The impact of combined oral contraceptives on ocular tissues:a review of ocular effects

The aim of this manuscript is to review the action and adverse effects of combined oral contraceptives（COCs）on ocular tissues.The percentage of unwanted pregnancies and the subsequent abortions make contraception crucial worldwide.Over 100 million women around the world use common contraceptive methods,including intrauterine devices,combined estrogen and progestin oral contraceptives,as well as progestin only preparations（oral contraceptives,implants or injections）.COCs are widely used for contraception,but they are also indicated in menorrhagia,endometriosis,acne and hirsutism,fibroid uterus and premenstrual syndrome.However,they have been associated with high rates of cardiovascular events,venous thromboembolic disease,ischemic strokes and breast cancer.The incidence of COCs-related ocular complications is estimated to be 1 in 230 000,including dry eye symptoms,corneal edema,lens opacities and retinal neuro-ophthalmologic or vascular complications.We may infer that the serious ocular complications of COCs can be prevented by eliminating the estrogen dosage and choosing third-generation progestins.In any case,doctors should take into consideration the systemic and ocular history of the patients before selecting any method of contraception.

Use of oral contraceptives and risk of pancreatic cancer in women:A recalculated meta-analysis of prospective cohort studies

In a recent systematic review and meta-analysis of observational studies,the author found potential errors in the selection and extraction processes.The recalculated summary relative risks and the results of a dose-response metaanalysis showed that oral contraceptive use may not be associated with the risk of pancreatic cancer in women.

The Use of Hormonal Contraceptives and Preeclampsia among Ghanaian Pregnant Women

Hormonal contraceptives (HC) are thought to play a role in the pathogenesis of cardiovascular diseases. The study evaluated the use of HC as a primary cause of preeclampsia (PE) among Ghanaians. This study comprised 30 preeclamptic women and 30 healthy normotensive pregnant women with over 20 weeks of gestation at the Comboni Hospital, Ghana using a randomized case-control study. Blood pressure, weight, height, socio-demographics, medical and previous obstetric history were taken and recorded. Blood samples were collected for the estimation of homocysteine and fasting lipids. Estimated foetal weight (EFW) and infant birthweight (BWT) were obtained from maternal records. This study was carried out in 2019. 80.0% of women with PE used the hormonal contraceptive “depot medroxyprogesterone acetate” (DMPA) prior to pregnancy. The use of DMPA was associated with about thirty-fold increase in the odds of developing PE (OR = 29.71, p < 0.001). Systolic blood pressure (P < 0.001), diastolic blood pressure (P < 0.001), triglycerides (P = 0.024), LDL-C (P = 0.026), and homocysteine levels (P < 0.001) were significantly elevated in the PE cases than the normal pregnant (NP) women, whilst EFW (P < 0.001), BWT (P < 0.001) and HDL-C levels (P = 0.001) were significantly reduced in the PE cases when compared to NP women. 50% and 47% of PE cases had intrauterine growth restriction and low birthweight infants, respectively. In conclusion, DMPA use predisposes women to a high risk of developing PE. DMPA could partly contribute to endothelial dysfunction, hyperhomocysteinaemia, dyslipidaemia and excessive weight gain, all of which characterize PE.

Effect of Hormonal Contraceptives on the Total Antioxidants Status of Women from Isolo, Lagos State, Nigeria

The use of hormonal contraceptives has been implicated in the depletion of serum antioxidants and resultant promotion of oxidative stress which is associated with various disorders including cardiovascular disease and cancer. This study investigated serum total antioxidant status (TAS) in women taking hormonal contraceptives and compared their results with non-contraceptive users (age- and sex-matched). Sixty women aged 30 - 45 years, were enrolled for the study which included forty-five users of hormonal contraceptives from the Planned Parenthood Federation of Nigeria, Isolo, Lagos state and fifteen age-matched, apparently healthy, non-contraceptive users from the same geographical location were selected as controls. The in vitro determination of the serum total antioxidant status (TAS) was performed using Biorex enzymatic kit. Data obtained were statistically analyzed using student’s t-test and P < 0.05 was considered significant. The serum levels of TAS in the users of hormonal contraceptives were significantly lower than non-users (P < 0.05). The study concluded that women on hormonal contraceptives especially those taking either combined oral or combined injectable contraceptives were at risk of developing disorders associated with reduced levels of serum antioxidants.

