Vit-D/PCOS: Evaluation of Vitamin D in Women With PCOS and Sexual Dysfunction

Sponsor
Wright State University (Other)
Overall Status
Completed
CT.gov ID
NCT02865187
Collaborator
Patty Brisben Foundation For Women's Sexual Health (Other)
47
2
2
46.8
23.5
0.5

Study Details

Study Description

Brief Summary

SUMMARY:

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive age women with a prevalence as high as 15%. The clinical symptoms of PCOS including menstrual dysfunction, infertility, hirsutism, alopecia, acne, and the possible increased risk of diabetes and cardiovascular disease have been reported to be significant contributors to psychological morbidity and impact health-related quality of life. For women with PCOS, the changes in physical appearance and the associated mood disorders appear to be deleterious for sexual function.

Vitamin D deficiency (<20 ng/ml serum concentration of 25[OH]D), which affects from 67% to 85% of women,4 is closely linked to symptoms of PCOS. The main physiologic role of vitamin D is to regulate calcium and phosphorus homeostasis and to promote bone health. Although there has been an increase in awareness of the importance of sexual dysfunction and QoL in women with PCOS, few studies have evaluated the outcomes of treatment for PCOS upon sexual and subjective health status of women.

The goals of this study are:
  1. To evaluate the prevalence of sexual dysfunction (SDy) in women with Polycystic Ovarian Syndrome (PCOS)

  2. To determine the effects of Vitamin D therapy, with and without hormonal contraceptives, on SDy in women with PCOS in the absence of depression.

METHODS:

The study will enroll 60 women diagnosed with PCOS and reporting SDy at the Wright State Physicians (WSP) OB-GYN Practice and the WSP Family Medicine Practice.

All participants will take vitamin D 600IU/day and will choose between hormonal and non-hormonal contraceptive methods (target of 30 participants in each group). Participants will complete three study visits (Initial, Month 3, and Month 6). Vitamin D levels will be drawn at the beginning of the study and again at 3 and 6 months after initiation of vitamin D therapy. Each participant will be asked to complete the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI) prior to initiation of treatment and again at 6 months.

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: Vitamin D
  • Drug: Hormonal contraception
N/A

Detailed Description

BACKGROUND:

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among reproductive age women with a prevalence as high as 15% using Rotterdam diagnostic criteria.1 PCOS is a heterogeneous clinical disorder characterized primarily by chronic anovulation and hyperandrogenism.2 A number of other metabolic and health complications are associated with PCOS including obesity, insulin resistance, dyslipidemia, type 2 diabetes, cardiovascular disease, and endometrial cancer.3

The clinical symptoms of PCOS including menstrual dysfunction, infertility, hirsutism, alopecia, acne, and the possible increased risk of diabetes and cardiovascular disease have been reported to be significant contributors to psychological morbidity and impact health-related quality of life (HRQoL)4,5 including depression and anxiety,6,7 suicide attempts,8 body dissatisfaction,9 eating disorders,10 lower overall health-related quality of life11 and diminished sexual satisfaction.12,13

For women with PCOS, the changes in physical appearance and the associated mood disorders appear to be deleterious for sexual function.6 Previous research in this area is scant, and what has been done reveals a large number of women with PCOS (60%) reporting sexual dysfunction and that the domains of desire and arousal are most commonly affected (in 98% - 99% of cases). Using the Changes in Sexual Functioning Questionnaire (CSFQ), others have reported that women with PCOS were similar to control women in the number of sexual thoughts and fantasies and in the frequency of sexual intercourse, but differed significantly with lower orgasm/completion scores than control women.13 The existing research is limited by the study populations used, which have consisted of infertile women with PCOS who have a high prevalence of sexual dysfunction that may be more related to infertility and not an underlying sexual dysfunction, and by the possible impact of depression and psychotropic medications on sexual dysfunction.

Vitamin D deficiency (<20 ng/ml serum concentration of 25[OH]D), which affects from 67% to 85% of women,4 is closely linked to symptoms of PCOS. Observational studies have shown that lower 25[OH]D levels are associated with insulin resistance, ovulatory and menstrual irregularities, lower pregnancy success, hirsutism, hyperandrogenism, obesity, and elevated cardiovascular disease risk factors14 as well as decreased HRQoL and depression in select populations.15 Nonetheless, there is limited research exploring the implications of vitamin D status and replacement on HRQoL issues including SDy.

The main physiologic role of vitamin D is to regulate calcium and phosphorus homeostasis and to promote bone health. However, accumulating evidence suggests that vitamin D deficiency may also be an important factor for many other diseases. Several mechanisms of action have been proposed to explain the association between vitamin D and depression.

