimated blood loss; LSH, laparoscopic supracervical hysterectomy; NA, not applicable; R, robot-assisted; TLH, total laparoscopic hysterectomy; SD, standard deviation.


Steep Trendelenburg positioning during robotic gynecologic surgery is associated with potentially serious perioperative morbidity. The robotic surgeon and the anesthesia team must be intimately familiar with these complications and take preventive measures to reduce the risk to patients. Routine adherence to the steepest degree of Trendelenburg achievable in robotic gynecologic surgery for benign indications should be questioned. Robotic gynecologic surgery without steep Trendelenburg appears to be feasible without compromising surgical outcomes and arguably will reduce several complications attributed to this position."

Thursday, July 18, 2013

Misplaced Stem Cells (Genetics in the origins of Endometriosis)

In this article, it discusses the role of misplaced stem cells in the formation of endometriosis, indicating the genetic involvement. Misplaced stem cells (outside the uterus) are activated in women with endometriosis and the cells will respond to hormonal changes the same way that the lining of the uterus does. This, in turn, initiates an immune response (macrophages) which releases several chemicals that can cause pain and inflammation.

Dysregulation of Wnt and/or Hox genes may affect cell migration during organogenesis and differentiation of Müllerian structures of the female reproductive tract, with possible dislocation and dissemination of primordial endometrial stem cells in ectopic regions, which have high plasticity to differentiation. We hypothesize that during postpubertal age, under the influence of different stimuli, these misplaced and quiescent endometriotic cells could acquire new phenotype, biological functions, and immunogenicity. So, these kinds of cells may differentiate, specializing in epithelium, glands, and stroma to form a functional ectopic endometrial tissue. This may provoke a breakdown in the peritoneal cavity homeostasis, with the consequent processes of immune alteration documented by peripheral mononuclear cells recruitment and secretion of inflammatory cytokines in early phases and of angiogenic and fibrogenic cytokines in the late stages of the disease."

Wednesday, July 17, 2013

Look At Different Hormonal Meds Often Used in Endometriosis

Birth Control In-Depth Report


Contraceptives are devices, drugs, or methods for preventing pregnancy, either by preventing the fertilization of the female egg by the male sperm or by preventing implantation of the fertilized egg.

Contraceptive Options

Choosing the appropriate contraceptive is a personal decision. Contraceptive options include:
  • Hormonal contraceptives (oral contraceptives, skin patch, vaginal ring, implant, injection)
  • Intrauterine devices (IUDs), which contain either a hormone or copper
  • Barrier devices with or without spermicides (diaphragm, cervical cap, sponge, condom)
  • Fertility awareness methods (temperature, cervical mucus, calendar, symptothermal)
  • Female sterilization (tubal ligation, Essure)
  • Vasectomy
The condom is the only birth control method that provides protection against sexually transmitted diseases (STDs).

Determining Effectiveness

Contraceptive effectiveness is characterized by "typical use" and "perfect use":
  • Typical use refers to real-life conditions, in which mistakes (such as forgetting to take a birth control pill at the right time) sometimes happen.
  • Perfect use refers to contraceptives that are used correctly each time intercourse occurs.
The most effective standard female contraceptives are surgical sterilization, intrauterine devices (IUDs), and the implant. They all have an estimated failure rate of 1% or less during the first year of normal (typical) use. Vasectomy (male surgical sterilization) is the only male contraceptive that is equally effective. By comparison, the estimated failure rate of the male latex condom is 17% with typical use and 2% with perfect use. To put these rates into perspective, a sexually active woman of reproductive age who does not use contraception faces an 85% likelihood of becoming pregnant in the course of a year.

Oral Contraception and Combination Hormonal Methods

Oral contraceptives (birth control pills) are available only by prescription and come in either a combination of estrogen and progestin or progestin alone. Many brands of each form are available. Although both are equally effective with typical use, the combined pill is more effective with perfect use, and most women choose this form.
Some women, however, experience severe headaches or high blood pressure from the estrogen in the combined pill and must take the progestin-only pill. Not all combined pills or progestin-only pills are alike, and brands differ in the amount of estrogen or progestin they contain. Many oral contraceptive combined brands now use lower estrogen doses and have fewer side effects than earlier oral contraceptives.
For all oral contraceptive users, a check-up at least once a year is essential. It is also important for women to have their blood pressure checked 3 months after beginning the pill. Once woman stop taking oral contraceptives they usually regain fertility within 3 - 6 months, but some women may regain it even sooner.