Electrical Activities and Pressure Pain Threshold in Oral Contraceptives Users and Nonusers

The aim is to evaluate the influence of oral contraceptive intake and menstrual cycle on the electrical activity and pressure pain threshold from anterior temporal and masseter muscles. Twenty-eight women on reproductive age were selected, 13 OC users and 15 nonusers. They were weekly submitted to electromyography and algometry of the anterior temporal and masseter muscles during three consecutive menstrual cycles. Electrical activities at rest position and PPTs of temporal and masseter muscles were not affected by menstrual cycle or by OCs uses. Comparison between groups demonstrated that working side electrical activity was increased in OC users in both muscles, except during lutheal phase for the anterior temporal. However, comparison within weeks did not demonstrate statistical difference. It was suggested that, in healthy women, oral contraceptive use may influence electrical activity, but different phases of the cycle may not.

Relieving the Impacts of Oral Contraceptives on Lipids Profile by Taking Pills in a Novel Scheme

Objective To explore whether the changes on lipids profile induced by oral contraceptives could be reduced through alternatively administering two oral contraceptives of different formulations (either predominant in progestogen or estrogen) Materials &. Methods A total of 59 women aged 25- 45 were divided into two treatment groups.The subjects in Group A received oral contraceptive A (Oc A: NET 0. 600 mg + EE 0. 035 mg) and B (OcB: LNG 0. 15mg + EEO. 03 mg) alternatively during 12 treatment cycles. Each contraceptive was administrated for three cycles consecutively with starting from OcA. The subjects in the B group received OcB only during 12 treatment cycles. Fasting blood were drawn before treatment, at the end of each trimester treatment and at the end of one cycle after stopping treatment respectively. The concentrations of lipids and apolipoproteins were measured.Results OcA increased the levels of triglyceride(TG) , total cholesterol (TC), high density lipoprotein-cholesterol(HDL-c) , and apolipoprotein AI (apo AI) with statistical significance, whereas OcB significantly decreased all parameters above. As compared with the control group, the overall mean of variation in the study group was much less than that of the control group.Conclusion It indicates that the impacts of oral contraceptives on lipids profile could be moderated by means of alternatively administering Ocs of two different formulations , with estrogen-dominant or progestogen-dominant.

A multivariate analysis of the factors that influence the modification of sexual desire in oral hormonal contraceptive (OC) users

Objective. This work studied the influencing factors of age, level of education, family planning awareness, relationship with partner, the age at which sexual relationships were initiated, parity, the method of contraceptive previously used, the type of contraceptive pill used and the duration of oral hormonal contraception (OC) use in relation to the modification of sexual desire in OC users. Materials and Methods. Prospective study of 760 OC users at the Family Planning Center “Marina Alta” in Alicante (Spain). A logistical regression analysis was carried out to study the relative risk of reduction in libido, taking other risk factors into account. Results. In the simple analysis, women who initiated sexual relationships between 18 and 25 years of age had a lower sexual desire in comparison with women who were sexually active before the age of 18 (OR = 2.11;CI: 1.15 - 3.91). Nulliparous women had a reduced sexual desire compared with those women that had given birth (OR = 2.32;CI: 1.41 - 3.82). An OC use of between 6 months and 1 year reduced sexual desire in comparison with a use of less than 6 months (OR = 0.24;CI: 0.09 - 0.64). In the multivariate analysis, age (OR = 1.12;CI: 1.01 - 1.21) and the use of OC within an initial 6 month to a year period (OR = 0.24;CI: 0.09 - 0.64) presented a statistically significant relationship with the modification of sexual desire. The level of education, family planning awareness, relationship with partner, the method of contraception previously used and the type of contraceptive pill prescribed showed no statistical significance with the modification of sexual desire in OC users. Conclusions. Sexual desire in OC users decreases as a woman’s age increases and in an early stage of use in the first six months after beginning OC treatment.