The role of calcitriol or 1,25 dihydroxy cholecalciferol, the bioactive form of vitamin D, in brain tissue has been confirmed by the presence of vitamin D receptors (VDRs) and hydroxylases in various brain regions. One area where VDRs and hydroxylases have been found in the amygdala, the center of the limbic system, where behavior and emotions are regulated.16 In addition, Vitamin D is involved in numerous brain processes including neuroimmunomodulation, regulation of neurotrophic factors, neuroprotection, neuroplasticity and brain development,16 making it biologically plausible that vitamin D might be associated with HRQoL and SDy.

Although there has been an increase in awareness of the importance of sexual dysfunction and QoL in women with PCOS, few studies have evaluated the outcomes of treatment for PCOS upon sexual and subjective health status of women. Therapy has been directed at treating the physical symptoms produced by chronic anovulation, hyperandrogenism and metabolic disturbances associated with insulin resistance of PCOS. Treatment for PCOS has included oral hypoglycemic agents, laparoscopic wedge resection, and cosmetic procedures, such as laser hair removal, but the mainstay remains combined hormonal contraception.

The specific contribution of estrogens and progestogens in oral contraceptives is not fully understood, particularly the latter as it has variable potency and androgenicity. In general, the most commonly used progestins are the 19-testosterone derivatives. Newer oral contraceptives, such as drospirenone, norgestimate, and desogestrel, contain less androgenic progestins. Drospirenone is a 17-alpha spironolactone derivative progestin with antiandrogenic and antimineralocorticoid activity. Studies have shown various benefits of combined hormonal contraceptives for PCOS patients who are not pursuing fertility, e.g., management of endocrine and metabolic profiles, androgen levels, and endometrial cancer.5

Vitamin D supplementation has also been reported to improve glucose metabolism and menstrual frequency in PCOS women17 and since Vitamin D deficiency is closely linked to PCOS and depression, its supplementation has been suggested to possibly play an important part in the treatment of PCOS and HRQoL and perhaps SDy.18

As such, the goal of this study is to evaluate the prevalence of sexual dysfunction and assess the impact of treatment using oral contraceptives with Vitamin D on SDy in absence of depression. The investigators anticipate this may provide a new treatment strategy in SDy issues for women with PCOS.

METHODS:

The study will enroll 60 women diagnosed with PCOS and reporting SDy at the Wright State Physicians (WSP) OB-GYN Practice and the WSP Family Medicine Practice.

All participants will take vitamin D 600IU/day (as recommended by the National Institutes of Health's Office of Dietary Supplements) and will choose between hormonal and non-hormonal contraceptive methods (target of 30 participants in each group). Participants will complete three study visits (Initial, Month 3, and Month 6). Vitamin D levels will be drawn at the beginning of the study and again at 3 and 6 months after initiation of vitamin D therapy. Each participant will be asked to complete the Female Sexual Function Index (FSFI) and the Beck Depression Inventory (BDI) prior to initiation of treatment and again at 6 months.

HUMAN SUBJECTS PROTECTION:

The PI is responsible for protection of human subjects. This protocol will be reviewed by the WSU Institutional Review Board. Only subjects who meet study eligibility criteria will be enrolled. All eligible participants will have the study explained to them. The informed consent process will be conducted appropriately and the informed consent will be obtained prior to proceeding with any study procedures.

The primary physician or the Principal Investigator and research associates will be the individuals obtaining informed consent from patients. They will be uniform in their explanations of the nature of the study to all patients who fit the selection criteria. Those patients interested in participating will be given time to read over the informed consent. The patients will be asked either in the clinic to be involved in the study. After the informed consent is reviewed by the patient any remaining questions will be answered.

Adverse events will be reviewed and evaluated by the PI throughout the study. In the event that any additional diagnoses are obtained during this study, the primary physician for the patient will be notified. It will be their responsibility to notify the patient of these diagnoses and any changes to management that may result.

Subjects' confidentiality will be protected. Participants will be assigned a unique identification (ID) number for the study that will be used on data collection forms rather than subjects' names. Only the minimum data necessary to conduct the study and meet the objectives will be collected. Data will be stored in a secure database (REDCap19) that uses a unique username and password for each team member. Data will be de-identified prior to analysis.

SIGNIFICANCE OF THE STUDY IN RELATION TO HUMAN HEALTH (BENEFITS):

PCOS is the most common reproductive endocrine disorder that has a number of health quality of life issues. The benefit of this study will be to identify SDy which is often overlooked and may potentially be helped with Vit D and/or birth control.

POTENTIAL HAZARDS (RISKS):

The study questionnaires may evoke stressful feelings taking a psychosocial questionnaire. In addition, there are rare potential risks related to OCPs including deep venous thrombosis, and stroke.

