U.S. patent application number 12/620725 was filed with the patent office on 2010-06-10 for pharmaceutical compositions containing testosterone and an aromatase inhibitor.
Invention is credited to Rebecca L. Glaser.
Application Number | 20100144687 12/620725 |
Document ID | / |
Family ID | 42231770 |
Filed Date | 2010-06-10 |
United States Patent
Application |
20100144687 |
Kind Code |
A1 |
Glaser; Rebecca L. |
June 10, 2010 |
PHARMACEUTICAL COMPOSITIONS CONTAINING TESTOSTERONE AND AN
AROMATASE INHIBITOR
Abstract
A pharmaceutical dosage comprising testosterone or an ester
thereof and an aromatase inhibitor; the aromatase inhibitor may be
selected from the group consisting of anastrozole, letrozole, and
exemestane. In one embodiment the dosage is an implant. Also
disclosed are therapies for patients with symptoms of relative
androgen deficiency, breast cancer survivors and other therapies in
which testosterone is indicated but elevated estradiol levels are
avoided.
Inventors: |
Glaser; Rebecca L.; (Dayton,
OH) |
Correspondence
Address: |
THOMPSON HINE L.L.P.;Intellectual Property Group
P.O. BOX 8801
DAYTON
OH
45401-8801
US
|
Family ID: |
42231770 |
Appl. No.: |
12/620725 |
Filed: |
November 18, 2009 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
61200867 |
Dec 5, 2008 |
|
|
|
Current U.S.
Class: |
514/171 |
Current CPC
Class: |
A61K 9/0024 20130101;
A61K 9/2013 20130101; A61K 31/568 20130101; A61K 31/565 20130101;
A61P 5/24 20180101; A61K 31/4196 20130101; A61K 31/4196 20130101;
A61K 2300/00 20130101; A61K 31/565 20130101; A61K 2300/00 20130101;
A61K 31/568 20130101; A61K 2300/00 20130101 |
Class at
Publication: |
514/171 |
International
Class: |
A61K 31/568 20060101
A61K031/568; A61P 5/24 20060101 A61P005/24 |
Claims
1. A pharmaceutical dosage comprising testosterone or an ester
thereof and an aromatase inhibitor.
2. The dosage of claim 1 wherein the aromatase inhibitor is
selected from the group consisting of anastrozole, letrozole, and
exemestane.
3. The dosage of claim 2 further including a pharmaceutically
acceptable excipient.
4. The dosage of claim 3 wherein the dosage is a subcutaneous
implant.
5. The dosage of claim 4 wherein the dosage contains about 30 to
200 mg. testosterone.
6. The dosage of claim 5 wherein the dosage contains about 1 to 90
mg. aromatase inhibitor.
7. The dosage of claim 6 wherein the excipient is capable of
releasing the testosterone and the aromatase inhibitor into the
blood at a controlled rate for a period of at least 30 days.
8. The dosage of claim 3 wherein the excipient is a lubricant or a
binder or a combination thereof.
9. The dosage of claim 6 wherein the dosage is suitable for
administration in an amount that provides less than 30 pg/ml
estradiol level in the blood serum.
10. The dosage of claim 8 wherein the amount of excipient is less
than about 5% by weight of the dosage.
11. The dosage of claim 10 wherein the aromatase inhibitor is
anastrozole.
12. The dosage of claim 11 wherein the dosage contains
testosterone.
13. The dosage of claim 12 wherein the dosage contains about 50 to
90 mg. testosterone.
14. The dosage of claim 13 wherein the dosage contains about 3 to
14 mg. aromatase inhibitor.
15. The dosage of claim 1 wherein the dosage provides approximately
zero order release of testosterone.
Description
CROSS-REFERENCE TO RELATED APPLICATIONS
[0001] This application claims the benefit of U.S. application Ser.
No. 61/200,867, filed Dec. 5, 2008.
BACKGROUND
[0002] Testosterone, delivered by subcutaneous pellet implant has
been used in the United States, Europe and Australia in both men
and women to treat symptoms of testosterone deficiency. Symptoms of
testosterone hormone deficiency include fatigue, lack of energy,
depression, memory loss, concentration difficulties, weakness,
aches, pains, anemia, suppressed immune system, insomnia, hot
flashes, night sweats, bone loss (osteopenia, osteoporosis), muscle
mass loss, inability to loose weight (fat mass), anxiety, emotional
lability, vaginal dryness, urinary urgency, urinary frequency, and
incontinence.
