Method and kits for monitoring women's health

• US 20040181167A1
• Filed: 03/10/2004
• Published: 09/16/2004
• Est. Priority Date: 03/13/2003
• Status: Abandoned Application

• Current Assignee: Novartis Ag
• Original Assignee: Novartis Ag
• Inventors: Carney, Fiona Patricia, Morris, Carol Ann
• Application Number:
  US10/797,678
• Publication Number:
  US 20040181167A1
• Time in Patent Office: Days
• US Class Current: 600/551
• CPC Class Codes: A61B 10/0012 Ovulation-period determination for animals A61D17/002
• CPC Class Codes: A61B 10/0045 Devices for taking samples of body liquids devices for taking blood samples A61B5/15
• CPC Class Codes: A61B 2010/0067 Tear or lachrymal fluid
• CPC Class Codes: A61B 5/145 Measuring characteristics of blood in vivo, e.g. gas concentration, pH value; Measuring characteristics of body fluids or tissues, e.g. interstitial fluid, cerebral tissuemeasuring of blood pressure or blood flow A61B5/02; non-radiation detecting or locating of foreign bodies in blood A61B5/06
• CPC Class Codes: A61B 5/14532 for measuring glucose, e.g. by tissue impedance measurement
• CPC Class Codes: A61B 5/14546 for measuring analytes not otherwise provided for, e.g. ions, cytochromes
• CPC Class Codes: A61B 5/1455 using optical sensors, e.g. spectral photometrical oximeters
• CPC Class Codes: A61B 5/42 Detecting, measuring or recording for evaluating the gastrointestinal, the endocrine or the exocrine systems A61B1/00, A61B5/4857, A61B5/486, A61B5/4866, A61B5/4869 take precedence
• CPC Class Codes: A61B 5/4306 for evaluating the female reproductive systems, e.g. gynaecological evaluations

Abstract

The invention provides methods and kits for monitoring the status of women'"'"'s health, including HRT monitoring and determination or diagnosis of ovulation, contraception, pregnancy, menopause, polycystic ovarian disease, and female sexual dysfunction. The method comprises the steps of: (a) collecting a tear fluid from a female human; (b) determining the tear concentration of at least one hormone of relevance to female fertility, sexual differentiation or sexual dysfunction in a female human, wherein the tear concentration is diagnostics of the status of women'"'"'s health.

Claims

1. A method for determining the fertility status of a current ovulation cycle of a female human, comprising the steps of:

(a) monitoring variation in tear concentration of at least one hormone of relevance to female fertility; and

(b) evaluating the correspondence of the variation in tear concentration of said hormone to onset of the transition phase, fertile phase, ovulation, or infertile phase of a menstrual cycle in said female human, wherein the step of monitoring is performed by periodically collecting a tear fluid from the female human and then determining the tear concentration of said hormone.

2. The method of claim 1, wherein the tear fluid is collected by the use of a tear-collecting device selected from the group consisting of a glass capillary tube and a hydrogel strip.

3. The method of claim 2, wherein said tear-collecting device is a hydrogel strip, wherein said strip has a first end and an opposite second end, wherein said strip is made of a hydrogel material in substantially dry state and is characterized by having a substantially uniform swelling along that hydrogel strip from the first end to the second end when fully wicked by a tear fluid and by having a correlation between the volume of tear uptake by that strip and the length of a tear-wicked end portion of that strip.

4. The method of claim 2, wherein the tear fluid is collected daily upon waking or at approximately a fixed time in the morning.

5. The method of claim 1, wherein the tear fluid is collected daily by having the female human wear a contact lens on an eye for at least 30 minutes and then by removing the contact lens from the eye.

6. The method of claim 5, wherein the tear fluid is collected daily at the end of each day, after wearing for more than 6 hour.

7. The method of claim 5, wherein said contact lens is a soft contact lens, a hydrogel soft contact lens, or a daily disposable hydrogel soft contact lens.

8. The method of claim 5, wherein said contact lens is a contact lens capable of binding said hormone, wherein the contact lens includes:

(1) surface charges present in a density sufficient to impart to the contact lens an increased adsorption of said hormone;

(2) a coating comprising a receptor which binds specifically said hormone;

(3) molecular imprints for said hormone;

or (4) a core material that is prepared from a composition containing a receptor which binds specifically said hormone.

9. The method of claim 1, wherein the first collecting of tear fluid in the current cycle is made at the cessation of menses.

10. The method of claim 1, wherein the first collecting of tear fluid in the current cycle is made at least at 3 days following the onset of menses.