Serious side effects of vitamin D include allergic reactions, swelling of the face, throat, and tongue, dizziness, irregular or racing heart beat, dry mouth, headache, vomiting, weakness and lack of energy, and fatigue

The risks of taking blood include pain, a bruise at the point where the blood is taken, redness and swelling of the vein and infection, and a rare risk of fainting.

Study Design

Study Type:
Interventional
Actual Enrollment :
47 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Evaluation of Vitamin D With and Without Hormonal Contraception on Sexual Function in Women With Polycystic Ovary Syndrome
Actual Study Start Date :
Feb 6, 2017
Actual Primary Completion Date :
Mar 31, 2020
Actual Study Completion Date :
Dec 31, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Vitamin D + hormonal contraception

600IU/day Vitamin D + hormonal contraception

Dietary Supplement: Vitamin D
Vitamin D 600IU/day

Drug: Hormonal contraception
Hormonal contraceptives

Active Comparator: Vit D + non-hormonal contraception

600IU/day Vitamin D

Dietary Supplement: Vitamin D
Vitamin D 600IU/day

Outcome Measures

Primary Outcome Measures

  1. Sexual Function [Month 6]

    Female Sexual Function Index (FSFI) scores at Month 6 (Total score ranges from 2 - 36; scores less than 26.55 represent presence/degree of sexual dysfunction)

Secondary Outcome Measures

  1. Prevalence of Sexual Dysfunction in Women With PCOS [Baseline]

    Prevalence rate of women with PCOS defined by scores of the FSFI (total scores range from 2-36; scores less than 26.55 represent presence/degree of sexual dysfunction) - For this outcome, total scores were converted, using the cutoff score of 26.55, into a dichotomous variable for presence or absence of sexual dysfunction.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 40 Years
Sexes Eligible for Study:
Female
Accepts Healthy Volunteers:
No
Inclusion Criteria:
    1. Reproductive age
    1. Have diagnosis of polycystic ovary syndrome by Rotterdam criteria (at least 2 of 3 criteria):
    1. Oligomenorrhea (cycles lasting > 35 days) or amenorrhea (< 3 cycles in last 6 months)
    1. Clinical signs of hyperandrogenism or elevated total testosterone level
    1. Polycystic appearing ovaries
    1. Report sexual dysfunction
    1. Have no evidence of depression
Exclusion Criteria:
    1. Has chronic medical illness such as diabetes mellitus, hypertension, and previous venous embolism
    1. Taking any prescription medications for at least 3 months prior to entry into the study with the exception of allergy or occasional pain medications
    1. Has other etiologies of anovulation and hyperandrogenism, e.g., Cushings disease, thyroid dysfunction, elevated prolactin levels, sighs of congenital adrenal hyperplasia
    1. Has any contraindications to hormonal contraception

Contacts and Locations

Locations

Site City State Country Postal Code
1 Wright State Physicians Dayton Ohio United States 45409
2 Pennsylvania State University Hershey Pennsylvania United States 17033

Sponsors and Collaborators

  • Wright State University
  • Patty Brisben Foundation For Women's Sexual Health

Investigators

  • Principal Investigator: Steven Lindheim, MD, Wright State University

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Steven Lindheim, MD, Professor, Director Reproductive Endocrinology and Infertility, Wright State University
ClinicalTrials.gov Identifier:
NCT02865187
Other Study ID Numbers:
  • 6145
First Posted:
Aug 12, 2016
Last Update Posted:
Mar 25, 2022
Last Verified:
Mar 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Steven Lindheim, MD, Professor, Director Reproductive Endocrinology and Infertility, Wright State University
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title Vitamin D + Hormonal Contraception Vit D + Non-hormonal Contraception
Arm/Group Description 600IU/day Vitamin D + hormonal contraception Vitamin D: Vitamin D 600IU/day Hormonal contraception: Hormonal contraceptives 600IU/day Vitamin D Vitamin D: Vitamin D 600IU/day
Period Title: Overall Study
STARTED 33 14
Visit 2 - at 3 Months 23 7
COMPLETED 20 7
NOT COMPLETED 13 7

Baseline Characteristics

Arm/Group Title Vitamin D + Hormonal Contraception Vit D + Non-hormonal Contraception Total
Arm/Group Description 600IU/day Vitamin D + hormonal contraception Vitamin D: Vitamin D 600IU/day Hormonal contraception: Hormonal contraceptives 600IU/day Vitamin D Vitamin D: Vitamin D 600IU/day Total of all reporting groups
Overall Participants 33 14 47
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
28.2
(5.6)
32.2
(5.1)
29.5
(5.7)
Sex: Female, Male (Count of Participants)
Female
33
100%
14
100%
47
100%
Male
0
0%
0
0%
0
0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native
0
0%
0
0%
0
0%
Asian
1
3%
1
7.1%
2
4.3%
Native Hawaiian or Other Pacific Islander
0
0%
0
0%
0
0%
Black or African American
3
9.1%
2
14.3%
5
10.6%
White
24
72.7%
10
71.4%
34
72.3%
More than one race
3
9.1%
0
0%
3
6.4%
Unknown or Not Reported
2
6.1%
1
7.1%
3
6.4%
Region of Enrollment (participants) [Number]
United States
33
100%
14
100%
47
100%
Female Sexual Function Inventory (FSFI) (score on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [score on a scale]
19.6
(8.3)
22.8
(4.6)
20.5
(7.5)