Hormones Used in Contraceptives

Estrogen (Estradiol)
Estrogen is the major female hormone and is responsible for female characteristics. The estrogen compound used in most oral contraceptives is estradiol , which is always used with a progestin.
Effects on Reproduction. When used throughout a menstrual cycle with progesterone, estrogen suppresses the actions of other reproductive hormones (luteinizing hormone, or LH, and follicle stimulating hormone, or FSH) and prevents ovulation.
Progesterone (Progestin)
When used in contraception, progesterone is referred to by one of several names:
  • Progesterone is the name for the natural hormone.
  • Progestogen is a synthetic form.
  • Progestin is the term for any hormone, natural or synthetic, that causes progesterone effects; it is used as the general term in this report.
Progestins may be used alone or with estrogen in oral contraceptives. In addition, certain specific progestins are used in other kinds of contraceptives, such as etonogestrel in the Implanon implant and depo-medroxyprogesterone acetate in the injectable contraceptive Depo-Provera.
Progesterone can prevent pregnancy by itself in several ways:
  • Blocking luteinizing hormone (LH) and preventing ovulation
  • Maintaining a powerful barrier against the entry of sperm into the uterus by keeping the cervical mucus thick and sticky
Progestins used in contraceptives are referred to as:
  • Second generation (levonorgestrel, norethisterone).
  • Third generation (desogestrel, gestodene, norgestimate, drospirenone). The third-generation progestins tend to have fewer side effects. Some studies suggest, however, they may pose a slightly higher risk for blood clots than the older progestins.

Combination Estrogen-Progestin Contraceptive Pills

Oral contraceptives that contain both estrogen and progestin are the more common type of oral contraceptive. At least 10 million American women and 100 million women worldwide use combination oral contraceptives. When they were first marketed in the early 1960s, oral contraceptives contained as much as 5 times the amount of estrogen and up to 10 times the amount of progestin currently used. After reports of severe complications (stroke, heart attack, and pulmonary embolisms) in young women, the hormone amounts were significantly reduced.
The estrogen compound used in most oral contraceptives is ethinyl estradiol (also called estradiol, or EE). Fifty micrograms of estradiol is considered high dose, 30 - 35 micrograms are considered average dose, and 20 micrograms or fewer is low-dose. (The high doses found in current oral contraceptives are still much lower than earlier forms of the pill.) Doctors recommend using the lowest possible progestin and estrogen doses. Estrogen doses should not exceed 50 micrograms, as higher doses increase the risk for complications.
Many different types of progestins are used in combination with estradiol. Some common types of progestin, and popular combination oral contraceptive brands, include:
  • Desogestrel is the progestrin used in Mircette. Approved in 1998, Mircette was the first oral contraceptive to offer a low estrogen dose and a new type of dosing regimen. Some studies suggest an increased risk for blood clots with desogesterel.
  • Drospirenone is used in Yasmin and Yaz. (Yaz contains a lower dose of estrogen than Yasmin.) Because drospirenone increases blood levels of potassium, women should not use Yasmin or Yaz if they have kidney, liver, or adrenal diseases.
  • Levonorgestrel is used in Seasonale and Seasonique, as well as many other oral and non-oral contraceptives.
  • Norethindrone is used in Loestrin and Loestrin 24 Fe (which adds iron supplements to the placebo pills).
  • Norgestrel is used in various generic and brand contraceptives.
Types of Regimens . Combination pills are sold in 21-day or 28-day packs:
  • Each pill in a 21-day pack contains estrogen and progestin. Women take 1 pill a day for 21 days, and then wait 7 days before starting a new 21-day pack.
  • 28-day packs typically start with 21 hormone pills and add 7 placebo pills that do not contain hormones. After taking hormone pills for 21 days, a woman takes the inactive pills for 7 days. Some newer brands, like Yaz, use 24 days of active pills and 4 days of inactive pills. Mircette uses 21 days of low-dose progestin and estrogen, followed by 2 placebo days, and then 5 days of very low-dose estrogen. Loestrin 24 Fe uses 24 days of active pills followed by 4 days of iron-containing placebo pills.
Oral contraceptives may be taken in cycles that include pills of the same or different strengths. These are categorized as monophasic (one-phase), biphasic (two-phase), or triphasic (three-phase). Monophasic pills contain the same amount of hormones in each dose. Biphasic and triphasic pills contain different dosages of hormones within the pill packs. Because monophasic pills have a consistent amount of hormones, they tend to cause fewer hormone-fluctuating side effects than biphasic or triphasic pills. Research shows little difference in effectiveness between these three types of oral contraceptives. Monophasic pills are often recommended as the best first-choice for birth control pills.
Taking the Pills. A woman usually takes the first pill either on the Sunday after her period starts or during the first 24 hours of her period. (The first pill can be started at any time during the menstrual cycle without affecting the bleeding patterns. Ovulation can occur that month, however.) The remaining pills are taken once a day, ideally at the same time of day, until the pack is used up. If a woman has a 21-day pack, she waits 7 days before starting a new pack. If she is on the 28-day pack, she takes the 7 inactive pills. Women should use another method of birth control during the first month taking the pill.
If you skip one or more pills, take the following precautions:
  • Missing the first pill in a new cycle. Take a tablet as soon as you remember and the next one at the usual time. Two tablets can be taken in one day. Use barrier contraception for 7 days after the missed dose.
  • Missing a pill 2 days in a row. Take 2 pills as soon as you remember and then 2 more the following day. Also use back-up barrier contraception until the next pill cycle.
  • Missing more than 2 days. Discard the pack, use a back-up birth control method, and begin a new cycle on the following Sunday, even if you have started bleeding.