Attributable Causes of Breast Cancer and Ovarian Cancer in China:Reproductive Factors,Oral Contraceptives and Hormone Replacement Therapy

Objective： To provide an evidence-based, consistent assessment of the burden of breast cancer attributable to reproductive factors （RFs, including nulliparity, mean number of children, age at first birth and breastfeeding）, use of oral contraceptives （OCs, restricted to the age group of 15-49 years）, and hormone replacement therapy （HRT）, as well as of the burden of ovarian cancer attributable to the mean number of children in China in 2005. Methods： We derived the prevalence of these risk factors and the relative risk of breast and ovarian cancer from national surveys or large-scale studies conducted in China. In the case of RFs, we compared the exposure distributions in 2001 and counterfactual exposure. Results： Exposure of RFs in 2002 was found to account for 6.74% of breast cancer, corresponding to 9,617 cases and 2,769 deaths, and for 2.78% of ovarian cancer （712 cases, 294 deaths）. The decrease in mean number of children alone was responsible for 1.47% of breast cancer and 2.78% of ovarian cancer. The prevalence of OC use was 1.74% and the population attributable fraction （PAF） of breast cancer was 0.71%, corresponding to 310 cases and 90 deaths. The PAF of breast cancer due to HRT was 0.31%, resulting in 297 cases and 85 deaths. Conclusion： RFs changes in China contributed to a sizable fraction of breast and ovarian cancer incidence and mortality, whereas HRT and OCs accounted for relatively low incidence of breast cancer in China.

Effect of Two Kinds of Different Combined Oral Contraceptives Used on Bone Mineral Density in Women of Reproductive Age

Objective To compare bone mineral density （BMD） among users of ethinylestradiol/ desogestrel, ethinylestradiol/cyproterone acetate and nonhormonal control subjects. Methods The study included 154 women aged 25-40 years. Forty-six women were using ethinylestradiol/desogestrel （group A） and 55 women using ethinylestradiol/cyproterone acetate （group B）for 24 months and 53 women using nonhormonal contraception as control subjects （group C）. BMD of the lumbar spine and femoral neck were obtained using dual energy X-ray absorptiometry, comparing mean BMD changes in combined oral contraceptives （COCs） users with nonusers. Results For 24 months of treatment, lumbar spine and femoral neck BMD values in women who used ethinylestradiol/desogestrel and ethinylestradiol/cyproterone acetate were not significantly different compared with the baseline and the values of subjects in nonuser （P〉0.05）. Conclusion There was no statistical difference in BMD between the users of ethinylestradiol/desogestrel or ethinylestradiol/cyproterone acetate and nonusers.

Comparison of Drospirenone-with Cyproterone Acetate-Containing Oral Contraceptives, Combined with Metformin and Lifestyle Modifications in Women with Polycystic Ovary Syndrome and Metabolic Disorders： A Prospective Randomized Control Trial