11. The method of claim 1, wherein said hormone is estrogen, and wherein a significant increase in its tear concentration or a determined estrogen tear concentration being higher than a threshold value, following the cessation of menses, is indicative of the onset of the fertile period.

12. The method of claim 1, wherein said hormone is LH, wherein detection of a LH surge or a determined LH tear concentration being higher than a threshold value, indicates that the female human will no longer be fertile four days hence (3 days after ovulation).

13. The method of claim 1, wherein said hormone is progesterone, wherein the end of the fertile period can be predicted by detecting a significant increase in progesterone tear concentration or by detecting a progesterone tear concentration being higher than a threshold value following the cessation of menses.

14. The method of claim 1, wherein at least two of estrogen, LH and progesterone are monitored to determine the status of a menstrual cycle of the female human.

15. The method of claim 14, wherein estrogen and progesterone are monitored to determine the status of a menstrual cycle of the female human.

16. The method of claim 15, wherein the estrogen is estradiol, wherein a significant increase in the tear concentration ratio of estradiol to progesterone or a determined value of the tear concentration ratio of estradiol to progesterone being higher than a threshold value, following the cessation of menses, is indicative of the onset of the fertile period.

17. A method for determining the fertility status of a current ovulation cycle of a female human, comprising a series of steps performed at least once per day for at least several days preceding and following ovulation, said steps comprising:

(a) collecting a tear fluid from the female human;

(b) determining variation in tear concentration of at least one hormone of relevance to female fertility to establish variation in tear concentration of said hormone; and

(c) evaluating the correspondence of the variation in tear concentration of said hormone to onset of the fertile phase, ovulation, or infertile phase of a menstrual cycle in said female human.

18. The method of claim 17, wherein the tear fluid is collected by the use of a tear-collecting device selected from the group consisting of a glass capillary tube and a hydrogel strip.

19. The method of claim 18, wherein the tear fluid is collected daily upon waking or at approximately a fixed time in the morning.

20. The method of claim 18, wherein said tear-collecting device is a hydrogel strip, wherein said strip has a first end and an opposite second end, wherein said strip is made of a hydrogel material in substantially dry state and is characterized by having a substantially uniform swelling along that hydrogel strip from the first end to the second end when fully wicked by a tear fluid and by having a correlation between the volume of tear uptake by that strip and the length of a tear-wicked end portion of that strip.

21. The method of claim 17, wherein the tear fluid is collected daily by having the female human wear a contact lens on an eye for at least 30 minutes and then by removing the contact lens from the eye.

22. The method of claim 21, wherein the tear fluid is collected daily at the end of each day, after wearing for more than 6 hour.

23. The method of claim 21, wherein said contact lens is a soft contact lens, a hydrogel soft contact lens, or a daily disposable hydrogel soft contact lens.

24. The method of claim 21, wherein said contact lens is a contact lens capable of binding said hormone, wherein the contact lens includes:

(1) surface charges present in a density sufficient to impart to the contact lens an increased adsorption of said hormone;

(2) a coating comprising a receptor which binds specifically said hormone;

(3) molecular imprints for said hormone;

or (4) a core material that is prepared from a composition containing a receptor which binds specifically said hormone.

25. The method of claim 17, wherein said hormone is estrogen, and wherein a significant increase in its tear concentration or a determined estrogen tear concentration being higher than a threshold value, following the cessation of menses, is indicative of the onset of the fertile period.

26. The method of claim 17, wherein said hormone is LH, wherein detection of a LH surge or a determined LH tear concentration being higher than a threshold value, indicates that the female human will no longer be fertile four days hence (3 days after ovulation).

27. The method of claim 17, wherein said hormone is progesterone, wherein the end of the fertile period can be predicted by detecting a significant increase in progesterone tear concentration or by detecting a progesterone tear concentration being higher than a threshold value following the cessation of menses.

28. The method of claim 17, wherein at least two of estrogen, LH and progesterone are monitored to determine the status of a menstrual cycle of the female human.

29. The method of claim 28, wherein estrogen and progesterone are monitored to determine the status of a menstrual cycle of the female human.

30. The method of claim 29, wherein the estrogen is estradiol, wherein a significant increase in the tear concentration ratio of estradiol to progesterone or a determined value of the tear concentration ratio of estradiol to progesterone being higher than a threshold value, following the cessation of menses, is indicative of the onset of the fertile period.