Continuous-Dosing Oral Contraceptives

Standard oral contraceptives come in a 28-pill pack that contains 21 active pills and 7 inactive pills. Newer "continuous-dosing" (also called "continuous-use") oral contraceptives aim to reduce -- or even eliminate -- monthly periods and thereby prevent the pain and discomfort that may still accompany menstruation in women taking oral contraceptives. Women who have medical conditions, (such as endometriosis), which cause heavy or painful menstrual periods may benefit from continuous-dosing oral contraceptives. These oral contraceptives contain a combination of estradiol and the progesterone levonorgestrel, but use extending dosing of active pills.
Seasonale, the first continuous-dosing contraceptive, contains 81 days of active pills followed by 7 days of inactive pills. Women who take Seasonale have on average a period every 3 months. Seasonique, a follow-up to Seasonale, also produces about 4 periods a year. With Seasonique, a woman takes 84 days of levonorgestrol-estradiol pills followed by 7 days of pills that contain only low-dose estradiol.
Lybrel supplies a daily low dose of levonorgestrol and estradiol with no inactive pills. Because Lybrel contains only active pills, which are taken 365 days a year, it completely eliminates monthly menstrual periods. About 60% of women who take Lybrel completely stop menstrual periods by the end of the first year. Some women, however, experience occasional unscheduled bleeding or spotting during the first 3 - 6 months.

Progestin-Only Oral Contraceptives ("Mini-Pills")

Progestin-only pill brands include:
  • Levonorgestrel (Plan B)
  • Norethindrone (Micronor, Aygestin, Nor-QD)
  • Norgestrel (Ovrette)
Progestin-only pills, which only contain progestins, are always sold in 28-day packs and all the pills are active. An exception is Plan B, which is emergency contraception. [For more information, see Emergency Contraception section in this report.) Progestin-only pills, which are also called “mini-pills,” must be taken at precisely the same time each day to maintain effectiveness. If a woman deviates from her pill schedule by even 3 hours, she should call her doctor about using back-up contraception for the next 2 days.
Progestin-only pill users experience even lighter periods than those taking combination pills. Some may not have periods at all. Because these pills do not contain estrogen, they may be a safer choice for women over age 35, smokers, and those who have other risk factors that contraindicate estrogen use.

Advantages of Oral Contraceptives

Oral contraceptives are the choice of most American women who use birth control, making them the most popular reversible contraceptives in the U.S. Oral contraceptives are among the most effective contraceptives. Failure rates are relatively low (9% with typical use) and are usually due to noncompliance.
Oral contraceptives also have the following advantages, which may vary depending on the type and brand used:
  • Reduce menorrhagia (heavy menstrual bleeding) and, therefore, reduce the risk of anemia.
  • Reduce dysmenorrhea (severe menstrual pain)
  • May help reduce symptoms of premenstrual syndrome. Yaz is specifically approved for treating premenstrual dysphoric disorder (premenstrual depression).
  • Improve acne
  • Improve symptoms of endometriosis.
  • Reduce risks of ovarian cysts
  • Possible protection against bone loss with estrogen-containing oral contraceptives
  • Reduce risks of ovarian and endometrial (uterine) cancers with long-term use (more than 3 years)

Disadvantages of Oral Contraceptives

Common Side Effects. Many women experience some side effects during the first 2 - 3 months of birth control use. These side effects usually subside. Estrogen and progesterone have different side effects, and women on the combined pill may experience different effects from those on the progestin-only pill.
Common side effects of oral contraceptives include:
  • Nausea and vomiting (can often be controlled by taking the pill during a meal or at bedtime)
  • Headaches (in women with a history of migraines, they may worsen)
  • Dizziness
  • Breast tenderness and enlargement
  • Irregular bleeding or bleeding between periods
  • Weight gain
Newer formulations of combination pills that use low-dose estrogen, and newer progestins, may reduce and even lower the risk of many of these side effects, including weight gain.
Serious Side Effects . Symptoms of serious problems may include severe abdominal pain, chest pain, unusual headaches, visual disturbances, or severe pain or swelling in the legs. If you experience any of these symptoms, you should immediately contact your doctor.
Potential Risks . Combination birth control pills can increase the risk of developing or worsening certain serious medical conditions. The risks depend in part on a woman’s medical history. You should discuss your health history with your doctor to determine if combination oral contraceptives are safe for you. This is especially important for women who are age 35 or older, smoke, or have a history of high blood pressure, high cholesterol or unhealthy blood lipid profile, diabetes, or migraine headaches.
Serious risks of birth control pills may include:
  • Heart and Circulation Problems. Combination birth control pills contain estrogen, which can increase the risk for stroke, heart attack, and blood clots in some women. The risk is highest for women who smoke or have a history of heart disease risk factors (such as high blood pressure or unhealthy cholesterol/lipid levels) or cardiac events. Women who have certain metabolic disorders, such as polycystic ovary syndrome (PCOS), are also at higher risk for heart-related complications associated with these pills. Women who have migraines may possibly be at increased risk for stroke and may need to consider progestin-only pills or other contraceptive methods in place of combination oral contraceptives.
  • Venous Thromboembolism. All combination estrogen/progestin birth control products carry an increased risk for blood clots in the veins (venous thromboembolism), which can lead to blood clots in the arteries of the leg or lung (pulmonary embolism). The risk is lower for oral contraceptives than for the birth control patch (Ortho Evra) or the ring (NuvaRing), which expose women to higher levels of estrogen than birth control pills. Women who smoke, who are obese, or who have heart disease risk factors may want to consider using alternatives to estrogen-containing contraceptives, such as progestin-only oral contraceptives ("mini-pills"), intrauterine devices, or barrier contraceptive methods.
  • Diabetes. Women who have diabetes, and high blood pressure, vascular disease, kidney disease, or other diabetes-related health problems, should not take birth control pills.
  • Cancer Risks. Several studies have reported a strong association between increased risk of cervical cancer and long-term use of oral contraception. Women who take oral contraceptives for more than 10 years appear to have a much higher risk of human papilloma virus (HPV) infection than those who do not use oral contraceptives. Women taking oral contraceptives for less than 5 years have no significantly higher risk. Although studies have been conflicting about whether estrogen in oral contraception increases the chances for breast cancer, the most recent research indicates that oral contraceptive use does not significantly increase breast cancer risk. Women who have used oral contraceptives may have slightly more risk for breast cancer than women who have never used them, but this risk declines once a woman stops using birth control pills. Long-term use of birth control pills reduces the risk for ovarian and uterine cancers.
  • Liver Problems. In rare cases, oral contraceptives have been associated with liver tumors, gallstones, or jaundice. Women with a history of liver disease, such as hepatitis, should consider other contraceptive options.
  • Interactions with Other Medications. Certain types of medications can interact with and decrease the effectiveness of oral contraceptives. These medications include anticonvulsants, antibiotics, antifungals, and antiretrovirals. The herbal remedy St. John’s wort can also interfere with birth control pills’ effectiveness. Make sure your doctor is aware of any drugs, vitamins, or herbal supplements that you take.