Background：While combined oral contraceptives （COCs） are commonly used to treat polycystic ovary syndrome （PCOS）,comparative data regarding metabolic effects of different progestogens on this patient population are missing.This study aimed to compare the different effects of drospirenone （DRP）-containing COCs with cyproterone acetate （CPA）-containing COCs,combined with metformin and lifestyle modifications in women with PCOS and metabolic disorders.Methods：Ninety-nine women with PCOS and a metabolic disorder between January 2011 and January 2013 were enrolled into this prospective randomized clinical trial.Participants were randomized into two groups such as DRP-containing COCs,and CPA-containing COCs.Participants took COCs cyclically for 6 months,combined with metformin administration （1.5 g/d） and lifestyle modifications （diet and exercise）.Clinical measures and biochemical and hormone profiles were compared.Comparisons for continuous variables were evaluated with paired and unpaired Student＆#39;s t-tests.The Wilcoxon signed rank test was used when the data were not normally distributed.Analysis of covariance was used to control for age,body mass index （BMI）,and baseline data of each analyzed parameter when compared between the two groups.Results：A total of 68 patients have completed the study.The combination regimen of COCs,metformin,and lifestyle modifications in these patients resulted in a significant decrease in BMI,acne,and hirsutism scores when compared to baseline levels in both groups （P 〈 0.05）.Blood pressure （BP） was significantly different in the CPA group when compared to baseline （75.14 ± 6.77 mmHg vs.80.70 ± 5.60 mmHg,P 〈 0.01）,and after 6 months of treatment,only the change in systolic BP was significantly different between the two groups （4.00 [-6.00,13.00] mmHg vs.-3.50 [-13.00,9.00] mmHg,P =0.009）.Fasting glucose,fasting insulin,and homeostasis model assessment-insulin resistance decreased significantly in the DRP group （5.40 ± 0.41 mmol/L vs.5.21 ± 0.32 mmol/L,P =0.041;13.90 [10.50,18.40] μU/ml vs.10.75 [8.60,13.50] μU/ml,P =0.020;3.74 [2.85,4.23] vs.2.55 [1.92,3.40],P =0.008） but did not differ between the two groups.While individual lipid profiles increased in both groups,no statistically significant difference was observed.Conclusions：DRP-containing COCs combined with metformin and lifestyle modifications could better control BP and correct carbohydrate metabolism in women with PCOS and metabolic disorders compared with CPA-containing COCs.

Constraints in the development of contraceptives for men

Considerable efforts have been made to develop a male contraceptive and the studies have provided very useful infor-mation in this field. At least five different strategies to develop a male contraceptive have been pursued, namely: inhi-bition of sperm production, interference with sperm function, interruption of sperm transport, prevention of sperm de-position, and prevention of sperm-egg interaction. Of all these approaches, inhibition of sperm production by using an-drogens either alone or in combination with progestins have given the most encouraging results. A nmnber of clinicaltrials substantiate that it is indeed possible to have a reversible, effective and safe hormonal method of contraception. Apostmeiotic and epididymal approach to interfere with sperm function or the secretory and metabolic processes of theepididymis is another attractive option of male contraceptive development. A number of chemical compounds have beenidentified which interfere with sperm function in the epididymis without affecting sperm production, however, the com-pounds evaluated so far were found to be toxic. Interruption of sperm transport through the vas either by vasectomy orpercutaneous intmvasal injection of liquids which form cure-in-place plugs is also an attractive option. However, re-versibility of the methods is of concern in their wide scale use. The major constraint in developing a long-acting male contraceptive seems to be the need for greater investment forproduct development. The clinical trials for evaluating the efficacy and safety of the new products and formulationsstretch over several years and require enormous financial commitment. Nevertheless, the long-term gain of having along-acting reversible contraceptive for men is far greater than the financial commitments over few years. Male attitudetowards using methods of family planning is much more favourable than originally believed. The pharmaceutical indus-try as well as the health care providers therefore have a greater responsibility. For early development of a contraceptivefor men, it is essential to increase investment and simplify the drug regulatory procedures. The advent of newer tech-nologies coupled with the convergent efforts of scientists will certainly make it possible to have an effective, safe andreversible male contraceptive in the near future.