31. The method of claim 17, further comprising conducting at least one test for the tear concentration of said hormone in the period from day 1 up to and including day 7 calculated from the onset of menses, to establish a base concentration value or signal for said hormone in the current cycle.

32. The method of claim 31, wherein the base concentration value is established from test(s) conducted on day 5 and/or day 6.

33. A birth control method, comprising the steps of:

(a) monitoring variation in tear concentration of at least one hormone of relevance to female fertility;

(b) evaluating the correspondence of the variation in tear concentration of said hormone to onset of the fertile phase, ovulation, and/or terminal infertile period of a menstrual cycle in said female human; and

(c) causing said female human to avoid exposure to fertilization beginning at least at the onset of the fertile phase and ending day “

+2”

relative to the day of actual ovulation, wherein the step of monitoring is performed by periodically collecting a tear fluid from the female human and then determining the tear concentration of said hormone.

34. The method of claim 33, wherein the tear fluid is collected by the use of a tear-collecting device selected from the group consisting of a glass capillary tube and a hydrogel strip.

35. The method of claim 34, wherein the tear fluid is collected daily upon waking or at approximately a fixed time in the morning.

36. The method of claim 34, wherein said tear-collecting device is a hydrogel strip, wherein said strip has a first end and an opposite second end, wherein said strip is made of a hydrogel material in substantially dry state and is characterized by having a substantially uniform swelling along that hydrogel strip from the first end to the second end when fully wicked by a tear fluid and by having a correlation between the volume of tear uptake by that strip and the length of a tear-wicked end portion of that strip.

37. The method of claim 33, wherein the tear fluid is collected daily by having the female human wear a contact lens on an eye for at least 30 minutes and then by removing the contact lens from the eye.

38. The method of claim 37, wherein the tear fluid is collected daily at the end of each day, after wearing for more than 6 hour.

39. The method of claim 37, wherein said contact lens is a soft contact lens, a hydrogel soft contact lens, or a daily disposable hydrogel soft contact lens.

40. The method of claim 37, wherein said contact lens is a contact lens capable of binding said hormone, wherein the contact lens includes:

(1) surface charges present in a density sufficient to impart to the contact lens an increased adsorption of said hormone;

(2) a coating comprising a receptor which binds specifically said hormone;

(3) molecular imprints for said hormone;

or (4) a core material that is prepared from a composition containing a receptor which binds specifically said hormone.

41. The method of claim 33, wherein the first collecting of tear fluid in the current cycle is made at the cessation of menses.

42. The method of claim 33, wherein the first collecting of tear fluid in the current cycle is made at least at 3 days following the onset of menses.

43. The method of claim 33, wherein said hormone is estrogen, and wherein a significant increase in its tear concentration or a determined estrogen tear concentration being higher than a threshold value, following the cessation of menses, is indicative of the onset of the fertile period.

44. The method of claim 33, wherein said hormone is LH, wherein detection of a LH surge or a determined LH tear concentration being higher than a threshold value, indicates that the female human will no longer be fertile four days hence (3 days after ovulation).

45. The method of claim 33, wherein said hormone is progesterone, wherein the end of the fertile period can be predicted by detecting a significant increase in progesterone tear concentration or by detecting a progesterone tear concentration being higher than a threshold value following the cessation of menses.

46. The method of claim 33, wherein at least two of estrogen, LH and progesterone are monitored to determine the status of a menstrual cycle of the female human.

47. The method of claim 46, wherein estrogen and progesterone are monitored to determine the status of a menstrual cycle of the female human.

48. The method of claim 47, wherein the estrogen is estradiol, wherein a significant increase in the tear concentration ratio of estradiol to progesterone or a determined value of the tear concentration ratio of estradiol to progesterone being higher than a threshold value, following the cessation of menses, is indicative of the onset of the fertile period.

49. A birth control method, comprising a series of steps performed at least once per day for at least several days preceding and following ovulation, said steps comprising:

(a) collecting a tear fluid from the female human;

(b) determining variation in tear concentration of at least one hormone of relevance to female fertility to establish variation in tear concentration of said hormone;

(c) evaluating the correspondence of the variation in tear concentration of said hormone to onset of the fertile phase, ovulation, and/or terminal infertile period of a menstrual cycle in said female human; and

(c) causing said female human to avoid exposure to fertilization beginning at least at the onset of the fertile phase and ending day “

+2”

relative to the day of actual ovulation.

50. The method of claim 49, wherein the tear fluid is collected by the use of a tear-collecting device selected from the group consisting of a glass capillary tube and a hydrogel strip.