Other Methods for Administering Combination Hormones (Patch and Ring)

New methods of administering the combination of progestin and estrogen are now available. Failure rates with perfect use (0.1 - 0.6%) are similar to those of combined oral contraceptives.
Skin Patch. Ortho Evra is a birth control skin patch. It contains a progestin (norelgestromin) and estrogen. The patch is placed on the lower abdomen, buttocks, or upper body (but not on the breasts). Each patch is worn continuously for a week and reapplied on the same day of each week. After three weekly patches, the fourth week is patch-free, which allows menstruation. (The patch remains effective for 9 days, so being slightly late in changing it should not increase the risk for pregnancy.)
The Ortho patch exposes women to higher levels of estrogen than most birth control pills, and therefore increases the risk for blood clots in the veins (venous thromboembolism). Venous thromboembolism can cause blockage in lung arteries and other serious side effects. Older women (over age 40) and women with risk factors for blood clots (such as cigarette smoking) may find other birth control products to be a safer choice. Discuss with your doctor whether the patch is appropriate for you.
Vaginal Ring. NuvaRing is a 2-inch flexible ring that contains both estrogen and progestin (etonogestrel). It is inserted into the vagina. Women can insert the ring by themselves once a month and take it out at the end of the third week to allow menstruation. It works well and may cause less irregular bleeding than oral contraceptives. Some women find it uncomfortable, and a few have reported vaginal irritation and discharge, but such problems rarely cause a woman to discontinue use. As with the patch, NuvaRing may put women who take it at higher risk for blood clots than oral contraceptives.

Implant Contraception

Implant contraception involves inserting a rod under the skin. The rod releases into the bloodstream tiny amounts of the hormone progestin.
The first implant was the Norplant system, which used six rods that contained levonorgestrel. Due in part to serious complications, Norplant was withdrawn from the U.S. market in 2002. The main complication was difficulty inserting and, in particular, removing the rods. (Many women experienced scarring.) In addition, some women who used Norplant experienced heavy irregular bleeding. A two-rod implant called Jadelle is sold in other countries, but not the United States.
In 2006, the Food and Drug Administration approved Implanon, a new implant contraceptive. In contrast to Norplant:
  • Implanon uses one rod, not six.
  • It is not inserted as deeply into the skin.
  • It uses etonogestrel, a different type of progestin than the levonorgestrel used in Norplant.
  • Only specially trained health care providers are allowed to insert and remove Implanon.
Implanon insertion takes about a minute and is performed with a local anesthetic in a doctor’s office. The rod remains in place for 3 years, although it can be removed at any time. (The removal procedure takes a few minutes longer than insertion.) After the rod is removed, a new one can be inserted.
Studies indicate that Implanon is safe. Irregular bleeding and headaches are the main side effects. However, some doctors are concerned that Implanon may have some of the same risks as Norplant.