[0003] Potential benefits of testosterone delivery by implant
include increased bone density, increased energy, relief of
lethargy, relief of depression and anxiety, improved memory and
concentration, improved sleep, increased muscle mass, decreased fat
mass, relief of aches and pains, relief of breast pain, relief of
migraine headaches, restoration of sex drive and libido, menopausal
syndrome relief (hot flashes, night sweats), prevention of uterine
bleeding caused by estrogens, use in dysmenorrheic patients with
endometriosis or small fibroids, relief of nocturia and
incontinence, relief of vaginal symptoms, arterial vaso-dilation,
increased arterial blood flow, lowering the risk of breast cancer
in women on estrogen/progestin therapy, palliative measure
(carcinoma of the breast), decreased proliferation of breast
tissue, reduction of ER (estrogen receptor) alpha, enhance immune
system, and increased red blood cell production.
[0004] Anastrozole is an aromatase inhibitor and has been used
orally as an adjuvant therapy in breast cancer in post-menopausal
women. By blocking the enzyme "aromatase," anastrozole inhibits the
conversion of testosterone to estradiol thus preventing the
stimulation of breast tissue and breast cancer cells by estradiol.
Oral anastrozole has been used in male patients to prevent the
conversion of testosterone to estradiol, thus raising testosterone
levels and lowering estradiol levels.
SUMMARY OF INVENTION
[0005] The invention relates to a pharmaceutical composition
comprising testosterone or an ester thereof and an aromatase
inhibitor. In one embodiment the pharmaceutical composition is
formulated as a sustained release, subcutaneous pellet implant. In
this composition, an aromatase inhibitor is combined with
testosterone to continuously deliver testosterone and
simultaneously prevent the conversion of testosterone to estradiol
by the aromatase inhibitor.
[0006] The composition and, more particularly, the
testosterone-anastrozole subcutaneous, sustained release implant,
is indicated for use in male and female patients. It may be used in
patients with symptoms of relative androgen deficiency (including
bone loss, joint/muscular pain, anemia, suppressed immune system,
depression, memory loss, fatigue, sexual problems and sleep
problems) who may benefit from testosterone therapy, where elevated
estradiol (estrogen) levels are to be avoided. In one embodiment it
is indicated for use in breast cancer survivors where the use of
testosterone has been cautioned against because of the
aromatization of testosterone to estradiol, a potent estrogen.
Estradiol is known to stimulate proliferation of breast tissue and
breast cancer. It may also be indicated for patients with a
diagnosis of invasive or non-invasive breast cancer (e.g., hormone
receptor positive (estrogen receptor positive) breast cancer
survivors); patients at high risk for breast cancer (e.g., family
history of breast cancer, gene positive (BRCA I or BRCA II) for
breast cancer, prior breast biopsy with `atypia` or a diagnosis of
`atypical ductal hyperplasia,` or diagnosis of Lobular Carcinoma in
Situ); patients with benign breast disease (e.g., fibrocystic
breast disease, breast tenderness, cystic mastitis); obese patients
(e.g., elevated aromatase (enzyme) levels are found in fat tissue
making this group of patients more likely to convert testosterone
to estradiol such that lowering estradiol levels may help with
weight loss); male patients on testosterone therapy who have
previously demonstrated elevated estrogen levels; and patients with
insulin resistance (e.g., elevated estrogen has been associated
with insulin resistance).
[0007] In one embodiment, an implant is composed of the active
ingredients testosterone and anastrozole. In one embodiment the
implant may consist of the active ingredients, however, to improve
the integrity of the pellet and facilitate its manufacture in one
embodiment the active ingredients are used with excipients such as
a lubricant and/or a binder. In one embodiment the lubricant is
stearic acid. In one embodiment the binder is povidone. In one
embodiment, the excipients make up less than 20%, more particularly
less than 10%, and still more particularly less than 5% of the
composition. In one embodiment, these ingredients are formed into
an implant such as cylindrical pellets measuring in one case
approximately 3.1 mm by 6.5 mm, then packaged and sterilized. In
one embodiment the implant contains the testosterone and the
aromatization inhibitor in a weight ratio of about 5:1 to about
30:1 and, more particularly in a ratio of about 15:1 to 25:1 and
still more particularly 10:1 to 20:1. For example in one instance
the implant includes 60mg testosterone and 6 mg inhibitor and in
another instance the implant contains 60 mg testosterone and 3 mg
inhibitor. Preferably the implant fits through a standard size, 3.2
mm pellet implanter (trocar/cannula) and can be inserted through a
small incision into subcutaneous tissue in an area that experiences
relatively little movement such as the lower abdomen or upper
buttocks. In one embodiment, a single implant may be used. In
another embodiment depending on the condition of the patient, two
or more implants may be used together.