51. The method of claim 50, wherein the tear fluid is collected daily upon waking or at approximately a fixed time in the morning.

52. The method of claim 50, wherein said tear-collecting device is a hydrogel strip, wherein said strip has a first end and an opposite second end, wherein said strip is made of a hydrogel material in substantially dry state and is characterized by having a substantially uniform swelling along that hydrogel strip from the first end to the second end when fully wicked by a tear fluid and by having a correlation between the volume of tear uptake by that strip and the length of a tear-wicked end portion of that strip.

53. The method of claim 49, wherein the tear fluid is collected daily by having the female human wear a contact lens on an eye for at least 30 minutes and then by removing the contact lens from the eye.

54. The method of claim 53, wherein the tear fluid is collected daily at the end of each day, after wearing for more than 6 hour.

55. The method of claim 53, wherein said contact lens is a soft contact lens, a hydrogel soft contact lens, or a daily disposable hydrogel soft contact lens.

56. The method of claim 53, wherein said contact lens is a contact lens capable of binding said hormone, wherein the contact lens includes:

(1) surface charges present in a density sufficient to impart to the contact lens an increased adsorption of said hormone;

(2) a coating comprising a receptor which binds specifically said hormone;

(3) molecular imprints for said hormone;

or (4) a core material that is prepared from a composition containing a receptor which binds specifically said hormone.

57. The method of claim 49, wherein said hormone is estrogen, and wherein a significant increase in its tear concentration or a determined estrogen tear concentration being higher than a threshold value, following the cessation of menses, is indicative of the onset of the fertile period.

58. The method of claim 49, wherein said hormone is LH, wherein detection of a LH surge or a determined LH tear concentration being higher than a threshold value, indicates that the female human will no longer be fertile four days hence (3 days after ovulation).

59. The method of claim 49, wherein said hormone is progesterone, wherein the end of the fertile period can be predicted by detecting a significant increase in progesterone tear concentration or by detecting a progesterone tear concentration being higher than a threshold value following the cessation of menses.

60. The method of claim 49, wherein at least two of estrogen, LH and progesterone are monitored to determine the status of a menstrual cycle of the female human.

61. The method of claim 60, wherein estrogen and progesterone are monitored to determine the status of a menstrual cycle of the female human.

62. The method of claim 61, wherein the estrogen is estradiol, wherein a significant increase in the tear concentration ratio of estradiol to progesterone or a determined value of the tear concentration ratio of estradiol to progesterone being higher than a threshold value, following the cessation of menses, is indicative of the onset of the fertile period.

63. The method of claim 49, further comprising conducting at least one test for the tear concentration of said hormone in the period from day 1 up to and including day 7 calculated from the onset of menses, to establish a base concentration value or signal for said hormone in the current cycle.

64. The method of claim 63, wherein the base concentration value is established from test(s) conducted on day 5 and/or day 6.

65. A method for monitoring the status of women'"'"'s health, comprising the steps of:

(a) collecting a tear fluid from an eye of a female;

(b) determining the tear concentration of at least one hormone of relevance to female fertility, sexual differentiation or sexual dysfunction in a female human, wherein the tear concentration of said hormone is diagnostics of the status of women'"'"'s health.

66. The method of claim 65, wherein the tear fluid is collected by the use of a tear-collecting device selected from the group consisting of a glass capillary tube, a hydrogel strip and a contact lens.

67. The method of claim 66, wherein said at least one hormone is selected from the group consisting of human chorionic gonadotropin (hCG), follicle stimulating hormone (FSH), estrogens, progesterone, testosterone, sex hormone binding globulin, LH, and prolactin.

68. The method of claim 66, wherein the tear concentration of human chorionic gonadotropin (hCG) is monitored for pregnancy tests.

69. The method of claim 66, wherein the tear concentration of follicle stimulating hormone (FSH) is monitored for menopausal diagnosis.

70. The method of claim 66, wherein the tear concentration of estradiol and/or progesterone is monitored to determine the amount of hormones required in hormonal replacement therapy.

71. The method of claim 66, wherein the tear concentration of testosterone, sex hormone binding globulin, progesterone, LH, FSH and/or prolactin is determined to diagnose/monitor polycystic ovarian disease.

72. The method of claim 66, wherein the tear concentration of testosterone is determined to diagnose female sexual dysfunction (FSD).