Injected Contraception

Injected contraceptives are given once every 3 months. Most injectables are progestin-only. In the United States, depo-medroxyprogesterone acetate (Depo-Provera) is the only approved injected contraceptive. Depo-Provera (also called Depo, or DMPA) uses a progestin called medroxyprogesterone.
Depo-Provera is very effective in preventing pregnancies. About 3 in 100 women who use it become pregnant. However, Depo also carries the risk for many mild and serious side effects. The most serious side effect is loss of bone density (see "Disadvantages"). Because of this complication, Depo-Provera should not be used for longer than 2 years.
Administering Injections :
  • A physical examination is necessary before beginning the injections.
  • Depo is injected into a muscle in the patient's arm or buttock. During months between injections, the hormone slowly diffuses out of the muscle into the bloodstream.
  • Depo requires an injection by the doctor once every 3 months.
  • If more than 2 weeks pass beyond the regular injection schedules, the woman should have a pregnancy test before receiving the next injection.


Because Depo-Provera does not contain estrogen, it is safe for many women who may be riskier candidates for combination oral contraceptive use, such as women over age 35, women with high blood pressure, obese women, and smokers.
Depo-Provera should not be given to women who have a history of:
  • Current or past breast cancer
  • Stroke or blood clots
  • Liver disease
  • Epilepsy, migraine, asthma, heart failure, or kidney disease (due to the fact that the drug causes fluid retention)
  • Unexplained vaginal bleeding
  • Risk for osteoporosis
Because of the long lag time between ending treatments and restoration of fertility, Depo-Provera is not recommended for women who are thinking of becoming pregnant within 2 years.

Advantages of Depo-Provera

  • Provides highly effective reversible protection against pregnancy without placing heavy demands on the user's time or memory.
  • Does not increase risk for breast, ovarian, or cervical cancer. May protect against endometrial cancer.
  • May be useful for women with painful periods, heavy bleeding (including heavy bleeding caused by fibroids), premenstrual syndrome, and endometriosis.

Disadvantages and Complications of Depo-Provera

  • Weight gain. Most women gain an average of 5 - 8 pounds.
  • Other common side effects include menstrual irregularities (bleeding or cessation of periods), abdominal pain and discomfort, dizziness, headache, fatigue, nervousness.
  • Most users of Depo-Provera stop menstruating altogether after a year. Depo can cause persistent infertility for up to 22 months after the last injection, although the average is 10 months.
  • Long-term (more than 2 years) use of Depo-Provera can cause loss of bone density. Depo-Provera’s label warns that the decline in bone density increases with duration of use and may not be completely reversible even after the drug is discontinued. The FDA recommends that Depo-Provera should not be used for longer than 2 years unless other birth control methods are inadequate. Some studies indicate that this bone loss may be reversible once Depo-Provera use is discontinued. Some doctors recommend that women take calcium and vitamin D supplements while on Depo-Provera.
  • The injections do not provide protection against sexually transmitted diseases.

Intrauterine Devices (IUDs)

The intrauterine device (IUD) is a small plastic T-shaped device that is inserted into the uterus. An IUD's contraceptive action begins as soon as the device is placed in the uterus and stops as soon as it is removed. IUDs have an effectiveness rate of close to 100%. They are also a reversible form of contraception. Once the device is removed, a woman regains her fertility.

Intrauterine Device Forms

Two types of intrauterine devices (IUDs) are available in the United States:
  • Copper-Releasing (ParaGard). This type of IUD can remain in the uterus for up to 10 years. Copper ions released by the IUD are toxic to sperm, thus preventing fertilization.
  • Progestin-Releasing (Mirena). This type of IUD can remain in the uterus for up to 5 years. Mirena is also known as a levonorgestrel-releasing intrauterine system, or LNG-IUS. Levonorgestrel impairs sperm motility and viability, thus preventing fertilization. LNG-IUS is long-acting, safe, very effective in preventing heavy bleeding, and helps reduce cramps. In fact, some doctors describe it as a nearly ideal contraceptive. In addition to being a contraceptive, it is approved as a treatment for heavy menstrual bleeding.

Inserting an Intrauterine Device

With some exceptions, an intrauterine device (IUD) can be inserted at any time, except during pregnancy or when an infection is present. It may be inserted immediately postpartum or after elective or spontaneous miscarriage. It is typically inserted in the following manner by a trained health professional:
  • A plastic tube containing the IUD (the inserter) is slid through the cervical canal into the uterus.
  • A plunger in the tube pushes the IUD into the uterus.
  • Attached to the base of the IUD are two thin but strong plastic strings. After the instruments are removed, the health care provider cuts the strings so that about an inch of each dangles outside the cervix within the vagina.
The strings have two purposes:
  • They enable the user or health care provider to check that the IUD is properly positioned. (Because the IUD has a higher rate of expulsion during menstruation, the woman should also check for the strings after each period, especially if she has heavy cramps.)
  • They are used for pulling the IUD out of the uterus when removal is warranted.
The insertion procedure can be painful and sometimes causes cramps, but for many women it is painless or only slightly uncomfortable. Patients are often advised to take an over-the-counter painkiller ahead of time. They can also ask for a local anesthetic to be applied to the cervix if they are sensitive to pain in that area. Occasionally a woman will feel dizzy or light-headed during insertion. Some women may have cramps and backaches for 1 - 2 days after insertion, and others may suffer cramps and backaches for weeks or months. Over-the-counter painkillers can usually moderate this discomfort.