[0008] In one embodiment, the implant may be formulated to deliver
continuous, therapeutic testosterone and anastrozole therapy for
12-16 weeks. In one embodiment, particularly when the amount of
excipients is minimal, the implant provides approximately zero
order release proportional to the surface area of the
pellet(s).
[0009] The implant can enable significantly lower dosing (for
example, 6 mg released over 100 days (0.06 mg/day) vs. 1.0 mg/d
oral dose) with fewer side effects than oral anastrozole therapy
(see below). In addition, avoiding the GI tract avoids nausea or
adverse effects to the GI tract. Subcutaneous delivery also avoids
adverse effects from `first pass` metabolism in the liver including
hepatic-toxicity or increase in clotting factors. Subcutaneous
delivery of the combination of testosterone and anastrozole also
can reduce or eliminate patient non-compliance.
[0010] One manifestation of the invention is a subcutaneous,
sustained release pellet implant. However, other dosages such as
oral tablets and capsules, and transdermal patches constitute
additional embodiments of the invention.
[0011] In one embodiment, the combination of testosterone (hormone)
with anastrozole (aromatase inhibitor) will elevate testosterone
levels without elevating or with reduced or limited elevation of
estradiol levels.
[0012] In one embodiment, the combination of testosterone with
anastrozole will relieve symptoms of hormone deficiency in patients
in whom elevated estrogen levels are contraindicated.
[0013] In one embodiment, the combination of subcutaneous
testosterone with anastrozole may offer breast protection and
reduce the risk of recurrent disease in breast cancer
survivors.
[0014] In one embodiment, subcutaneous anastrozole appears to
prevent the conversion of DHEA (dehydro-epiandrosterone), an
adrenal androgen to estrone, an estrogen that may stimulate breast
tissue and elevate with obesity.
DETAILED DESCRIPTION
[0015] While testosterone is used in one embodiment of the
invention, it will be understood that esters of testosterone may be
used such as testosterone propionate, cypionate, enanthate,
decanoate, and undecanoate. Herein, with the exception of the
claims, the use of the term "testosterone" shall be understood to
include testosterone and its esters. The testosterone is used in
its crystalline form in one embodiment but it may be used in its
noncrystalline or amorphous form in another embodiment. The amount
of testosterone in the composition, will be an amount that delivers
a pharmaceutically effective serum blood level. In one embodiment,
the testosterone is used in implants in an amount of about 30 to
200 mg. In a more particular embodiment, the testosterone is used
in an amount of about 50 to 90 mg. As indicated earlier, one or
more implants may be used depending on the size, weight and
condition of the patient.
[0016] Representative examples of aromatase inhibitors useful in
accordance with this disclosure include, but are not limited to,
anastrozole, letrozole and exemestane. The inhibitor is used in an
amount effective to prevent formation of the estradiol from the
testosterone. The amount is selected to inhibit the aromatase
enzyme will depend on the condition of the patient. More
particularly, the inhibitor is used in an amount that is effective
in keeping estradiol blood serum levels less than about 54 pg/ml in
males and more particularly less than about 45 pg/ml and still more
particularly less than about 30 pg/ml. In females, the estradiol
blood levels are less than 30 pg/ml in one embodiment. Because the
aromatase inhibitor tends to reside in fat tissue, higher doses may
be desirable in patients who are obese. In one embodiment the
implant contains the inhibitor in an amount of about 1 to 90 mg. In
a more particular embodiment, the inhibitor may be used in an
amount of about 2 to 50 mg. and in a still more particular
embodiment, the inhibitor may be used in the implant in an amount
of about 3 to 14 mg.
[0017] In accordance with one embodiment of the invention an
implant is provided that is able to provide nearly zero order
release of the testosterone. In one embodiment the implant is in
excess of 90% or 98% active and contains only a small amount of
excipient. In one embodiment the implant contains a small amount of
a pharmaceutically acceptable lubricant (such as stearic acid)
sufficient to facilitate removal of the implant from the pellet
forming mold without damage. In another embodiment, to improve the
structural integrity of the pellet a small amount of a
pharmaceutically acceptable binder is used (e.g., PVP (povidone)
(0.2-2 mg) may be used). Neither the stearic acid, nor povidone
appears to affect release rate of the active ingredients.