73. A kit for determining the fertility status of a current ovulation cycle of a female human, for birth control, or for monitoring the status of women'"'"'s health, the kit comprising:

a plurality of tear-collecting devices, a testing reagent composition which specifically reacts or interacts with at least one hormone of relevance to female fertility, sexual differentiation or sexual dysfunction in a female human to form a detectable signal which changes in a concentration-dependent manner, and optionally instruction.

74. The kit of claim 73, wherein the tear-collecting devices are selected from the group consisting of glass capillary tubes, hydrogel strips, contact lenses, and combinations thereof.

75. The kit of claim 74, wherein the tear-collecting device are hydrogel strips, wherein each of said strip has a first end and an opposite second end, wherein each of said strip is made of a hydrogel material in substantially dry state and is characterized by having a substantially uniform swelling along that hydrogel strip from the first end to the second end when fully wicked by a tear fluid and by having a correlation between the volume of tear uptake by that strip and the length of a tear-wicked end portion of that strip.

76. The kit of claim 74, wherein the tear-collecting devices are contact lenses.

77. The kit of claim 76, wherein the contact lenses are soft contact lenses, hydrogel soft contact lenses, or daily disposable hydrogel soft contact lenses.

78. The kit of claim 76, wherein each of the contact lenses includes:

(1) surface charges present in a density sufficient to impart to the contact lens an increased adsorption of said hormone;

(2) a coating comprising a receptor which binds specifically said hormone;

(3) molecular imprints for said hormone;

or (4) a core material that is prepared from a composition containing a receptor which binds specifically said hormone.

79. The kit of claim 78, wherein each of the contact lenses has surface charges which are introduced by:

(1) preparing the contact lens from a composition comprising a positively or negatively charged monomer or macromer;

(2) altering the chemical nature of chemical groups on the surface of the contact lens;

(3) applying an LbL coating composed of at least one layer of a polyionic material onto the contact lens;

or (4) combinations of (1), (2) and (3).

80. The kit of claim 78, wherein each of the contact lenses has a coating comprising a receptor which binds one or more hormones of relevance to female fertility, sexual differentiation or sexual dysfunction in a female human.

81. The kit of claim 80, wherein the receptor is selected from the group consisting of antibodies, lectins, hormone receptors, drug receptors, enzymes, aptamers, nucleic acids, nucleic acid analogs, and fragments thereof.

82. The kit of claim 78, wherein each of the contact lenses has molecular imprints for at least one hormone of relevance to female fertility, sexual differentiation or sexual dysfunction in a female human.

83. The kit of claim 78, wherein each of the contact lenses has a core material that is prepared from a composition containing a receptor which binds specifically at least one hormone of relevance to female fertility, sexual differentiation or sexual dysfunction in a female human.

84. A method for determining the fertility status of a current ovulation cycle of a female non-human mammal, comprising the steps of:

(a) monitoring variation in tear concentration of at least one hormone of relevance to female fertility; and

(b) evaluating the correspondence of the variation in tear concentration of said hormone to onset of the transition phase, fertile phase, ovulation, or infertile phase of a menstrual cycle in said female nonhuman mammal, wherein the step of monitoring is performed by periodically collecting a tear fluid from the female nonhuman mammal and then determining the tear concentration of said hormone.

85. The method of claim 84, wherein the tear fluid is collected by the use of a tear-collecting device selected from the group consisting of a glass capillary tube and a hydrogel strip.

86. The method of claim 84, wherein said hormone is estrogen, and wherein a significant increase in its tear concentration or a determined estrogen tear concentration being higher than a threshold value, following the cessation of menses, is indicative of the onset of the fertile period.

87. The method of claim 84, wherein said hormone is LH, wherein detection of a LH surge or a determined LH tear concentration being higher than a threshold value, indicates that the female nonhuman mammal will no longer be fertile four days hence (3 days after ovulation).

88. The method of claim 84, wherein said hormone is progesterone, wherein the end of the fertile period can be predicted by detecting a significant increase in progesterone tear concentration or by detecting a progesterone tear concentration being higher than a threshold value following the cessation of menses.

89. The method of claim 84, wherein at least two of estrogen, LH and progesterone are monitored to determine the status of a menstrual cycle of the female nonhuman mammal.

90. The method of claim 89, wherein estrogen and progesterone are monitored to determine the status of a menstrual cycle of the female nonhuman mammal.

91. The method of claim 90, wherein the estrogen is estradiol, wherein a significant increase in the tear concentration ratio of estradiol to progesterone or a determined value of the tear concentration ratio of estradiol to progesterone being higher than a threshold value, following the cessation of menses, is indicative of the onset of the fertile period.