Two cases of venous sinus thrombosis in women taking the oral contraceptive pill, Yaz (dropirenone/ ethinyl estradiol), and review of the literature

Cerebral venous sinus thrombosis (CVT) is a rare cause of stroke and the clinical presentation is variable, thus mimicking other neurologic pathologies. One of the more common acquired risk factors of venous sinus thrombosis is oral contraceptive medications such as Yaz. While the prognosis for CVT is favorable, it is important to identify and treat early to prevent neurologic deficits. We report two cases of young female patients who presented with sinus thrombosis and review the current literature on this topic. CVT accounts for 0.5% of strokes and most commonly presents with headaches and in many cases focal neurologic deficits. Diagnosis is confirmed with neuroimaging including CT angiography or MR angiography. Treatment consists of anticoagulation and in some cases, thrombolytic therapy is beneficial. The overall prognosis of CVT is favorable but, further research is needed to outline optimal treatment options including the duration of anticoagulation therapy and the role of thrombolytic therapy to prevent serious neurologic deficits.

Association between oral contraceptive use and pancreatic cancer risk:A systematic review and meta-analysis

BACKGROUND Studies on the association of oral contraceptive(OC)use and pancreatic cancer showed inconsistent findings.AIM To evaluate the relationship between OC use and pancreatic cancer risk.METHODS A literature search for observational studies(case-control and cohort studies)was conducted up to December 2020.A meta-analysis was performed by calculating pooled relative risks(RRs)and 95%confidence intervals(CIs).Heterogeneity was assessed using Cochran’s chi-square test and I2 statistic.Subgroup analyses were performed by study design,source of controls in case-control studies,number of cases of pancreatic cancers,study quality according to Newcastle-Ottawa Scale score,geographical region and menopausal status.All analyses were performed using Review Manager 5.3(RevMan 5.3).RESULTS A total of 21 studies(10 case-control studies and 11 cohort studies)were finally included in the present meta-analysis,comprising 7700 cases of pancreatic cancer in total.A significant association was observed between the ever use of OC and pancreatic cancer risk in the overall analysis(RR=0.85;95%CI=0.73-0.98;P=0.03).Duration of OC use(<1 year,<5 years,5-10 years,>10 years)was not significantly associated with the risk of pancreatic cancer.Subgroup analyses revealed a statistically significant subgroup difference for the geographic region in which the study was conducted(Europe vs Americas vs Asia;P=0.07).Subgroup analyses showed a statistically significant decrease in pancreatic cancer risk and OC use in high-quality studies,studies conducted in Europe,and in postmenopausal women.CONCLUSION Despite the suggested protective effects of OC use in this meta-analysis,further epidemiological studies are warranted to fully elucidate the association between the use of OC and pancreatic cancer risk.

ABCB4 mutations underlie hormonal cholestasis but not pediatric idiopathic gallstones

AIM:To investigate the contribution of ABCB4 mutations to pediatric idiopathic gallstone disease and the potential of hormonal contraceptives to prompt clinical manifestations of multidrug resistance protein 3 deficiency.METHODS:Mutational analysis of ABCB4,screening for copy number variations by multiplex ligation-dependent probe amplification,genotyping for low expression allele c.1331T>C of ABCB11 and genotyping for variation c.55G>C in ABCG8 previously associated with cholesterol gallstones in adults was performed in 35 pediatric subjects with idiopathic gallstones who fulfilled the clinical criteria for low phospholipid-associated cholelithiasis syndrome(LPAC,OMIM#600803)and in 5young females with suspected LPAC and their families(5 probands,15 additional family members).The probands came to medical attention for contraceptiveassociated intrahepatic cholestasis.RESULTS:A possibly pathogenic variant of ABCB4was found only in one of the 35 pediatric subjects with idiopathic cholesterol gallstones whereas 15 members of the studied 5 LPAC kindreds were confirmed and another one was highly suspected to carry predictably pathogenic mutations in ABCB4.Among these 16,however,none developed gallstones in childhood.In 5index patients,all young females carrying at least one pathogenic mutation in one allele of ABCB4,manifestation of LPAC as intrahepatic cholestasis with elevated serum activity of gamma-glutamyltransferase was induced by hormonal contraceptives.Variants ABCB11c.1331T>C and ABCG8 c.55G>C were not significantly overrepresented in the 35 examined patients with suspect LPAC.CONCLUSION:Clinical criteria for LPAC syndrome caused by mutations in ABCB4 cannot be applied topediatric patients with idiopathic gallstones.Sexual immaturity even prevents manifestation of LPAC.