[0018] Those skilled in the art will appreciate that the implant
can also be formulated as a "matrix" type device, in which an
active compound is dispersed in a matrix of carrier material. The
carrier material may be either porous or non-porous, solid or
semi-solid, and permeable or impermeable to the active compound.
Matrix devices may be biodegradable, i.e., they may slowly erode
after administration. Alternatively, matrix devices may be
nondegradable, and rely on diffusion of the active compound through
the walls or pores of the matrix. Other devices may be "reservoir"
type, and consist of a central reservoir of active compound
surrounded by a rate controlling membrane. The membrane may be
porous or non-porous. The release rate often depends only on the
surface area of the device. In some cases the sustained release
devices are hybrids, having a matrix core surrounded by a
membrane.
[0019] A number of implant devices are known in the art that may be
adopted for use in accordance with this disclosure. For
example:
[0020] H. Nash, et al., "Steroid Release From Silastic Capsules and
Rods" Contraception, 18, 367-394 (1978) discloses both reservoir
and matrix implants fashioned from Silastic.RTM.,
polydimethylsiloxane, for sustained administration of contraceptive
steroids. The steroids used are testosterone and testosterone
propionate.
[0021] Shippy, et al., "Controlled Release of Testosterone Using
Silicone Rubber" J. Biomed. Mater. Res., 7, 95-110 (1973) discloses
a reservoir device comprising a crystalline testosterone cylinder
dipped in Silastic.RTM. or a Silastic.RTM../testosterone
suspension.
[0022] Japanese application J5 9044-310A to Nippon Kayaku discloses
a matrix device of a silicone rubber formulation containing a
crystalline powdered dissolution assistant (especially a monobasic
amino acid, e.g., glycine or alanine, NaCl or mannitol) and an
antibiotic or anticancer drug. These devices are reported to
achieve a release time of one week to one month.
[0023] UK Patent Application 2,167,662A to Dick discloses a matrix
implant device in the form of a solid cylinder. The matrix is
formed from a hydrophobic polymer such as polypropylene,
polyethylene, polyvinyl chloride, ethylvinyl acetate, polystyrene
and polymethacrylate, as well as glycerol esters of the glycerol
palmitostearate, glycerol stearate and glycerol behenate type.
[0024] U.S. Pat. No. 3,948,254 to Zaffaroni discloses a hybrid
device comprising a solid matrix drug reservoir encapsulated in a
microporous membrane, where the membrane pores are filled with a
carrier material.
[0025] UK Patent Application 2,154,138A to Roche discloses a hybrid
subcutaneous implant using silicone rubber. The device is formed as
a substantially hollow cylinder of the silicone rubber, with a core
consisting of active ingredients dispersed in a biocompatible,
biosoluble polymer which dissolves within days of implantation. The
biocompatible, biosoluble polymer is a mixture of high molecular
weight polyethylene glycol (PEG) and low molecular weight PEG, for
example, PEG 3,000-10,000 with PEG 200-600.
[0026] U.S. Pat. No. 5,035,891 to Runkel discloses a subcutaneous
implant made by formulating compressed pellets containing a
biologically active compound, a solubilizing agent, a solid,
hydrophilic, non-toxic polymer sufficient to cause swelling by
osmotic pressure after implantation, followed by wrapping the
pellet(s) in a rate-controlling membrane which is permeable to the
biologically active compound but is impermeable to the solubilizing
agent. The implants so obtained are particularly advantageous in a
number of respects:
[0027] The invention is illustrated in more detail by the following
non-limiting example:
EXAMPLE 1
[0028] USP testosterone (50-90 mg) and USP anastrozole (4-12 mg)
are mixed with a carrier such as stearic acid (0-4 mg). The mixed
ingredients are moulded/compressed in a standard pellet press using
2000 pounds (1 ton) of pressure into cylindrical pellets 3.1 mm
diameter.
[0029] The individual testosterone/anastrozole pellets are then
placed into sealed glass ampoules or standard pharmaceutical `peel
packs.` They are then sterilized using gamma radiation or
autoclaved at 121.degree. C. for 40 minutes, steam generator
pressure 20-25 psi, autoclave jacket pressure 15-25. Release rate
also appears to be independent of compression pressure.
[0030] Each sterile implant is supplied in a sealed glass ampoule
or standard pharmaceutical peel pack. Do not store above 25.degree.