Candidates for the Intrauterine Device

Intrauterine devices are an excellent choice of contraception for women who are seeking a long-term and effective birth control method, particularly those wishing to avoid risks and side effects of contraceptive hormones. The LNG-IUS may be better suited for women with heavy or regular menstrual flow.
Around the time of insertion and shortly afterwards, women should be considered at low risk for sexually transmitted disease (mutually monogamous relationship, using condoms, or not currently sexually active).
Women with risk factors that preclude hormonal contraceptives should probably avoid progestin-releasing IUDs, although the progestin doses are much lower with LNG-IUS and probably do not pose the same risks.
Women with the following history or conditions may be poor candidates for IUDs:
  • Current or recent history of pelvic infection (the risk of pelvic inflammatory disease is higher for all women who have multiple sex partners or who are in non-monogamous relationships--not just those with IUDs)
  • Current pregnancy
  • Abnormal Pap tests
  • Cervical or uterine cancer
  • A very large or very small uterus
IUDs have the following advantages:
  • The IUD is more effective than oral contraceptives at preventing pregnancy, and it is reversible. Once it is removed, fertility returns. (Studies have found no adverse effects on fertility with the current IUDs.)
  • Unlike the pill, there is no daily routine to follow.
  • Unlike the barrier methods (spermicides, diaphragm, cervical cap, and the male or female condom), there is no insertion procedure to cope with before or during sex.
  • Intercourse can resume at any time, and, as long as the IUD is properly positioned, neither the user nor her partner typically feels the IUD or its strings during sexual activity.
  • It is the least expensive form of contraception over the long term.
Additional advantages, depending on the specific IUD, include:
  • The progestin-releasing LNG-IUS (Mirena) is now considered to be one of the best options for treating menorrhagia (heavy menstrual bleeding). (However, irregular breakthrough bleeding can occur during the first 6 months.)
  • The copper-releasing IUDs do not have hormonal side effects and may help protect against endometrial (uterine) cancer.

Complications of Specific Intrauterine Devices

Menstrual Bleeding. Both intrauterine device (IUD) forms have effects on menstruation, although they differ significantly by type:
  • Copper releasing IUDs can cause cramps, longer and heavier menstrual periods, and spotting between periods. Prescription medications are available to control the bleeding and pain, which, in any event, usually subside after a few months.
  • Progestin-releasing IUDs produce irregular bleeding and spotting during the first few months. Bleeding may disappear altogether. (This characteristic is a major advantage for women who suffer from heavy menstrual bleeding but may be perceived as a problem for others.)
Ovarian Cysts . The LNG-IUS may increase the risk for benign ovarian cysts, but such cysts usually do not cause symptoms and resolve on their own.
Expulsion. About 2 - 8% of IUDs are expelled from the uterus within the first year. Expulsion is most likely to occur during the first 3 months after insertion. Expulsion rates may be higher than average if the IUD is inserted immediately after delivery of a child. In 1 in 5 cases, the woman fails to notice that the device is gone, and thus faces the risk of unintended pregnancy. The risk for expulsion is highest during menstruation, so women should be sure to check the strings to make sure the IUD is in place.
Pelvic infections . What was thought to be an increased risk of pelvic inflammatory disease has proven not to be true. The risk does not seem to be any greater than the risk in the general population The risk for infection may be increased around the time of insertion of the IUD, but routine screening before insertion is generally not recommended. There is also no evidence that IUD usage increases the risk of HIV infection.
Effects on Pregnancy.
  • None of the current IUDs increase the risk for infertility. Women with a history of using an IUD are no more likely to be diagnosed with infertility than those who have not used IUDs. This seems to be true both for women who have never been pregnant or women who have been pregnant previously.
  • In the very unlikely event that a woman conceives with an IUD in place, however, there is a higher risk of an ectopic pregnancy or miscarriage. Ectopic pregnancy is when the fertilized egg implants outside of the uterus. Most ectopic pregnancies occur in the fallopian tubes. However, overall, women who use IUDs have a significantly lower rate of ectopic pregnancies than women who do not use any contraception. Even for women who have a history of ectopic pregnancies when not using contraception, the IUD is considered safe and may even lower their risk for another one.
If the IUD is removed right after conception, the risk for miscarriage is close to average (about 20%). There is no evidence that the IUD in a pregnant woman increases the risk for birth defects in the infant.
Perforation. A potentially serious complication of the IUD is the accidental perforation of the uterus during insertion or later perforation if the IUD shifts position. Such an occurrence is very rare, particularly if the doctor is experienced with insertion.


Monday, July 15, 2013

Effects of simvastatin in prevention of pain recurrences after surgery for endometriosis

Med Sci Monit. 2013; 19: 534–539.
Published online 2013 July 5. doi:  10.12659/MSM.883967
PMCID: PMC3706410

Effects of simvastatin in prevention of pain recurrences after surgery for endometriosis



To compare efficacy of simvastatin with GnRHa (Decapeptyl 3.75 mg) on endometriosis-related pains following surgery for endometriosis.


