Evaluation of Vitamin D in Women With PCOS and Sexual Dysfunction
Condition: Female Sexual Dysfunction; Polycystic Ovary Syndrome
MeSH terms: Polycystic Ovary Syndrome; Syndrome
Study type: Interventional

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.
    

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.
    

Intervention name(s): Vitamin D; Hormonal contraception
Intervention type(s): Dietary Supplement; Drug
Intervention description(s): Vitamin D 600IU/day; Hormonal contraceptives
Intervention MeSH terms: Vitamin D
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Vitamin D; polycystic ovary syndrome; polycystic ovarian syndrome; PCOS; sexual dysfunction; female sexual dysfunction; low libido