C. Store in the original package.
CLINICAL DATA
[0031] Efficacy and Safety of subcutaneous anastrozole/testosterone
combination in the elevation of testosterone levels and the
prevention of the conversion of testosterone to estradiol is
illustrated by the following case presentations: [0032] 1. 315
pound, 58 year old male patient previously treated with
subcutaneous testosterone replacement therapy (TRT) that presented
with an extremely elevated estradiol 8 days following implantation
with testosterone pellets (123 pg/mL, optimal range <30 for
males). Two weeks following testosterone pellet implantation, two
60 mg testosterone/6 mg anastrozole pellets were implanted into the
subcutaneous tissue. One week following implantation of the
combination pellets, estradiol measured <30 pg/mL. Testosterone
measured 1341 ng/dL. This was confirmed at day 13. Estradiol
remained optimal, <30pg/mL and testosterone measured 1269 ng/dL.
[0033] 2. 67 year old, 214-pound male treated with subcutaneous TRT
with pellet implants presented with an elevated estradiol prior to
re-implantation (54 pg/mL). At the time of testosterone pellet
implantation, one testosterone 60 mg/anastrozole 6 mg pellet was
implanted with 14, 100 mg testosterone pellet implants. Follow up
serum levels at one month revealed a therapeutic testosterone
levels (842 ng/dL) and estradiol <30 pg.mL. FU serum estradiol
level at 21/2 months was 45 pg/mL, within range for males (0-54).
<30 pg/mL is felt to be optimal. Follow up estradiol at week 15
was <30 pg/mL. Next insert, two testosterone/anastrozole pellet
implants will be placed. [0034] 3. 55 year old, 63 inch, 135 pound
female with a history of invasive breast cancer was treated for
symptoms of hormone deficiency with one testosterone 60
mg/anastrozole 6 mg pellet implant in addition to a 55 mg
testosterone pellet. Symptoms of androgen/hormone deficiency were
relieved and the patient had no side effects from therapy.
Ultra-sensitive estradiol measured <7 pg/mL at week 6.
Testosterone measured 369 ng/dL. Follow up estradiol at week ten
remained low (10 pg/mL) despite a therapeutic testosterone level of
139.6 ng/dL. A second testosterone/anastrozole insert was performed
12 weeks later. Follow up estradiol measures 10 pg/mL (optimal)
with a therapeutic testosterone level of 305 ng/dL, consistent with
previous results. [0035] 4. 50 year old, 71 inch, 210 pound female
with a history of metastatic breast cancer, currently on
chemotherapy, treated with one testosterone 60 mg/anastrozole 6 mg
pellet implant in addition to a 100 mg testosterone pellet implant.
Estradiol at day 18 measured <30 pg/mL. Patient noted
significant improvement in bone pain from metastatic disease. An
additional testosterone 60 mg/anastrozole 6 mg pellet implant was
placed 5 weeks after initial insert. Patient experienced further
reduction of bone pain. Follow up estradiol remained <30 pg/mL.
[0036] 5. 50 year old, 62 inch, 146 pound female with a history of
invasive breast cancer, was treated with one testosterone 60
mg/anastrozole 6 mg pellet implant in addition to a 55 mg
testosterone pellet implant. Serum estradiol at day 7 measured
<30 pg/mL. [0037] 6. 57 year old, 68 inch, 192 pound female with
a history of invasive breast cancer, was treated with one
testosterone 60 mg/anastrozole 6 mg pellet implant in addition to a
75 mg testosterone pellet. Serum estradiol at day 13 measured
<30mg/mL. Testosterone measured 165 ng/dL. [0038] 7. 58 year
old, 64 inch, 160 pound female with a history of breast cancer was
treated with one testosterone 60 mg/anastrozole 6 mg pellet implant
in addition to an 80 mg testosterone pellet. Serum estradiol at day
24 measured <30 pg/mL and testosterone measured 169 ng/dL.