Sixty women with pelvic endometriosis, after laparoscopic diagnosis and conservative laparoscopic surgery, were treated with either simvastatin (n=30) for 16 weeks or Decapeptyl (n=30) every 4 weeks for 4 doses.


Using VAS, the score of dyspareunia, dysmenorrhea, and pelvic pain 6 months after laparoscopic surgery declined significantly in both groups (p=0.001), but the difference between results of the 2 groups was not significant (p>0.05).


Both treatment modalities showed comparable effectiveness in the treatment of pains related to endometriosis.
Keywords: statin, GnRHa, endometriosis, chronic pelvic pain, dysmenorrhea, dyspareunia


The presence of endometrial glandular and stromal cells outside the uterine cavity is called endometriosis. Endometriosis is one of the most common benign diseases affecting quality of life and fertility of women. Endometriosis is diagnosed by visual inspection of the pelvis during laparoscopy and positive histology confirms the diagnosis, but negative histology does not exclude it []. Multiple factors are responsible for endometriosis. The most important one is regurgitation of menstrual blood, but cytokines play a critical role in facilitation of the implantation of ectopic endometrial tissues []. Numerous data indicate that eutopic endometrial glandular and stromal cells may be functioning differently in women with endometriosis compared to normal endometrium in disease-free women []. Expression of Importin13, a possible marker for endometrial stem cells, compared to secretory endometrium, might support the hypothesis that this disease originates from stem cells []. The most prominent symptoms of endometriosis are dyspareunia, dysmenorrhea, pelvic pain, and infertility. All endometriosis lesion types are associated with pelvic pain and dysmenorrhea. Current treatment of endometriosis is mainly based on surgery and ovarian suppressive agents. Some medical treatments have been suggested for endometriosis, including oral contraceptive pills, medroxy progesterone acetate, and gonadotropin-releasing hormone agonists (GnRHa) []. In some studies statins were effective in prevention of endometriotic cells proliferation in vitro.
Statins are potent inhibitors of cholesterol biosynthesis to reduce serum cholesterol in patients with hyperlipidemia. Statins act by inhibiting 3-Hydroxy-3-Methyl Glutaryl Coenzyme A (HMG-CoA) reductase to block the conversion of HMG-CoA to L-mevalonate, a rate-limiting step in cholesterol synthesis. Statins were effective in inhibiting the mechanisms of cell proliferation and angiogenesis in experimental models for the development of endometriosis-like tissue []. In 1 study using a nude mouse model, simvastatin induced a dose-dependent decrease of the number and size of endometrial implants in mice. At the highest dose of simvastatin, the number of endometrial implants decreased by 87% and the volume by 98% []. In another study on endometriotic cyst walls and endometrial biopsy in vitro, atorvastatin treatment had no effect on 17βE2 levels in endometriotic stromal cell culture supernatant, and concluded that atorvastatin can be used as a treatment for endometriosis in humans [].
Different studies have suggested that the role of statins in inhibition of aromatase activity may represent a new therapeutic option for endometriosis. After approval by ethics committee of Tehran University of Medical Sciences (TUMS) and after counseling with patients with pelvic endometriosis, we compared the clinical symptoms of patients after prescription of GnRHa with simvastatin.

Material and Methods

This study was conducted as a prospective, randomized, controlled trial to compare the effectiveness of simvastatin with that of GnRHa treatment, after surgery for endometriosis, on pain due to endometriosis. In our gynecology ward, all the patients with the laparoscopic diagnosis of pelvic endometriosis were included in the study. All of the subjects underwent conservative laparoscopic surgery. Laparoscopy was performed under general anesthesia, using the triple puncture technique. In laparoscopy, the surgeons tried to excise or ablate all the endometriotic implants and performed adhesiolysis. The night before laparoscopy, a data collection form was completed by a physician. The cause of laparoscopy and the severity of dyspareunia, dysmenorrhea, and pelvic pain were estimated by use of the Visual Analogue Scale test (VAS test), with a score of 0 being no pain and 10 being the most severe pain ever experienced. After the operation, the severity of endometriosis was entered into the data collection form as revised according to the American Society for Reproductive Medicine classification for endometriosis [,]. The staging was done intraoperatively by the 2 surgeons who were involved in the operations. Following ethics committee approval and obtaining informed consent in cases of simvastatin prescription, we prescribed simvastatin (film-coated tablet simvaHEXAL, 20 mg daily for 4 months) or GnRHa (Decapeptyl 3.75 mg IM each 28 day period for 4 doses) at the time of discharge. The patients were randomly assigned to either the simvastatin or Decapeptyl group (assigned to each group alternately in order of admission). Although the patient selection was random, in patients who wanted to become pregnant immediately, we had the obligation to prescribe simvastatin rather than GnRHa. None of the patients had a history of previous surgery or GnRHa treatment. We followed the patients for continuation of drugs and adverse effects of simvastatin. Each group had 30 patients and we tried to match the two groups for age, the severity of endometriosis and severity of endometriotic pain. Six months after operation, we reassessed the patients’ symptoms by VAS.
We analyzed the data by SPSS 13, using the KS test (one-sample Kolmogorov-Smirnov test) for normality of data distribution, Levene’s test for equality of variances, and independent samples t-test for equality of means for comparing quantitative normal data between the 2 groups, paired sample t-tests for comparing quantitative normal data between before and after treatment in each group and Pearson chi-square test for matching and comparing categorical variables between the 2 groups. According to the KS test, we compared the non-normal quantitative data by Mann-Whitney U nonparametric test between the 2 groups and Wilcoxon signed ranks test for comparing before and after treatment data in each group.