Hepatic Adenoma Secondary to Long-Term Oral Contraception Use in a Young Female

Hepatic adenomas are a rare byproduct of oral contraceptive pill (OCP) use. Laboratory workup is often inconclusive. Diagnosis can be made via MRI;however, select cases may require further testing such as fine needle aspiration or core needle biopsy. We report a case of a 36-year-old female who was referred to gastroenterology for further evaluation of several liver lesions found incidentally on imaging. Due to risk factors, such as age, long-term oral contraceptive use and obesity, adenoma was high on the differential. Although infrequent, this case emphasizes the importance of a detailed history, including medication review, and physical examination.

Retinal vein occlusion associated with combined hormonal contraceptive vaginal ring use

Dear Editor,We read with interest your recent article on the impact of combined oral contraceptives on ocular tissues.We report a case of a branch retinal vein occlusion（BRVO）associated with use of an etonogestrel/ethinyl estradiol vaginal ring（NuvaR ing）,an implantable combined hormonal contraceptive,in a young healthy female with no other identifiable risk factors.

Predictors for partial suppression of spermatogenesis of hormonal male contraception

Aim： To analyze factors influencing the efficacy of hormonal suppression of spermatogenesis for male contraception. Methods： A nested case-control study was conducted, involving 43 subjects, who did not achieve azoospermia or severe oligozoospermia when given monthly injections of 500 mg testosterone undecanoate （TU）, defined as partial suppressors compared with 855 subjects who had suppressed spermatogenesis （complete suppressors）. Sperm density, serum testosterone, luteinizing hormone （LH） and follicle stimulating hormone （FSH） concentrations at the baseline and the suppression phase were compared between partial and complete suppressors. Polymorphisms of androgen receptor （AR） and three single nucleotide variants and their haplotypes of FSH receptor （FSHR） genes determined by polymerase chain reaction （PCR） and DNA sequencing technique were compared between 29 partial and 34 complete suppressors. Results： Baseline serum LH level was higher and serum LH as well as FSH level during the suppression phase was less suppressed in partial suppressors. Additionally, in a logistic regression analysis larger testis volume, higher serum FSH concentrations alone, or interaction of serum LH, FSH, testosterone and sperm concentrations were associated with degree of suppression. The distribution of polymorphisms of AR or FSH receptor genes did not differ between partial and complete suppressors. In cases with incomplete FSH suppression （FSH 〉 0.2 IU/L）, the chances of reaching azoospermia were 1.5 times higher in the subjects with more than 22 CAG triplet repeats. Conclusion： Partial suppression of spermatogenesis induced by 500 mg TU monthly injections is weakly influenced by hormonal and clinical features but not polymorphism in AR and FSHR genes.

Combined Oral Contraceptive Use at the University of Port Harcourt Teaching Hospital, Port Harcourt, Southern Nigeria: A-20 Year Review