[0039] 8. 73 year old, 62.5 inch, 170 pound female with a history
of non-invasive (DCIS), bilateral breast cancer, was treated with
one testosterone 60 mg/anastrozole 6 mg pellet implant in addition
to a 100 mg testosterone pellet implant. Serum estradiol at day 13
measured <30 pg/mL and testosterone measured 290 ng/dL. [0040]
9. 56 year old, 65.5 inch, 220 pound female with a history of
breast cancer, was treated with one testosterone 60 mg/anastrozole
6 mg pellet implant in addition to a 100 mg testosterone pellet
implant. Estradiol at day 25 measured <30 pg/mL and testosterone
measured 247 ng/dL. [0041] 10. 53 year old, 59 inch, 183 pound
female with a history of invasive breast cancer treated with
chemotherapy was treated with one testosterone 60 mg/anastrozole 6
mg pellet implant in addition to a 100 mg testosterone pellet
implant. Serum estradiol at day 7 measured <30 pg/mL, estrone
<10 pg/mL and testosterone measured 220 ng/dL. Previously she
had been unable to tolerate `low dose` (0.5 mg twice weekly) oral
anastrozole, complaining of severe hot flashes, night sweats "all
through the night`, and headaches. She had discontinued the oral
anastrozole. She experienced no side effects with the subcutaneous
anastrozole with testosterone pellet implant. [0042] 11. 54 year
old, 67 inch, 145 pound female with a history of non-invasive
breast cancer
[0043] (DCIS), was treated with one testosterone 60 mg/anastrozole
6 mg pellet implant in addition to a 55 mg testosterone pellet
implant. Serum `sensitive` estradiol at day 7 measured 25 pg/mL.
Serum estrone also remained low, 22 pg/mL. [0044] 12. 64 year old,
144 pound female with a history of breast cancer, was treated with
one testosterone 60 mg/anastrozole 6 mg pellet implant in addition
to a 55 mg testosterone pellet implant. Serum estradiol measured
<10 pg/mL and testosterone measured 313.9 ng/dL at week one.
[0045] 13. 78 year old, 140 pound female with a history of breast
cancer, was treated with one testosterone 60 mg/anastrozole 6 mg
pellet implant in addition to a 55 mg testosterone pellet implant.
Day 9, serum estrone measured <10 pg/mL, estriol <0.10 and
testosterone 300 ng/dL. [0046] 14. 45 year old, 66 inch, 135 pound
female with a history of breast cancer, was treated with one
testosterone 60 mg/anastrozole 6 mg pellet implant in addition to a
55 mg testosterone pellet implant. Serum estradiol at week one
measured <30 pg/mL, estrone<10 pg/mL with a therapeutic
testosterone of 136 ng/dL. [0047] 15. 51 year old, 154 pound female
with a history of metastatic breast cancer, was treated with one
testosterone 60 mg/anastrozole 6 mg pellet implant in addition to a
100 mg testosterone pellet implant. Day 18, serum estradiol
measured <10 ng/dL, total estrogens <1.0 ng/dL and
testosterone 404 ng/dL. [0048] 16. 48 year old, 66 inch, 155 pound
female with a history of invasive breast cancer, was treated with
one testosterone 60 mg/anastrozole 6 mg pellet implant in addition
to a 100 mg testosterone pellet implant. Serum estradiol at week
one measured <30 pg/mL with a therapeutic testosterone of 232
ng/dL. [0049] 17. 61 year old, 64 inch, 160 pound female with a
history of invasive breast cancer 15 years prior treated with
chemotherapy and tamoxifen treated with one testosterone 60
mg/anastrozole 6 mg pellet implant in addition to a 75 mg
testosterone pellet implant. Serum estradiol at week one measured
<30 pg/mL, Estrone was 15 pg/mL (optimal) with a therapeutic
testosterone of 191 ng/dL. [0050] 18. 67 year old, 67 inch, 170
pound female with a history of DCIS, ductal carcinoma in situ (non
invasive breast cancer), treated with lumpectomy and radiation
therapy. The patient with one testosterone 60 mg/anastrozole 6 mg
pellet implant in addition to a 65 mg testosterone pellet implant.
Serum estradiol measured <10 pg/mL, Estrone 4.3 pg/mL (3-32
pg/mL post men), with a therapeutic testosterone level of 453
ng/dL. [0051] 19. 47 year old, 210 pound female with a history of
breast cancer, was treated with one testosterone 60 mg/anastrozole
6 mg pellet implant in addition to a 100 mg testosterone pellet
implant. Day 12, serum estradiol measured 41 pg/mL (not considered
elevated, but slightly above post menopausal levels) with a
therapeutic testosterone of 338 ng/dL. Patient felt great.
Estradiol was remeasured at week 4, and testosterone was 460 ng/dL,
and estradiol was <30 pg/mL, FSH 50.2.
[0052] While the invention has been illustrated by several
expressions of several embodiments, and enablements, and
applications, thereof, the invention is defined by the appended
claims and is not limited to the specific examples. Numerous
variations, modifications, and substitutions are possible without
departing from the scope of the invention as defined in the
appended claims. It will be understood that the foregoing
description is provided by way of example, and that other
modifications may occur to those skilled in the art without
departing from the scope and spirit of the appended Claims.
* * * * *