In these 60 patients, 40 had endometrioma of ovary; the size of endometrioma was most often 3–10 centimeters (n=37). In this study, marital status of the 2 patient groups – the simvastatin group (S) and the GnRHa group (G) – was matched (P=0.793), but the difference for presence of endometrioma between the two groups was significant (P=0.045), (Table 1).
Table 1
Comparison of marital status in two patient groups.
The major reasons for laparoscopy in the simvastatin group were infertility (40.0%) and ovarian cyst (33.3%) and ovarian cyst (40.0%) and dysmenorrhea (30.0%) in the GNRHa group (Table 2).
Table 2
Frequency of different reasons for laparoscopy in two groups.
Severity of endometriosis in the 2 patient groups was not significantly different (P=0.253) (Table 3).
Table 3
Severity of endometriosis in two patient groups.
The severity of dyspareunia, dysmenorrhea, and pelvic pain before and after treatment were not significantly different between the 2 groups (Table 4). However, after treatment, the severity of dyspareunia, dysmenorrhea, and pelvic pain in the 2 groups was significantly reduced and the difference between before and after treatment in 3 parameters in each group was significant (Table 5). None of the patients showed adverse effects of simvastatin and all continued medical treatment for 4 months. Three of the patients in the simvastatin group became pregnant 4 months after surgery. All of them had mild endometriosis.
Table 4
comparison of age and severity of dyspareunia, dysmenorrhea and pelvic pain in two patient groups.
Table 5
Comparison of parameters before and after treatment in each group.


The major finding of this prospective, randomized, double-blind trial of simvastatin versus Decapeptyl in the treatment of endometriotic pains was that after ablative surgery, prescription of simvastatin or Decapeptyl resulted in no significant difference in outcome.
Endometriosis is a common, often painful, condition, frequently associated with infertility. Endometriosis is found in 33% of infertile women []. Laparoscopy is recognized as the first option for diagnosis and treatment of endometriosis, but the rate of pain recurrence after conservative surgery is high. GnRH agonists have long been used successfully in the treatment of endometriosis [,], but because of their adverse effects (loss of bone minerals and vasomotor symptoms), physicians need better choices.
Statins, inhibitors of 3-hydroxy-3methylglutaryl-coenzyme A reductase (HMGCR), have been shown to decrease proliferation of several mesenchymal tissues. Actions of statins may be related to decrease in availability of cholesterol, as well as intermediate metabolites of mevalonate pathway downstream of HMGCR. Statin affects the growth of endometriotic tissues by inhibiting angiogenesis [,]. This could be important in non-hormonal and non-surgical treatment of endometriosis. The effectiveness of simvastatin in inhibition of endometriotic tissue has been confirmed in vitro. Proliferation of endometrial stromal cells has been inhibited with simvastatin in endometrial tissue obtained from 4 women with endometriosis. Therefore, it is suggested that simvastatin could potentially be a therapeutic agent for treatment of endometriosis []. The in vitro studies demonstrated that simvastatin induced a concentration-dependent inhibition of human endometrial stromal cell proliferation, evidenced by reduced DNA synthesis and a decrease in number of viable cells []. It has also shown that simvastatin inhibits the proliferation of stromal cells derived from human endometriotic implants in ovaries [].
Simvastatin reduced both the number and volume of endometriotic lesions in nude mice in a dose-dependent manner. About 85% of the mice in the control group developed lesions, whereas 58% of the mice receiving low-dose simvastatin and only 17% of those given high-dose simvastatin had lesions. These findings suggested that the use of statins for treatment of endometriosis can be effective [,].
In our study, after conservative surgical treatment, the result of prescription of simvastatin (20 mg daily for 4 months) was similar to Decapeptyl (3.75 mg IM for 4 doses) in control of endometriotic pain.

Limitations of study

Our study has some limitations. The sample size was small and the study must be repeated with larger sample sizes and with other doses of simvastatin. In addition, none of the patients accepted second-look laparoscopy to evaluate size and number of endometriotic lesions after medical treatment. Finally, our study lacked a third group without medical treatment after conservative surgical treatment.
The important aspect of this study is that it is the first to evaluate use of simvastatin to relieve endometriotic pains.
Further investigations without the limitations of the present study should provide more precise assessment of the effects of simvastatin on endometriotic lesions.


GnRHa is one of the most accepted medical treatments of endometriosis, but the role of statins in endometriosis had been assessed only in vitro or in animal models. Our study assessed the effect of simvastatin on symptoms of endometriosis and found that it is comparable with Decapeptyl.


Source of support: Minimally Invasive Surgery Research Center, Rasool Akram Hospital, Tehran University of Medical Sciences (T.U.M.S), Tehran, Iran


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