Outcome Measures

1. Primary Outcome
Title Sexual Function
Description Female Sexual Function Index (FSFI) scores at Month 6 (Total score ranges from 2 - 36; scores less than 26.55 represent presence/degree of sexual dysfunction)
Time Frame Month 6

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Vitamin D + Hormonal Contraception Vit D + Non-hormonal Contraception
Arm/Group Description 600IU/day Vitamin D + hormonal contraception Vitamin D: Vitamin D 600IU/day Hormonal contraception: Hormonal contraceptives 600IU/day Vitamin D Vitamin D: Vitamin D 600IU/day
Measure Participants 23 7
Mean (Standard Deviation) [score on a scale]
24.8
(7.6)
26.0
(4.7)
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin D + Hormonal Contraception, Vit D + Non-hormonal Contraception
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 0.71
Comments a priori threshold for significance was set at p<0.05
Method t-test, 2 sided
Comments
Method of Estimation Estimation Parameter Mean Difference (Final Values)
Estimated Value 0
Confidence Interval (2-Sided) 95%
-7.4 to 5.1
Parameter Dispersion Type: Standard Deviation
Value: 7.0
Estimation Comments
2. Secondary Outcome
Title Prevalence of Sexual Dysfunction in Women With PCOS
Description Prevalence rate of women with PCOS defined by scores of the FSFI (total scores range from 2-36; scores less than 26.55 represent presence/degree of sexual dysfunction) - For this outcome, total scores were converted, using the cutoff score of 26.55, into a dichotomous variable for presence or absence of sexual dysfunction.
Time Frame Baseline

Outcome Measure Data

Analysis Population Description
[Not Specified]
Arm/Group Title Vitamin D + Hormonal Contraception Vit D + Non-hormonal Contraception
Arm/Group Description 600IU/day Vitamin D + hormonal contraception Vitamin D: Vitamin D 600IU/day Hormonal contraception: Hormonal contraceptives 600IU/day Vitamin D Vitamin D: Vitamin D 600IU/day
Measure Participants 33 14
Count of Participants [Participants]
26
78.8%
11
78.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Vitamin D + Hormonal Contraception, Vit D + Non-hormonal Contraception
Comments
Type of Statistical Test Superiority
Comments
Statistical Test of Hypothesis p-Value 1.00
Comments a priori threshold for significance was set at p< 0.05.
Method Chi-squared
Comments
Method of Estimation Estimation Parameter Chi square
Estimated Value .000
Confidence Interval (2-Sided) %
to
Parameter Dispersion Type:
Value:
Estimation Comments

Adverse Events

Time Frame 6 months
Adverse Event Reporting Description
Arm/Group Title Vitamin D + Hormonal Contraception Vit D + Non-hormonal Contraception
Arm/Group Description 600IU/day Vitamin D + hormonal contraception Vitamin D: Vitamin D 600IU/day Hormonal contraception: Hormonal contraceptives 600IU/day Vitamin D Vitamin D: Vitamin D 600IU/day
All Cause Mortality
Vitamin D + Hormonal Contraception Vit D + Non-hormonal Contraception
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/23 (0%) 0/7 (0%)
Serious Adverse Events
Vitamin D + Hormonal Contraception Vit D + Non-hormonal Contraception
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/23 (0%) 0/7 (0%)
Other (Not Including Serious) Adverse Events
Vitamin D + Hormonal Contraception Vit D + Non-hormonal Contraception
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/23 (4.3%) 0/7 (0%)
Psychiatric disorders
worsening depression 1/23 (4.3%) 1 0/7 (0%) 0

Limitations/Caveats

Participants were allowed to choose their treatment group. There was a large number of lost to follow-up participants.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/Title Steven R Lindheim
Organization Wright State University
Phone 858-740-1083
Email doclalalindheim@gmail.com
Responsible Party:
Steven Lindheim, MD, Professor, Director Reproductive Endocrinology and Infertility, Wright State University
ClinicalTrials.gov Identifier:
NCT02865187
Other Study ID Numbers:
  • 6145
First Posted:
Aug 12, 2016
Last Update Posted:
Mar 25, 2022
Last Verified:
Mar 1, 2022