Background: While the combined oral contraceptive pill (COCP) is one of the most commonly used methods of birth control especially in the developed countries, robust and current information on the pill use in developing countries including Nigeria is at best lacking. Objectives: The study was conducted to determine the prevalence rate, efficacy and side effects of COCP at the University of Port Harcourt Teaching Hospital (UPTH), Port Harcourt, Southern Nigeria. Methods: It was a retrospective analysis of all clients who used the COCP between 1st January 1997 and 31st December, 2016, at the family planning clinic of UPTH Port Harcourt. Data on sociodemographic profile, side effects and source of information were extracted from the clients’ case notes coded and fed into Excel spread sheet and analysed. Results: Of the 8310 new acceptors of modern contraceptive methods in UPTH, 399 clients used the COCP, giving a prevalence rate of 4.8%. The mean age of the acceptors was 26.42 ± 4.27 years while the mean parity was 1.90 ± 0.36. Menstrual disruption was the most common complications with 78 episodes constituting 47.0% of all the complications. One unintended pregnancy occurred during the period of observation, giving a Pearl index of 0.01. Conclusion: The study showed that although COCP is very effective, readily available, safe and reliable method of fertility control, the acceptance rate is very low and the patronage rapidly declining and may therefore go into extinction as a family planning method in Port Harcourt, Southern, Nigeria.

A drospirenone-containing oral contraceptive improved bleeding pattern and personal satisfaction in 914 women from Jordan, Lebanon and Syria

Aim: We assessed bleeding pattern, tolerance and patient satisfaction of an oral contraceptive containing 3 mg drospirenone and 30 mcg ethinyl estradiol (DRSP/EE) under real-life conditions. Study Design: We performed a multicenter, prospective, 6-cycle, observational study in Canada, Europe and the Middle East. Detailed analyses of the three Middle East countries, Jordan, Lebanon andSyriawere presented here. The efficacy variables included an assessment of bleeding patterns, premenstrual symptoms of water retention and patient satisfaction, as determined by a visual analogue scale. Results: A total of 914 women were enrolled. The percentage of women with intermenstrual bleeding decreased from 37.4%, 48.7% and 32.2% at baseline to 9.7%, 6.1% and 10.9% at the end of cycle6 inJordan, Lebanon and Syria, respectively (creased sharply in all three countries (p Amenorrhea decreased significantly in Lebanon and Syria (p < 0.005). In addition, signs of water retention like abdominal bloating, breast tenderness and swelling of extremities decreased significantly over the course of 6 treatment cycles (p < 0.001). Patient satisfaction increased for all investigated items. Upon completion of the study, 82.7% of women answered “Yes” to continue treatment with this oral contraceptive. Conclusion: The oral contraceptive containing 3 mg drospirenone and 30 mcg ethinyl estradiol has beneficial effects on bleeding pattern, symptoms of water retention and patient satisfaction.

Symptomatic changes in postmenopause with different methods of hormonal therapy

Objective: The diversity of opinions on the adverse effects of medications used to treat postmenopausal symptoms has prompted the use of various routes and mechanisms of action that need to be explored because bioavailability of the medications can vary. In order to select the appropriate route of administration for hormonal therapy (HT), it is necessary to determine baseline therapeutic efficacy. Design: We designed a prospective, randomized study consisting of four groups of postmenopausal wo-men: group 1 received oral conjugated estrogens, group 2 received a synthethic steroid, group 3 received estradiol nasally in spray form, and group 4 used transdermal estradiol in the form of patches. Criteria used to evaluate effectiveness was the Greene scale, which evaluate six components. These criteria were applied to each patient before hormonal intervention and then each month for 6 months. Luteinizing hormone (LH), follicle stimulating horone (FSH) and estradiol concentration were determined by chemiluminescence. Student’s t-test was used for intra-group comparisons before and after treatment. Results: There was a significant decrease in the vasomotor and sexual component (p < 0.05) with the use of four HT types. For depression, a difference was observed with synthetic steroids and oral estrogens. Upon analyzing the somatic component there was a decrease in symptoms with nasal and transdermal routes. Psychological changes were observed with the use of oral synthethic steroids and transdermal patches. Anxiety component demonstrated differences with nasal spray and oral estrogens, although all HT forms in this component showed a pattern of irregular changes. Conclusions: Changes in the response could be due each route of administration and medication used. Absorption variability may exist, which has repercussions in the control of symptoms and should be taken into consideration when selecting the appropriate route of administration for patients beginning HT.